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Sample records for variants hb tripoli

  1. Hb variants in Korea: effect on HbA1c using five routine methods.

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    Yun, Yeo-Min; Ji, Misuk; Ko, Dae-Hyun; Chun, Sail; Kwon, Gye Cheol; Lee, Kyunghoon; Song, Sang Hoon; Seong, Moon Woo; Park, Sung Sup; Song, Junghan

    2017-07-26

    Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

  2. Comparison of the characteristics of two hemoglobin variants, Hb D-Iran and Hb E, eluting in the Hb A2 window.

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    Dass, Jasmita; Gupta, Aastha; Mittal, Suchi; Saraf, Amrita; Langer, Sabina; Bhargava, Manorama

    2017-06-01

    Cation exchange-high performance liquid chromatography (CE-HPLC) is most commonly used to evaluate hemoglobin (Hb) variants, which elute in the Hb A2 window. This study aimed to assess prevalence of an uncommon Hb variant, Hb D-Iran, and compare its red cell parameters and peak characteristics with those of Hb E that commonly elutes in the Hb A2 window. Generally, we assess abnormal Hb using CE-HPLC as the primary technique along with alkaline and acid electrophoresis. All cases with Hb A2 window >9%, as assessed by CE-HPLCs during 2009-2013, were selected. Twenty-nine cases with Hb D-Iran variant were identified-25 heterozygous, 2 homozygous, 1 compound heterozygous Hb D-Iran/β-thalassemia, and 1 Hb D-Iran/Hb D-Punjab. Overall prevalence of Hb D-Iran was 0.23%. Compared to patients with Hb E, those with Hb D-Iran had significantly higher Hb (12.1 vs. 11.3 g/dL, P =0.03), MCV (82.4 vs. 76.4 fL, P =0.0044), MCH (27.9 vs. 25.45 pg, P =0.0006), and MCHC (33.9 vs. 33.3 g/dL, P =0.0005). Amount of abnormal Hb (40.7 vs. 26.4%, P =0.0001) was significantly higher while retention time (3.56 vs. 3.70 min, P =0.0001) was significantly lower in Hb D-Iran than in Hb E. Hb D-Iran peak can be easily missed if area and retention time of the Hb A2 window are not carefully analyzed. To distinguish between variants, careful analysis of peak area and retention time is sufficient in most cases and may be further confirmed by the second technique-alkaline electrophoresis.

  3. Characterization of Hb Lepore variants in the UK population.

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    Guo, Lina; Kausar, Anika; Old, John M; Henderson, Shirley J; Gallienne, Alice E

    2015-01-01

    A molecular study of Hb Lepore heterozygotes identified by the UK population screening program has revealed four out of the five known Lepore variants. The region of homologous δ- and β-globin gene sequence was determined in 58 unrelated Hb Lepore heterozygotes referred for confirmation of their carrier status by DNA analysis through the national thalassemia and sickle cell screening program over a period of 10 years. The most common variant found was Hb Lepore-Boston-Washington (Hb LBW, HBD: c.265 C > c.315 + 7 C) observed in 46 carriers (79.0%). Hb Lepore-Hollandia (HBD: c.69 A > c.92 + 16 A) was found in nine cases (16.0%); Hb Lepore-Baltimore (HBD: c.208 G > c.254 C) in two cases (4.0%) and Hb Lepore-ARUP (HBD: c.97 C > c.150 C) in one carrier (2.0%). Analysis of the hematological findings showed no significant differences between the four groups. The wide range of Hb Lepore variants observed in this study confirms the very diverse range of α- and β-globin gene mutations observed in the UK population by previous studies.

  4. Hb Melusine and Hb Athens-Georgia: potentially underreported in the Belgian population? Four cases demonstrating the lack of detection using common CE-HPLC methods either for glycated hemoglobin (HbA1C) analysis or Hb variant screening.

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    Peeters, Bart; Brandt, Inger; Desmet, Koenraad; Harteveld, Cornelis L; Kieffer, Davy

    2016-12-01

    Suspected hemoglobin (Hb) variants, detected during HbA 1C measurements should be further investigated, determining the extent of the interference with each method. This is the first report of Hb Melusine and Hb Athens-Georgia in Caucasian Belgian patients. Intervention & Technique: Since common CE-HPLC methods for HbA 1C analysis or Hb variant screening are apparently unable to detect these Hb variants, their presence might be underestimated. HbA 1C analysis using CZE, however, alerted for their presence. Moreover, in case of Hb Melusine, even Hb variant screening using CZE was unsuccessful in its detection. Fortunately, carriage of Hb Melusine or Hb Athens-Georgia variants has no clinical implications and, as shown in this report, no apparent difference in HbA 1C should be expected.

  5. Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography.

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    Zhang, Xiu-Ming; Wen, Dong-Mei; Xu, Sheng-Nan; Suo, Ming-Huan; Chen, Ya-Qiong

    2018-01-01

    To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and α-thalassemia HbH on the results of HbA1c assessment using ion-exchange high-performance liquid chromatography (IE-HPLC). We enrolled five patients in which the results of the IE-HPLC HbA1c assay were inconsistent with the average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis using whole-blood samples. We also sequenced the genes encoding Hb using dideoxy-mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA-HPLC) and turbidimetric inhibition immunoassay (TINIA). Two patients had the HbJ Bangkok variant. Hb genotypes of these patients were β 41-42 /β J Bangkok and β N /β J Bangkok , and the content of HbJ Bangkok was 93.9% and 52.4%, respectively. The remaining three patients had the following: HbE (β N /β E Hb genotype, 23.6% HbE content), HbG Taipei (β N /β G Taipei Hb genotype, 39.4% HbG Taipei content), and α-thalassemia HbH (6.1% HbH content, 2.8% Hb Bart's content). In the patients with β-thalassemia and HbJ Bangkok variants, the presence of the variants interfered with the results of HbA1c analyses using IE-HPLC and TINIA; in the remaining four patients, there was interference with the results of HbA1c IE-HPLC but not with the TINIA assay. There was no interference with BA-HPLC HbA1c results. HbJ Bangkok, HbE, HbG Taipei Hb, and α-thalassemia HbH disease cause varying degrees of interference with the analysis of HbA1c using IE-HPLC. In these patients, we suggest using methods free from such interference for the analysis of HbA1c and other indicators to monitor blood glucose levels. © 2017 Wiley Periodicals, Inc.

  6. Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods.

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    Xu, Anping; Chen, Weidong; Xia, Yong; Zhou, Yu; Ji, Ling

    2018-04-07

    HbA1c is a widely used biomarker for diabetes mellitus management. Here, we evaluated the accuracy of six methods for determining HbA1c values in Chinese patients with common α- and β-globin chains variants in China. Blood samples from normal subjects and individuals exhibiting hemoglobin variants were analyzed for HbA1c, using Sebia Capillarys 2 Flex Piercing (C2FP), Bio-Rad Variant II Turbo 2.0, Tosoh HLC-723 G8 (ver. 5.24), Arkray ADAMS A1c HA-8180V fast mode, Cobas c501 and Trinity Ultra2 systems. DNA sequencing revealed five common β-globin chain variants and three common α-globin chain variants. The most common variant was Hb E, followed by Hb New York, Hb J-Bangkok, Hb G-Coushatta, Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2 and Hb G-Taipei. Variant II Turbo 2.0, Ultra2 and Cobas c501 showed good agreement with C2FP for most samples with variants. HLC-723 G8 yielded no HbA1c values for Hb J-Bangkok, Hb Q-Thailand and Hb G-Honolulu. Samples with Hb E, Hb G-Coushatta, Hb G-Taipei and Hb Ube-2 produced significant negative biases for HLC-723 G8. HA-8180V showed statistically significant differences for Hb E, Hb G-Coushatta, Hb G-Taipei, Hb Q-Thailand and Hb G-Honolulu. HA-8180V yielded no HbA1c values for Hb J-Bangkok. All methods showed good agreement for samples with Hb New York. Some common hemoglobin variants can interfere with HbA1c determination by the most popular methods in China.

  7. HbA1c levels in individuals heterozygous for hemoglobin variants.

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    Tavares, Ricardo Silva; Souza, Fábio Oliveira de; Francescantonio, Isabel Cristina Carvalho Medeiros; Soares, Weslley Carvalho; Mesquita, Mauro Meira

    2017-04-01

    To evaluate the levels of glycated hemoglobin (HbA1c) in patients heterozygous for hemoglobin variants and compare the results of this test with those of a control group. This was an experimental study based on the comparison of HbA1c tests in two different populations, with a test group represented by individuals heterozygous for hemoglobin variants (AS and AC) and a control group consisting of people with electrophoretic profile AA. The two populations were required to meet the following inclusion criteria: Normal levels of fasting glucose, hemoglobin, urea and triglycerides, bilirubin > 20 mg/dL and non-use of acetylsalicylic acid. 50 heterozygous subjects and 50 controls were evaluated between August 2013 and May 2014. The comparison of HbA1c levels between heterozygous individuals and control subjects was performed based on standard deviation, mean and G-Test. The study assessed a test group and a control group, both with 39 adults and 11 children. The mean among heterozygous adults for HbA1c was 5.0%, while the control group showed a rate of 5.74%. Heterozygous children presented mean HbA1c at 5.11%, while the controls were at 5.78%. G-Test yielded p=0.93 for children and p=0.89 for adults. Our study evaluated HbA1c using ion exchange chromatography resins, and the patients heterozygous for hemoglobin variants showed no significant difference from the control group.

  8. HbQ-India associated with microcytosis: An uncommon hemoglobin variant associated with a common hematologic condition

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    Amit Kumar Yadav

    2010-09-01

    Full Text Available HbQ-India is a rare alpha chain variant that usually presents in the heterozygous state. Normally, HbQ-India is clinically silent. It becomes symptomatic when present in association with other conditions. We report a case of HbQ-India with concomitant presence of iron deficiency anemia. A 16-year-old female presented with weakness and pallor intermittently for six years. Complete blood count showed severe microcytic hypochromic anemia. Hemoglobin electrophoresis showed a prominent band in the S,D,G region. Tests for sickling were negative. High performance liquid chromatography (HPLC showed a peak in the unknown window (4.70-4.90 min suggestive of HbQ-India. Serum iron profile was suggestive of iron deficiency anemia. Based on the above findings, a diagnosis of coexistent HbQ-India–iron deficiency anemia was made. A family study revealed the father as having moderate anemia with similar findings while the mother was normal. Abnormal hemoglobin in the patient was confirmed by molecular diagnosis.HbQ variants are the alpha globin chain variants due to structural mutations (α64 Asp→His inherited in autosomal dominant fashion. Three molecular variant types have been documented, namely HbQ-India, HbQ-Thailand and HbQ-Iran. Normally, HbQ is clinically silent. Therefore, careful screening of the samples using routine techniques like Hb electrophoresis and HPLC are needed for identification of such abnormal hemoglobin variants like HbQ-India.

  9. Novel interactions of two α-Hb variants with SEA deletion α0-thalassemia: hematological and molecular analyses.

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    Srivorakun, Hataichanok; Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan

    2018-04-01

    To report the hematological and molecular features as well as diagnostic aspects of the hitherto un-described interactions of two rare α-globin chain variants with α 0 -thalassemia commonly found among Southeast Asian populations. The study was done on two adult Thai patients (P1 and P2) who had hypochromic microcytic anemia. Hb analysis was carried out using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Mutations were identified by PCR and related techniques. Hb analysis of P1 using HPLC showed a normal Hb pattern, but CE demonstrated an abnormal peak at zone 7. DNA sequencing identified a CCG-CTG mutation at codon 95 of the α2 globin gene corresponding to the Hb G-Georgia [α95(G2)Pro → Leu(α2)] previously undescribed in the Thai population. In contrast, Hb analysis of P2 demonstrated an abnormal peak not fully separated from Hb A on HPLC, but not on CE. DNA analysis identified the rarely described Hb Nakhon Ratchasima [α63(E12)Ala → Val(α2)] mutation. Routine DNA analysis detected the SEA deletion α 0 -thalassemia in trans to the Hb variants in both cases. Hematological parameters were compared with those of patients with compound heterozygote for other α-globin variants and α 0 -thalassemia previously documented. Identification of the patients confirmed that interaction of these rare Hb variants with α 0 -thalassemia does not lead to the Hb H disease. Differentiation of these two Hb variants from other clinically relevant hemoglobinopathies in a routine setting is, however, necessary. This can be accomplished using a combined Hb-HPLC and CE analysis followed by PCR-RFLP assays.

  10. Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarte α(2)β(2)).

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    Fais, Antonella; Casu, Mariano; Ruggerone, Paolo; Ceccarelli, Matteo; Porcu, Simona; Era, Benedetta; Anedda, Roberto; Sollaino, Maria Carla; Galanello, Renzo; Corda, Marcella

    2011-01-01

    WE REPORT THE FIRST CASE OF COSEGREGATION OF TWO HAEMOGLOBINS (HBS): HbG-Philadelphia [α68(E17)Asn → Lys] and HbDuarte [β62(E6)Ala → Pro]. The proband is a young patient heterozygous also for β°-thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG-Philadelphia/Duarte. Functional study of the new double variant HbG-Philadelphia/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to β62Ala → Pro instead of α68Asn → Lys substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the β62 position produces displacement of the E helix and modifications of the tertiary structure. The substitution α68(E17)Asn → Lys does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested.

  11. A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy.

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    Rodríguez-Capote, Karina; Estey, Mathew P; Barakauskas, Vilte; Bordeleau, Pierre; Christensen, Cathie-Lou; Zuberbuhler, Peter; Higgins, Trefor N

    2015-09-01

    To report the finding of a novel double heterozygous hemoglobinopathy, the coinheritance of Hb Fontainebleau (α-chain variant) with HbD-Punjab (β-chain variant) discovered upon investigation of unexplained microcytosis in an infant. Hemoglobinopathy investigation was performed by high performance liquid chromatography (HPLC) using the β-thalassemia Short Program on the Bio-Rad Variant II(TM) followed by gel electrophoresis at alkaline and acid pH (Sebia Hydrasys 2 Electrophoresis System) and molecular diagnostic testing. This study complied with our institutional board ethics requirements. HPLC and electrophoresis suggested a complex α- and β-chain hemoglobinopathy with presumptive identification of the beta Hb variant as Hb D-Punjab. DNA sequencing analysis revealed the presence of a double heterozygous status for Hb Fontainebleau/Hb D-Punjab. In this paper we report the coinheritance of Hb Fontainebleau with Hb D-Punjab. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. Co-inheritance of the rare β hemoglobin variants Hb Yaounde, Hb Görwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling.

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    Vinciguerra, Margherita; Passarello, Cristina; Leto, Filippo; Cassarà, Filippo; Cannata, Monica; Maggio, Aurelio; Giambona, Antonino

    2015-04-01

    Nearly 1183 different molecular defects of the globin genes leading to hemoglobin variants have been identified (http://globin.bx.psu.edu) over the past decades. The purpose of this study was to report three cases, never described in the literature, of co-inheritance of three β hemoglobin variants with other alterations in globin genes and to evaluate the clinical significance to conduct an appropriate genetic counseling. We report the molecular study performed in three probands and their families, sampling during the screening program conducted at the Laboratory for Molecular Prenatal Diagnosis of Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy. This work allowed us to describe the co-inheritance of three rare β hemoglobin variants with other alterations in globin genes: the β hemoglobin variant Hb Yaounde [β134(H12)Val>Ala], found for the first time in combination with ααα(anti3.7) arrangement, and the β hemoglobin variants Hb Görwihl [β5(A2)Pro>Ala] and Hb City of Hope [β69(E13)Gly>Ser], found both in association with β(0) -thalassemia. The present work emphasizes the importance of a careful evaluation of the hematological data, especially in cases of atypical hematological parameters, to carry out an adequate and complete molecular study and to formulate an appropriate genetic counseling for couples at risk. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Hb A1c Determination by Capillary Electrophoresis is an Efficient Method for Detecting β-Thalassemias and Hemoglobin Variants.

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    Orts, Juan A; Zúñiga, Ángel; Bello, Yanis; Fabregat, Aleix B; Vicente, Ana I

    2016-09-01

    Glycated hemoglobin (Hb A 1c ) determination by multicapillary zone electrophoresis (MZE) can additionally be used to detect Hb A 2 , Hb F and most common hemoglobin (Hb) variants. We assessed the effectiveness of this method for detecting β-thalassemia (β-thal), δβ-thalassemia (δβ-thal) and most common Hb variants. Moreover, Hb F/Hb A 2 is evaluated as an index for discriminating between β- and δβ-thal traits. The theoretical β-thalassemia major (β-TM) birth rate in our healthcare area is calculated and contrasted with real data. A MZE technique was used for Hb A 1c measurements in 27,724 patients. Previous criteria for carrier detection were established and subsequently confirmed by molecular biology techniques. Positive predictive value (PPV) was 100.0%. The prevalence of β-thal trait (including δβ-thal) was 0.34%. The most prevalent mutations (estimated per 100,000 population) were HBB: c.118C > T (57.7%), HBB: c.93-21G>A (50.5%), HBB: c.92 + 1G > A (43.3%), HBB: c.92 + 6T > C (32.5%) and HBB: c.20delA (18.0%) for β-thalassemias, and Hb S (HBB: c.20A > T) (32.5%) and Hb J-Baltimore (HBB:c.3880T>A) (28.9%) for Hb variants. We found a paradoxical result between the theoretical β-TM birth rate and real data. We calculated an optimal Hb F/Hb A 2 index cutoff of 0.71 for discriminating between β- and δβ-thal traits. This method is highly cost-effective for detecting β-thalassemias and common Hb variants. Prevalence results match previous data for the Spanish population. Heterogeneity of mutations in Spain has markedly increased as a consequence of migration. The Hb F/Hb A 2 index cutoff could be used to predict δβ-thal trait.

  14. Hb F Levels in Indian Sickle Cell Patients and Association with the HBB Locus Variant rs10128556 (C>T), and the HBG XmnI (Arab-Indian) Variant.

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    Bhanushali, Aparna A; Himani, Kumari; Patra, Pradeep K; Das, Bibhu R

    The prevalence of sickle cell disease in India is very high. Hb F is one of the most powerful modulators of disease severity in sickle cell disease patients. It was traditionally thought that the disease is milder in Indian sickle cell disease patients predominantly due to the Arab-Indian haplotype characterized by the HBG XmnI [rs7482144 (G>A)] variant, which is associated with increased Hb F levels. In the current study, we investigated the Hb F levels in individuals with the rs10128556 (C>T) variant and also determined its linkage with the HBG XmnI variant. The present study was conducted on a cohort of 275 individuals, which consisted of 221 patients with sickle cell disease and 54 patients with sickle cell trait. Analysis of hemoglobin (Hb) fractions and variants was done on the high performance liquid chromatography (HPLC) system. Genotyping for rs10128556 was done by direct sequencing of the products. Mean Hb F levels in the sickle cell disease patients was 19.36 ± 6.79. The genotypic frequencies for rs10128556 were 82.0% (TT), 16.7% (CT) and 1.3% (CC) for sickle cell disease patients. The minor C allele resulted in 52.0% decrease in Hb F levels when homozygous and 7.0% decrease when heterozygous. The rs10128556 single nucleotide polymorphism (SNP) was in strong but not complete linkage with the HBG XmnI variant. In conclusion, the study determined for the first time the frequency and association of rs10128556 in Indian sickle cell disease patients with Hb F. It also established that it was not in complete linkage with the HBG XmnI variant in this high risk population.

  15. [Hb Burgos (α1 CD64(E13)(Asp→Asn)): a new hemoglobin variant detected during follow-up of diabetic patients].

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    de la Fuente-Gonzalo, Félix; Martínez Nieto, Jorge; Torrejón, María José; Mayor, Luis Antonio; Velasco, Diego; González Fernández, Fernando Ataulfo; Ropero Gradilla, Paloma

    2015-01-06

    The glycated hemoglobin (HbA1c) test by high performance liquid chromatography is a useful tool for the follow-up of diabetes mellitus patients. Some structural hemoglobin (Hb) variants are known to cause interference in the analytical measurement of HbA1c. In this study, it has been characterized a new Hb variant in 4 patients during their regular control of HbA1c. Selective α1 gene sequencing showed a mutation GAC>AAC at codon 64 within exon 2. This produces a change of aspartic acid (Asp) by asparagine (Asn) that does not produce any functional alteration so the resultant molecule behaves as a silent hemoglobinopathy. The structural Hb variants can be detected during the analysis of HbA1c and may alter its values. Though rare, this occurrence signals the need to being aware when measuring HbA1c. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. A Clinical Update of the Hb Siirt [β27(B9)Ala→Gly; HBB: c.83C>G] Hemoglobin Variant.

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    Cappabianca, Maria Pia; Colosimo, Alessia; Sabatucci, Annalaura; Dainese, Enrico; Di Biagio, Paola; Piscitelli, Roberta; Sarra, Ofelia; Zei, Daniela; Amato, Antonio

    2017-01-01

    We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly; HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (-CT) (HBB: c.17_18delCT) frameshift mutation and of the ααα anti 3.7 triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ∼40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and ααα anti 3.7 triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82 G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β + -thalassemia (β + -thal) phenotype.

  17. Diagnosis of a rare double heterozygous Hb D Punjab/Hb Q India hemoglobinopathy using Sebia capillary zone electrophoresis

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    Sushama Parab

    2014-01-01

    Full Text Available In India, hemoglobinopathies constitute a major genetic disorder and hemoglobin variants such as Hb S, Hb D Punjab, and Hb E are the most common ones. Other variants include Hb Q India, Hb Lepore, Hb J Meerut, Hb D Iran, etc. These variants show heterozygous state along with beta thalassemia. However, compound heterozygosities among these variants are very rare. Ethylenediaminetetraacetic acid whole blood sample received for routine thalassemia screening was subjected to alkaline electrophoresis using automated capillary zone electrophoresis. Suspecting the presence of rare variants, further analysis was carried out using Bio-Rad D10 and Tosoh G8 high-performance liquid chromatography (HPLC systems. Capillary zone electrophoretograms showed the presence of peaks in zone Hb A, Hb D, a fused peak in Hb A2, and a small peak in Z1 zone. Bio-Rad and Tosoh chromatograms also indicated the presence of four peaks which are identified as Hb A, Hb D Punjab, Hb Q India, and hybrid of Hb D Punjab/Hb Q India. A peak in Hb D zone of capillary was due to co-migration of Hb D Punjab and Hb Q India variants. Small peak in Z1 zone indicated the presence of alpha chain variant Hb Q India. The findings were further confirmed by HPLC results and molecular genetic studies. The present study reports for the 1 st time a rare hemoglobinopathy of double heterozygosity for Hb D Punjab, Hb Q India on Capillarys 2 Flex Piercing analyzer and is forth reported case for this rare hemoglobinopathy.

  18. A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

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    Wang, Mei-Chun; Tsai, Kuo-Wang; Chu, Chih-Hsun; Yu, Ming-Sun; Lam, Hing-Chung

    2015-01-01

    Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

  19. Aldimine Formation Reaction, the First Step of the Maillard Early-phase Reaction, Might be Enhanced in Variant Hemoglobin, Hb Himeji.

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    Koga, Masafumi; Inada, Shinya; Shimizu, Sayoko; Hatazaki, Masahiro; Umayahara, Yutaka; Nishihara, Eijun

    2015-01-01

    Hb Himeji (β140Ala→Asp) is known as a variant hemoglobin in which glycation is enhanced and HbA1c measured by immunoassay shows a high value. The phenomenon of enhanced glycation in Hb Himeji is based on the fact that the glycation product of variant hemoglobin (HbX1c) shows a higher value than HbA1c. In this study, we investigated whether aldimine formation reaction, the first step of the Maillard early-phase reaction, is enhanced in Hb Himeji in vitro. Three non-diabetic subjects with Hb Himeji and four non-diabetic subjects without variant hemoglobin were enrolled. In order to examine aldimine formation reaction, whole blood cells were incubated with 500 mg/dl of glucose at 37°C for 1 hour and were analyzed by high-performance liquid chromatography. Both HbA1c and HbX1c were not increased in this condition. After incubation with glucose, labile HbA1c (LA1c) fraction increased in the controls (1.1±0.3%). In subjects with Hb Himeji increases in the labile HbX1c (LX1c) fraction as well as the LA1c fraction were observed, and the degree of increase in the LX1c fraction was significantly higher than that of the LA1c fraction (1.8±0.1% vs. 0.5±0.2%, Preaction might be enhanced in Hb Himeji in vitro. The 140th amino acid in β chain of hemoglobin is suggested to be involved in aldimine formation reaction. © 2015 by the Association of Clinical Scientists, Inc.

  20. Hb Belluno [β111(G13)Val→Gly;β133(H11)Val→Val (HBB: c.335T > G;402G > C)]: Incidental Detection of a New Clinically Silent β Chain Variant During Hb A1c Determination by High Performance Liquid Chromatography.

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    Pianezze, Graziano; Toniolo, Manuele; Taddei Masieri, Marina; Dolcini, Bernardetta; Ravani, Anna

    2016-06-01

    A previously unreported β chain variant, Hb Belluno [β111(G13)Val→Gly;β133(H11)Val→Val (HBB: c.335T > G;402G > C)], was incidentally discovered in a woman suffering from diabetes, during glycated hemoglobin (Hb A1c) assay. Its presence was suspected because of a small abnormal peak with a retention time just shorter than that of normal Hb A1c. Standard high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE) and agarose gel electrophoresis did not allow to separate the variant from Hb A. The reversed phase HPLC of globin chains showed the presence of a heterozygous β-globin variant amounting to approximately 43.5% of the total β chains. Later, this variant was found in five other members of the same family and DNA sequencing analysis confirmed a β-globin gene mutation. The variant is clinically silent in all patients and showed a slight instability with both heat and isopropanol tests. The other three mutations at this locus also affect stability. Hemoglobin (Hb) variants may invalidate the results of Hb A1c analysis and could result in mismanagement of diabetes. A comment alerting the requesting clinician to the presence of the Hb variant must be appended to the Hb A1c result. Additionally, many Hb variants can be chromatographically and/or electrophoretically silent. Therefore, when the clinician suspects a variant Hb, it is not sufficient to get a negative response from an HPLC screening test to rule it out. A dialogue with the pathologist is essential, involving exchange of information and sharing a diagnostic work-up including surveys to assess Hb stability and oxygen affinity, as much as DNA sequencing.

  1. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations

    NARCIS (Netherlands)

    B. Giardine (Belinda); J. Borg (Joseph); E. Viennas (Emmanouil); C. Pavlidis (Cristiana); K. Moradkhani (Kamran); P. Joly (Philippe); M. Bartsakoulia (Marina); C. Riemer (Cathy); W. Miller (Webb); G. Tzimas (Giannis); H. Wajcman (Henri); R.C. Hardison (Ross); G.P. Patrinos (George)

    2014-01-01

    textabstractHbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and

  2. HbD Punjab/HbQ India compound heterozygosity: An unusual association.

    Directory of Open Access Journals (Sweden)

    Stacy Colaco

    2014-11-01

    Full Text Available Background: Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. Both beta thalassaemia and structural haemoglobin variants are relatively common in north western India. Here we report a 29 year old Sindhi female who was referred to us for a haemoglobinopathy work up and genetic counseling since her spouse was a classical beta thalassaemia carrier. Method: A complete blood count was done on an automated cell counter. Haemoglobin analysis was carried out using HPLC Variant Haemoglobin Testing System.  The cellulose acetate electrophoresis was carried out [pH 8.9]. Confirmation of mutations was done by automated DNA sequencing. Results: HPLC analysis showed four major peaks, HbA0, a peak in the HbD window, an unknown peak [retention time 4.74 minutes] and a peak in the HbC window. The HbA2 level was 2.2% and the HbF level was 0.7%.Cellulose acetate electrophoresis at alkaline pH, a slow moving band was seen at the HbS/D position along with a prominent band at the HbA2 position. DNA sequencing of the β and α genes showed presence of the 2 hemoglobin variants :Hb D [b 121GAA à CAA] and Hb Q [a 64 AAG à GAG]. The δ globin gene was normal. The additional peak in the HbC window was due to the formation of a heterodimer hybrid. Conclusion: Both HbD Punjab and HbQ India are relatively common in India but their co-inheritance has not been described in the country. This is the second report of compound heterozygosity for HbQ India/HbD Punjab haemoglobinopathy globally, and the first one from India.

  3. Description of Three New α Variants and Four New β Variants: Hb Montluel [α110(G17)Ala → Val; HBA1: c.332C > T], Hb Cap d'Agde [α131(H14)Ser → Cys; HBA2: c.395C > G] and Hb Corsica [α100(G7)Leu → Pro; HBA1: 302T > C]; Hb Nîmes [β104(G6)Arg → Gly; HBB: c.313A > G], Hb Saint Marcellin [β112(G14)Cys → Gly; HBB: c.337T > G], Hb Saint Chamond [β80(EF4)Asn → 0; HBB: c.241_243delAAC] and Hb Dompierre [β29(B11)Gly → Arg; HBB: c.88G > C].

    Science.gov (United States)

    Renoux, Céline; Feray, Cécile; Joly, Philippe; Lacan, Philippe; Francina, Alain

    2015-01-01

    We present here seven new hemoglobin (Hb) variants identified during routine Hb analysis. All of them are caused by a missense mutation except Hb Saint Chamond, which results from an in-frame deletion of the asparagine residue at β80. All these variants are clinically silent in the heterozygous state but two of them (Hb Cap d'Agde and Hb Dompierre) may be unstable, whereas Hb Nîmes could present a very slightly elevated oxygen affinity. These data are to be confirmed by appropriate biochemical tests.

  4. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

    2010-01-01

    A case of Hb Canebière [ß102(G4)Asn¿His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb Canebi...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  5. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

    2010-01-01

    A case of Hb Canebière [β102(G4)Asn→His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  6. Erroneous HbA1c results in a patient with elevated HbC and HbF.

    Science.gov (United States)

    Adekanmbi, Joy; Higgins, Trefor; Rodriguez-Capote, Karina; Thomas, Dylan; Winterstein, Jeffrey; Dixon, Tara; Gifford, Jessica L; Krause, Richard; Venner, Allison A; Clarke, Gwen; Estey, Mathew P

    2016-11-01

    HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. A Novel Variant with Positive Natural Selection Influenced Hb A2 Levels in Chinese Individuals with β-Thalassemia.

    Science.gov (United States)

    Yu, Shanjuan; Chen, Yang; Lai, Ketong; Dewan, Roma Kajal; He, Yunyan

    2017-05-01

    β-Thalassemia (β-thal) is the most common inherited hemolytic anemia worldwide. Elevated Hb A 2 is a mark of β-thal carriers. The aim of this study was to identify the pathogenic variants associated with the Hb A 2 levels. One thousand and thirty β-thal carriers were recruited for this study. Using positive natural expression quantitative trait loci (eQTL) analysis, a significant variant was selected. Genotyping for the rs231841 polymorphism was performed by the Sequenom MassARRAY IPLEX platform. All genetic association analyses were performed with the PLINK program. The linear regression analysis showed that rs231841 in the intron region of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene on chromosome 11p15 was significantly associated with Hb A 2 levels. The presence of the C allele was associated with elevated Hb A 2 levels. Our results suggest that rs231841 on the KCNQ1 gene with positive natural selection is related to Hb A 2 levels in Chinese β-thal carriers, and KCNQ1 is probably associated with the expression of the β-like globin gene cluster.

  8. Tripoli-4 version 4 user guide; Tripoli-4 version 4 manuel de l'utilisateur

    Energy Technology Data Exchange (ETDEWEB)

    Petit, O.; Hugot, F.X.; Lee, Y.K.; Jouanne, C.; Mazzolo, A

    2008-07-01

    TRIPOLI-4 is a general purpose radiation transport code. It uses the Monte Carlo method to simulate neutron and photon behaviour in three-dimensional geometries. The main areas of applications include but are not restricted to: radiation protection and shielding, nuclear criticality safety, fission and fusion reactor design, nuclear instrumentation. Any pointwise cross-section data in ENDF/B format may be used: JEF2, ENDF/B-VI, JEFF3, ENDF/B-VII, JENDL3.3 etc. As for thermal neutrons, both free gas and S(alpha, beta) models are available. Easy-to-use powerful variance-reduction tools help the user to solve deep penetration problems. TRIPOLI-4 features a versatile and robust parallel operation mode, for heterogeneous network of workstations, or massively parallel machines. TRIPOLI-4 is supported by a range of graphics and algorithmic productivity tools which means that checking for geometry and input deck errors is easy. As for the qualification, TRIPOLI-4 benefits from an extensive range of benchmarks and comparisons with real measurements, and is therefore qualified for R and D, teaching as well as industrial use. (authors)

  9. A new β chain hemoglobin variant with increased oxygen affinity: Hb Santa Giusta Sardegna [β93(F9)Cys→Trp; HBB c.282T>G].

    Science.gov (United States)

    Fais, Antonella; Sollaino, Maria Carla; Barella, Susanna; Perseu, Lucia; Era, Benedetta; Corda, Marcella

    2012-01-01

    During a screening program for the identification of β-thalassemia (β-thal) carriers in Sardinia, Italy, we identified two subjects with increased hemoglobin (Hb) levels and an abnormal Hb variant. The same variant was detected in a family member. DNA sequencing revealed a TGT > TGG mutation at codon 93 of the β-globin gene. Structural analysis demonstrated that the cystine residue at position 93 of the β chain was substituted by tryptophan. Since this amino acid substitution had not yet been reported, we designated this variant Hb Santa Giusta Sardegna for the place of birth of the subjects. This amino acid substitution occurs at the tyrosine pocket of the β chain as well as at the α1β2/α2β1 contact of the quaternary structure of the molecule. The presence of this Hb in the hemolysate causes an increased oxygen affinity, a slightly reduced Bohr effect and a reduced heme-heme interaction (n(50), Hill's constant) in comparison with those of Hb A.

  10. Incidence of hemoglobinopathies and thalassemias in Northern Alberta. Establishment of reference intervals for HbF and HbA2.

    Science.gov (United States)

    Rodriguez-Capote, Karina; Higgins, Trefor N

    2015-07-01

    The aims of this study were to identify the incidence of hemoglobinopathies and thalassemias in Northern Alberta and calculate the reference intervals (RI) for hemoglobin (Hb) HbF and HbA2. A retrospective ad-hoc analysis of the structural Hb variants and thalassemias identified on patients who had a hemoglobinopathy/thalassemia investigation performed between February 1 to December 31, 2013. Results were extracted from the Laboratory Information System. Statistical analysis was performed using MedCalc® version 11.4.2.0 for Windows software. 6616 hemoglobinopathy/thalassemia investigations and HbS screens were physician requested and 602 Hb variants were fortuitously found during HbA1c analysis. 3438 were interpreted as "normal" and 532 were classified as iron deficient. 3306 individuals, with age ranging from 3 to 92 years were included in the RI calculation. HbA2 RI was 2.3% to 3.4% and HbF 0.0% to 1.8%. 524 and 423 α and β thalassemia traits respectively were identified. Additionally ten δβ thalassemia traits and twelve cases of HbH disease were identified. Regarding hemoglobinopathies, 7% were classified as α-chain variants and 93% as β-chain variants with HbS (46%), HbE (16%), HbD Punjab (8%) and HbC (7%) traits being the most prevalent. We also documented 20 homozygous hemoglobinopathies and 36 compound/double heterozygous hemoglobinopathies. A wide diversity of hemoglobinopathies is found in the Northern Alberta population, 80% of the hemoglobinopathies were found as a reflex to HbA1c testing. Reference intervals for HbF and HbA2 were established. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. Hb Tianshui (HBB: C.119A > G) in Compound Heterozygosity with Hb S (HBB: C.20A > T) from Odisha, India.

    Science.gov (United States)

    Meher, Satyabrata; Dehury, Snehadhini; Mohanty, Pradeep Kumar; Patel, Siris; Pattanayak, Chinmayee; Bhattacharya, Subhra; Das, Kishalaya; Sarkar, Biswanath

    2016-08-01

    We describe here a rare β-globin gene variant, Hb Tianshui [β39(C5)Glu→Arg; HBB: c.119A > G], detected during routine screening in Odisha, India. This is the second report of Hb Tianshui and the first to describe the cation exchange high performance liquid chromatography (HPLC) and DNA studies of two cases of this variant. Both cases had coinherited Hb S (HBB: c.20A > T) but none presented with typical symptoms of sickle cell disease. One of the cases was heterozygous for a common α-thalassemia (α-thal) allele (-α(3.7)) (rightward) (NG_000006.1: g.34164_37967del3804) and marginally raised Hb F percentage, while the other Hb S/Hb Tianshui case was completely benign and healthy. An atypical Asian Indian haplotype [+ - + - +] could be assigned to the Hb Tianshui variant. Hb Tianshui seems to mimic a few other Hb variants in cation exchange HPLC. However, we report two specific patterns in the chromatograms that are characteristic to Hb Tianshui. Combining an alkaline electrophoresis result with cation exchange HPLC at screening would be preferred to detect this rare variant, especially in regions with considerable frequency of Hb E [β26(B8)Glu→Lys; HBB: c.79G > A] or Hb S.

  12. Tripoli-4 version 4 user guide

    International Nuclear Information System (INIS)

    Petit, O.; Hugot, F.X.; Lee, Y.K.; Jouanne, C.; Mazzolo, A.

    2008-01-01

    TRIPOLI-4 is a general purpose radiation transport code. It uses the Monte Carlo method to simulate neutron and photon behaviour in three-dimensional geometries. The main areas of applications include but are not restricted to: radiation protection and shielding, nuclear criticality safety, fission and fusion reactor design, nuclear instrumentation. Any pointwise cross-section data in ENDF/B format may be used: JEF2, ENDF/B-VI, JEFF3, ENDF/B-VII, JENDL3.3 etc. As for thermal neutrons, both free gas and S(alpha, beta) models are available. Easy-to-use powerful variance-reduction tools help the user to solve deep penetration problems. TRIPOLI-4 features a versatile and robust parallel operation mode, for heterogeneous network of workstations, or massively parallel machines. TRIPOLI-4 is supported by a range of graphics and algorithmic productivity tools which means that checking for geometry and input deck errors is easy. As for the qualification, TRIPOLI-4 benefits from an extensive range of benchmarks and comparisons with real measurements, and is therefore qualified for R and D, teaching as well as industrial use. (authors)

  13. Common Hemoglobin Variants in Southern Taiwan and Their Effect on the Determination of HbA1c by Ion-exchange High-performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Chih-Hsun Chu

    2009-07-01

    Conclusion: The existence of Hb variants may result in false HbA1c measurement. The possible presence of spuriously low HbA1c levels or abnormal HPLC chromatograms by using ion-exchange methods should be kept in mind.

  14. First Report of a Chinese Family Carrying a Double Heterozygosity for Hb Q-Thailand and Hb J-Bangkok.

    Science.gov (United States)

    Jiang, Fan; Zhou, Jian-Ying; Yan, Jin-Mei; Lu, Yue-Cheng; Li, Dong-Zhi

    2016-11-01

    The double heterozygosity for α and β chain variants leads to the formation of abnormal heterodimer hybrids, which could render laboratory diagnostics in a routine setting difficult. The following is the first report of a double heterozygosity for Hb Q-Thailand [α74(EF3)Asp→His; HBA1: c.223G>C] with α + -thalassemia (α + -thal) and Hb J-Bangkok [β56(D7)Gly→Asp; HBB: c.170G>A] found in a Chinese family. Both subjects were healthy with normal or borderline hematological parameters. Hemoglobin (Hb) analyses showed a novel variant, Hb Q-Thailand and Hb J-Bangkok. Family studies helped in the initial recognition and in making presumptive diagnoses, but definitive diagnoses of these cases with complex α and β chain variants could only be obtained after DNA analysis.

  15. A Coincidental Discovery of a New Stable Variant (Hb Hachioji or HBB: c.187C>T) in a Patient with Chronic Hemolytic Anemia of Unexplained Origin.

    Science.gov (United States)

    Mella, Ferania; Yamashiro, Yasuhiro; Adhiyanto, Chris; Tanaka, Tatehiko; Nitta, Takenori; Amao, Yuki; Kimoto, Masafumi

    2018-01-01

    We report a new hemoglobin (Hb) variant, Hb Hachioji (HBB: c.187C>T), which was detected in a 32-year-old male with hemolytic anemia. The proband had undergone splenectomy in his childhood after being diagnosed with hereditary spherocytosis (HS) with no clinical improvement. A recent study showed that Heinz bodies were frequently observed in his red cells, however, no abnormal band was separated by isoelectric focusing (IEF), and the isopropanol (instability) test was negative. Direct sequencing revealed that the proband was a heterozygous carrier of a novel mutation (GCT>GTT) at codon 62 of the β-globin gene, leading to an alanine to valine substitution. This variant was named Hb Hachioji. Characterization at the mRNA level by cDNA sequencing detected β Hachioji mRNA, as well as β A mRNA. Subsequently, study of the proband's family indicated that his father was a carrier of this Hb variant, although unexpectedly, the father was asymptomatic and clinically healthy. Oxygen affinity measurement of total Hb showed no alteration in the P 50 and oxygen equilibrium curve. The presence of Hb Hachioji was confirmed by mass spectrometry (MS). Hb Hachioji comprised approximately 50.0% of the total Hb and was a stable variant. The phenotypic discrepancy between these two carriers suggests that Hb Hachioji may not be associated with the hemolytic involvement in the proband. P4.2Nippon, which is the primary cause of most cases of Japanese HS, was absent in the proband's parents. The coexistence of glucose-6-phosphate dehydrogenase (G6PD) deficiency was ruled out. Thus, the cause of hemolytic involvement in this patient remains unclear.

  16. Hematological and Molecular Characterization of a Novel Hb A2 Variant with Homozygous α-Thalassemia-2 in a Southern Thai Individual.

    Science.gov (United States)

    Nuinoon, Manit; Jeenduang, Nutjaree; Kesornsit, Aumpika; Horpet, Dararat; Plyduang, Thunyaluk

    2017-05-01

    We report here the hematological and molecular features of a novel δ-globin chain variant found in a Southern Thai woman. Her complete blood count was as follows: red blood cell (RBC) count 5.90 × 10 12 /L, hemoglobin concentration (Hb) 12.6 g/dL, packed cell volume (PCV) 0.41 L/L, mean corpuscular volume (MCV) 69.5 fL, mean corpuscular Hb (MCH) 21.4 pg, mean corpuscular Hb concentration (MCHC) 30.7 g/dL and RBC distribution width (RDW) 13.1%. The blood smear demonstrated microcytic hypochromic RBCs suggestive of thalassemia trait. Hemoglobin analysis identified Hb A 2  + Hb A 2 -Kiriwong (2.4%) and Hb F (0.1%) on high performance liquid chromatography (HPLC). To characterize the α-thalassemia (α-thal) genotype, common α-thal-1 and α-thal-2 alleles were characterized by multiplex gap-polymerase chain reaction (gap-PCR). The results revealed homozygous α-thal-2 (-α 3.7 /-α 3.7 ) in this case. DNA sequencing showed the presence of a novel δ-globin gene mutation [δ77(EF1)His→Arg; HBD: c.233A>G] that we named Hb A 2 -Kiriwong for the village from where the proband lived. In summary, the presence of microcytic hypochromic RBCs in this case was likely the result of the homozygous -α 3.7 (rightward) deletion and was not affected by this Hb A 2 variant.

  17. Automatic modeling for the monte carlo transport TRIPOLI code

    International Nuclear Information System (INIS)

    Zhang Junjun; Zeng Qin; Wu Yican; Wang Guozhong; FDS Team

    2010-01-01

    TRIPOLI, developed by CEA, France, is Monte Carlo particle transport simulation code. It has been widely applied to nuclear physics, shielding design, evaluation of nuclear safety. However, it is time-consuming and error-prone to manually describe the TRIPOLI input file. This paper implemented bi-directional conversion between CAD model and TRIPOLI model. Its feasibility and efficiency have been demonstrated by several benchmarking examples. (authors)

  18. A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    Science.gov (United States)

    Chen, Peng; Ong, Rick Twee-Hee; Tay, Wan-Ting; Sim, Xueling; Ali, Mohammad; Xu, Haiyan; Suo, Chen; Liu, Jianjun; Chia, Kee-Seng; Vithana, Eranga; Young, Terri L; Aung, Tin; Lim, Wei-Yen; Khor, Chiea-Chuen; Cheng, Ching-Yu; Wong, Tien-Yin; Teo, Yik-Ying; Tai, E-Shyong

    2013-01-01

    Glycated hemoglobin A1C (HbA1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  19. A study assessing the association of glycated hemoglobin A1C (HbA1C associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    Directory of Open Access Journals (Sweden)

    Peng Chen

    Full Text Available Glycated hemoglobin A1C (HbA1C level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  20. A Novel Heme Pocket Hemoglobin Variant Associated with Normal Hematology: Hb Zara or α91(FG3)Leu→Ile (α2) (HBA2: c.274C > A).

    Science.gov (United States)

    Trova, Sandro; Mereu, Paolo; Decandia, Luca; Cocco, Elena; Masala, Bruno; Manca, Laura; Pirastru, Monica

    2015-08-13

    We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [α91(FG3)Leu→Ile (α2); HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A 2 , and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed the CTT > ATT mutation at codon 91 on an α2 gene of a normal α-globin gene arrangement. This new variant represents the sixth described mutation at codon α91 and fourth on the α2 locus. As a result of the slight instability due to the significant role of the α91 residue in the α1β2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the α2 locus.

  1. A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis.

    Science.gov (United States)

    Schiemsky, Toon; Van Hoovels, Lieve; Desmet, Koen J O; Phylipsen, Marion; Harteveld, Cornelis L; Kieffer, Davy M J

    2015-01-01

    We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [β17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing.

  2. Hb H disease resulting from the association of an αº-thalassemia allele [-(α20.5] with an unstable α-globin variant [Hb Icaria]: first report on the occurrence in Brazil

    Directory of Open Access Journals (Sweden)

    Elza M. Kimura

    2009-01-01

    Full Text Available Hb H Disease is caused by the loss or inactivation of three of the four functional a-globin genes. Patients present chronic hemolytic anemia and splenomegaly. In some cases, occasional blood transfusions are required. Deletions are the main cause of this type of thalassemia (α-thalassemia. We describe here an unusual case of Hb H disease caused by the combination of a common αº deletion [-(α20.5] with a rare point mutation (c.427T > A, thus resulting in an elongated and unstable α-globin variant, Hb Icaria, (X142K, with 31 additional amino-acid residues. Very high levels of Hb H and Hb Bart's were detected in the patient's red blood cells (14.7 and 19.0%, respectively. This is the first description of this infrequent association in the Brazilian population.

  3. Hb San Cataldo [β144(HC1)Lys→Thr; HBB: C.434A > C]: A New Hemoglobin Variant with Increased Affinity for Oxygen.

    Science.gov (United States)

    Vinciguerra, Margherita; Passarello, Cristina; Cassarà, Filippo; Leto, Filippo; Cannata, Monica; Crivello, Anna; Di Salvo, Veronica; Maggio, Aurelio; Giambona, Antonino

    2016-08-01

    A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire β-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the β-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys→Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C-terminal of the β chain. We called this new variant Hb San Cataldo for the native city of proband.

  4. Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang β-Thalassemia Intermedia Patients.

    Science.gov (United States)

    Lai, Yunli; Chen, Yun; Chen, Biyan; Zheng, Haiyang; Yi, Sheng; Li, Guojian; Wei, Hongwei; He, Sheng; Zheng, Chenguang

    2016-11-01

    Increased Hb F levels can ameliorate the symptoms of β-thalassemia (β-thal). Due to the genetic heterogenicity of β-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of β-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of β-thal intermedia (β-TI) patients in this population have not been reported. To explore the association between modifier loci (β-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang β-TI patients, 96 unrelated β-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for β-thal.

  5. TRIPOLI-4R Version 8 User Guide

    International Nuclear Information System (INIS)

    Brun, Emeric; Damian, Frederic; Dumonteil, Eric; Hugot, Francois-Xavier; Lee, Yi-Kang; Malvagi, Fausto; Mazzolo, Alain; Petit, Odile; Trama, Jean-Christophe; Visonneau, Thierry; Zoia, Andrea

    2013-02-01

    TRIPOLI-4 R solves the linear Boltzmann equation for neutrons, photons, electrons and positrons, with the Monte Carlo method, in any 3D geometry. The code uses ENDF format continuous energy cross-sections, from various international evaluations including JEFF-3.1.1, ENDF/B-VII.0, JENDL4 and FENDL2.1. Its official nuclear data library for applications, named CEAV5.1.1, is mainly based on the European evaluation JEFF-3.1.1. TRIPOLI-4 R solves fixed source as well as eigenvalue problems. It has advanced variance reduction methods to address deep penetration issues. Thanks to its robust and efficient parallelism capability, calculations are easily performed on multi-core single units, heterogeneous networks of workstations and massively parallel machines. Additional productivity tools, graphical as well as algorithmic, allow the user to efficiently set its input decks. With its large V and V data base, TRIPOLI-4 R is used as a reference code for industrial purposes, as well as a R and D and teaching tool, for radiation protection and shielding, core physics, nuclear criticality-safety and nuclear instrumentation. TRIPOLI-4 R is a registered trademark of CEA. (authors)

  6. A Novel β-Globin Chain Hemoglobin Variant, Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp], Associated with Low Oxygen Saturation, Intermittent Aplastic Crises and Splenomegaly.

    Science.gov (United States)

    Collier, Anderson B; Coon, Lea M; Monteleone, Philip; Umaru, Samuel; Swanson, Kenneth C; Hoyer, James D; Oliveira, Jennifer L

    2016-01-01

    Hemoglobin (Hb) variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb variants characterized by a single method is discouraged, as the Hb variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.

  7. Hb A2 Episkopi - a novel δ-globin chain variant [HBD:c.428C>T] in a family of mixed Cypriot-Lebanese descent.

    Science.gov (United States)

    Lederer, Carsten W; Pavlou, Eleni; Tanteles, George A; Evangelidou, Paola; Sismani, Carolina; Kolnagou, Annita; Sitarou, Maria; Christou, Soteroulla; Hadjigavriel, Michael; Kleanthous, Marina

    2017-06-01

    Thalassaemia is a potentially lethal inherited anaemia, caused by reduced or absent synthesis of globin chains. Measurement of the minor adult haemoglobin Hb A 2 , combining α- with δ-globin, is critical for the routine diagnosis of carrier status for α- or β-thalassaemia. Here, we aim to characterize a novel δ-globin variant, Hb A 2 Episkopi, in a single family of mixed Lebanese and Cypriot ancestry with mild hypochromic anaemia and otherwise normal globin genotype, which also presents with a coincidental 0.78-Mb sequence duplication on chromosome 1 (1q44) and developmental abnormalities. Analyses included comprehensive haematological analyses, cation-exchange high-performance liquid chromatography (CE-HPLC), cellulose acetate electrophoresis (CAE), Sanger sequencing and structure-based stability predictions for Hb A 2 Episkopi. The GCT > GTT missense mutation, underlying Hb A 2 Episkopi, HBD:c.428C > T, introduces a cd142 codon change in the mature protein, resulting in reduced normal Hb A 2 amounts and a novel, less abundant Hb A 2 variant (HGVS: HBD:p.A143V), detectable as a delayed peak by CE-HPLC. The latter was in line with structure-based stability predictions, which indicated that the substitution of a marginal, non-helical and non-interface residue, five amino acids from the δ-globin chain carboxy-terminus, was moderately destabilizing. Detection of the new variant depends on the diagnostic set-up and had failed by CAE and on an independent CE-HPLC system, which, in unfavourable circumstances, may lead to misdiagnoses of β-thalassaemia as α-thalassaemia. Given the mixed background of the affected family, the ethnic origin of the mutation is unclear, and this study thus suggests awareness for possible detection of Hb A 2 Episkopi in both the Cypriot and the Lebanese populations.

  8. Low oxygen saturation and severe anemia in compound heterozygous Hb Louisville [β42(CD1)Phe→Leu] and Hb La Desirade [β129(H7)Ala→Val].

    Science.gov (United States)

    Kamseng, Parin; Trakulsrichai, Satariya; Trachoo, Objoon; Yimniam, Walaiporn; Panthan, Bhakbhoom; Jittorntam, Paisan; Niparuck, Pimjai; Sanguanwit, Pitsucha; Wananukul, Winai; Jindadamrongwech, Sumalee

    2017-03-01

    To investigate the cause(s) of a Thai male proband presenting low oxygen saturation by pulse oximetry (SpO 2 ) and severe anemia. As Hb variant was suspected, Hb typing was determined by high-performance liquid chromatography and capillary electrophoresis, and subsequently Hb variant was identified by DNA sequencing. Complete blood counts were performed using automated blood cell counter and oxygen saturation was measured by pulse oximetry. Proband was compound heterozygous for Hb Louisville [β42(CD1)Phe→Leu] and Hb La Desirade [β129(H7)Ala→Val]. Of the proband's two sons, one was compound heterozygous for Hb Louisville and Hb E and the other for Hb La Desirade and Hb E. The former son had similar clinical features and laboratory findings with those of the proband while the latter showed had no abnormal clinical manifestations. This the first report of compound heterozygosity of Hb Louisville and Hb La Desirade in an individual of Southeast Asian ethnicity. Hb variant identification is crucial for genetic counseling and appropriate treatment in regions where hemoglobinopathies are common.

  9. Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies.

    NARCIS (Netherlands)

    G.P. Patrinos (George); B. Giardine (Belinda); C. Riemer (Cathy); W. Miller (Webb); D.H. Chui (David); N.P. Anagnou (Nicholas); H. Wajcman (Henri); R.C. Hardison (Ross)

    2004-01-01

    textabstractHbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and

  10. Interaction of Hb Grey Lynn (Vientiane) [α91(FG3)Leu>Phe (α1)] with Hb E [β26(B8) Glu>Lys] and α(+)-thalassemia: Molecular and Hematological Analysis.

    Science.gov (United States)

    Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan

    2015-01-01

    Hemoglobin (Hb) Grey Lynn is a Hb variant caused by a mutation at codon 91 of α1-globin gene whereas Hb E is a common β-globin chain variant among Southeast Asian population. We report two hitherto undescribed conditions of Hb Grey Lynn found in Thai individuals. The study was done on two unrelated Thai subjects. Hematological parameters were recorded and Hb analysis was carried out using automated Hb analyzers. Mutations were identified by DNA analysis. Hematological features of the patients were compared with those of various forms of Hb Grey Lynn documented previously. Hb and DNA analyses identified a heterozygous Hb Grey Lynn in one patient and a double heterozygous Hb Grey Lynn and Hb E with α(+)-thalassemia in another. Interaction of α(Grey Lynn) with β(E) chains leads to the formation of a new Hb variant, namely the Hb Grey Lynn E (α(GL)2β(E)2), detectable by liquid chromatography (10.3%) but masked by Hb E on capillary electrophoresis. Interaction of these multiple globin gene defects could lead to complex hemoglobinopathies requiring combined analysis with multiple Hb analyzers followed by DNA testing to provide accurate diagnosis of the cases.

  11. Diagnosis of Compound Heterozygous Hb Tak/β-Thalassemia and HbD-Punjab/β-Thalassemia by HbA2 Levels on Capillary Electrophoresis.

    Science.gov (United States)

    Panyasai, Sitthichai; Sakkhachornphop, Supachai; Pornprasert, Sakorn

    2018-01-01

    A misdiagnosis of β-thalassemia carrier in samples with Hb Tak and HbD-Punjab, the β-variants, can be a cause of inappropriate genetic counseling thus having a new case of β-thalassemia major. A capillary electrophoresis (CE) is very efficient in separating and quantifying HbA 2 . In this study, HbA 2 levels of samples which were doubted for compound heterozygous Hb Tak/β-thalassemia or heterozygous HbD-Punjab/β-thalassemia were measured and compared between CE and high performance liquid chromatography (HPLC). The molecular confirmation for Hb Tak, HbD-Punjab and β-thalassemia codons 17 (A > T), 41/42 (-TCTT), 71/72 (+A) and IVSI-nt1 (G > T) mutations and 3.4 kb deletion were also performed. Based on DNA analysis, 3 cases were diagnosed as compound heterozygous Hb Tak/β-thalassemia and one for HbD-Punjab/β-thalassemia. The elevated HbA 2 levels were found in all 4 samples with rages of 4.6-7.3% on CE while those were not found on HPLC. Thus, the elevated HbA 2 measured by CE can be used as a screening parameter for differentiating the homozygote of Hb Tak and HbD-Punjab from the compound heterozygote of these hemoglobinopathies and β-thalassemia.

  12. TRIPOLI 01, a three-dimensional polykinetic Monte Carlo program. Pt.1. Presentation of the TRIPOLI code

    International Nuclear Information System (INIS)

    Baur, A.; Bourdet, L.; Gonnord, J.; Nimal, J.C.; Vergnaud, T.

    1977-01-01

    TRIPOLI is a package of programs intended for solving the neutron polykinetic transport in any three-dimensional geometry. It is written in FORTRAN for IBM computers and the 400 kilo octets are not overflown (buffers excluded). The Monte Carlo method is used. Particular emphasis is put on the problems of reducing the calculating time through two different ways: weighting or smoothing techniques have been used for processing the strong attenuations with a reasonable computer time consumption, and the quantities have been pre-calculated to reduce to a maximum the simulation time. TRIPOLI has been conceived to solve a large scale of neutron propagation problems involving fast neutrons (calculation of radiation damage in materials, biological dose or inelastic γ production), slow neutrons (mechanical structure activation, neutron flux on control chambers or sources of capture γ radiation); near the cores (materials irradiation inside power or experimental reactors) or at large distances from the sources (activation of the secondary fluid or radiation streaming through the shields). Three new possibilities appear in TRIPOLI 2: calculations in unsteady operation, point calculations of the reaction rates using the method of 'the shockless flux after the shock', and the FINE RESPONSE method in opposition to INTEGRAL RESPONSES [fr

  13. HB Puerta del Sol [HBA1:c.148A>C], HB Valdecilla [HBA2:c.3G>T], HB Gran Vía [HBA2:c.98T>G], HB Macarena [HBA2:c.358C>T] and HB El Retiro [HBA2:c.364_366dupGTG]: description of five new hemoglobinopathies.

    Science.gov (United States)

    de la Fuente-Gonzalo, Félix; Nieto, Jorge M; Velasco, Diego; Cela, Elena; Pérez, Germán; Fernández-Teijeiro, Ana; Escudero, Antonio; Villegas, Ana; González-Fernández, Fernando A; Ropero, Paloma

    2016-04-01

    Structural hemoglobinopathies do not usually have a clinical impact, but they can interfere with the analytical determination of some parameters, such as the glycated hemoglobin in diabetic patients. Thalassemias represent a serious health problem in areas where their incidence is high. The defects in the post-translational modifications produce hyper-unstable hemoglobin that is not detected by most of electrophoretic or chromatographic methods that are available so far. We studied seven patients who belong to six unrelated families. The first two families were studied because they had peak abnormal hemoglobin (Hb) during routine analytical assays. The other four families were studied because they had microcytosis and hypochromia with normal HbA2 and HbF without iron deficiency. HbA2 and F quantification and abnormal Hb separation were performed by chromatographic and electrophoretic methods. The molecular characterization was performed using specific sequencing. The Hb Puerta del Sol presents electrophoretic mobility and elution in HPLC that is different from HbA and similar to HbS. The electrophoretic and chromatographic profiles of the four other variants are normal and do not show any anomalies, and their identification was only possible with sequencing. Some variants, such as Hb Valdecilla, Hb Gran Vía, Hb Macarena and Hb El Retiro, have significant clinical impact when they are associated with other forms of α-thalassemia, which could lead to more serious forms of this group of pathologies as for HbH disease. Therefore, it is important to maintain an adequate program for screening these diseases in countries where the prevalence is high to prevent the occurrence of severe forms.

  14. The three-dimensional Monte-Carlo code TRIPOLI-02

    International Nuclear Information System (INIS)

    Baur, A.; Bourdet, L.; Dejonghe, G.; Gonnord, J.; Monnier, A.; Nimal, J.C.; Vergnaud, T.

    1980-04-01

    TRIPOLI-2 solves the transport equation for neutrons or gamma rays in tridimensional geometrical configurations. TRIPOLI uses the Monte Carlo method. This method allows to treat exactly the geometrical configurations, the energy losses and the scattering laws. TRIPOLI 2 allows to treat the following problems: gamma transport problems, neutrons transport problems with fixed source (the problems can be time dependent or not), critical problems without fixed source and research of multiplication factor due to fissions, subcritical problems with fixed source and with multiplication by fission. These problems can be separate in two types. First type: shielding problems essentially with deep penetration and streaming through voids. Biasing technics are used to reduce the computing time. Second type: core problems for cell calculations or for small core calculations. In this case, it is necessary to have a fine representation of the cross sections. The thermalization is also treated exactly [fr

  15. beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0].

    Science.gov (United States)

    Adams, J G; Steinberg, M H; Newman, M V; Morrison, W T; Benz, E J; Iyer, R

    1981-01-01

    Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation.

  16. α-Thalassemia Associated with Hb Instability: A Tale of Two Features. The Case of Hb Rogliano or α1 Cod 108(G15)Thr→Asn and Hb Policoro or α2 Cod 124(H7)Ser→Pro.

    Science.gov (United States)

    Musollino, Gennaro; Cardiero, Giovanna; Flagiello, Angela; La Porta, Gaetana; Lagona, Laura; Prezioso, Romeo; Qualtieri, Gabriele; Gaudiano, Carlo; Medulla, Emilia; Merlino, Antonello; Pucci, Piero; Lacerra, Giuseppina

    2015-01-01

    We identified two new variants in the third exon of the α-globin gene in families from southern Italy: the Hb Rogliano, α1 cod108 ACC>AAC or α1[α108(G15)Thr→Asn] and the Hb Policoro, α2 cod124 TCC>CCC or α2[α124(H7)Ser→Pro]. The carriers showed mild α-thalassemia phenotype and abnormal hemoglobin stability features. These mutations occurred in the G and H helices of the α-globin both involved in the specific recognition of AHSP and β1 chain. Molecular characterization of mRNA, globin chain analyses and molecular modelling studies were carried out to highlight the mechanisms causing the α-thalassemia phenotype. The results demonstrated that the α-thalassemia defect associated with the two Hb variants originated by different defects. Hb Rogliano showed an intrinsic instability of the tetramer due to anomalous intra- and inter-chain interactions suggesting that the variant chain is normally synthesized and complexed with AHSP but rapidly degraded because it is unable to form the α1β1 dimers. On the contrary in the case of Hb Policoro two different molecular mechanisms were shown: the reduction of the variant mRNA level by an unclear mechanism and the protein instability due to impairment of AHSP interaction. These data highlighted that multiple approaches, including mRNA quantification, are needed to properly identify the mechanisms leading to the α-thalassemia defect. Elucidation of the specific mechanism leads to the definition of a given phenotype providing important guidance for the diagnosis of unstable variants. PMID:25730315

  17. Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis.

    Science.gov (United States)

    Pornprasert, Sakorn; Saoboontan, Supansa; Wiengkum, Thanatcha

    2016-06-01

    Hemoglobin Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA IN α2)] is often missed by routine laboratory testing, especially in subjects with co-inheritance of β-thalassemia or β-variants. We reported the case of a 1-year-old female with Hb H-CS disease who was born from a father with heterozygous of α-thalassemia-1 Southeast Asian type deletion and a mother with the combination of Hb CS and Hb E [β26 (B8) Glu→Lys, GAG>AAG] trait. A very tiny peak of Hb CS of the mother was easily ignored on the high performance liquid chromatography chromatogram while it was clearly seen on the capillary electrophoresis (CE) electrophoregram. Therefore, the CE is useful in screening for heterozygous Hb CS in a person with Hb E trait. This is of potential benefit for prevention of new cases of Hb H-CS disease.

  18. Coinheritance of High Oxygen Affinity Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] with Hb H Disease.

    Science.gov (United States)

    Lee, Shir-Ying; Goh, Jia-Hui; Tan, Karen M L; Liu, Te-Chih

    2017-05-01

    Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] is a high oxygen affinity hemoglobin (Hb) causing polycythemia, whereas Hb H (β4) disease causes mild to severe chronic hemolytic anemia. The clinical characteristics, gel electrophoresis, capillary electrophoresis (CE) and molecular genotyping of a case of Hb Helsinki coinherited with Hb H disease in an ethnic Malay is described, illustrating the interaction between the β-globin variant and coinheritance of three α gene deletions. The proband was asymptomatic, exhibited microcytosis and a normal with Hb value.

  19. A review of variant hemoglobins interfering with hemoglobin A1c measurement.

    Science.gov (United States)

    Little, Randie R; Roberts, William L

    2009-05-01

    Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences. 2009 Diabetes Technology Society.

  20. Molecular Characteristics of Hb New York [β113(G15)Val→Glu, HBB: c.341T>A] in Thailand.

    Science.gov (United States)

    Chaibunruang, Attawut; Singha, Kritsada; Srivorakun, Hataichanok; Fucharoen, Goonnapa; Fucharoen, Supan

    2018-01-01

    Hb New York or Hb Kaohsiung [β113(G15)Val→Glu (GTG>GAG), HBB: c.341T>A] has been considered a rare β hemoglobin (Hb) variant found originally in an Iranian woman and later in diverse populations but its genetic origin has not been elucidated. Here we report molecular and hematological descriptions of this variant found in the Thai population. Among 5643 subjects referred for hemoglobinopathy investigation during January 2015 to September 2017, 183 (3.2%) were found to carry several Hb variants, including β chain variants (n = 135, 2.4%), α chain variants (n = 33, 0.6%), Hb Lepore-Hollandia (NG_000007.3: g.63290_70702del) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del) (δβ hybrid Hb) (n = 12, 0.2%) and δ chain variants (n = 3, 0.05%). Of patients with β chain variants, six with normal high performance liquid chromatography (HPLC) patterns, had an abnormal Hb in zone 11 of capillary electrophoresis (CE), the amounts of which ranged from 29.6-45.4% with normal levels of Hb A 2 and Hb F. DNA analysis identified a heterozygous Hb New York mutation in all cases. Further screening of α-thalassemia (α-thal) identified coinheritance of α + - and α 0 -thal in two of them who had reduced levels of Hb New York. Haplotype analysis suggested that the Thai Hb New York was likely associated with a single β-globin haplotype [+ - - - - + +], indicating that it was of the same origin. Hematological findings and simple DNA assay based on allele-specific polymerase chain reaction (PCR) for rapid detection of Hb New York are presented.

  1. Overview of TRIPOLI 2

    International Nuclear Information System (INIS)

    Baur, A.; Bourdet, L.; Dejonghe, G.; Gonnord, J.; Monnier, A.; Nimal, J.C.; Vergnaud, T.

    1980-01-01

    The tridimensional Monte Carlo code TRIPOLI 2, which solves transport problems for neutrons or gamma rays, is presented. This code is used either for shielding calculations with deep penetration or for core calculations with fixed sources or for critical or subcritical problems. The principal block diagram of the system is given. The geometry characteristics, cross section utilization, weighting, source distribution, and results obtained by the code are described. 5 figures

  2. Avaliação eletroforética, cromatográfica e molecular da Hb D Los Angeles no Brasil Electrophoretical, chromatographic and molecular valuations of Hb D Los Angeles in Brazil

    Directory of Open Access Journals (Sweden)

    Ana R. Chinelato-Fernandes

    2003-01-01

    Full Text Available A variante de hemoglobina (Hb D mais comum, Hb D Los Angeles ou D Punjab, é originada de uma transversão GAA->CAA no códon 121 da globina beta; essa mutação resulta na substituição do ácido glutâmico por glutamina na proteína. É a terceira variante de hemoglobina mais freqüente da população brasileira. Como as hemoglobinas D apresentam migração similar à hemoglobina S em pH alcalino, e com a hemoglobina A em pH ácido, são necessários vários testes para o correto diagnóstico. No presente estudo objetivou-se relacionar os diferentes procedimentos laboratoriais de rotina diagnóstica, além da análise molecular, para estabelecer o perfil de Hb D Los Angeles no Brasil. Foram analisados 47 indivíduos da população brasileira com provável Hb D Los Angeles, por vários procedimentos eletroforéticos em diferentes condições de pH, além da cromatografia líquida de alta pressão, e testes moleculares para confirmação da mutação. Foram encontrados quatro tipos de combinações de hemoglobinas: 42 indivíduos portadores de hemoglobina AD Los Angeles, dois indivíduos com doença de Hb S/D Los Angeles, dois indivíduos com Hb D Los Angeles e talassemia beta e um indivíduo com Hb D Los Angeles e Hb Lepore. Os indivíduos heterozigotos para D Los Angeles são assintomáticos, entretanto, em associação com outras variantes e talassemias podem apresentar graus variáveis de manifestações clínicas. Os resultados apresentados enfatizaram a necessidade da associação de várias metodologias para a identificação da Hb D Los Angeles, além de auxiliar na elucidação de combinações raras.The most common Hb D variant, the Hb D-Los Angeles, also know as Hb D-Punjab, originates through a GAA->CAA change at the 121 codon of the beta globin gene; this mutation results in the replacement of glutamic acid for glutamine in the protein. It is the third most common hemoglobin variant in the Brazilian population. This variant has

  3. Tripoli-4, a three-dimensional poly-kinetic particle transport Monte-Carlo code

    International Nuclear Information System (INIS)

    Both, J.P.; Lee, Y.K.; Mazzolo, A.; Peneliau, Y.; Petit, O.; Roesslinger, B.; Soldevila, M.

    2003-01-01

    In this updated of the Monte-Carlo transport code Tripoli-4, we list and describe its current main features. The code computes coupled neutron-photon propagation as well as the electron-photon cascade shower. While providing the user with common biasing techniques, it also implements an automatic weighting scheme. Tripoli-4 enables the user to compute the following physical quantities: a flux, a multiplication factor, a current, a reaction rate, a dose equivalent rate as well as deposit of energy and recoil energies. For each interesting physical quantity, a Monte-Carlo simulation offers different types of estimators. Tripoli-4 has support for execution in parallel mode. Special features and applications are also presented

  4. Tripoli-4, a three-dimensional poly-kinetic particle transport Monte-Carlo code

    Energy Technology Data Exchange (ETDEWEB)

    Both, J P; Lee, Y K; Mazzolo, A; Peneliau, Y; Petit, O; Roesslinger, B; Soldevila, M [CEA Saclay, Dir. de l' Energie Nucleaire (DEN/DM2S/SERMA/LEPP), 91 - Gif sur Yvette (France)

    2003-07-01

    In this updated of the Monte-Carlo transport code Tripoli-4, we list and describe its current main features. The code computes coupled neutron-photon propagation as well as the electron-photon cascade shower. While providing the user with common biasing techniques, it also implements an automatic weighting scheme. Tripoli-4 enables the user to compute the following physical quantities: a flux, a multiplication factor, a current, a reaction rate, a dose equivalent rate as well as deposit of energy and recoil energies. For each interesting physical quantity, a Monte-Carlo simulation offers different types of estimators. Tripoli-4 has support for execution in parallel mode. Special features and applications are also presented.

  5. A survey of TRIPOLI-4

    International Nuclear Information System (INIS)

    Both, J.P.; Derriennic, H.; Morillon, B.; Nimal, J.C.

    1994-01-01

    A survey of the new version of the TRIPOLI code used in shielding calculations, is presented. The main new features introduced in this version are: combinatorial geometry, a multigroup automatic weighting scheme, and complete treatment of nuclear evaluation files; a simulation implementation including strategy for parallelization of the code is presented. Some benchmark calculations are also presented. 7 figs., 5 tabs., 4 refs

  6. Overview on TRIPOLI-2

    International Nuclear Information System (INIS)

    Baur, A.; Bourdet, L.; Dejonghe, G.; Gonnord, J.; Monnier, A.; Nimal, J.C.; Vergnaud, T.

    1980-04-01

    We present in this paper the three-dimensional Monte Carlo code TRIPOLI 2 which solve transport problems for neutrons or gamma rays. This code is used either for shielding calculations with deep penetration or for core calculations with fixed sources or for critical or subcritical problems. The principal block diagram of the system is given. We describe successively the geometry characteristics, the cross sections utilization, the weighting, the source distribution and the results obtained by the code

  7. Detection of the Unstable Hb Köln (HBB: c.295G>A) by a Capillary Electrophoresis Method.

    Science.gov (United States)

    Li, You-Qiong; Ye, Li-Hua; Mo, Yun

    2016-11-01

    Hb Köln (HBB: c.295G>A) is an unstable β-globin gene variant with a GTG>ATG substitution at codon 98. This variant is quite frequent in Europe and the USA but rare in China. It can easily be misdiagnosed as Hb Constant Spring (Hb CS; HBA2: c.427T>C) by high performance liquid chromatography (HPLC), but detection and quantification of both Hb Köln and degraded Hb Köln by capillary electrophoresis (CE) are possible. Thus, we concluded that CE was the preferred method for Hb Köln detection.

  8. Thrombosis in Hb Taybe [codons 38/39 (-ACC) (α1)

    DEFF Research Database (Denmark)

    Juul, Maja Bech; Vestergaard, Hanne; Petersen, Jesper

    2012-01-01

    Hb Taybe is a highly unstable hemoglobin (Hb) variant caused by a 3 bp deletion at codons 38/39 (-ACC) on the α1-globin gene. We report for the first time, a patient with a compound heterozygosity for Hb Taybe and a 5 bp deletion at the splice donor site of IVS-I on the α2-globin gene and ischemic...

  9. febrile seizures, Tripoli, Libya, knowledge, attitude

    African Journals Online (AJOL)

    kim

    the knowledge, attitude and practice of mothers regarding febrile seizures in Tripoli, Libya. ... aim of the audit is to assess the attitude and knowledge of parents of children with .... The following exclusion criteria were used: child who has fever due CNS ... department after giving prior first aid-a similar results was reported.

  10. Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography

    NARCIS (Netherlands)

    Bots, Michael; Stroobants, An K.; Delzenne, Barend; Soeters, Maarten R.; de Vries, Johan E.; Weykamp, Cas W.; Norg, Roelf J. C.; Veldthuis, Martijn; van Zwieten, Rob

    2015-01-01

    Haemoglobin (Hb) variants are well-known factors interfering with accurate HbA1c testing. This report describes two novel Hb variants leading to inappropriate quantification of HbA1c by ion-exchange chromatography. Glycated forms of novel Hb variants were recognised in the blood of two patients with

  11. The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

    Science.gov (United States)

    Al Balushi, Halima W M; Wali, Yasser; Al Awadi, Maha; Al-Subhi, Taimoora; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

    2017-10-01

    Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K + permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K + was markedly abnormal with elevated activities of P sickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca 2+ entry and Mg 2+ loss via P sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K + transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype. © 2017 John Wiley & Sons Ltd.

  12. Can the Afinion HbA1c Point-of-Care instrument be an alternative method for the Tosoh G8 in the case of Hb-Tacoma?

    Science.gov (United States)

    Lenters-Westra, Erna; Strunk, Annuska; Campbell, Paul; Slingerland, Robbert J

    2017-02-01

    Hb-variant interference when reporting HbA1c has been an ongoing challenge since HbA1c was introduced to monitor patients with diabetes mellitus. Most Hb-variants show an abnormal chromatogram when cation-exchange HPLC is used for the determination of HbA1c. Unfortunately, the Tosoh G8 generates what appears to be normal chromatogram in the presence of Hb-Tacoma, yielding a falsely high HbA1c value. The primary aim of the study was to investigate if the Afinion HbA1c point-of-care (POC) instrument could be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma. Whole blood samples were collected in K 2 EDTA tubes from individuals homozygous for HbA (n = 40) and heterozygous for Hb-Tacoma (n = 20). Samples were then immediately analyzed with the Afinion POC instrument. After analysis, aliquots of each sample were frozen at -80 °C. The frozen samples were shipped on dry ice to the European Reference Laboratory for Glycohemoglobin (ERL) and analyzed with three International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMPs). The Premier Hb9210 was used as the reference method. When compared to the reference method, samples with Hb-Tacoma yielded mean relative differences of 31.8% on the Tosoh G8, 21.5% on the Roche Tina-quant Gen. 2 and 16.8% on the Afinion. The Afinion cannot be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma.

  13. Avaliação de Hb A2 e Hb F em doadores de sangue de região malarígena da Amazônia Oriental brasileira por HPLC Evaluation of Hb A2 and Hb F by HPLC in blood donors from the malaria endemic region of Eastern Amazon of Brazil

    Directory of Open Access Journals (Sweden)

    Wanessa C. Souza

    2003-01-01

    Full Text Available In malaria endemic regions of Africa, resistance to infection by Plasmodium has been observed in under 6-month-old children, when there are higher fetal hemoglobin (Hb F levels. Research performed in the São José do Rio Preto region, central-east Brazil, reported increased levels of Hb F in blood donors. The purpose of this work was to evaluate the A2 hemoglobin (Hb A2 and Hb F concentrations in blood donors deriving from the Brazilian malaria endemic region. Forty-five blood donor samples from Macapá, from patients with varying genders, ages and ethnic origins, were collected by venous puncture after informed consent was obtained. The samples were analyzed by High Performance Liquid Chromatography (HPLC - System Variant (Bio-Rad. The HPLC demonstrated sensitivity and rapidity in the identification and measurement of the hemoglobins and gave precise results. Moreover, it provided measurement of hemoglobin variants, even when they were present in small amounts, providing a diagnosis of hemoglobinopathies. Hb F levels above the normal were observed in 33.3% of the analyzed samples. The presence of increased Hb F can suggest resistance to infection by Plasmodium falciparum, as there have been reports that infected red blood cells interfere in the development of the parasite.

  14. First Case of a Compound Heterozygosity for Two Nondeletional α-Thalassemia mutations, Hb Constant Spring and Hb Quong Sze.

    Science.gov (United States)

    Zhou, Jian-Ying; Yan, Jin-Mei; Li, Jian; Li, Dong-Zhi

    2016-06-01

    Nondeletional α-thalassemia (α-thal) is the result of point mutations in critical regions of the α-globin genes, affecting mRNA processing, mRNA translation, or α-globin stability. Hb Constant Spring (Hb CS, HBA2: c.427T > C) is the most common nondeletional α-thal that results from a nucleotide substitution at the termination codon of the α2-globin gene. Hb Quong Sze (Hb QS, HBA2: c.377T > C) is another nondeletional α-thal in South China with the missense mutation at codon 125 of the α2-globin gene making this hemoglobin (Hb) variant highly unstable. Although homozygosity for Hb CS (α(CS)α/α(CS)α) or Hb QS (α(QS)α/α(QS)α) has been reported, clinical pictures vary from severe hemolysis that developed early in life to only mild anemia, no clinical phenotypic data of compound heterozygosity for Hb CS/Hb QS (α(CS)α/α(QS)α) has been described. In this report we describe an adult case with such a compound heterozygosity who presented with a mild α-thal.

  15. The Prevalence and Role of Hemoglobin Variants in Biometric Screening of a Multiethnic Population: One Large Health System's Experience.

    Science.gov (United States)

    Wilburn, Clayton R; Bernard, David W; Zieske, Arthur W; Andrieni, Julia; Miller, Tara; Wang, Ping

    2017-06-01

    To characterize and quantitate hemoglobin (Hb) variants discovered during biometric hemoglobin A1c (HbA1c) analyses in a large multiethnic population with a focus on the effect of variants on testing method and results. In total, 13,913 individuals had their HbA1c measured via ion-exchange high-performance liquid chromatography. Samples that had a variant Hb detected or HbF fraction more than 25% underwent variant Hb characterization and confirmation by gel electrophoresis. RBC indices were also evaluated for possible concomitant thalassemia. Of the 13,913 individuals evaluated, 524 (3.77%) had an Hb variant. The prevalence of each variant was as follows: HbS trait (n = 396, 2.85%), HbSS disease (n = 4, 0.03%), HbC trait (n = 85, 0.61%), HbCC disease (n = 2, 0.01%), HbSC disease (n = 5, 0.04%), HbE trait (n = 18, 0.13%), HbD or G trait (n = 9, 0.06%), HbS β-thalassemia + disease (n = 1, 0.01%), hereditary persistence of HbF (n = 2, 0.01%), and HbMontgomery trait (n = 1, 0.01%). Concomitant α-thalassemia was detected in 20 (3.82%) of the 524 individuals with an Hb variant. This study represents one of the largest epidemiologic investigations into the prevalence of Hb variants in a North American metropolitan, multiethnic workforce and their dependents and reinforces the importance of method selection in populations with Hb variants. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  16. 76 FR 16236 - Prohibition Against Certain Flights Within the Tripoli (HLLL) Flight Information Region (FIR)

    Science.gov (United States)

    2011-03-23

    ... Tripoli (HLLL) Flight Information Region (FIR) AGENCY: Federal Aviation Administration (FAA), Department... the Tripoli (HLLL) Flight Information Region (FIR) by all U.S. air carriers; U.S. commercial operators...) Flight Information Region (FIR). (a) Applicability. This section applies to the following persons: (1...

  17. Hb TAYBE: clinical and morphological findings IN 43 patients.

    Science.gov (United States)

    Koren, Ariel; Levin, Carina; Zalman, Luci; Palmor, Haya; Filon, Dvora; Chubar, Evgeny; Resnitzky, Peretz; Bennett, Michael

    2016-08-01

    Hereditary sequence variants in globin genes are usually silent and are rarer in α-globin chains than β-globin chains. Some may lead to an unstable protein with a hemolytic or thalassemic phenotype. Hb Taybe is an unstable α-chain hemoglobin variant caused by the deletion of a threonine residue at codon 38 or 39 of the α1 globin gene. This deletion results in a structural abnormality that affects the α1 β2 contact and the α1 β1 interface, producing a highly unstable Hb. We describe the clinical, laboratory, and morphological characteristics of 43 patients with Hb Taybe, sixteen of whom are heterozygous, eight are homozygous, and nineteen are double heterozygous for Hb Taybe and other α-gene mutations or deletions. The clinical presentation is very variable from a mild hemolytic anemia to the need for red cell transfusion. Morphological characteristics include erythroid hyperplasia, defective hemoglobin production, and dyserythropoietic features. On electron microscopy dyserythropoiesis and cytoplasmic precipitation of globin compatible optical dense material is seen. This is the largest report of Hb Taybe patients. Previous reported cohorts are not related to these cases. We conclude that patients carrying Hb Taybe have a unique hematological and clinical phenotype distinct from other hemoglobinopathies and from congenital dyserythropoietic anemia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Hemoglobin analyses in the Netherlands reveal more than 80 different variants including six novel ones.

    Science.gov (United States)

    van Zwieten, Rob; Veldthuis, Martijn; Delzenne, Barend; Berghuis, Jeffrey; Groen, Joke; Ait Ichou, Fatima; Clifford, Els; Harteveld, Cornelis L; Stroobants, An K

    2014-01-01

    More than 20,000 blood samples of individuals living in The Netherlands and suspected of hemolytic anemia or diabetes were analyzed by high resolution cation exchange high performance liquid chromatography (HPLC). Besides common disease-related hemoglobins (Hbs), rare variants were also detected. The variant Hbs were retrospectively analyzed by capillary zone electrophoresis (CZE) and by isoelectric focusing (IEF). For unambiguous identification, the globin genes were sequenced. Most of the 80 Hb variants detected by initial screening on HPLC were also separated by capillary electrophoresis (CE), but a few variants were only detectable with one of these methods. Some variants were unstable, had thalassemic properties or increased oxygen affinity, and some interfered with Hb A2 measurement, detection of sickle cell Hb or Hb A1c quantification. Two of the six novel variants, Hb Enschede (HBA2: c.308G  > A, p.Ser103Asn) and Hb Weesp (HBA1: c.301C > T, p.Leu101Phe), had no clinical consequences. In contrast, two others appeared clinically significant: Hb Ede (HBB: c.53A > T, p.Lys18Met) caused thalassemia and Hb Waterland (HBB: c.428C > T, pAla143Val) was related to mild polycytemia. Hb A2-Venlo (HBD: c.193G > A, p.Gly65Ser) and Hb A2-Rotterdam (HBD: c.38A > C, p.Asn13Thr) interfered with Hb A2 quantification. This survey shows that HPLC analysis followed by globin gene sequencing of rare variants is an effective method to reveal Hb variants.

  19. Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T], A Second and Third Case Described in Two Unrelated Dutch Families.

    Science.gov (United States)

    Pondman, Kirsten M; Brinkman, Jacoline W; van der Straaten, Hanneke M; Stroobants, An K; Harteveld, Cornelis L

    2018-01-01

    We report two families, members of which are carriers of a hemoglobin (Hb) variant previously described as Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T; p.Pro115Leu]. In the first family of Dutch origin, the proband, a 32-year-old male and his 65-year-old father, were both carriers of Hb Nouakchott. Of the second family we tested, only the proband, a 56-year-old Dutch female was a Hb Nouakchott carrier. Hematological analyses of these cases showed the anomaly behaves as a silent Hb variant without clinical consequences. The Hb variant remained unnoticed using high performance liquid chromatography (HPLC), while an additional peak was detected by capillary electrophoresis (CE). These independent findings of Hb Nouakchott indicate that this Hb variant might not be very rare, but simply remains under diagnosed depending on the Hb separation technique used.

  20. [Hemoglobin variants in Colombian patients referred to discard hemoglobinopathies].

    Science.gov (United States)

    Romero-Sánchez, Consuelo; Gómez Gutiérrez, Alberto; Duarte, Yurani; Amazo, Constanza; Manosalva, Clara; Chila M, Lorena; Casas-Gómez, María Consuelo; Briceño Balcázar, Ignacio

    2015-10-01

    Oxygen transport is altered in hemoglobinopathies. To study the distribution of hemoglobinopathies in Andean subjects without African ancestry. We analyzed blood samples of 1,407 subjects aged 18 to 59 years (58% females), living in the central Andean region of Colombia, referred to discard hemoglobinopathies. The frequency and type of hemoglobinopathy was established by capillary and agarose gel electrophoresis. The frequency of hemoglobinopathies was 34.5% and higher among females. The structural variants found were: AS-heterozygous hemoglobin (8.1%), homozygous SS (3.7%), heterozygous SC (2.2%), AC heterozygotes (0.5%) and heterozygous AE (0.3%). Quantitative variants found were Hb A-Beta thalassemia (13.91%) and Hb H (0.06%), Beta-thalassemia heterozygotes C (0.88%), S-Beta thalassemia heterozygotes (6.07%) and compound heterozygous SC/Beta thalassemia (0.25%), with a persistence of fetal hemoglobin 0. Composite thalassemia was also found in 31%. All techniques showed good correlation and capillary electrophoresis demonstrated a greater detection of hemoglobin variants. The frequency of hemoglobin variants in the analyzed population was high, which is an important public health indicator. The most common hemoglobin variant was HbA/Increased structural Hb A2 and the mos frequent structural hemoglobinopathy was sickle cell trait. Capillary electrophoresis can discern any Hb variants present in the population.

  1. C-Window Peaks on CE-HPLC are Extremely Rare in Northern India, and Only Infrequently Represent HbC.

    Science.gov (United States)

    Dass, Jasmita; Mittal, Suchi; Saraf, Amrita; Kotwal, Jyoti

    2018-01-01

    Hemoglobin C (HbC, HBB:c.19G > A) is a structural variant that has been reported rarely from India. This was a retrospective review of all high performance liquid chromatography (HPLCs) submitted over a 14 year period to a tertiary care center in North India with an aim of finding hemoglobins that elute in the C-window. Of the 32,364 HPLCs screened, 6 cases showed peaks in the C-window. Of these 6 cases, only two cases contained hemoglobin C. These was one case each of HbC/β thalassemia and compound heterozygosity for HbC and HbD. There were 4 cases which showed very similar red cell indices and chromatograms with multiple peaks eluting in D-window, C-window and an additional peak with a retention time of 4.74 min. These four cases were compound heterozygous for an α chain variant HbQ-India and a β-chain variant HbD.

  2. TRIPOLI-4: Monte Carlo transport code functionalities and applications; TRIPOLI-4: code de transport Monte Carlo fonctionnalites et applications

    Energy Technology Data Exchange (ETDEWEB)

    Both, J P; Lee, Y K; Mazzolo, A; Peneliau, Y; Petit, O; Roesslinger, B [CEA Saclay, Dir. de l' Energie Nucleaire (DEN), Service d' Etudes de Reacteurs et de Modelisation Avancee, 91 - Gif sur Yvette (France)

    2003-07-01

    Tripoli-4 is a three dimensional calculations code using the Monte Carlo method to simulate the transport of neutrons, photons, electrons and positrons. This code is used in four application fields: the protection studies, the criticality studies, the core studies and the instrumentation studies. Geometry, cross sections, description of sources, principle. (N.C.)

  3. Tripoli-3: monte Carlo transport code for neutral particles - version 3.5 - users manual

    International Nuclear Information System (INIS)

    Vergnaud, Th.; Nimal, J.C.; Chiron, M.

    2001-01-01

    The TRIPOLI-3 code applies the Monte Carlo method to neutron, gamma-ray and coupled neutron and gamma-ray transport calculations in three-dimensional geometries, either in steady-state conditions or having a time dependence. It can be used to study problems where there is a high flux attenuation between the source zone and the result zone (studies of shielding configurations or source driven sub-critical systems, with fission being taken into account), as well as problems where there is a low flux attenuation (neutronic calculations -- in a fuel lattice cell, for example -- where fission is taken into account, usually with the calculation on the effective multiplication factor, fine structure studies, numerical experiments to investigate methods approximations, etc). TRIPOLI-3 has been operational since 1995 and is the version of the TRIPOLI code that follows on from TRIPOLI-2; it can be used on SUN, RISC600 and HP workstations and on PC using the Linux or Windows/NT operating systems. The code uses nuclear data libraries generated using the THEMIS/NJOY system. The current libraries were derived from ENDF/B6 and JEF2. There is also a response function library based on a number of evaluations, notably the dosimetry libraries IRDF/85, IRDF/90 and also evaluations from JEF2. The treatment of particle transport is the same in version 3.5 as in version 3.4 of the TRIPOLI code; but the version 3.5 is more convenient for preparing the input data and for reading the output. The french version of the user's manual exists. (authors)

  4. Hb Dartmouth (HBA2: c.200T>C): An α2-Globin Gene Associated with Hb H Disease in One Homozygous Patient.

    Science.gov (United States)

    Farashi, Samaneh; Faramarzi Garous, Negin; Ashki, Mehri; Vakili, Shadi; Zeinali, Fatemah; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein

    2015-01-01

    Hb H (β4) disease is caused by deletion or inactivation of three out of four α-globin genes. A high incidence of Hb H disease has been reported all over the world. There is a wide spectrum of phenotypic presentations, from clinically asymptomatic to having significant hepatosplenomegaly and requiring occasional or even regular blood transfusions, even more severe anemia, Hb Bart's (γ4) hydrops fetalis syndrome that can cause death in the affected fetuses late in gestation. We here present a case who was diagnosed with Hb H disease that represents a new genotype for this hereditary disorder. Hb Dartmouth is a variant caused by a missense mutation at codon 66 of the α2-globin gene (HBA2: c.200T>C), resulting in the substitution of leucine by proline. We here emphasize the importance of this point mutation involving Hb H disease and also the necessity for prenatal diagnosis (PND) for those who carry this point mutation in the heterozygous state.

  5. [Application of the polymerase chain reaction (PCR) in the diagnosis of Hb S-beta(+)-thalassemia].

    Science.gov (United States)

    Harano, K; Harano, T; Kushida, Y; Ueda, S

    1991-08-01

    Isoelectric focusing of the hemolysate prepared from a two-year-old American black boy with microcytic hypochromia showed the presence of a high percentage (63.3%) of such Hb variant as Hb S, while the levels of Hb A, Hb F and Hb A2 were 20.0%, 12.7%, and 4.0%, respectively. The ratio of the non-alpha-chain to the alpha-chain of the biosynthesized globin chains was 0.49. The variant was identified as Hb S by amino acid analysis of the abnormal peptide (beta T-1) and digestion of DNA amplified by the polymerase chain reaction with enzyme Eco 81 I. This was further confirmed by DNA sequencing. DNA sequencing of a beta-gene without the beta s-mutation revealed a nucleotide change of T to C in the polyadenylation signal sequence AATAAA 3' to the beta-gene, resulting in beta(+)-thalassemia. These results are consistent with the existence of a beta s-gene and a beta(+)-thalassemia gene in trans.

  6. Tripoli-3: monte Carlo transport code for neutral particles - version 3.5 - users manual; Tripoli-3: code de transport des particules neutres par la methode de monte carlo - version 3.5 - manuel d'utilisation

    Energy Technology Data Exchange (ETDEWEB)

    Vergnaud, Th; Nimal, J C; Chiron, M

    2001-07-01

    The TRIPOLI-3 code applies the Monte Carlo method to neutron, gamma-ray and coupled neutron and gamma-ray transport calculations in three-dimensional geometries, either in steady-state conditions or having a time dependence. It can be used to study problems where there is a high flux attenuation between the source zone and the result zone (studies of shielding configurations or source driven sub-critical systems, with fission being taken into account), as well as problems where there is a low flux attenuation (neutronic calculations -- in a fuel lattice cell, for example -- where fission is taken into account, usually with the calculation on the effective multiplication factor, fine structure studies, numerical experiments to investigate methods approximations, etc). TRIPOLI-3 has been operational since 1995 and is the version of the TRIPOLI code that follows on from TRIPOLI-2; it can be used on SUN, RISC600 and HP workstations and on PC using the Linux or Windows/NT operating systems. The code uses nuclear data libraries generated using the THEMIS/NJOY system. The current libraries were derived from ENDF/B6 and JEF2. There is also a response function library based on a number of evaluations, notably the dosimetry libraries IRDF/85, IRDF/90 and also evaluations from JEF2. The treatment of particle transport is the same in version 3.5 as in version 3.4 of the TRIPOLI code; but the version 3.5 is more convenient for preparing the input data and for reading the output. The french version of the user's manual exists. (authors)

  7. High Frequency of Hb E-Saskatoon (HBB: c.67G > A) in Brazilians: A New Genetic Origin?

    Science.gov (United States)

    Wagner, Sandrine C; Lindenau, Juliana D; Castro, Simone M de; Santin, Ana Paula; Zaleski, Carina F; Azevedo, Laura A; Ribeiro Dos Santos, Ândrea K C; Dos Santos, Sidney E B; Hutz, Mara H

    2016-08-01

    Hb E-Saskatoon [β22(B4)Glu→Lys, HBB: c.67G > A] is a rare, nonpathological β-globin variant that was first described in a Canadian woman of Scottish and Dutch ancestry and has since then been detected in several populations. The aim of the present study was to identify the origin of Hb E-Saskatoon in Brazil using β-globin haplotypes and genetic ancestry in carriers of this hemoglobin (Hb) variant. Blood samples were investigated by isoelectric focusing (IEF) and high performance liquid chromatography (HPLC) using commercial kits. Hb E-Saskatoon was confirmed by amplification of the HBB gene, followed by sequence analysis. Haplotypes of the β-globin gene were determined by polymerase chain reaction (PCR), followed by digestion with specific restriction enzymes. Individual ancestry was estimated with 48 biallelic insertion/deletions using three 16-plex PCR amplifications. The IEF pattern was similar to Hbs C (HBB: c.19G > A) and Hb E (HBB: c.79G > A) [isoelectric point (pI): 7.59-7.65], and HPLC results showed an elution in the Hb S (HBB: c.20A > T) window [retention time (RT): 4.26-4.38]. DNA sequencing of the amplified β-globin gene showed a mutation at codon 22 (GAA>AAA) corresponding to Hb E-Saskatoon. A total of 11 cases of this variant were identified. In nine unrelated individuals, Hb E-Saskatoon was in linkage disequilibrium with haplotype 2 [+ - - - -]. All subjects showed a high degree of European contribution (mean = 0.85). Hb E-Saskatoon occurred on the β-globin gene of haplotype 2 in all Brazilian carriers. These findings suggest a different genetic origin for this Hb variant from that previously described.

  8. Implementation of the dynamic Monte Carlo method for transient analysis in the general purpose code Tripoli

    Energy Technology Data Exchange (ETDEWEB)

    Sjenitzer, Bart L.; Hoogenboom, J. Eduard, E-mail: B.L.Sjenitzer@TUDelft.nl, E-mail: J.E.Hoogenboom@TUDelft.nl [Delft University of Technology (Netherlands)

    2011-07-01

    A new Dynamic Monte Carlo method is implemented in the general purpose Monte Carlo code Tripoli 4.6.1. With this new method incorporated, a general purpose code can be used for safety transient analysis, such as the movement of a control rod or in an accident scenario. To make the Tripoli code ready for calculating on dynamic systems, the Tripoli scheme had to be altered to incorporate time steps, to include the simulation of delayed neutron precursors and to simulate prompt neutron chains. The modified Tripoli code is tested on two sample cases, a steady-state system and a subcritical system and the resulting neutron fluxes behave just as expected. The steady-state calculation has a constant neutron flux over time and this result shows the stability of the calculation. The neutron flux stays constant with acceptable variance. This also shows that the starting conditions are determined correctly. The sub-critical case shows that the code can also handle dynamic systems with a varying neutron flux. (author)

  9. Implementation of the dynamic Monte Carlo method for transient analysis in the general purpose code Tripoli

    International Nuclear Information System (INIS)

    Sjenitzer, Bart L.; Hoogenboom, J. Eduard

    2011-01-01

    A new Dynamic Monte Carlo method is implemented in the general purpose Monte Carlo code Tripoli 4.6.1. With this new method incorporated, a general purpose code can be used for safety transient analysis, such as the movement of a control rod or in an accident scenario. To make the Tripoli code ready for calculating on dynamic systems, the Tripoli scheme had to be altered to incorporate time steps, to include the simulation of delayed neutron precursors and to simulate prompt neutron chains. The modified Tripoli code is tested on two sample cases, a steady-state system and a subcritical system and the resulting neutron fluxes behave just as expected. The steady-state calculation has a constant neutron flux over time and this result shows the stability of the calculation. The neutron flux stays constant with acceptable variance. This also shows that the starting conditions are determined correctly. The sub-critical case shows that the code can also handle dynamic systems with a varying neutron flux. (author)

  10. User manual for version 4.3 of the Tripoli-4 Monte-Carlo method particle transport computer code

    International Nuclear Information System (INIS)

    Both, J.P.; Mazzolo, A.; Peneliau, Y.; Petit, O.; Roesslinger, B.

    2003-01-01

    This manual relates to Version 4.3 TRIPOLI-4 code. TRIPOLI-4 is a computer code simulating the transport of neutrons, photons, electrons and positrons. It can be used for radiation shielding calculations (long-distance propagation with flux attenuation in non-multiplying media) and neutronic calculations (fissile medium, criticality or sub-criticality basis). This makes it possible to calculate k eff (for criticality), flux, currents, reaction rates and multi-group cross-sections. TRIPOLI-4 is a three-dimensional code that uses the Monte-Carlo method. It allows for point-wise description in terms of energy of cross-sections and multi-group homogenized cross-sections and features two modes of geometrical representation: surface and combinatorial. The code uses cross-section libraries in ENDF/B format (such as JEF2-2, ENDF/B-VI and JENDL) for point-wise description cross-sections in APOTRIM format (from the APOLLO2 code) or a format specific to TRIPOLI-4 for multi-group description. (authors)

  11. PLANNING TRIPOLI METRO NETWORK BY THE USE OF REMOTE SENSING IMAGERY

    Directory of Open Access Journals (Sweden)

    O. Alhusain

    2012-08-01

    Full Text Available Tripoli, the capital city of Libya is going through significant and integrated development process, this development is expected to continue in the next few decades. The Libyan authorities have put it as their goal to develop Tripoli to an important metropolis in North Africa. To achieve this goal, they identified goals for the city's future development in all human, economic, cultural, touristic, and nonetheless infrastructure levels. On the infrastructure development level, among other things, they have identified the development of public transportation as one of the important development priorities. At present, public transportation in Tripoli is carried out by a limited capacity bus network alongside of individual transportation. However, movement in the city is characterized mainly by individual transportation with all its disadvantages such as traffic jams, significant air pollution with both carbon monoxide and dust, and lack of parking space. The Libyan authorities wisely opted for an efficient, modern, and environment friendly solution for public transportation, this was to plan a complex Metro Network as the backbone of public transportation in the city, and to develop and integrate the bus network and other means of transportation to be in harmony with the planned Metro network. The Metro network is planned to provide convenient connections to Tripoli International Airport and to the planned Railway station. They plan to build a system of Park and Ride (P+R facilities at suitable locations along the Metro lines. This paper will present in details the planned Metro Network, some of the applied technological solutions, the importance of applying remote sensing and GIS technologies in different planning phases, and problems and benefits associated with the use of multi-temporal-, multi-format spatial data in the whole network planning phase.

  12. Planning Tripoli Metro Network by the Use of Remote Sensing Imagery

    Science.gov (United States)

    Alhusain, O.; Engedy, Gy.; Milady, A.; Paulini, L.; Soos, G.

    2012-08-01

    Tripoli, the capital city of Libya is going through significant and integrated development process, this development is expected to continue in the next few decades. The Libyan authorities have put it as their goal to develop Tripoli to an important metropolis in North Africa. To achieve this goal, they identified goals for the city's future development in all human, economic, cultural, touristic, and nonetheless infrastructure levels. On the infrastructure development level, among other things, they have identified the development of public transportation as one of the important development priorities. At present, public transportation in Tripoli is carried out by a limited capacity bus network alongside of individual transportation. However, movement in the city is characterized mainly by individual transportation with all its disadvantages such as traffic jams, significant air pollution with both carbon monoxide and dust, and lack of parking space. The Libyan authorities wisely opted for an efficient, modern, and environment friendly solution for public transportation, this was to plan a complex Metro Network as the backbone of public transportation in the city, and to develop and integrate the bus network and other means of transportation to be in harmony with the planned Metro network. The Metro network is planned to provide convenient connections to Tripoli International Airport and to the planned Railway station. They plan to build a system of Park and Ride (P+R) facilities at suitable locations along the Metro lines. This paper will present in details the planned Metro Network, some of the applied technological solutions, the importance of applying remote sensing and GIS technologies in different planning phases, and problems and benefits associated with the use of multi-temporal-, multi-format spatial data in the whole network planning phase.

  13. User manual for version 4.3 of the Tripoli-4 Monte-Carlo method particle transport computer code; Notice d'utilisation du code Tripoli-4, version 4.3: code de transport de particules par la methode de Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    Both, J.P.; Mazzolo, A.; Peneliau, Y.; Petit, O.; Roesslinger, B

    2003-07-01

    This manual relates to Version 4.3 TRIPOLI-4 code. TRIPOLI-4 is a computer code simulating the transport of neutrons, photons, electrons and positrons. It can be used for radiation shielding calculations (long-distance propagation with flux attenuation in non-multiplying media) and neutronic calculations (fissile medium, criticality or sub-criticality basis). This makes it possible to calculate k{sub eff} (for criticality), flux, currents, reaction rates and multi-group cross-sections. TRIPOLI-4 is a three-dimensional code that uses the Monte-Carlo method. It allows for point-wise description in terms of energy of cross-sections and multi-group homogenized cross-sections and features two modes of geometrical representation: surface and combinatorial. The code uses cross-section libraries in ENDF/B format (such as JEF2-2, ENDF/B-VI and JENDL) for point-wise description cross-sections in APOTRIM format (from the APOLLO2 code) or a format specific to TRIPOLI-4 for multi-group description. (authors)

  14. Tripoli-3: monte Carlo transport code for neutral particles - version 3.5 - users manual; Tripoli-3: code de transport des particules neutres par la methode de monte carlo - version 3.5 - manuel d'utilisation

    Energy Technology Data Exchange (ETDEWEB)

    Vergnaud, Th.; Nimal, J.C.; Chiron, M

    2001-07-01

    The TRIPOLI-3 code applies the Monte Carlo method to neutron, gamma-ray and coupled neutron and gamma-ray transport calculations in three-dimensional geometries, either in steady-state conditions or having a time dependence. It can be used to study problems where there is a high flux attenuation between the source zone and the result zone (studies of shielding configurations or source driven sub-critical systems, with fission being taken into account), as well as problems where there is a low flux attenuation (neutronic calculations -- in a fuel lattice cell, for example -- where fission is taken into account, usually with the calculation on the effective multiplication factor, fine structure studies, numerical experiments to investigate methods approximations, etc). TRIPOLI-3 has been operational since 1995 and is the version of the TRIPOLI code that follows on from TRIPOLI-2; it can be used on SUN, RISC600 and HP workstations and on PC using the Linux or Windows/NT operating systems. The code uses nuclear data libraries generated using the THEMIS/NJOY system. The current libraries were derived from ENDF/B6 and JEF2. There is also a response function library based on a number of evaluations, notably the dosimetry libraries IRDF/85, IRDF/90 and also evaluations from JEF2. The treatment of particle transport is the same in version 3.5 as in version 3.4 of the TRIPOLI code; but the version 3.5 is more convenient for preparing the input data and for reading the output. The french version of the user's manual exists. (authors)

  15. Identificação de variantes de hemoglobina em doadores de sangue Identification of hemoglobin variants in blood donor

    Directory of Open Access Journals (Sweden)

    Ana C. Bonini-Domingos

    2004-03-01

    Full Text Available Hemoglobinopathies are the most common genetic diseases and affect a great number of individuals in the world, with diverse clinical complications ranging from the almost unnoticeable to lethal consequences. In Brazil the occurrence of hemoglobinopathies is very frequent and influenced by the ethnical groups that are the basis of populations in different regions. The phenotype may be influenced by environmental and genetic factors and by migration. An understanding of these genetic diseases is important for the health and quality of life of the population. In this work we assessed the presence of Hb variants in blood donors from São José do Rio Preto and region, and we observed the occurrence of variants including Hb S and Hb C but in particular the so-called "S-Like" variants. Good determination of the forms of variant hemoglobins is very important to give better guidance to blood donors and their families, and to improve the quality of blood transfusion.

  16. Hb H Hydrops Fetalis Syndrome Caused by Association of the - -(SEA) Deletion and Hb Constant Spring (HBA2: c.427T > C) Mutation in a Chinese Family.

    Science.gov (United States)

    He, Sheng; Zheng, Chenguang; Meng, Dahua; Chen, Rongyu; Zhang, Qiang; Tian, Xiaoxian; Chen, Shaoke

    2015-01-01

    Hb Constant Spring (Hb CS; HBA2: c.427T > C) is an unstable hemoglobin (Hb) variant that results from a nucleotide substitution at the termination codon of the α2-globin gene. Compound heterozygosity for α(0)-thalassemia (α(0)-thal) and Hb CS (- -(SEA)/α(CS)α) results in Hb H/Hb CS disease, which is generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. Here, we describe one case with Hb H/Hb CS disease that presented with fetal anemia and fetal hydrops, known as Hb H (β4) hydrops fetalis. This is the first report of fetal hydrops caused by association of the - -(SEA) deletion and the α(CS)α mutation. Our study highlights the significance of watchful observation using a serial ultrasound method and care of pregnant women who have fetuses found to carry Hb H/Hb CS disease during pregnancy, to guard against the occurrence of fetal hydrops.

  17. Tripoli-4.4 Jeff-3.1 based libraries; Les bibliotheques Jeff-3.1 pour Tripoli-4.4

    Energy Technology Data Exchange (ETDEWEB)

    Jouanne, C. [CEA Saclay Dept. Modelisation de Systemes et Structures, 91 - Gif sur Yvette (France); Sublet, J.Ch. [CEA Cadarache, Dept. d' Etudes des Reacteurs, 13 - Saint Paul lez Durance (France)

    2006-07-01

    Continuous-energy and multi-temperatures TRIPOLI-4.4 libraries, derived from the Joint European Fusion-Fission JEFF-3.1 evaluations, have been generated using the NJOY-99.112 processing code system. They include the continuous-energy neutron JEFF-3.1/General Purpose and thermal S({alpha},{beta}) JEFF-3.1/Thermal libraries and data tables. The processing steps and features are explained together with the Quality Assurance processes and records linked to the generation of such multipurpose libraries. (authors)

  18. Analysis of the ITER computational shielding benchmark with the Monte Carlo TRIPOLI-4® neutron gamma coupled calculations

    International Nuclear Information System (INIS)

    Lee, Yi-Kang

    2016-01-01

    Highlights: • Verification and validation of TRIPOLI-4 radiation transport calculations for ITER shielding benchmark. • Evaluation of CEA-V5.1.1 and FENDL-3.0 nuclear data libraries on D–T fusion neutron continuous energy transport calculations. • Advances in nuclear analyses for nuclear heating and radiation damage in iron. • This work also demonstrates that the “safety factors” concept is necessary in the nuclear analyses of ITER. - Abstract: With the growing interest in using the continuous-energy TRIPOLI-4 ® Monte Carlo radiation transport code for ITER applications, a key issue that arises is whether or not the released TRIPOLI-4 code and its associated nuclear data libraries are verified and validated for the D–T fusion neutronics calculations. Previous published benchmark results of TRIPOLI-4 code on the ITER related activities have concentrated on the first wall loading, the reactor dosimetry, the nuclear heating, and the tritium breeding ratio. To enhance the TRIPOLI-4 verification and validation on neutron-gamma coupled calculations for fusion device application, the computational ITER shielding benchmark of M. E. Sawan was performed in this work by using the 2013 released TRIPOLI-4.9S code and the associated CEA-V5.1.1 data library. First wall, blanket, vacuum vessel and toroidal field magnet of the inboard and outboard components were fully modelled in this 1-D toroidal cylindrical benchmark. The 14.1 MeV source neutrons were sampled from a uniform isotropic distribution in the plasma zone. Nuclear responses including neutron and gamma fluxes, nuclear heating, and material damage indicator were benchmarked against previous published results. The capabilities of the TRIPOLI-4 code on the evaluation of above physics parameters were presented. The nuclear data library from the new FENDL-3.0 evaluation was also benchmarked against the CEA-V5.1.1 results for the neutron transport calculations. The results show that both data libraries can be

  19. Measurements of red cell deformability and hydration reflect HbF and HbA2 in blood from patients with sickle cell anemia.

    Science.gov (United States)

    Parrow, Nermi L; Tu, Hongbin; Nichols, James; Violet, Pierre-Christian; Pittman, Corinne A; Fitzhugh, Courtney; Fleming, Robert E; Mohandas, Narla; Tisdale, John F; Levine, Mark

    2017-06-01

    Decreased erythrocyte deformability, as measured by ektacytometry, may be associated with disease severity in sickle cell anemia (SCA). Heterogeneous populations of rigid and deformable cells in SCA blood result in distortions of diffraction pattern measurements that correlate with the concentration of hemoglobin S (HbS) and the percentage of irreversibly sickled cells. We hypothesize that red cell heterogeneity, as well as deformability, will also be influenced by the concentration of alternative hemoglobins such as fetal hemoglobin (HbF) and the adult variant, HbA 2 . To test this hypothesis, we investigate the relationship between diffraction pattern distortion, osmotic gradient ektacytometry parameters, and the hemoglobin composition of SCA blood. We observe a correlation between the extent of diffraction pattern distortions and percentage of HbF and HbA 2 . Osmotic gradient ektacytometry data indicate that minimum elongation in the hypotonic region is positively correlated with HbF, as is the osmolality at which it occurs. The osmolality at both minimum and maximum elongation is inversely correlated with HbS and HbA 2 . These data suggest that HbF may effectively improve surface-to-volume ratio and osmotic fragility in SCA erythrocytes. HbA 2 may be relatively ineffective in improving these characteristics or cellular hydration at the levels found in this patient cohort. Copyright © 2017. Published by Elsevier Inc.

  20. Top-Down Proteomics and Direct Surface Sampling of Neonatal Dried Blood Spots: Diagnosis of Unknown Hemoglobin Variants

    Science.gov (United States)

    Edwards, Rebecca L.; Griffiths, Paul; Bunch, Josephine; Cooper, Helen J.

    2012-11-01

    We have previously shown that liquid microjunction surface sampling of dried blood spots coupled with high resolution top-down mass spectrometry may be used for screening of common hemoglobin variants HbS, HbC, and HbD. In order to test the robustness of the approach, we have applied the approach to unknown hemoglobin variants. Six neonatal dried blood spot samples that had been identified as variants, but which could not be diagnosed by current screening methods, were analyzed by direct surface sampling top-down mass spectrometry. Both collision-induced dissociation and electron transfer dissociation mass spectrometry were employed. Four of the samples were identified as β-chain variants: two were heterozygous Hb D-Iran, one was heterozygous Hb Headington, and one was heterozygous Hb J-Baltimore. The fifth sample was identified as the α-chain variant heterozygous Hb Phnom Penh. Analysis of the sixth sample suggested that it did not in fact contain a variant. Adoption of the approach in the clinic would require speed in both data collection and interpretation. To address that issue, we have compared manual data analysis with freely available data analysis software (ProsightPTM). The results demonstrate the power of top-down proteomics for hemoglobin variant analysis in newborn samples.

  1. Analysis of JSI TRIGA MARK II reactor physical parameters calculated with TRIPOLI and MCNP.

    Science.gov (United States)

    Henry, R; Tiselj, I; Snoj, L

    2015-03-01

    New computational model of the JSI TRIGA Mark II research reactor was built for TRIPOLI computer code and compared with existing MCNP code model. The same modelling assumptions were used in order to check the differences of the mathematical models of both Monte Carlo codes. Differences between the TRIPOLI and MCNP predictions of keff were up to 100pcm. Further validation was performed with analyses of the normalized reaction rates and computations of kinetic parameters for various core configurations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Analysis of the ITER computational shielding benchmark with the Monte Carlo TRIPOLI-4{sup ®} neutron gamma coupled calculations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yi-Kang, E-mail: yi-kang.lee@cea.fr

    2016-11-01

    Highlights: • Verification and validation of TRIPOLI-4 radiation transport calculations for ITER shielding benchmark. • Evaluation of CEA-V5.1.1 and FENDL-3.0 nuclear data libraries on D–T fusion neutron continuous energy transport calculations. • Advances in nuclear analyses for nuclear heating and radiation damage in iron. • This work also demonstrates that the “safety factors” concept is necessary in the nuclear analyses of ITER. - Abstract: With the growing interest in using the continuous-energy TRIPOLI-4{sup ®} Monte Carlo radiation transport code for ITER applications, a key issue that arises is whether or not the released TRIPOLI-4 code and its associated nuclear data libraries are verified and validated for the D–T fusion neutronics calculations. Previous published benchmark results of TRIPOLI-4 code on the ITER related activities have concentrated on the first wall loading, the reactor dosimetry, the nuclear heating, and the tritium breeding ratio. To enhance the TRIPOLI-4 verification and validation on neutron-gamma coupled calculations for fusion device application, the computational ITER shielding benchmark of M. E. Sawan was performed in this work by using the 2013 released TRIPOLI-4.9S code and the associated CEA-V5.1.1 data library. First wall, blanket, vacuum vessel and toroidal field magnet of the inboard and outboard components were fully modelled in this 1-D toroidal cylindrical benchmark. The 14.1 MeV source neutrons were sampled from a uniform isotropic distribution in the plasma zone. Nuclear responses including neutron and gamma fluxes, nuclear heating, and material damage indicator were benchmarked against previous published results. The capabilities of the TRIPOLI-4 code on the evaluation of above physics parameters were presented. The nuclear data library from the new FENDL-3.0 evaluation was also benchmarked against the CEA-V5.1.1 results for the neutron transport calculations. The results show that both data libraries

  3. TRIPOLI-4: Monte Carlo transport code functionalities and applications

    International Nuclear Information System (INIS)

    Both, J.P.; Lee, Y.K.; Mazzolo, A.; Peneliau, Y.; Petit, O.; Roesslinger, B.

    2003-01-01

    Tripoli-4 is a three dimensional calculations code using the Monte Carlo method to simulate the transport of neutrons, photons, electrons and positrons. This code is used in four application fields: the protection studies, the criticality studies, the core studies and the instrumentation studies. Geometry, cross sections, description of sources, principle. (N.C.)

  4. A novel base change leading to Hb Vanderbilt [β89(F5)Ser→Arg, AGT>AGA].

    Science.gov (United States)

    Goodyer, Matthew J; Elhassadi, Ezzat I; Percy, Melanie J; McMullin, Mary F

    2011-01-01

    We describe a high oxygen affinity hemoglobin (Hb) variant (Hb Vanderbilt) as a result of a heterozygous novel base change from T to A at codon 89 (AGT>AGA) leading to an amino acid change from serine to arginine.

  5. Hb Heathrow [β103(G5)Phe→Leu], a First Report in an Asian Patient with Erythrocytosis.

    Science.gov (United States)

    Shin, Sang Yong; Kim, Hyun Young; Kim, Hee Jin; Kim, Hoon Gu

    2017-05-01

    Congenital erythrocytosis (CE) is a rare and heterogeneous disease. The high oxygen affinity hemoglobin (Hb) variants are the most common cause of CE. Herein, we report a Korean patient with isolated erythrocytosis. A 25-year-old man was referred to our hospital for evaluation of high Hb level (Hb 20.4 g/dL, hematocrit 58%, reticulocyte count 2.90%, white blood cell count 6.83×10⁹/L, and platelet count 195×10⁹/L). Bone marrow biopsy revealed normocellular marrow without myeloproliferative features. JAK2 (V617F, exon 12), CALR (exon 9), and MPL W515K/L mutations were not detected. P₅₀ (partial pressure at which Hb is half saturated with oxygen), which is an indicator of left-shift of oxygen dissociation curve (high oxygen affinity state), was 14.3 mm Hg (reference value 22.6-29.4 mm Hg). He was suspected to have CE. Mutation analysis of the HBB gene revealed the known Hb variant, Hb Heathrow [β103(G5)Phe→Leu]. This is the first report of Hb Heathrow in Asian. © Copyright: Yonsei University College of Medicine 2017.

  6. Secondary polycythaemia in a Malay girl with homozygous Hb Tak.

    Science.gov (United States)

    Amran, H S; Aziz, M A; George, E; Mahmud, N; Lee, T Y; Md Noor, S

    2017-12-01

    Hb Tak is one of more than 200 high affinity haemoglobin variants reported worldwide. It results from the insertion of two nucleotides (AC) at the termination codon, between codon 146 and codon 147 of the beta-globin gene [Beta 147 (+AC)]. Polycythaemia is the main clinical feature although affected carriers are usually asymptomatic and do not require intervention. Several case studies in this region have reported the co-inheritance of Hb Tak with Hb E, delta beta and beta thalassaemia with one case of homozygous Hb Tak in a Thai boy. In this case report, a cluster of haemoglobin Tak was found in a family of Malay ethnic origin. Cascade family screening was conducted while investigating a 4-year old girl who presented with symptomatic polycythaemia. She had 2 previous Hb analysis done, at 7-month and 2-year-old with the diagnosis of possible Hb Q Thailand and Homozygous Hb D, respectively. Both diagnosis did not fit her clinical presentations. She was plethoric, had reduced exercise tolerance as well as cardiomyopathy. Her parents were consanguineously married and later diagnosed as asymptomatic carriers of Hb Tak. Consequently, re-analysis of the girl's blood sample revealed a homozygous state of Hb Tak. In conclusion, high oxygen affinity haemoglobin like Hb Tak should be considered in the investigation of polycythaemic patients with abnormal Hb analyses. In this case, DNA analysis was crucial in determining the correct diagnosis.

  7. A case of iron deficiency anemia with co-existing Hb Fontainebleau.

    Directory of Open Access Journals (Sweden)

    Abhishek HL Purohit

    2014-06-01

    Full Text Available Hb Fontainebleaue is a rare alpha chain variant in the Indian population which generates an unknown peak on hemoglobin HPLC study and does cause diagnostic difficulty to those who are not acquainted with this entity. We present a case of Hb Fontainebleau, an eighteen year old patient who presented with symptoms related to anemia to our department and unknown peak observed in HPLC plots lead us to family study and molecular characterization for this case.

  8. TRIPOLI I: energy-dependent three-dimensional Monte Carlo Program. Volume I. Conception and presentation of the TRIPOLI I System

    International Nuclear Information System (INIS)

    Katz, S.; Nimal, J.C.

    In its present version TRIPOLI/1/ is an energy dependent three-dimensional program which treats the slowing down and diffusion of neutrons for source problems. The version presented here is essentially oriented towards reactor shielding problems. It is written in FORTRAN for IBM (series 360) computer. This volume is devoted to a summary of the essential characteristics of the program as well as to a description of the constants required for the description of the chaining together of the work to be carried out

  9. First Cases of Hb Agrinio Described in Patients from the Republic of Macedonia.

    Science.gov (United States)

    Dimishkovska, Marija; Kuzmanovska, Maja; Kocheva, Svetlana; Martinova, Kata; Karanfilski, Oliver; Stojanoski, Zlate; Plaseska-Karanfilska, Dijana

    Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identified the following genetic defects: -α 3.7 (rightward), -(α) 20.5 and - - MED I deletions and Hb Icaria [α142, Term→Lys (α2), HBA2: c.427T>A] and polyadenylation signal (polyA) [AATAAA>AATGAA (α2), HBA2: c.*92A>G] point mutations. Here, we report two unrelated patients from the Romani population in the Republic of Macedonia, homozygotes for the α2-globin gene variant Hb Agrinio [α29(B10)Leu→Pro; HBA2: c.89T>C]. To date, Hb Agrinio has been described only in individuals of Greek, Cypriot and Spanish origin. Both of our patients had early presentation of the disease (3.5 years and 2 months, respectively) with frequent blood transfusions from early infancy. They have a severe intermediate phenotype of thalassemia (Hb H disease) with hemoglobin (Hb) levels of 7.8 and 7.7 g/dL, respectively. Although the HBA2: c.89T>C mutation results in an α + allele, the severe phenotype of the homozygotes is due to the production of hyperunstable α chains that undergo post translational precipitation. This leads to a greater degree of red cell damage and hemolytic anemia. The detection of Hb Agrinio in two unrelated families of Romani ethnic origin, may suggest it is a founder mutation in this population living in the Republic of Macedonia. Considering the severity of the clinical presentation of the homozygotes or compound heterozygotes for this rare Hb variant, a targeted molecular screening for Hb Agrinio mutation carriers should be considered in all patients of Romani ethnic origin with manifested microcytosis.

  10. Analysis of the KANT experiment on beryllium using TRIPOLI-4 Monte Carlo code

    International Nuclear Information System (INIS)

    Lee, Yi-Kang

    2011-01-01

    Beryllium is an important material in fusion technology for multiplying neutrons in blankets. However, beryllium nuclear data are differently presented in modern nuclear data evaluations. Recent investigations with the TRIPOLI-4 Monte Carlo simulation of the tritium breeding ratio (TBR) demonstrated that beryllium reaction data are the main source of the calculation uncertainties between ENDF/B-VII.0 and JEFF-3.1. To clarify the calculation uncertainties from data libraries on beryllium, in this study TRIPOLI-4 calculations of the Karlsruhe Neutron Transmission (KANT) experiment have been performed by using ENDF/B-VII.0 and new JEFF-3.1.1 data libraries. The KANT Experiment on beryllium has been used to validate neutron transport codes and nuclear data libraries. An elaborated KANT experiment benchmark has been compiled and published in the NEA/SINBAD database and it has been used as reference in the present work. The neutron multiplication in bulk beryllium assemblies was considered with a central D-T neutron source. Neutron leakage spectra through the 5, 10, and 17 cm thick spherical beryllium shells were calculated and five-group partial leakage multiplications were reported and discussed. In general, improved C/E ratios on neutron leakage multiplications have been obtained. Both ENDF/B-VII.0 and JEFF-3.1.1 beryllium data libraries of TRIPOLI-4 are acceptable now for fusion neutronics calculations.

  11. Evaluation of the DCA Vantage analyzer for HbA 1c assay.

    Science.gov (United States)

    Szymezak, Jean; Leroy, Nathalie; Lavalard, Emmanuelle; Gillery, Philippe

    2008-01-01

    Measurement of HbA 1c is key in monitoring diabetic patients in both laboratories and clinical units, where HbA 1c results are used as part of patient education. We have evaluated the DCA Vantage, a new device for immunological assay of HbA 1c. HbA 1c results obtained were evaluated in terms of precision, linearity, specificity and practicability, and were compared with results obtained by a Variant II HPLC method. The method exhibited intra- and inter-assay coefficients of variation lower than 2.6% and 4.0%, respectively, and good correlation with the comparison HPLC method (r2=0.9776). No interference was noted in the presence of labile HbA 1c or carbamylated hemoglobin. The new device exhibited improved practicability characteristics and allowed better sample identification, better management of quality control routines and greater connectivity possibilities compared to the previous DCA 2000 analyzer. This new analyzer exhibited analytical and practical characteristics very suitable for HbA 1c assay for laboratory or point-of-care use according to good laboratory practice.

  12. Two α1-Globin Gene Point Mutations Causing Severe Hb H Disease.

    Science.gov (United States)

    Jiang, Hua; Huang, Lv-Yin; Zhen, Li; Jiang, Fan; Li, Dong-Zhi

    Hb H disease is generally a moderate form of α-thalassemia (α-thal) that rarely requires regular blood transfusions. In this study, two Chinese families with members carrying transfusion-dependent Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2). In one family, Hb Zürich-Albisrieden [α59(E8)Gly→Arg; HBA1: c.178G>C] in combination with the Southeast Asian (- - SEA ) deletion was the defect responsible for the severe phenotype. In another family, a novel hemoglobin (Hb) variant named Hb Sichuan (HBA1: c.393_394insT), causes α-thal and a severe phenotype when associated with the - - SEA deletion. As these two HBA1 mutations can present as continuous blood transfusion-dependent α-thal, it is important to take this point into account for detecting the carriers, especially in couples in which one partner is already a known α 0 -thal carrier.

  13. MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies

    Science.gov (United States)

    Théberge, Roger; Dikler, Sergei; Heckendorf, Christian; Chui, David H. K.; Costello, Catherine E.; McComb, Mark E.

    2015-08-01

    Hemoglobinopathies are the most common inherited disorders in humans and are thus the target of screening programs worldwide. Over the past decade, mass spectrometry (MS) has gained a more important role as a clinical means to diagnose variants, and a number of approaches have been proposed for characterization. Here we investigate the use of matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF MS) with sequencing using in-source decay (MALDI-ISD) for the characterization of Hb variants. We explored the effect of matrix selection using super DHB or 1,5-diaminonaphthalene on ISD fragment ion yield and distribution. MALDI-ISD MS of whole blood using super DHB simultaneously provided molecular weights for the alpha and beta chains, as well as extensive fragmentation in the form of sequence defining c-, (z + 2)-, and y-ion series. We observed sequence coverage on the first 70 amino acids positions from the N- and C-termini of the alpha and beta chains in a single experiment. An abundant beta chain N-terminal fragment ion corresponding to βc34 was determined to be a diagnostic marker ion for Hb S (β6 Glu→Val, sickle cell), Hb C (β6 Glu→Lys), and potentially for Hb E (β26 Glu→Lys). The MALDI-ISD analysis of Hb S and HbSC yielded mass shifts corresponding to the variants, demonstrating the potential for high-throughput screening. Characterization of an alpha chain variant, Hb Westmead (α122 His→Gln), generated fragments that established the location of the variant. This study is the first clinical application of MALDI-ISD MS for the determination and characterization of hemoglobin variants.

  14. Advances in Monte-Carlo code TRIPOLI-4®'s treatment of the electromagnetic cascade

    Science.gov (United States)

    Mancusi, Davide; Bonin, Alice; Hugot, François-Xavier; Malouch, Fadhel

    2018-01-01

    TRIPOLI-4® is a Monte-Carlo particle-transport code developed at CEA-Saclay (France) that is employed in the domains of nuclear-reactor physics, criticality-safety, shielding/radiation protection and nuclear instrumentation. The goal of this paper is to report on current developments, validation and verification made in TRIPOLI-4 in the electron/positron/photon sector. The new capabilities and improvements concern refinements to the electron transport algorithm, the introduction of a charge-deposition score, the new thick-target bremsstrahlung option, the upgrade of the bremsstrahlung model and the improvement of electron angular straggling at low energy. The importance of each of the developments above is illustrated by comparisons with calculations performed with other codes and with experimental data.

  15. Genetic Variants in Transcription Factors Are Associated With the Pharmacokinetics and Pharmacodynamics of Metformin

    Science.gov (United States)

    Goswami, S; Yee, SW; Stocker, S; Mosley, JD; Kubo, M; Castro, R; Mefford, JA; Wen, C; Liang, X; Witte, J; Brett, C; Maeda, S; Simpson, MD; Hedderson, MM; Davis, RL; Roden, DM; Giacomini, KM; Savic, RM

    2014-01-01

    One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor to this high failure rate. Here, we investigate, for the first time, the effect of genetic variants in transcription factors on metformin pharmacokinetics (PK) and response. Overall, 546 patients and healthy volunteers contributed their genome-wide, pharmacokinetic (235 subjects), and HbA1c data (440 patients) for this analysis. Five variants in specificity protein 1 (SP1), a transcription factor that modulates the expression of metformin transporters, were associated with changes in treatment HbA1c (P < 0.01) and metformin secretory clearance (P < 0.05). Population pharmacokinetic modeling further confirmed a 24% reduction in apparent clearance in homozygous carriers of one such variant, rs784888. Genetic variants in other transcription factors, peroxisome proliferator–activated receptor-α and hepatocyte nuclear factor 4-α, were significantly associated with HbA1c change only. Overall, our study highlights the importance of genetic variants in transcription factors as modulators of metformin PK and response. PMID:24853734

  16. Glycaemic control status among type 2 diabetic patients and the role of their diabetes coping behaviours: a clinic-based study in Tripoli, Libya.

    Science.gov (United States)

    Ashur, Sana Taher; Shah, Shamsul Azhar; Bosseri, Soad; Fah, Tong Seng; Shamsuddin, Khadijah

    2016-01-01

    Achieving good glycaemic control is important in diabetes management. However, poor glycaemic control is widely reported. This article assessed the prevalence of uncontrolled and poor glycaemic control among Libyans with type 2 diabetes and examined the relative contribution of diabetes coping behaviours to their glycaemic control status. A cross-sectional study was undertaken in 2013 in a large diabetes centre in Tripoli. The study included 523 respondents. Diabetes coping behaviours were measured using the revised version of the Summary of Diabetes Self-Care Activities measure (SDSCA) and the eight-item Morisky Medication Adherence Scale (MMAS-8(©)), while glycaemic control status was based on the HbA1c level. Mean HbA1c was 8.9 (±2.1), and of the 523 patients, only 114 (21.8%) attained the glycaemic control target of HbAc1 of less than 7.0%. Females (OR=1.74, 95% CI=1.03-2.91), patients on insulin and oral hypoglycaemic agents (OR=1.92, 95% CI=1.05-3.54), patients on insulin (OR=3.14, 95% CI=1.66-6.03), and low-medication adherents (OR=2.25, 95% CI=1.36-3.73) were more likely to have uncontrolled and poor glycaemic control, while exercise contributed to glycaemic control status as a protective factor (OR=0.85, 95% CI=0.77-0.94). The findings from this study showed the considerable burden of uncontrolled and poor glycaemic control in one of the largest diabetes care settings in Libya. Medication adherence as well as exercise promotion programs would help in reducing the magnitude of poor glycaemic control.

  17. HbA2 levels in β-thalassaemia carriers with the Filipino β0-deletion: are the levels higher than what is found with non-deletional forms of β0-thalassaemia?

    Science.gov (United States)

    George, E; Teh, Lai Kuan; Tan, Jama; Lai, Mei I; Wong, Lily

    2013-01-01

    Classical carriers of β-thalassaemia are identified by a raised HbA2 level. Earlier studies indicated that the Filipino β-deletion has high raised HbA2 levels. The introduction of automated high performance liquid chromatography (HPLC) for thalassaemia screening is an important advance in technology for haematology laboratories. The BioRad Variant II Hb analyser is a common instrument used to quantify HbA2 levels in thalassaemia screening. This study aimed to determine HbA2 levels in carriers of Filipino β-mutation using the BioRad Variant II Hb analyser. The Filipino β-deletion was identified using gap-polymerase chain reaction (PCR) in the parents of transfusion dependent β-thalassaemia patients who were homozygous for the Filipino β-deletion in the indigenous population of Sabah, Malaysia. Hb subtypes were quantified on the BioRad Variant II Hb analyser. Concurrent α-thalassaemia was identified by multiplex gap-PCR for deletions and amplification refractory mutation system (ARMS)-PCR for non-deletional mutations. The mean HbA2 level for Filipino β-thalassaemia trait was 5.9 ± 0.47 and with coinheritance of α-thalassaemia was 6.3 ± 0.44 (-α heterozygous) and 6.7 ± 0.36 (-α homozygous). The HbA2 levels were all >4% in keeping with the findings of classical β-thalassaemia trait and significantly higher than levels seen in non-deletional forms of β-thalassaemia. The HbA2 level measured on the BioRad Variant II Hb analyser was lower than the level in the first description of the Filipino β-thalassaemia. β-thalassaemia trait with coinheritance of α-thalassaemia (-α) is associated with significantly higher HbA2 level.

  18. Hb Mozhaisk [β92(F8)His→Arg; HBB: c.278A>G] as a De Novo Mutation in a Child of Mixed Ethnic Origins.

    Science.gov (United States)

    Benzoni, Elena; Giannone, Valentina; Michetti, Laura; Seia, Manuela; Cavalleri, Laura; Curcio, Cristina

    Approximately 150 variants described in the HbVar database have been found to be unstable and about 80.0% of these are on the β-globin gene. We describe the case of a 3-year-old child who presented at the emergency room with fever and asthenia. Hematological data suggested severe hemolytic anemia. Sequencing of the β-globin gene revealed the mutation HBB: c.278A>G at codon 92 in a heterozygous state, reported as Hb Mozhaisk in the HbVar database. Other family members did not have Hb Mozhaisk, thus, this variant is due to a de novo mutation. Because of the rarity of this globin variant, we believe it is important to report similar cases, to have a more complete phenotype description of the pathology and define an adequate reproductive risk for couples, considering the dominant inheritance pattern (hence an inheritance risk of 50.0%).

  19. Fundamental aspects of municipal refuse generated in Beirut and Tripoli: field studies 1994-1996

    International Nuclear Information System (INIS)

    Ayoub, G.M.; Acra, A.; Abdallah, R.; Merhebi, F.

    1996-01-01

    This study presents socio-economic survey on collection and analysis of data pertaining to the municipal refuse generated in Beirut and Tripoli, Two big cities of Lebanon.Although the collection process applied in Beirut has progressed immensely in the past two years, the unsatisfactory methods of disposal that have been employed until now has an impact on the environment:marine environment as well as the air pollution becoming problems in the city of Beirut. In this respect, solid wastes characterization and generation rates in both cities of Beirut and Tripoli are presented. Mapping of refuse collection and disposal services in the two cities is described. Sources of refuse like hospitals, industries, household,...are enumerated. Recycling potentials of plastics, paper and cardboard, glass wastes, metallic wastes, textile wastes are described

  20. Hb Matera (HBB: c.167 T > A): A Second Case Detected in a Pregnant Chinese Woman by the Capillary Electrophoresis Method.

    Science.gov (United States)

    Li, You-qiong; Ye, Li-Hua; Mo, Yun

    2016-01-01

    Hb Matera (HBB: c.167 T > A) is an unstable β-globin gene variant with an ATG > AAG substitution at codon 55. Its coelution with Hb A2 on high performance liquid chromatography (HPLC) makes it difficult to discriminate between Hb Matera and Hb E (HBB: c.79 G > A) that also coelutes with Hb A2 in this method. However, we found that capillary electrophoresis (CE) was able to detect Hb Matera and discriminate it from Hb E, based on the quantification of the peaks and on hematological parameters.

  1. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia.

    Science.gov (United States)

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth

    2016-06-08

    Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α(codon 59)α/α(CS)α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.

  2. Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli

    OpenAIRE

    Taher, Yousef A.; Samud, Awatef M.; Ratimy, Aya H.; Seabe, Areeje M.

    2012-01-01

    Background: The effect of sleep difficulties has achieved a great deal of attention recently, with university students considered as a homogenized population, particularly affected by sleep habits.Aim: The objective of this study was to investigate whether Libyan college students experience sleep disturbance during their academic programmes. Methods: A cross-sectional survey was conducted in the college of Pharmacy, Tripoli University, during February 2010. A total of 201 students, including ...

  3. Hematological Characterizations and Molecular Diagnostic Aspects of Hb Wiangpapao [α44(CE2)Pro→Ser (α1), CCG>TCG; HBA1: c.133C>T], a New α-Globin Variant Found in a Pregnant Thai Woman.

    Science.gov (United States)

    Panyasai, Sitthichai; Pornprasert, Sakorn

    2017-03-01

    We report the hematological parameters and provide a rapid molecular analysis method for detection of Hb Wiangpapao [α44(CE2)Pro→Ser, CCG>TCG; HBA1: c.133C>T], a new α-globin variant found in a pregnant Thai woman. Her red cell indices were measured by an automated blood counter. The results were: red blood cell (RBC) count 4.03 × 10 12 /L, Hb 13.1 (g/dL), packed cell volume (PCV) 0.39 L/L, mean corpuscular volume (MCV) 97.0 fL, mean corpuscular hemoglobin (Hb) (MCH) 32.5 pg, mean corpuscular Hb concentration (MCHC) 33.4 g/dL, and RBC distribution width (RDW) 9.4%. The Hb typing by high performance liquid chromatography (HPLC) showed 13.6% abnormal Hb at a retention time of 2.20 min. that was difficult to distinguish from Hb A. On the capillary electrophoresis (CE) electropherogram, this hemoglobinopathy peak did not separate from the Hb A peak. DNA sequencing showed a C>T transition at the first position of codon 44 (CCG>TCG) of the α1-globin gene that led to a substitution of proline for serine. This mutation has not been recorded in the public databases. Therefore, we named it Hb Wiangpapao as it was first discovered in the Wiangpapao District, Chiang Rai, Thailand. The multiplex allele-specific polymerase chain reaction (ASPCR) for detection of Hb Wiangpapao was developed and revealed a 510 bp specifically amplified fragment. The better understanding of hematological characterizations and the newly developed multiplex ASPCR for diagnosis of Hb Wiangpapao are useful for genetic counseling and family education.

  4. Advances in Monte-Carlo code TRIPOLI-4®’s treatment of the electromagnetic cascade

    Directory of Open Access Journals (Sweden)

    Mancusi Davide

    2018-01-01

    Full Text Available TRIPOLI-4® is a Monte-Carlo particle-transport code developed at CEA-Saclay (France that is employed in the domains of nuclear-reactor physics, criticality-safety, shielding/radiation protection and nuclear instrumentation. The goal of this paper is to report on current developments, validation and verification made in TRIPOLI-4 in the electron/positron/photon sector. The new capabilities and improvements concern refinements to the electron transport algorithm, the introduction of a charge-deposition score, the new thick-target bremsstrahlung option, the upgrade of the bremsstrahlung model and the improvement of electron angular straggling at low energy. The importance of each of the developments above is illustrated by comparisons with calculations performed with other codes and with experimental data.

  5. Application of Six Sigma Model to Evaluate the Analytical Quality of Four HbA1c Analyzers.

    Science.gov (United States)

    Maesa, Jos Eacute M; Fern Aacute Ndez-Riejos, Patricia; S Aacute Nchez-Mora, Catalina; Toro-Crespo, Mar Iacute A De; Gonz Aacute Lez-Rodriguez, Concepci Oacute N

    2017-01-01

    The Six Sigma Model is a global quality management system applicable to the determination of glycated hemoglobin (HbA1c). In addition, this model can ensure the three characteristics influencing the patient risk: the correct performance of the analytical method with low inaccuracy and bias, the quality control strategy used by the laboratory, and the necessary quality of the analyte. The aim of this study is to use the Six Sigma Model for evaluating quality criteria in the determination of glycated hemoglobin HbA1c and its application to assess four different HbA1c analyzers. Four HbA1c analyzers were evaluated: HA-8180V®, D-100®, G8®, and Variant II Turbo®. For 20 consecutive days, two levels of quality control (high and low) provided by the manufacturers were measured in each of the instruments. Imprecision (CV), bias, and Sigma values (σ) were calculated with the data obtained and a method decision chart was developed considering a range of quality requirements (allowable total error, TEa). For a TEa = 3%, HA-8180V = 1.54 σ, D-100 = 1.63 σ, G8 = 2.20 σ, and Variant II Turbo = -0.08 σ. For a TEa = 4%, HA-8180V = 2.34 σ, D-100 = 2.32 σ, G8 = 3.74 σ, and Variant II Turbo = 0.16 σ. For a TEa = 10%, HA8180V = 7.12 σ, D-100 = 6.46 σ, G8 = 13.0 σ, and Variant II Turbo = 1.56 σ. Applying the Stockholm consensus and its subsequent Milan review to the results: the maximum level in quality requirements for HbA1c is an allowable total error (TEa) = 3%, G8 is located in region 2 σ (2.20), which is a poor result, and HA-8180V and D-100 are both in region 1 σ (1.54 and 1.63, respectively), which is an unacceptable analytical performance.

  6. Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

    Science.gov (United States)

    Tan, J; Tay, J S; Wong, Y C; Kham, S K; Bte Abd Aziz, N; Teo, S H; Wong, H B

    1995-01-01

    Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

  7. Hb taradale [beta82(EF6)Lys-->Arg]: a novel mutation at a 2,3-diphosphoglycerate binding site.

    Science.gov (United States)

    Brennan, Stephen O; Sheen, Campbell; Chan, Tim; George, Peter M

    2005-01-01

    Hb Taradale [beta82(EF6)Lys-->Arg] was initially detected as a split Hb A0 peak on Hb A1c, monitoring. Red cell parameters, hemoglobin (Hb) electrophoresis and stability tests were normal. Mass spectrometry (ms) clearly identified a variant beta chain with a mass increase of 28 Da and peptide mapping located the mutation site to peptide betaT-9. DNA sequencing confirmed the presence of a novel beta82(EF6)Lys-->Arg mutation. This conservative substitution at a 2,3-diphosphoglycerate (2,3-DPG) binding site did not, however, appear to affect the P50 for oxygen binding.

  8. Comparison of the BioRad Variant and Primus Ultra2 high-pressure liquid chromatography (HPLC) instruments for the detection of variant hemoglobins.

    Science.gov (United States)

    Gosselin, R C; Carlin, A C; Dwyre, D M

    2011-04-01

    Hemoglobin variants are a result of genetic changes resulting in abnormal or dys-synchronous hemoglobin chain production (thalassemia) or the generation of hemoglobin chain variants such as hemoglobin S. Automated high-pressure liquid chromatography (HPLC) systems have become the method of choice for the evaluation of patients suspected with hemoglobinopathies. In this study, we evaluated the performance of two HPLC methods used in the detection of common hemoglobin variants: Variant and Ultra2. There were 377 samples tested, 26% (99/377) with HbS, 8.5% (32/377) with HbC, 20.7% (78/377) with other hemoglobin variant or thalassemia, and 2.9% with increased hemoglobin A(1) c. The interpretations of each chromatograph were compared. There were no differences noted for hemoglobins A(0), S, or C. There were significant differences between HPLC methods for hemoglobins F, A(2), and A(1) c. However, there was good concordance between normal and abnormal interpretations (97.9% and 96.2%, respectively). Both Variant and Ultra2 HPLC methods were able to detect most common hemoglobin variants. There was better discrimination for fast hemoglobins, between hemoglobins E and A(2), and between hemoglobins S and F using the Ultra2 HPLC method. © 2010 Blackwell Publishing Ltd.

  9. Haemoglobin Pierre-Benite--a high affinity variant associated with relative polycythaemia.

    Science.gov (United States)

    Beard, M E; Potter, H C; Spearing, R L; Brennan, S O

    2001-12-01

    This is the second reported example of Hb Pierre--Benite (beta90 Glu-->Asp). This mutation is associated with increased oxygen affinity and polycythaemia. No instability was found and there was no charge shift detected by cellulose acetate electrophoresis at pH 8.3. The mutation was however, clearly indicated by electrospray ionization mass spectrometry (ESI MS), which showed an abnormal beta chain with a 14 Da decrease in mass. Blood volume studies documented a relative rather than a true polycythaemia and this finding has been reported in at least two other high affinity haemoglobin variants--Hb Heathrow and Hb Rahere. This finding led to delay in diagnosis because high oxygen affinity variants are conventionally considered to cause a true polycythaemia.

  10. Glycaemic control status among type 2 diabetic patients and the role of their diabetes coping behaviours: a clinic-based study in Tripoli, Libya

    Directory of Open Access Journals (Sweden)

    Sana Taher Ashur

    2016-03-01

    Full Text Available Background: Achieving good glycaemic control is important in diabetes management. However, poor glycaemic control is widely reported. This article assessed the prevalence of uncontrolled and poor glycaemic control among Libyans with type 2 diabetes and examined the relative contribution of diabetes coping behaviours to their glycaemic control status. Methods: A cross-sectional study was undertaken in 2013 in a large diabetes centre in Tripoli. The study included 523 respondents. Diabetes coping behaviours were measured using the revised version of the Summary of Diabetes Self-Care Activities measure (SDSCA and the eight-item Morisky Medication Adherence Scale (MMAS-8©, while glycaemic control status was based on the HbA1c level. Results: Mean HbA1c was 8.9 (±2.1, and of the 523 patients, only 114 (21.8% attained the glycaemic control target of HbAc1 of less than 7.0%. Females (OR=1.74, 95% CI=1.03–2.91, patients on insulin and oral hypoglycaemic agents (OR=1.92, 95% CI=1.05–3.54, patients on insulin (OR=3.14, 95% CI=1.66–6.03, and low-medication adherents (OR=2.25, 95% CI=1.36–3.73 were more likely to have uncontrolled and poor glycaemic control, while exercise contributed to glycaemic control status as a protective factor (OR=0.85, 95% CI=0.77–0.94. Conclusion: The findings from this study showed the considerable burden of uncontrolled and poor glycaemic control in one of the largest diabetes care settings in Libya. Medication adherence as well as exercise promotion programs would help in reducing the magnitude of poor glycaemic control.

  11. Alternate site testing for HbA1c using the Primus CLC330 GHb analyzer.

    Science.gov (United States)

    Phillipov, G; Charles, P; Beng, C; Phillips, P J

    1997-04-01

    To determine whether the Primus high-pressure liquid chromatography (HPLC) is suited to alternate site testing (AST) for HbA1c in a hospital diabetes outpatient clinic. Patients were attending the clinic for routine management of their diabetes. A number of diabetic patients with uremia (n = 11) were also investigated. HbA1c levels were measured in the outpatient setting by the Primus HPLC and in a more limited study the DCA-2000 instrument using the new 6-min assay cartridge. HbA1c measurements were also performed with Pierce affinity minicolumns and a Bio-Rad Variant HPLC. The Primus HPLC assay had low imprecision of 2.3, 1.6, and 1.0% for HbA1c levels of 4.7, 7.3, and 11.1%, respectively, and was not prone to interference by carbamylated hemoglobin as found for the ion-exchange Variant HPLC method. Method comparison studies showed that the bias and proportional error between the Pierce affinity minicolumn procedure (standardized with respect to an external quality control program) and the Primus HPLC (Y) was -0.4 and 1.2% respectively (n = 32). Similarly the bias and proportional error between the Primus and DCA-2000 methods was 0.7 and -2.5%. The Primus was shown to give falsely elevated HbA1c concentrations if the time between sequential injections was > 28 min. The Primus HPLC has a decided advantage over specialty AST instruments, like the DCA-2000, in not only meeting AST requirements but also allowing rapid automated batch processing of all laboratory HbA1c samples.

  12. Detection of Hb Rothschild HBB: c.[112T>A or 112T>C], Through High Index of Suspicion on Abnormal Pulse Oximetry.

    Science.gov (United States)

    Alli, Nazeer A; Wessels, Piet; Rampersad, Narisha; Clark, Barnaby E; Thein, Swee Lay

    2017-03-01

    We describe a case with a low oxygen affinity hemoglobin (Hb) variant who presented with cyanosis in the absence of cardiopulmonary disease. The patient, a 27-year-old pregnant female (P1G2), complained of a productive cough and bluish discoloration of the lips that started 3 days prior to seeking attention. She had no previous episodes and has generally been in good health. A positive family history of cyanosis was obtained in one sibling. Systematic examination, notably the cardiorespiratory system, revealed no abnormalities. The arterial Hb oxygen saturation (SpO 2 ) on pulse oximetry was 81.0% and Hb separation studies revealed an Hb variant identified as Hb Rothschild [β37(C3)Trp→Arg] (HBB: c.[112 T>A or 112 T>C]) by gene sequencing. The amino acid substitution (Trp→Arg) is an important contact point at the α1β2 interface and favors a T-quaternary state of the Hb tetramer. This leads to a low oxygen affinity state, which results in premature release of oxygen and drop in oxygen saturation. In the absence of cardiopulmonary disease, a decreased oxygen saturation reading, with or without cyanosis, should arouse suspicion for a possible dysHb.

  13. Molecular analysis of abnormal hemoglobins in beta chain in Aegean region of Turkey and first reports of hemoglobin Andrew-Minneapolis and Hb Hinsdale from Turkey.

    Science.gov (United States)

    Aykut, Ayça; Onay, Hüseyin; Durmaz, Asude; Karaca, Emin; Vergin, Canan; Aydınok, Yeşim; Özkınay, Ferda

    2015-07-01

    The Agean is one of the regions in Turkey where thalassemias and abnormal hemoglobins (Hbs) are prevalent. Combined heterozygosity of thalassemia mutations with a variety of structural Hb variants lead to an extremely wide spectrum of clinical and hematological phenotypes which is of importance for prenatal diagnosis. One hundred and seventeen patients and carriers diagnosed by hemoglobin electrophoresis (HPLC), at risk for abnormal hemoglobinopathies were screened for mutational analysis of the beta-globin gene. The full coding the 5' UTR, and the 3' UTR sequences of beta-globin gene (GenBank accession no. U01317) were amplified and sequenced. In this study, a total of 118 (12.24%) structural Hb variant alleles were identified in 1341 mutated beta-chain alleles in Medical Genetics Department of Ege University between January 2006 and November 2013. Here, we report the mutation spectrum of abnormal Hbs associated with the beta-globin gene in Aegean region of Turkey. In the present study, the Hb Hinsdale and Hb Andrew-Minneapolis variants are demonstrated for the first time in the Turkish population.

  14. Quantitative analysis of urban sprawl in Tripoli using Pearson's Chi-Square statistics and urban expansion intensity index

    International Nuclear Information System (INIS)

    Al-sharif, Abubakr A A; Pradhan, Biswajeet; Shafri, Helmi Zulhaidi Mohd; Mansor, Shattri

    2014-01-01

    Urban expansion is a spatial phenomenon that reflects the increased level of importance of metropolises. The remotely sensed data and GIS have been widely used to study and analyze the process of urban expansions and their patterns. The capital of Libya (Tripoli) was selected to perform this study and to examine its urban growth patterns. Four satellite imageries of the study area in different dates (1984, 1996, 2002 and 2010) were used to conduct this research. The main goal of this work is identification and analyzes the urban sprawl of Tripoli metropolitan area. Urban expansion intensity index (UEII) and degree of freedom test were used to analyze and assess urban expansions in the area of study. The results show that Tripoli has sprawled urban expansion patterns; high urban expansion intensity index; and its urban development had high degree of freedom according to its urban expansion history during the time period (1984-2010). However, the novel proposed hypothesis used for zones division resulted in very good insight understanding of urban expansion direction and the effect of the distance from central business of district (CBD)

  15. Prevalência de talassemias e hemoglobinas variantes no estado de Goiás, Brasil Prevalence of thalassemias and variant hemoglobins in the state of Goiás, Brazil

    Directory of Open Access Journals (Sweden)

    Paulo Roberto de Melo-Reis

    2006-12-01

    Full Text Available As anemias hereditárias, em especial as talassemias e hemoglobinas (Hb variantes, são as mais comuns das alterações genéticas humanas; sua freqüência na população brasileira é muito variável, dependendo dos grupos raciais formadores de cada região. O povoamento de Goiás, que teve início logo após o seu descobrimento, em 1726, motivado pela procura de ouro, foi composto principalmente por portugueses e escravos africanos, contexto que favoreceu a mestiçagem entre eles. Considerando que esses povos apresentam genes para as hemoglobinas anormais com freqüências variadas, é esperado que se encontrem essas alterações genéticas na nossa população. O objetivo deste trabalho foi avaliar a prevalência de talassemias e hemoglobinas variantes na população de Goiás. Para isso a casuística foi composta por 404 alunos participantes dos diversos cursos da Universidade Católica de Goiás (UCG, oriundos de 55 cidades do estado de Goiás. A prevalência de anemia hereditária por talassemias e hemoglobinas variantes em Goiás foi de 10,1%, cuja ordem decrescente foi a seguinte: talassemia alfa heterozigótica (5,2%, heterozigose para hemoglobina S (Hb AS (2,2%, heterozigose para hemoglobina C (Hb AC (1%, talassemia beta menor (0,7%, associação entre talassemia alfa e heterozigose para Hb S (0,5%, associação entre talassemia alfa e heterozigose para Hb C (0,3% e heterozigose para hemoglobina D (Hb AD (0,3%. Nenhum caso de homozigose foi encontrado no presente estudo. Este trabalho demonstrou a dispersão dos genes para Hb S, Hb C e Hb D, bem como de talassemias alfa e beta em uma população do estado de Goiás. Por essa razão, concluímos que é importante realizar programas com maior abrangência da população para estudo da epidemiologia das talassemias e hemoglobinas variantes no estado de Goiás.The hereditary anemias, especially the thalassemies and hemoglobinopathies are the most common human genetic abnormalities. Their

  16. Compound Heterozygosity for Hb Alperton (HBB: c.407C>T) and IVS-I-5 (G>C) (HBB: c.92+5G>C) Mutations Presenting as a Moderate Anemia in an Indian Family.

    Science.gov (United States)

    Godbole, Koumudi G; Ramachandran, Angelina; Karkamkar, Ashwini S; Dalal, Ashwin B

    2018-04-13

    While knowledge of HBB gene mutations is necessary for offering prenatal diagnosis (PND) of β-thalassemia (β-thal), a genotype-phenotype correlation may not always be available for rare variants. We present for the first time, genotype-phenotype correlation for a compound heterozygous status with IVS-I-5 (G>C) (HBB: c.92+5G>C) and HBB: c.407C>T (Hb Alperton) mutations on the HBB gene in an Indian family. Hb Alperton is a very rare hemoglobin (Hb) variant with scant published information about its clinical presentation, especially when accompanied with another HBB gene mutation. Here we provide biochemical as well as clinical details of this variant.

  17. Complex Interaction of Hb Q-Thailand with α0- and β0-Thalassemia in a Chinese Family.

    Science.gov (United States)

    He, Sheng; Qin, Qian; Lin, Li; Chen, Qiuli; Yi, Shang; Wei, Honhwei; Du, Juan; Zheng, Chenguang; Qiu, Xiaoxia; Chen, Biyan

    2017-01-01

    Hb Q-Thailand [α74(EF3)Asp→His (α1); HBA1: c.223 G>C] is an abnormal hemoglobin (Hb), variant found mainly in China and Southeast Asian countries. The association of the α Q -Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report a hitherto undescribed condition of patients with a double heterozygosity for Hb Q-Thailand with α 0 -thalassemia (α 0 -thal) and in combination with β 0 -thalassemia (β 0 -thal) in a Chinese family. Our study will provide some clinical manifestations, laboratory diagnosis and genetic counseling for complex hemoglobinopathies.

  18. The Properties of Red Blood Cells from Patients Heterozygous for HbS and HbC (HbSC Genotype

    Directory of Open Access Journals (Sweden)

    A. Hannemann

    2011-01-01

    Full Text Available Sickle cell disease (SCD is one of the commonest severe inherited disorders, but specific treatments are lacking and the pathophysiology remains unclear. Affected individuals account for well over 250,000 births yearly, mostly in the Tropics, the USA, and the Caribbean, also in Northern Europe as well. Incidence in the UK amounts to around 12–15,000 individuals and is increasing, with approximately 300 SCD babies born each year as well as with arrival of new immigrants. About two thirds of SCD patients are homozygous HbSS individuals. Patients heterozygous for HbS and HbC (HbSC constitute about a third of SCD cases, making this the second most common form of SCD, with approximately 80,000 births per year worldwide. Disease in these patients shows differences from that in homozygous HbSS individuals. Their red blood cells (RBCs, containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome. Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes. This paper reviews what is known about SCD in HbSC individuals and will compare the properties of their RBCs with those from homozygous HbSS patients. Important areas of similarity and potential differences will be emphasised.

  19. Stability study for magnetic reagent assaying Hb and HbA1c

    International Nuclear Information System (INIS)

    Hsieh, Wen-Pin; Chieh, J.J.; Yang, C.C.; Yang, S.Y.; Chen, Po-Yu; Huang, Yu-Hao; Hong, Y.W.; Horng, H.E.

    2013-01-01

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe 3 O 4 magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2–8 °C. This means that the reagents synthesized in this work are promising for practical applications. - Highlights: ► The properties of assaying Hb and HbA1c using immunomagnetic reduction are studied. ► The magnetic nanoparticles with antibodies are highly stable in solutions. ► No significant mutual interference between Hb and HbA1c in assays is observed. ► High-sensitivity assays on Hb and HbA1c using immunomagnetic reduction are achieved.

  20. Spectrum of hemoglobin variants in the population of northern region of West Bengal: An ethnogenetic proposition

    Directory of Open Access Journals (Sweden)

    Bidyut Krishna Goswami

    2014-01-01

    Full Text Available Context: The birth of transfusion-dependent states of hemoglobinopathies including thalassemias is preventable by population screening and genetic counseling. Magnitude is not addressed in the Northern Region of West Bengal where many ethnic variants inhabit. Aims and Objectives: The aim of the following study is to find out the burden of different entities of hemoglobinopathies, their correlation with ethnicity and the "at risk" groups. Subjects and Methods: A descriptive study was conducted from the Hematology Unit of North Bengal Medical College over 1 year on the subjects underwent screening for hemoglobinopathies for detection of abnormal hemoglobin (Hb variants by "cation-exchange high-performance liquid chromatography" principle along with other relevant tests. Statistical Analysis: Data was analyzed by frequency distribution and Chi-square test assuming P value as 95% of the level of significance using the SPSS version 16 (SPSS Inc., Chicago, Illinois, U.S.A. Result: Abnormal Hb variant was 47.5% among 1872. Hb E trait (34.4% was most common followed by Hb E disease (25.3% and others. Hb E disorders (92.7% were observed mostly among Rajbangsi population while E-β-thalassemias (40% in the Muslims and a heterogeneous pattern noted among tribal and mongoloid. Conclusion: Hb E hemoglobinopathies was high among Rajbangsi and Muslims with identification of some other hemoglobinopathies involving tribal and mongoloid.

  1. Comparison of MCNPX-C90 and TRIPOLI-4-D for fuel depletion calculations of a Gas-cooled Fast Reactor

    International Nuclear Information System (INIS)

    Reyes-Ramirez, Ricardo; Martin-del-Campo, Cecilia; Francois, Juan-Luis; Brun, Emeric; Dumonteil, Eric; Malvagi, Fausto

    2010-01-01

    The Gas-cooled Fast Reactor is one of the reactor concepts selected by the Generation IV International Forum for the next generation of innovative nuclear energy systems. Several fuel design concepts are being investigated. Burnup depletion of mixed fuel of uranium and plutonium, cooled with gas in a fast neutron energy spectrum must be simulated. Various codes are being developed and/or adapted to improve the quality of the results, and also to reduce the computing time required for the simulations. The main objective of this work is to compare the fuel depletion results obtained with MCNPX-CINDER90 code and the new TRIPOLI-4-Depletion code (developed by the Commissariat a l'Energie Atomique) of a fuel design concept for the Gas-cooled Fast Reactor. Calculations were made for an equivalent homogeneous model of fuel rods in a hexagonal mesh assembly. Total reflection conditions were applied on the six lateral faces and the two axial faces of the assembly. The materials used in the fuel assembly are: carbide of uranium and plutonium as fuel, silicon carbide as cladding, and helium gas as coolant. JEFF libraries of effective cross sections were used in both codes. Two methods of burnup step calculations were performed with TRIPOLI-4-D, the Euler and the CSADA, and their results were compared with the MCNPX-CINDER90 CSADA method. A period of 300 days of irradiation time was considered, which was divided into 12 steps. Results of the infinite multiplication factor as function of the irradiation time, and the evolution of the isotope concentrations for a selected group of nuclides were compared. The main conclusion is that very similar results were obtained for the three types of depletion calculations which were compared: (1) MCNPX-C90 CSADA; (2) TRIPOLI-4-D CSADA, and (3) TRIPOLI-4-D EULER. The best calculation time was obtained with the TRIPOLI-4-D EULER method, which needed approximately half the time than the other two. In summary, it is sufficiently good to use

  2. Stability study for magnetic reagent assaying Hb and HbA1c

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Wen-Pin [Actherm Inc., Hsinchu 200, Taiwan (China); Chieh, J.J.; Yang, C.C. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Yang, S.Y. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); MagQu Co., Ltd., Sindian Dist., New Taipei City 231, Taiwan (China); Chen, Po-Yu; Huang, Yu-Hao [Actherm Inc., Hsinchu 200, Taiwan (China); Hong, Y.W. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Horng, H.E., E-mail: phyfv001@ntnu.edu.tw [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China)

    2013-01-15

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe{sub 3}O{sub 4} magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2-8 Degree-Sign C. This means that the reagents synthesized in this work are promising for practical applications. - Highlights: Black-Right-Pointing-Pointer The properties of assaying Hb and HbA1c using immunomagnetic reduction are studied. Black-Right-Pointing-Pointer The magnetic nanoparticles with antibodies are highly stable in solutions. Black-Right-Pointing-Pointer No significant mutual interference between Hb and HbA1c in assays is observed. Black-Right-Pointing-Pointer High-sensitivity assays on Hb and HbA1c using immunomagnetic reduction are achieved.

  3. A1c Gear: Laboratory quality HbA1c measurement at the point of care.

    Science.gov (United States)

    Ejilemele, Adetoun; Unabia, Jamie; Ju, Hyunsu; Petersen, John R

    2015-05-20

    HbA1c is an important part of assessing the diabetic control and since the use of point-of-care devices for monitoring HbA1c is increasing, it is important to determine how these devices compare to the central laboratory. One hundred and twenty patient samples were analyzed on the Bio-Rad Variant™II and one POC analyzer (Sakae A1c Gear). Three patient sample pools containing ~5%, ~7%, and ~10% HbA1c levels were run over 20 days. Three reagent lots and three instruments were evaluated for the A1c Gear. The 120 patient samples showed strong correlation (R(2)>0.989) when compared to the Variant™II with means=8.06% and 7.81%, for Variant IIand A1c Gear, respectively. Changing reagent lots or instruments had no impact for the A1c Gear. The ~5%, ~7%, and ~10% pools within-run and between-run imprecision was between 0.87-1.33% and 1.03-1.32%, and 1.41-2.35% and 1.24-1.89% with total imprecision of 1.67-2.35% and 1.61-2.31% for the A1c Gear and Variant II, respectively. The A1c Gear showed a small negative bias (0.25% HbA1c) across HbA1c measurement ranges of Gear meets the criteria of total CV Gear can give results as precise as the laboratory at the POC. Copyright © 2015. Published by Elsevier B.V.

  4. Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T], A Second and Third Case Described in Two Unrelated Dutch Families

    NARCIS (Netherlands)

    Pondman, Kirsten M.; Brinkman, Jacoline W.; van der Straaten, Hanneke M.; Stroobants, An K.; Harteveld, Cornelis L.

    2018-01-01

    We report two families, members of which are carriers of a hemoglobin (Hb) variant previously described as Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T; p.Pro115Leu]. In the first family of Dutch origin, the proband, a 32-year-old male and his 65-year-old father, were both carriers of Hb

  5. Extensions of the MCNP5 and TRIPOLI4 Monte Carlo Codes for Transient Reactor Analysis

    Science.gov (United States)

    Hoogenboom, J. Eduard; Sjenitzer, Bart L.

    2014-06-01

    To simulate reactor transients for safety analysis with the Monte Carlo method the generation and decay of delayed neutron precursors is implemented in the MCNP5 and TRIPOLI4 general purpose Monte Carlo codes. Important new variance reduction techniques like forced decay of precursors in each time interval and the branchless collision method are included to obtain reasonable statistics for the power production per time interval. For simulation of practical reactor transients also the feedback effect from the thermal-hydraulics must be included. This requires coupling of the Monte Carlo code with a thermal-hydraulics (TH) code, providing the temperature distribution in the reactor, which affects the neutron transport via the cross section data. The TH code also provides the coolant density distribution in the reactor, directly influencing the neutron transport. Different techniques for this coupling are discussed. As a demonstration a 3x3 mini fuel assembly with a moving control rod is considered for MCNP5 and a mini core existing of 3x3 PWR fuel assemblies with control rods and burnable poisons for TRIPOLI4. Results are shown for reactor transients due to control rod movement or withdrawal. The TRIPOLI4 transient calculation is started at low power and includes thermal-hydraulic feedback. The power rises about 10 decades and finally stabilises the reactor power at a much higher level than initial. The examples demonstrate that the modified Monte Carlo codes are capable of performing correct transient calculations, taking into account all geometrical and cross section detail.

  6. Extensions of the MCNP5 and TRIPOLI4 Monte Carlo codes for transient reactor analysis

    International Nuclear Information System (INIS)

    Hoogenboom, J.E.

    2013-01-01

    To simulate reactor transients for safety analysis with the Monte Carlo method the generation and decay of delayed neutron precursors is implemented in the MCNP5 and TRIPOLI4 general purpose Monte Carlo codes. Important new variance reduction techniques like forced decay of precursors in each time interval and the branch-less collision method are included to obtain reasonable statistics for the power production per time interval. For simulation of practical reactor transients also the feedback effect from the thermal-hydraulics must be included. This requires the coupling of the Monte Carlo code with a thermal-hydraulics (TH) code, providing the temperature distribution in the reactor, which affects the neutron transport via the cross section data. The TH code also provides the coolant density distribution in the reactor, directly influencing the neutron transport. Different techniques for this coupling are discussed. As a demonstration a 3*3 mini fuel assembly with a moving control rod is considered for MCNP5 and a mini core existing of 3*3 PWR fuel assemblies with control rods and burnable poisons for TRIPOLI4. Results are shown for reactor transients due to control rod movement or withdrawal. The TRIPOLI4 transient calculation is started at low power and includes thermal-hydraulic feedback. The power rises about 10 decades and finally stabilises the reactor power at a much higher level than initial. The examples demonstrate that the modified Monte Carlo codes are capable of performing correct transient calculations, taking into account all geometrical and cross section detail. (authors)

  7. Avaliação eletroforética, cromatográfica e molecular da Hb D Los Angeles no Brasil

    OpenAIRE

    Chinelato-Fernandes Ana R.; Leoneli Guilherme G.; Calderan Patrícia O.; Oliveira Rute Blasi de; Silva Jr. Wilson Araújo da; Hidalgo Claudia Augusta; Bonini- Domingos Claudia Regina

    2003-01-01

    A variante de hemoglobina (Hb) D mais comum, Hb D Los Angeles ou D Punjab, é originada de uma transversão GAA->CAA no códon 121 da globina beta; essa mutação resulta na substituição do ácido glutâmico por glutamina na proteína. É a terceira variante de hemoglobina mais freqüente da população brasileira. Como as hemoglobinas D apresentam migração similar à hemoglobina S em pH alcalino, e com a hemoglobina A em pH ácido, são necessários vários testes para o correto diagnóstico. No presente estu...

  8. Contributions at the Tripoli Monte Carlo code qualifying on critical experiences and at neutronic interaction study of fissile units

    International Nuclear Information System (INIS)

    Nouri, A.

    1994-01-01

    Criticality studies in nuclear fuel cycle are based on Monte Carlo method. These codes use multigroup cross sections which can verify by experimental configurations or by use of reference codes such Tripoli 2. In this Tripoli 2 code nuclear data are errors attached and asked for experimental studies with critical experiences. This is one of the aim of this thesis. To calculate the keff of interacted fissile units we have used the multigroup Monte Carlo code Moret with convergence problems. A new estimator of reactions rates permit to better approximate the neutrons exchange between units and a new importance function has been tested. 2 annexes

  9. Hematological and Molecular Characterization of Hb J-Buda [α61(E10)Lys → Asn, AAG > AAT].

    Science.gov (United States)

    Panyasai, Sitthichai; Permsripong, Nopphadol; Jaiping, Kanokwan; Khantarag, Pisuttinee; Pornprasert, Sakorn

    2016-06-01

    Hemoglobin (Hb) J-Buda [α61(E10)Lys → Asn, AAG > AAT] is a very rare α-chain variant found in South-East Asia. We analyzed hematological parameters and provided a rapid molecular analysis method for detection of this hemoglobinopathy in two Thai women who had severe microcytic anemia with Hb and MCV AAG → AAT mutation at codon 61 for Hb J-Buda on one allele of the α1-globin gene. The developed Allele-specific PCR (ASPCR) showed the 455 bp amplified fragment from Hb J-Buda allele. Thus, understanding of hematological characterizations and the developed ASPCR for diagnosis of Hb J-Buda are essential for genetic counseling of this hemoglobinopathy.

  10. A porous silica rock ("tripoli") in the footwall of the Jurassic Úrkút manganese deposit, Hungary: composition, and origin through carbonate dissolution

    Science.gov (United States)

    Polgari, Marta; Szabo, Zoltan; Szabo-Drubina, Magda; Hein, James R.; Yeh, Hsueh-Wen

    2005-01-01

    The mineralogical, chemical, and isotopic compositions were determined for a white tripoli from the footwall of the Jurassic Úrkút Mn-oxide ore deposit in the Bakony Mountains, Hungary. The tripoli consists of quartz and chalcedony, with SiO2 contents up to 100 wt.%; consequently, trace-element contents are very low. Oxygen isotopes and quartz crystallinity indicate a low-temperature diagenetic origin for this deposit. The tripoli was formed by dissolution of the carbonate portion of the siliceous (sponge spicules) Isztimér Limestone. Dissolution of the carbonate was promoted by inorganic and organic acids generated during diagensis and left a framework composed of diagenetic silica that preserved the original volume of the limestone layer. The relative enrichment of silica and high porosity is the result of that carbonate dissolution. The silty texture of this highly friable rock is due to the structurally weak silica framework.

  11. Biochemical and Molecular Analysis of the Hb Lepore Boston Washington in a Syrian Homozygous Child

    Directory of Open Access Journals (Sweden)

    Monica Pirastru

    2017-01-01

    Full Text Available Hemoglobin (Hb Lepore is composed of two normal α chains and two δβ fusion globins that arise from unequal crossover events between the δ- and β-globin genes. The Hb Lepore is widespread all over the world and in many ethnic groups. It includes some of the few clinically significant Hb variants that are associated with a β-thalassemia phenotype. Here, we describe the first occurrence of Hb Lepore Boston Washington in a Syrian individual. The patient, a 10-year-old child, shows severe anemia with a Hb level of 6.85 g/dL and typical thalassemic red cell indices. The diagnostic procedure implies hematological, biochemical, and molecular analysis, including multiplex ligation-dependent probe amplification (MLPA assay, GAP-PCR, and DNA sequencing. This latter allowed us to define the correct structure of the hybrid δβ-globin gene. The knowledge of the spectrum of mutations associated with different geographical areas is the prerequisite to set up large-scale screening programs and be able to offer genetic counseling to couples at risk.

  12. THE SURVIVING HISTORIC HAMMĀMS OF THE MEDINA OF TRIPOLI - LIBYA: TANGIBLE AND INTANGIBLE DIMENSIONS

    Directory of Open Access Journals (Sweden)

    Magda Sibley

    2008-11-01

    Full Text Available Unlike the other medinas in the Arab-Islamic world, the medina of Tripoli (capital city of Libya, has never had many historic public baths. This is probably due to a more conservative tradition where most of the Libyan women use the hamm.m only once, as part of their pre-wedding preparation and celebration. This paper presents an analysis of the three and only remaining hamm.ms of Tripoli and the way they are used and perceived today. Based on the results of a survey conducted by the authors in July 2008 (as part of an AHRC funded research project on the historic hammams of North Africa the architectural characteristics of these historic structures are presented along with their increasing usage by a cosmopolitan population (Tunisians, Moroccans and Sudanese living inside the medina. This paper also outlines a number of guidelines for the sustainable use and adaptation of the hamm.m within the Libyan context.

  13. Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype

    Directory of Open Access Journals (Sweden)

    A. Hannemann

    2015-11-01

    Full Text Available Sickle cell disease (SCD in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

  14. Interaction between Hb E and Hb Yala (HBB:c.129delT); a novel frameshift beta globin gene mutation, resulting in Hemoglobin E/β0 thalassemia.

    Science.gov (United States)

    Ekwattanakit, Supachai; Riolueang, Suchada; Viprakasit, Vip

    2018-03-01

    There are more than 200 known mutations found in patients with β-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia. A comprehensive hematology and DNA analysis was applied in the index patient and her mother. Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/β 0 -thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the β-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the β-globin gene which we named 'Hb Yala' according to the origin of this index family. This mutation was assumed to generate a truncated β-globin chain terminating at codon 60 with possible unstable variant leading to a 'null' or β 0 -thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found. This report has provided evidence that genotype-phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.

  15. Hb Agenogi [β90(F6)Glu→Lys (GAG>AAG) HBB: c.271G>A)] in a Pregnant Thai Woman.

    Science.gov (United States)

    Panyasai, Sitthichai; Thongsuk, Pollawat; Pornprasert, Sakorn

    2016-01-01

    Hb Agenogi [β90(F6)Glu→Lys (GAG>AAG) HBB: c.271G>A)] is a very rare β-globin chain variant. We report for the first time this hemoglobinopathy in a pregnant 20-year-old Thai woman. She was seen by an obstetrician at her 14th week of gestation. She was pale and had an inflammatory lesion of her lower left leg. The hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) and low pressure liquid chromatography (LPLC) showed a peak of abnormal Hb at the C window. On capillary electrophoresis (CE), the abnormal Hb peak was observed at electrophoretic zone 4 that corresponded to the Hb E (HBB: c.79G>A) peak. Direct DNA sequencing revealed a GAG>AAG mutation at codon 90 of the β-globin gene. Thus, even though Hb Agenogi is very rare, it can be found in Thai people. The knowledge and understanding of this hemoglobinopathy will be used to assist in diagnosis, management and counseling for patients.

  16. Automatic treatment of the variance estimation bias in TRIPOLI-4 criticality calculations

    International Nuclear Information System (INIS)

    Dumonteil, E.; Malvagi, F.

    2012-01-01

    The central limit (CLT) theorem States conditions under which the mean of a sufficiently large number of independent random variables, each with finite mean and variance, will be approximately normally distributed. The use of Monte Carlo transport codes, such as Tripoli4, relies on those conditions. While these are verified in protection applications (the cycles provide independent measurements of fluxes and related quantities), the hypothesis of independent estimates/cycles is broken in criticality mode. Indeed the power iteration technique used in this mode couples a generation to its progeny. Often, after what is called 'source convergence' this coupling almost disappears (the solution is closed to equilibrium) but for loosely coupled systems, such as for PWR or large nuclear cores, the equilibrium is never found, or at least may take time to reach, and the variance estimation such as allowed by the CLT is under-evaluated. In this paper we first propose, by the mean of two different methods, to evaluate the typical correlation length, as measured in cycles number, and then use this information to diagnose correlation problems and to provide an improved variance estimation. Those two methods are based on Fourier spectral decomposition and on the lag k autocorrelation calculation. A theoretical modeling of the autocorrelation function, based on Gauss-Markov stochastic processes, will also be presented. Tests will be performed with Tripoli4 on a PWR pin cell. (authors)

  17. Recent R and D around the Monte-Carlo code Tripoli-4 for criticality calculation

    International Nuclear Information System (INIS)

    Hugot, F.X.; Lee, Y.K.; Malvagi, F.

    2008-01-01

    TRIPOLI-4 [1] is the fourth generation of the TRIPOLI family of Monte Carlo codes developed from the 60's by CEA. It simulates the 3D transport of neutrons, photons, electrons and positrons as well as coupled neutron-photon propagation and electron-photons cascade showers. The code addresses radiation protection and shielding problems, as well as criticality and reactor physics problems through both critical and subcritical neutronics calculations. It uses full pointwise as well as multigroup cross-sections. The code has been validated through several hundred benchmarks as well as measurement campaigns. It is used as a reference tool by CEA as well as its industrial and institutional partners, and in the NURESIM [2] European project. Section 2 reviews its main features, with emphasis on the latest developments. Section 3 presents some recent R and D for criticality calculations. Fission matrix, Eigen-values and eigenvectors computations will be exposed. Corrections on the standard deviation estimator in the case of correlations between generation steps will be detailed. Section 4 presents some preliminary results obtained by the new mesh tally feature. The last section presents the interest of using XML format output files. (authors)

  18. Evolution calculations of fuel for a GFR using MCNPX-C90 and Tripoli-4-D; Calculos de evolucion de combustible para un GFR usando MCNPX-C90 y TRIPOLI-4-D

    Energy Technology Data Exchange (ETDEWEB)

    Reyes R, R.; Martin del Campo M, C.; Francois L, J. L. [UNAM, Facultad de Ingenieria, Departamento de Sistemas Energeticos, Paseo Cuauhnahuac 8532, 62550 Jiutepec, Morelos (Mexico); Brun, E.; Dumonteil, E.; Malvagi, F., E-mail: emeric.brun@cea.fr [Commissariat a l' Energie Atomique et aux Energies Alternative, Service d' Etude des Reacteurs et de Mathematiques Appliquees, Saclay, DEN/DM2S/SERMA/LTSD, Bat 470, 91191 Gif-sur-Yvette Cedex (France)

    2011-11-15

    Burnt calculations were realized for a fuel model based on the technology of the Gas-cooled Fast Reactor, GFR. The fuel design is based on bars. The code MCNPX-CINDER90 and the CSADA method for the burnt calculations were used. Models of homogeneous and heterogeneous fuel assembly were studied; for the burnt calculations of the fuel homogeneous model was considered the tracking of three series (Tiers) of evolution of the fission products. The Tier 1 tracks a reduced group of fission products, the Tier 2 tracks to the arrangement of fission products that are contained in the library of cross sections XSDIR of MCNPX; and the Tier 3 tracks 1325 fission products. The results were compared with those obtained with Tripoli-4-D in function of the calculation methods: 1) Explicit Euler, as method of first order; and 2) CSADA, as method of second order. According to the results was observed that the infinite multiplication factor varies in function of the fission products quantity that are tracked. The calculation time used by MCNPX-C90 with the series Tier 3 is more than double than the used by Tripoli-4-D, therefore this last code has advantage over MCNPX-C90 in the case of neutrons analysis of fast reactors. (Author)

  19. Misidentification of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals in Tripoli, Libya

    Science.gov (United States)

    Ahmed, Mohamed O.; Abuzweda, Abdulbaset R.; Alghazali, Mohamed H.; Elramalli, Asma K.; Amri, Samira G.; Aghila, Ezzeddin Sh.; Abouzeed, Yousef M.

    2010-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial (hospital-acquired) pathogen of exceptional concern. It is responsible for life-threatening infections in both the hospital and the community. Aims To determine the frequency of MRSA misidentification in hospitals in Tripoli, Libya using current testing methods. Methods One hundred and seventy S. aureus isolates previously identified as MRSA were obtained from three hospitals in Tripoli. All isolates were reidentified by culturing on mannitol salt agar, API 20 Staph System and retested for resistance to methicillin using the cefoxitin disk diffusion susceptibility test and PBP2a. D-tests and vancomycin E-tests (Van-E-tests) were also performed for vancomycin-resistant isolates. Results Of the 170 isolates examined, 86 (51%) were confirmed as MRSA (i.e. 49% were misidentified as MRSA). Fifteen (17%) of the confirmed MRSA strains exhibited inducible clindamycin resistance. Of the 86 confirmed MRSA isolates, 13 (15%) were resistant to mupirocin, 53 (62%) were resistant to ciprofloxacin, 41 (48%) were resistant to trimethoprim-sulfamethoxazole, and none were resistant to linezolid. Although disc-diffusion testing indicated that 23 (27%) of the isolates were resistant to vancomycin, none of the isolates were vancomycin-resistant by Van-E-test. Conclusions Misidentification of nosocomial S. aureus as MRSA is a serious problem in Libyan hospitals. There is an urgent need for the proper training of microbiology laboratory technicians in standard antimicrobial susceptibility procedures and the implementation of quality control programs in microbiology laboratories of Libyan hospitals. PMID:21483574

  20. Automatic treatment of the variance estimation bias in TRIPOLI-4 criticality calculations

    Energy Technology Data Exchange (ETDEWEB)

    Dumonteil, E.; Malvagi, F. [Commissariat a l' Energie Atomique et Aux Energies Alternatives, CEA SACLAY DEN, Laboratoire de Transport Stochastique et Deterministe, 91191 Gif-sur-Yvette (France)

    2012-07-01

    The central limit (CLT) theorem States conditions under which the mean of a sufficiently large number of independent random variables, each with finite mean and variance, will be approximately normally distributed. The use of Monte Carlo transport codes, such as Tripoli4, relies on those conditions. While these are verified in protection applications (the cycles provide independent measurements of fluxes and related quantities), the hypothesis of independent estimates/cycles is broken in criticality mode. Indeed the power iteration technique used in this mode couples a generation to its progeny. Often, after what is called 'source convergence' this coupling almost disappears (the solution is closed to equilibrium) but for loosely coupled systems, such as for PWR or large nuclear cores, the equilibrium is never found, or at least may take time to reach, and the variance estimation such as allowed by the CLT is under-evaluated. In this paper we first propose, by the mean of two different methods, to evaluate the typical correlation length, as measured in cycles number, and then use this information to diagnose correlation problems and to provide an improved variance estimation. Those two methods are based on Fourier spectral decomposition and on the lag k autocorrelation calculation. A theoretical modeling of the autocorrelation function, based on Gauss-Markov stochastic processes, will also be presented. Tests will be performed with Tripoli4 on a PWR pin cell. (authors)

  1. Evaluating new HbA1c methods for adoption by the IFCC and NGSP reference networks using international quality targets.

    Science.gov (United States)

    Lenters-Westra, Erna; English, Emma

    2017-08-28

    As a reference laboratory for HbA1c, it is essential to have accurate and precise HbA1c methods covering a range of measurement principles. We report an evaluation of the Abbott Enzymatic (Architect c4000), Roche Gen.3 HbA1c (Cobas c513) and Tosoh G11 using different quality targets. The effect of hemoglobin variants, other potential interferences and the performance in comparison to both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the National Glycohemoglobin Standardization Program (NGSP) reference systems was assessed using certified evaluation protocols. Each of the evaluated HbA1c methods had CVs HbA1c. Partly based on the result of this study, the Abbott Enzymatic method on the Architect c4000 and the Roche Gen.3 HbA1c on the Cobas c513 are now official, certified IFCC and NGSP SRMPs in the IFCC and NGSP networks. Sigma metrics quality criteria presented in a graph distinguish between good and excellent performance.

  2. Unfolding of hemoglobin variants--insights from urea gradient gel electrophoresis photon correlation spectroscopy and zeta potential measurements

    International Nuclear Information System (INIS)

    Bhattacharya, Jaydeep; GhoshMoulick, Ranjita; Choudhuri, Utpal; Chakrabarty, Prantar; Bhattacharya, Pranab K.; Lahiri, Prabir; Chakraborti, Bikas; Dasgupta, Anjan Kr.

    2004-01-01

    The unfolding pattern of crystal human hemoglobin and variants of hemoglobin obtained from hemolysate were studied using transverse urea gradient gel electrophoresis (TUGGE). A smooth sigmoid like increase of electrophoretic mobility was observed with increasing urea concentrations. A decrease in electrophoretic mobility resulted, if the protein was unfolded with guanidium hydrochloride (GdnHCl). The anomaly was resolved after the Stoke's radii (obtained using the photon correlation spectroscopy) and zeta potential (measured using laser Doppler velocimetry) measurements were made at different denaturant concentrations. Addition of denaturant led to formation of extended structure, irrespective of the nature of the denaturant, as indicated by increase in Stoke's radii in both cases (urea and GdnHCl). The unexpected increase in electrophoretic mobility in case of urea could be explained in terms of a critical redistribution of negative charge at intermediate stages of the unfolding process. In case of GdnHCl, the higher ionic strength masked the charge effect. The mobility, being solely dependent on size, decreased at higher denaturant concentration. Incidentally, folding loci of other hemoglobin variants (e.g. HbE) or that of post-translationally modified hemoglobin (e.g. HbA1c) could be determined by studying the charge distribution and hydrodynamic radius at varying denaturing stress and in each case the gel migration profile could be approximately scaled by the ratio of charge and hydrodynamic diameter of the protein. While unfolding induced charge effect was most pronounced in HbA0 (and crystal ferrous hemoglobin), the unfolding induced aggregation (manifested by the increase in Stoke's radii) was predominantly observed in the variant forms HbE and HbA1c. Representing the proteins by a plot, in which charge and hydrodynamic diameter are on independent axes, may be a useful way of characterizing protein variants having similar migration profiles on native gels

  3. Nuclear data libraries for Tripoli-3.5 code; Bibliotheques de donnees nucleaires pour le code tripoli-3.5

    Energy Technology Data Exchange (ETDEWEB)

    Vergnaud, Th

    2001-07-01

    The TRIPOLI-3 code uses multigroup nuclear data libraries generated using the NJOY-THEMIS suite of modules: for neutrons, they are produced from the ENDF/B-VI evaluations and cover the range between 20 MeV and 10{sup -5} eV, either in 315 groups and for one temperature, or in 3209 groups and for five temperatures; for gamma-rays, they are from JEF2 and are processed in groups between 14 MeV and keV. The probability tables used for the neutron transport calculations have been derived from the ENDF/B-VI evaluations using the CALENDF code. Cross sections for gamma production by neutron interaction (fission, capture or inelastic scattering) have been derived from ENDF/B-VI in 315 neutron groups and 75 gamma groups. The code also uses two response function libraries: for neutrons; based on several sources, in particular the dosimetry libraries IRDF/85 and IRDF/90; for gamma-rays it is based on the JEF2 evaluation and contains the kerma factors for all the elements and cross sections for all interactions. (author)

  4. Identification of Hb Constant Spring (HBA2: c.427T > C) by an Automated High Performance Liquid Chromatography Method.

    Science.gov (United States)

    Wisedpanichkij, Raewadee; Jindadamrongwech, Sumalee; Butthep, Punnee

    2015-01-01

    Laboratory investigation of hemoglobinopathies includes complete blood count (CBC), hemoglobin (Hb) typing by high performance liquid chromatography (HPLC) and DNA analysis. DNA analysis is the most reliable method but requires a manually laborious procedure and is time consuming. A more practical method of detecting abnormal Hbs is the HPLC technique, because it is more rapid and easier to interpret. Hb Constant Spring (Hb CS; HBA2: c.427T > C) is an abnormal variant that is labile and difficult to detect using conventional methods. To evaluate the efficiency of Hb CS determination by HPLC, blood samples from 578 subjects were analyzed using an automated cell analyzer for hematological parameters, automated HPLC for Hb identification, and polymerase chain reaction (PCR) for α-thalassemia (α-thal) and Hb CS confirmation. These included 169 normal, 119 heterozygous α-thal-2, 30 homozygous α-thal-2, 177 heterozygous α-thal-1, 59 heterozygous Hb CS, seven homozygous Hb CS and 17 compound heterozygous α-thal-2 and Hb CS subjects. The results showed that sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Hb CS by HPLC were 93.78, 99.80, 98.73 and 99.00%, respectively. The mean of misdiagnosis value of the three groups of Hb CS subjects (total 83) was 6.02% (n = 5), with percentages for heterozygous Hb CS, homozygous Hb CS, and compound heterozygous α-thal-2 and Hb CS being 6.8, 0.0 and 5.9%, respectively. The HPLC method yielded good results, although it may also lead to misdiagnosis of Hb CS due to the relatively small amount and lability.

  5. Co-inheritance of α0 -thalassemia elevates Hb A2 level in homozygous Hb E: Diagnostic implications.

    Science.gov (United States)

    Singha, K; Srivorakun, H; Fucharoen, G; Fucharoen, S

    2017-10-01

    Differentiation of homozygous hemoglobin (Hb) E with and without α 0 -thalassemia is subtle on routine hematological ground. We examined in a large cohort of homozygous Hb E if the level of Hb A 2 is helpful. A total of 592 subjects with homozygous Hb E were recruited from ongoing thalassemia screening program. Additionally, five couples at risk of having fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also investigated. Hb analysis was performed using capillary electrophoresis system. Globin genotypes were defined by DNA analysis. Subjects were classified into four groups including pure homozygous Hb E (n=532), homozygous Hb E/α 0 -thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's disease (n=4). The levels of Hb A 2 were found, respectively, to be 4.97±0.69, 6.64±1.02, 4.86±0.87, and 7.60±1.04%. Among five couples at risk, α 0 -thalassemia was identified in three subjects with Hb A 2 >6.0%. Increased Hb A 2 level is a useful marker for differentiation of homozygous Hb E with and without α 0 -thalassemia. This should lead to a significant reduction in number of referral cases of homozygous Hb E for molecular testing of α 0 -thalassemia in routine practice. © 2017 John Wiley & Sons Ltd.

  6. Detection of Co-inheritance of Hb Hope and Hb Constant Spring in Three Thai Samples by Capillary Electrophoresis.

    Science.gov (United States)

    Panyasai, Sitthichai; Pornprasert, Sakorn

    2016-06-01

    The diagnosis of co-inheritance of Hb Hope [β136(H14)Gly → Asp, GGT > GAT] and Hb constant spring [Hb CS; α142, Term → Gln (TAA > CAA IN α2)] by high performance liquid chromatography (HPLC) is difficult because Hb Hope has a HPLC elution pattern similar to that of Hb Pyrgos, Hb New York, Hb Kodaira, and Hb Phimai. Moreover, the Hb CS mRNA, as well as the gene product, are unstable and present at a low level in peripheral blood. We report the use of a capillary electrophoresis (CE) for diagnosis of co-inheritance of Hb Hope and Hb CS in 3 Thai females who had mild anemia with Hb and Hct varying from 91-114 g/L to 0.28-0.36 L/L, respectively. Hb Hope eluted with a retention time of 125-140 s (Zone 10) of CE electrophoregram. Furthermore, the peak of Hb CS at the retention time of 245-250 s (Zone 2) was observed in these samples. In addition, the manual analysis by taking the non-black area under both peaks of HbA and Hb Hope (inverted V) into account provided the corrected Hb CS levels which are useful in screening of heterozygote or homozygote for Hb CS. Thus, the CE method provides an accurate diagnosis of Hb Hope and Hb CS which is useful in genetic counseling, prevention and control programs for these hemoglobinopathies.

  7. Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia.

    Science.gov (United States)

    Ke, Peifeng; Liu, Jiawei; Chao, Yan; Wu, Xiaobin; Xiong, Yujuan; Lin, Li; Wan, Zemin; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

    2017-10-01

    Thalassemia could interfere with some assays for haemoglobin A 1c (HbA 1c ) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA 1c . We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA 1c programme to simultaneously measure HbA 1c and screen for thalassemia. Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA 1c programme (Sebia, France). For method comparison, HbA 1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA 1c from eight thalassaemia patients was confirmed by IFCC reference method. Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA 1c result in three samples with HbH due to the overlapping of HbBart's with HbA 1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA 1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA 2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Our results demonstrated the Capillarys 2FP HbA 1c system could report an accurate HbA 1c value in thalassemia silent/trait, and HbA 2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart's for HbH disease, HbF for β-thalassemia) may provide valuable information for screening.

  8. Calculation of the effective delayed neutron fraction by TRIPOLI-4 code for IPEN/MB-01 research reactor

    International Nuclear Information System (INIS)

    Lee, Y.K.; Hugot, F.X.

    2011-01-01

    The effective delayed neutron fraction βeff is an important reactor physics parameter. Its calculation within the multi-group deterministic transport code can be performed with the aid of adjoint flux weighted integrations. However, in continuous energy Monte Carlo transport code, the adjoint weighted βeff calculation becomes complicated due to the backward treatment of the anisotropy scattering. In TRIPOLI-4 continuous energy Monte Carlo code, the βeff calculation was performed by a two-run method, one run with delayed neutrons and second with only the contribution from prompt fission neutrons. To improve the uncertainty of the βeff two-run calculation for the experimental reactors, two simple and fast one-run methods to estimate the βeff in the continuous energy simulation have been implemented into the TRIPOLI-4 code. First approach is an improved one of the Bretscher's prompt method and second one based on the proposal of Nauchi and Kameyama. In these one-run methods, the prompt and the delayed neutrons are first tagged. Their tracking and statistics are separated performed. The new βeff calculations have been optimized in the power iteration cycles so as to estimate the production of prompt and delayed neutrons from the prompt and delayed neutrons of previous generation. To validate the new βeff calculation by TRIPOLI-4, several benchmarks including fast and thermal systems have been considered. In this paper the recent measurements of βeff in the research reactor IPEN/MB-01 have been benchmarked. The basic components of the βeff and the Keff have been also calculated so as to understand the influences of the cross sections and the delayed neutron yields on the reactor reactivity calculations. Three nuclear data libraries, ENDF/BVI.r4, ENDF/B-VII.0, and JEFF-3.1 were taken into account in this study. (author)

  9. Abnormal haemoglobin variants, ABO and Rh blood groups among ...

    African Journals Online (AJOL)

    Background: Abnormal haemoglobin variants ( HbSS,AS,AC,SC,etc) have been known to be common among blacks. Patients with sickle cell disease are often faced with the risk of alloimmunization from allogeneic blood transfusion. Objectives: The study was designed to sample students population of African descents for ...

  10. Probing the diphosphoglycerate binding pocket of HbA and HbPresbyterian (beta 108Asn --> Lys).

    Science.gov (United States)

    Gottfried, D S; Manjula, B N; Malavalli, A; Acharya, A S; Friedman, J M

    1999-08-31

    HbPresbyterian (beta 108Asn --> Lys, HbP) contains an additional positive charge (per alpha beta dimer) in the middle of the central cavity and exhibits a lower oxygen affinity than wild-type HbA in the presence of chloride. However, very little is known about the molecular origins of its altered functional properties. In this study, we have focused on the beta beta cleft of the Hb tetramer. Recently, we developed an approach for quantifying the ligand binding affinity to the beta-end of the Hb central cavity using fluorescent analogues of the natural allosteric effector 2, 3-diphosphoglycerate (DPG) [Gottfried, D. S., et al. (1997) J. Biol. Chem. 272, 1571-1578]. Time-correlated single-photon counting fluorescence lifetime studies were used to assess the binding of pyrenetetrasulfonate to both HbA and HbP in the deoxy and CO ligation states under acidic and neutral pH conditions. Both the native and mutant proteins bind the probe at a weak binding site and a strong binding site; in all cases, the binding to HbP was stronger than to HbA. The most striking finding was that for HbA the binding affinity varies as follows: deoxy (pH 6.35) > deoxy (pH 7.20) > CO (pH 6.35); however, the binding to HbP is independent of ligation or pH. The mutant oxy protein also hydrolyzes p-nitrophenyl acetate, through a reversible acyl-imidazole pathway linked to the His residues of the beta beta cleft, at a considerably higher rate than does HbA. This implies a perturbation of the microenvironment of these residues at the DPG binding pocket. Structural consequences due to the presence of the new positive charge in the middle of the central cavity have been transmitted to the beta beta cleft of the protein, even in its liganded conformation. This is consistent with a newly described quaternary state (B) for liganded HbPresbyterian and an associated change in the allosteric control mechanism.

  11. Hemoglobin variants as models for investigation of dissociation of intact polypeptide chains by ESI tandem mass spectrometry

    International Nuclear Information System (INIS)

    Light, K.J.; Loo, J.A.; Edmonds, C.G.; Smith, R.D.

    1991-06-01

    Electrospray ionization mass spectroscopy (ESI-MS) is rapidly becoming a practical biochemical tool for peptide and protein sequence analysis. The utility of ESI-MS is through use of Collisionally Activated Dissociation (ESI-CAD-MS). Human hemoglobin (Hb, ∼62 kDa) consists of four polypeptide chains and a prosthetic heme group. There are over 400 Hb variants, characterized by amino acid substitutions in either the alpha or beta polypeptide chains. We investigated ESI-CAD-MS as a tool for rapidly analyzing amino acid substitutions, using eight Hb beta chain variants. The approximate location of the modification can be deduced from comparison of the CAD mass spectra and observance of the mass shifts of the fragment ion containing the substitution. Fragmentation occurs preferentially at the amino terminus of proline residues. For most substitutions, differences in CAD mass spectra were not seen. 2 figs

  12. Hb I-Toulouse in association with homozygosity for the α3.7 deletion in a Pacific Island woman

    Directory of Open Access Journals (Sweden)

    Beverley Pullon

    2016-11-01

    Full Text Available Only four cases of Hb I-Toulouse have been reported to date. Current literature associates Hb I-Toulouse in the heterozygote with a mild chronic hemolytic anemia. The variant is mildly unstable with a tendency to form metHb. The quantity of the variant in heterozygotes has been reported as varying between 33 to 40%. This report confirms the finding from a single case, that a reduced percentage of Hb IToulouse along with microcytosis can be attributed to the co-inheritance of an abnormal α globin genotype. This current case was found in a woman of Pacific People ethnicity residing in New Zealand. There is a high prevalence of α thalassemia in this ethnic group and New Zealand has the highest Pacific population in the world. Therefore, if a reduced percentage of Hb I-Toulouse is found with microcytosis and normal iron studies, co-inheritance with α thalassemia should be considered. 目前仅有四例Hb I-Toulouse的病例报告。 当前的文献将杂合子中的Hb I-Toulouse与慢性溶血性贫血相关联。 这种变异体轻度不稳定,有形成高铁血红蛋白(metHb)的倾向。 杂合子中变异体数量据报道为33%至40%不等。 本报告证实从单一病例得到的结果,即伴有小红细胞症的更低Hb I-Toulouse百分比可被归结为异常α球蛋白基因型的合并遗传。 该例当前病例在一名居住在新西兰的太平洋诸岛族裔女性身上发现。 在这个族群中存在较高的α地中海贫血患病率,而在全世界新西兰的太平洋诸岛族裔人口最多。 因此,如果发现Hb I-Toulouse的百分比更低,同时伴有小红细胞症并且检查铁含量正常,则应考虑α地中海贫血的合并遗传。

  13. Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women

    DEFF Research Database (Denmark)

    Outzen, Malene; Egeberg, Rikke; Dragsted, Lars

    2011-01-01

    in erythrocytes were analysed by liquid chromatography/MS/MS. Dietary determinants were evaluated by multiple linear regression analyses adjusted for age and smoking behaviour among ex-smokers. The median for Hb-AA was 35 pmol/g globin (5th percentile 17, 95th percentile 89) and for Hb-GA 21 pmol/g globin (5th......Acrylamide (AA) is a probable human carcinogen that is formed in heat-treated carbohydrate-rich foods. The validity of FFQ to assess AA exposure has been questioned. The aim of the present cross-sectional study was to investigate dietary determinants of Hb-AA and Hb-glycidamide (GA) adducts....... The study included 537 non-smoking women aged 50–65 years who participated in the Diet, Cancer and Health cohort (1993–97). At study baseline, blood samples and information on dietary and lifestyle variables obtained from self-administered questionnaires were collected. From blood samples, Hb-AA and Hb-GA...

  14. A Novel Double Heterozygous Hb D-Punjab/Hb J-Meerut Hemoglobinopathy.

    Science.gov (United States)

    Chandra, Dinesh; Tyagi, Seema; Deka, Roopam; Chauhan, Richa; Seth, Tulika; Saxena, Renu; Pati, H P

    2017-12-01

    A comprehensive laboratory diagnosis of hemoglobinopathies forms an integral part in workup of disorders of globin chain synthesis. Clinical findings, complete blood counts, peripheral smear examination along with hemoglobin (Hb) electrophoresis and/or cation exchange high performance liquid chromatography findings and parental study helps to clinch a final diagnosis. Compound heterozygous hemoglobinopathy presents with variable clinical findings and some of them are picked up on screening tests done as part of routine antenatal workup. Here we report a rare double heterozygous hemoglobinopathy of Hb D-Punjab and Hb J-Meerut in a 35 year antenatal female.

  15. Spa typing and identification of pvl genes of meticillin-resistant Staphylococcus aureus isolated from a Libyan hospital in Tripoli.

    Science.gov (United States)

    Ahmed, Mohamed O; Baptiste, Keith E; Daw, Mohamed A; Elramalli, Asma K; Abouzeed, Yousef M; Petersen, Andreas

    2017-09-01

    The purpose of the study was to investigate the molecular characteristics of meticillin-resistant Staphylococcus aureus (MRSA) isolated from clinical sources in Tripoli, Libya. A total of 95 MRSA strains collected at the Tripoli medical Centre were investigated by spa typing and identification of the Panton-Valentine Leukocidin (pvl) genes. A total of 26 spa types were characterized and distributed among nine clonal complexes; CC5 (n=32), CC80 (n=18), CC8 (n=17) and CC22 (n=12) were the most prevalent clonal complexes. In total, 34% of the isolates were positive for PVL. This study demonstrated the presence of CA-MRSA and pvl positive strains in hospital settings and underlines the importance of using molecular typing to investigate the epidemiology of MRSA. Preventative measures and surveillance systems are needed to control and minimize the spread of MRSA in the Libyan health care system. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  16. Quantitative Trait Loci Influencing Hb F Levels in Southern Thai Hb E (HBB: c.79G>A) Heterozygotes.

    Science.gov (United States)

    Kesornsit, Aumpika; Jeenduang, Nutjaree; Horpet, Dararat; Plyduang, Thunyaluk; Nuinoon, Manit

    2018-01-01

    Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB: c.79G>A) individuals is associated with several genetic modifiers and not well understood. This study was undertaken in order to determine the effect of single nucleotide polymorphisms (SNPs), including XmnI G γ (rs7482144), rs766432 on the BCL11A gene and rs9376074 on the HBS1L gene, on Hb F levels in Southern Thai heterozygous Hb E individuals. A total of 97 Southern Thai subjects carrying heterozygous Hb E were selected for the hematological study. After excluding the samples with α-thalassemia (α-thal) interaction or moderate anemia, because both conditions can affect the hematological parameters, the remaining 74 samples were submitted to SNP analysis. Hematological parameters were measured using an automated hematology analyzer and high performance liquid chromatography (HPLC). The results show that rs766432 was strongly associated with increased Hb F levels and rs7482144 was associated with Hb F levels in each subgroup (genotype) of rs766432. This study suggested that the BCL11A locus has a major effect on Hb F levels compared with the XmnI polymorphism in Hb E heterozygotes. This association of Hb F levels with SNPs is useful for the interpretation of hemoglobin (Hb) typing in heterozygous Hb E samples with high Hb F levels. Future research will need to address the better understanding of the mechanisms of the SNPs that regulate Hb F production without stress erythropoiesis in Hb E heterozygotes.

  17. Unfolding of hemoglobin variants--insights from urea gradient gel electrophoresis photon correlation spectroscopy and zeta potential measurements

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Jaydeep; GhoshMoulick, Ranjita; Choudhuri, Utpal; Chakrabarty, Prantar; Bhattacharya, Pranab K.; Lahiri, Prabir; Chakraborti, Bikas; Dasgupta, Anjan Kr

    2004-09-27

    The unfolding pattern of crystal human hemoglobin and variants of hemoglobin obtained from hemolysate were studied using transverse urea gradient gel electrophoresis (TUGGE). A smooth sigmoid like increase of electrophoretic mobility was observed with increasing urea concentrations. A decrease in electrophoretic mobility resulted, if the protein was unfolded with guanidium hydrochloride (GdnHCl). The anomaly was resolved after the Stoke's radii (obtained using the photon correlation spectroscopy) and zeta potential (measured using laser Doppler velocimetry) measurements were made at different denaturant concentrations. Addition of denaturant led to formation of extended structure, irrespective of the nature of the denaturant, as indicated by increase in Stoke's radii in both cases (urea and GdnHCl). The unexpected increase in electrophoretic mobility in case of urea could be explained in terms of a critical redistribution of negative charge at intermediate stages of the unfolding process. In case of GdnHCl, the higher ionic strength masked the charge effect. The mobility, being solely dependent on size, decreased at higher denaturant concentration. Incidentally, folding loci of other hemoglobin variants (e.g. HbE) or that of post-translationally modified hemoglobin (e.g. HbA1c) could be determined by studying the charge distribution and hydrodynamic radius at varying denaturing stress and in each case the gel migration profile could be approximately scaled by the ratio of charge and hydrodynamic diameter of the protein. While unfolding induced charge effect was most pronounced in HbA0 (and crystal ferrous hemoglobin), the unfolding induced aggregation (manifested by the increase in Stoke's radii) was predominantly observed in the variant forms HbE and HbA1c. Representing the proteins by a plot, in which charge and hydrodynamic diameter are on independent axes, may be a useful way of characterizing protein variants having similar migration profiles on

  18. TRIPOLI-4.3.3 and 4.4, Coupled Neutron, Photon, Electron, Positron 3-D, Time Dependent Monte-Carlo, Transport Calculation

    International Nuclear Information System (INIS)

    Both, J.P.; Mazzolo, A.; Petit, O.; Peneliau, Y.; Roesslinger, B.

    2008-01-01

    1 - Description of program or function: TRIPOLI-4 is a general purpose radiation transport code. It uses the Monte Carlo method to simulate neutron and photon behaviour in three-dimensional geometries. The main areas of applications include but are not restricted to: radiation protection and shielding, nuclear criticality safety, fission and fusion reactor design, nuclear instrumentation. In addition, it can simulate electron-photon cascade showers. It computes particle fluxes and currents and several related physical quantities such as, reaction rates, dose rates, heating, energy deposition, effective multiplication factor, perturbation effects due to density, concentration or partial cross-section variations. The summary precises the types of particles, the nuclear data format and cross sections, the energy ranges, the geometry, the sources, the calculated physical quantities and estimators, the biasing, the time-dependant transport for neutrons, the perturbation, the coupled particle transport and the qualification benchmarks. Data libraries distributed with the TRIPOLI-4: ENDFB6R4, ENDL, JEF2, Mott-Rutherford and Qfission. NEA-1716/04: TRIPOLI-4.4 does not contain the source programs. New features available in TRIPOLI-4 version 4 concern the following points: New biasing features, neutron collision in multigroup homogenized mode, display of the collision sites, ENDF format evaluations, computation of the gamma source produced by neutrons, output format for all results, Verbose level for output warnings, photons reactions rates, XML format output, ENDF format evaluations, combinatorial geometry checks, Green's functions files, and neutronics-shielding coupling. 2 - Methods: The geometry package allows the user to describe a three dimensional configuration by means of surfaces (as in the MCNP code) and also through predefined shapes combine with operators (union, intersection, subtraction...). It is also possible to repeat a pattern to built a network of networks

  19. FIFRELIN - TRIPOLI-4® coupling for Monte Carlo simulations with a fission model. Application to shielding calculations

    Science.gov (United States)

    Petit, Odile; Jouanne, Cédric; Litaize, Olivier; Serot, Olivier; Chebboubi, Abdelhazize; Pénéliau, Yannick

    2017-09-01

    TRIPOLI-4® Monte Carlo transport code and FIFRELIN fission model have been coupled by means of external files so that neutron transport can take into account fission distributions (multiplicities and spectra) that are not averaged, as is the case when using evaluated nuclear data libraries. Spectral effects on responses in shielding configurations with fission sampling are then expected. In the present paper, the principle of this coupling is detailed and a comparison between TRIPOLI-4® fission distributions at the emission of fission neutrons is presented when using JEFF-3.1.1 evaluated data or FIFRELIN data generated either through a n/g-uncoupled mode or through a n/g-coupled mode. Finally, an application to a modified version of the ASPIS benchmark is performed and the impact of using FIFRELIN data on neutron transport is analyzed. Differences noticed on average reaction rates on the surfaces closest to the fission source are mainly due to the average prompt fission spectrum. Moreover, when working with the same average spectrum, a complementary analysis based on non-average reaction rates still shows significant differences that point out the real impact of using a fission model in neutron transport simulations.

  20. Le Discours historique de l’estat du royaume de Borno, genèse et construction d’une histoire du Borno par un captif de Tripoli au XVIIe siècle The Discours historique de l’estat du royaume de Borno, genesis and construction of history of Borno by a seventeenth century’s captive in Tripoli

    Directory of Open Access Journals (Sweden)

    Rémi Dewière

    2013-05-01

    Full Text Available Le Discours historique de l’estat du royaume de Borno, écrit par un ancien captif de Tripoli en 1685, est l’une des sources les plus importantes de l’histoire de ce royaume sahélien situé sur la rive ouest du lac Tchad. Malheureusement, son analyse fut délaissée du fait d’incohérences, et l’intérêt de la source fut dévalué. Cependant, une étude du contexte de rédaction du manuscrit ainsi que de la construction du récit montre la grande richesse de ce texte. Tout en s’inscrivant dans un contexte favorable à la mise à l’écrit de l’expérience de captivité, celui que nous appellerons le « chirurgien français » effectue un réel travail de recherche tant à Tripoli qu’à son retour en France, où il rédige avec l’aide d’une tierce personne ce chapitre dans un ouvrage bien plus volumineux sur l’histoire de Tripoli. Le plus intéressant reste la façon dont le « chirurgien français » a recueilli ses sources : leur recensement permet un premier classement de celles-ci et une première analyse de l’apport du Discours historique de l’estat du royaume de Borno pour l’histoire moderne du sultanat de Borno.The Discours historique de l’estat du royaume de Borno, written by a former French slave in Tripoli in 1685, is one of the most important sources for the history of Borno sultanate. Unfortunately, its study has been neglected due to inconsistencies between the manuscript and other sources. The manuscript was then considered as a second hand source. However, a close study of the context where the manuscript was conceived and written shows that we can deeply learn from it. The work of whom we call the « French surgeon », comes within the scope of a context favorable for writing the experience of captivity. It is the consequence of the author’s intense works of research in Tripoli and in France. The « French surgeon » wrote this chapter in a voluminous manuscript on the history of Tripoli

  1. Correlated Production and Analog Transport of Fission Neutrons and Photons using Fission Models FREYA, FIFRELIN and the Monte Carlo Code TRIPOLI-4® .

    Science.gov (United States)

    Verbeke, Jérôme M.; Petit, Odile; Chebboubi, Abdelhazize; Litaize, Olivier

    2018-01-01

    Fission modeling in general-purpose Monte Carlo transport codes often relies on average nuclear data provided by international evaluation libraries. As such, only average fission multiplicities are available and correlations between fission neutrons and photons are missing. Whereas uncorrelated fission physics is usually sufficient for standard reactor core and radiation shielding calculations, correlated fission secondaries are required for specialized nuclear instrumentation and detector modeling. For coincidence counting detector optimization for instance, precise simulation of fission neutrons and photons that remain correlated in time from birth to detection is essential. New developments were recently integrated into the Monte Carlo transport code TRIPOLI-4 to model fission physics more precisely, the purpose being to access event-by-event fission events from two different fission models: FREYA and FIFRELIN. TRIPOLI-4 simulations can now be performed, either by connecting via an API to the LLNL fission library including FREYA, or by reading external fission event data files produced by FIFRELIN beforehand. These new capabilities enable us to easily compare results from Monte Carlo transport calculations using the two fission models in a nuclear instrumentation application. In the first part of this paper, broad underlying principles of the two fission models are recalled. We then present experimental measurements of neutron angular correlations for 252Cf(sf) and 240Pu(sf). The correlations were measured for several neutron kinetic energy thresholds. In the latter part of the paper, simulation results are compared to experimental data. Spontaneous fissions in 252Cf and 240Pu are modeled by FREYA or FIFRELIN. Emitted neutrons and photons are subsequently transported to an array of scintillators by TRIPOLI-4 in analog mode to preserve their correlations. Angular correlations between fission neutrons obtained independently from these TRIPOLI-4 simulations, using

  2. Detection of compound heterozygous of hb constant spring and hb q-Thailand by capillary electrophoresis and high performance liquid chromatography.

    Science.gov (United States)

    Pornprasert, Sakorn; Punyamung, Manoo

    2015-06-01

    A capillary electrophoresis (CE) has proven to be superior to a high performance liquid chromatography (HPLC) in the detection of hemoglobin Constant Spring (Hb CS). Thus the aim of this study was to analyze the efficacy of CE and HPLC for the detection of Hb CS in samples with compound heterozygous of Hb CS and Hb Q-Thailand. Hemoglobin analysis was performed in blood samples of 2 patients with compound heterozygous of Hb CS and Hb Q-Thailand by using HPLC and CE. The HPLC chromatogram and CE electrophoregram of the two techniques were compared. Hb CS was not found on HPLC chromatogram while Hb QA2 (α2 (QT)δ2), a derivative of Hb Q-Thailand, was presented at the retention time of 4.70-4.80 min and it was close to the retention time of Hb CS. On CE electrophoregram, Hb CS was presented at zone 2 (Z2) and it was distinctly separated from Hb QA2 which was presented at Z1. Therefore, CE was more efficient to the HPLC for diagnosis of compound heterozygous of Hb CS and Hb Q-Thailand.

  3. Nuclear data libraries for Tripoli-3.5 code

    International Nuclear Information System (INIS)

    Vergnaud, Th.

    2001-01-01

    The TRIPOLI-3 code uses multigroup nuclear data libraries generated using the NJOY-THEMIS suite of modules: for neutrons, they are produced from the ENDF/B-VI evaluations and cover the range between 20 MeV and 10 -5 eV, either in 315 groups and for one temperature, or in 3209 groups and for five temperatures; for gamma-rays, they are from JEF2 and are processed in groups between 14 MeV and keV. The probability tables used for the neutron transport calculations have been derived from the ENDF/B-VI evaluations using the CALENDF code. Cross sections for gamma production by neutron interaction (fission, capture or inelastic scattering) have been derived from ENDF/B-VI in 315 neutron groups and 75 gamma groups. The code also uses two response function libraries: for neutrons; based on several sources, in particular the dosimetry libraries IRDF/85 and IRDF/90; for gamma-rays it is based on the JEF2 evaluation and contains the kerma factors for all the elements and cross sections for all interactions. (author)

  4. Iron deficiency anemia interfering the diagnosis of compound heterozygosity for Hb constant spring and Hb Paksé: The first case report.

    Science.gov (United States)

    Chiasakul, Thita; Uaprasert, Noppacharn

    2018-01-01

    Diagnosis of thalassemia or hemoglobinopathy concomitant with iron deficiency anemia (IDA) is challenging. We report a case of 43-year-old female whose diagnosis of compound heterozygosity for hemoglobin Constant Spring (HbCS) and Hb Paksé became apparent after the treatment of IDA. Prior to treatment, Hb analysis using isoelectric focusing (IEF) showed HbA 95.6%, HbA 2 2.7%, and HbCS 1.7% compatible with heterozygous HbCS. After 4 months of oral iron therapy resulting in an improved Hb level, her HbCS level was substantially increased to 8.7% on IEF suggesting homozygous HbCS. Subsequent DNA analysis using multiplex amplification refractory mutation system analysis revealed compound heterozygosity for HbCS and Hb Paksé. This case demonstrated that IDA can significantly reduce HbCS/Hb Paksé levels and probably mask the diagnosis of homozygous HbCS, homozygous Hb Paksé or the compound heterozygosity for both hemoglobinopathies by hemoblogin analysis. The test should be repeated after resolution of IDA, or molecular testing should be performed to confirm the diagnosis. © 2017 Wiley Periodicals, Inc.

  5. Auto-Baecklund transformation and similarity reductions to the variable coefficients variant Boussinesq system

    Energy Technology Data Exchange (ETDEWEB)

    Moussa, M.H.M. [Department of Mathematic, Faculty of Education, Ain Shams University, Roxy, Hiliopolis, Cairo (Egypt)], E-mail: m_h_m_moussa@yahoo.com; El Shikh, Rehab M. [Department of Mathematic, Faculty of Education, Ain Shams University, Roxy, Hiliopolis, Cairo (Egypt)

    2008-02-25

    Based on the closed connections among the homogeneous balance (HB) method, Weiss-Tabor-Carneval (WTC) method and Clarkson-Kruskal (CK) method, we study Baecklund transformation and similarity reductions of the variable coefficients variant Boussinesq system. In the meantime, new exact solutions also are found.

  6. Neutron transport by TRIPOLI-2 code in the lower part of a PWR pit and in the pit-access cell

    International Nuclear Information System (INIS)

    Vergnaud, T.; Bourdet, L.; Gonnord, J.; Nimal, J.C.; Champion, G.

    1984-09-01

    The neutrons, which exit the reactor vessel, leak between the reactor vessel and the primary concrete shield and provide high dose rate in the lower part of the reactor pit. In this part of the reactor the biological shield is reduced at the level of the pit-access cell door and of the ventilation duct. Consequently there is a pin-point increase of dose rate at reactor place where access must be free during power operation. Studies concern 900 MWe and 1300 MWe plants; calculation results are compared with dose rate measurements which have been done at several interesting points of reactor. Neutron transport is studied in two steps: - first Monte Carlo calculation carried out by the TRIPOLI-2 system gives the current of neutrons entering into the pit-access cell; - a second calculation is about neutron transport in this cell; it is also performed with the TRIPOLI-2 code which uses a very realistic model for cell geometry. Then the door efficiency is evaluated by a SN one dimension code

  7. Relationship between Hb and HbA1c in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database.

    Science.gov (United States)

    Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

    2014-06-01

    We investigated the effect of Hb on HbA1c levels in 265,427 Japanese individuals. The divergence between fasting plasma glucose (FPG) and HbA1c levels increased with lower Hb, resulting in HbA1c levels that were higher in relation to than the FPG levels. Similarly, the correlation between FPG and HbA1c levels, stratified by Hb, weakened as Hb decreased. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab.

    Science.gov (United States)

    Torres, Lidiane S; Okumura, Jéssika V; Belini-Júnior, Édis; Oliveira, Renan G; Nascimento, Patrícia P; Silva, Danilo G H; Lobo, Clarisse L C; Oliani, Sonia M; Bonini-Domingos, Claudia R

    2016-09-01

    Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.364G > C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [- + - - - -] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8 ± 2.3% and 43.3 ± 1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.

  9. Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

    Science.gov (United States)

    Albiti, Anisa H; Nsiah, Kwabena

    2014-04-01

    Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

  10. Incidence of sickle cell disease and other hemoglobin variants in 10,095 Lebanese neonates.

    Directory of Open Access Journals (Sweden)

    Evelyne Khoriaty

    Full Text Available Hemoglobinopathies are highly prevalent diseases and impose a public health burden. Early diagnosis and treatment can ameliorate the course of these diseases and improve survival. Despite purported high incidence of hemoglobinopathies in Lebanon, there are no nationwide screening programs. In this study, newborn screening utilizing high pressure liquid chromatography was executed in all public hospitals across Lebanon between 2010 and 2013. All newborns with an abnormal hemoglobin (Hb were offered genetic counseling and all those with disease were enrolled in comprehensive hemoglobinopathy clinics. Among newborns, 2.1% were found to have an abnormal Hb variant with sickle Hb being the most common while 0.1% were found to have sickle cell disease (SCD. The majority of those with SCD had non-Lebanese origins. The most common causes of hospitalizations in infants with SCD were acute splenic sequestration and pain crises. No bacteremia or other life threatening infections were noted. At a median follow up 14 months (follow up range 7 to 34 months, all children with disease are alive and compliant with treatment. Systematic screening for SCD and other Hb variants was shown to be feasible, cost effective, and of accurate predictive value. This program was also clinically effective because it led to the identification of babies with disease and to providing them with free early multidisciplinary care. Conclusively, a newborn screening program should be implemented across Lebanon to detect hemoglobinopathies and initiate early therapeutic and preventive strategies and genetic counseling.

  11. Validation of the 3D transport monte carlo code TRIPOLI-4.3 for moderated and unmoderated metallic fissile media configurations with JEF2.2 and ENDF/B-VI.4 cross section evaluations

    International Nuclear Information System (INIS)

    Gagnier, E.; Lee, Y.K.; Aguiar, L.; Vedrenne, N.

    2003-01-01

    This paper presents an extended validation of TRIPOLI-4.3 covering all the metallic fissile media configurations present in the CEA facilities. More than 300 ICSBEP benchmarks have been calculated with TRIPOLI-4.3 and compared to the experimental results. These benchmarks include high-enriched uranium fissile media and plutonium fissile media with a low content of plutonium 240. The configurations are calculated with continuous-energy cross-section libraries JEF2.2 and ENDF/B-VI.4 and compared to MCNP or SCALE results presented in the ICSBEP reports. (author)

  12. Hydroxyurea decreases hospitalizations in pediatric patients with Hb SC and Hb SB+ thalassemia

    Directory of Open Access Journals (Sweden)

    Lebensburger JD

    2015-12-01

    Full Text Available Jeffrey D Lebensburger, Rakeshkumar J Patel, Prasannalaxmi Palabindela, Christina J Bemrich-Stolz, Thomas H Howard, Lee M HilliardDivision of Pediatric Hematology Oncology, University of Alabama at Birmingham, Birmingham, AL, USAPurpose: Patients with hemoglobin SC (Hb SC and hemoglobin SB+ (Hb SB+ thalassemia suffer from frequent hospitalizations yet strong evidence of a clinical benefit of hydroxyurea (HU in this population is lacking. Patients with recurrent hospitalizations for pain crisis are offered HU at our institution based on small cohort data and anecdotal benefit. This study identifies outcomes from a large cohort of patients with Hb SC and SB+ thalassemia who were treated with HU for 2 years.Materials and methods: A retrospective review was conducted of 32 patients with Hb SC and SB+ thalassemia who were treated with HU. We reviewed the number, and reasons for hospitalization in the 2 years prior to, and 2 years post-HU treatment as well as laboratory changes from baseline, over 1 year.Results: Patients with Hb SC and SB+ thalassemia started on HU for frequent pain, had a significant reduction in hospitalizations over 2 years as compared to the 2 years prior to HU initiation (mean total hospitalizations/year: pre-HU: 1.6 vs post-HU 0.4 hospitalizations, P<0.001; mean pain hospitalizations/year: pre-HU 1.5 vs post-HU 0.3 hospitalizations, P<0.001. Patients demonstrated hematologic changes including an increase in percent fetal hemoglobin (%HbF pre–post HU (4.5% to 7.7%, P=0.002, mean corpuscular volume (74 to 86 fL, P<0,0001, and decrease in absolute neutrophil count (5.0 to 3.2×109/L, P=0.007. Patients with higher doses of HU demonstrated the greatest reduction in hospitalizations but this was unrelated to absolute neutrophil count.Conclusion: This cohort of patients with Hb SC and SB+ thalassemia provides additional support for using HU in patients with recurrent hospitalizations for pain. A large randomized multicenter trial of

  13. TRIPOLI.2. A 3D Monte Carlo system for thermal reactor applications

    International Nuclear Information System (INIS)

    Baur, A.; Bourdet, L.; Dejonghe, G.; Gonnord, J.; Monnier, A.; Nimal, J.C.; Vergnaud, T.

    1982-05-01

    TRIPOLI.2 solves the Boltzmann equation for source and critical problems, time depending or not, by the Monte Carlo method. The code can handle all types of interactions and uses a library processed from ENDF/B. Special attention has been given to the resonance region processing and to the thermal kernel treatment. Sampling using the free gas and the S (α, β) model is described in details. The three dimensional geometry is composed of volumes limited by any portion of linear or quadratic surfaces. Extended facilities to process the output are provided. Two comparisons with experiment and computational benchmark are presented: comparison of a calculated spectra in borated water with measurements; computational benchmark of a standard PWR cell showing the influence of cross section data (UKNDL-ENDF/B4-ENDF/B5)

  14. Interação entre Hb C [beta6(A3Glu>Lys] e IVS II-654 (C>T beta-talassemia no Brasil Hb C [beta6(A3Glu>Lys] and IVS II - 654 (C>T beta thalassemia interaction in Brazil

    Directory of Open Access Journals (Sweden)

    Claudia R. Bonini-Domingos

    2003-06-01

    Full Text Available Thalassemias are a heterogeneous group of inherited disorders characterized by a microcytic hypochromic anemia and an imbalance in the synthesis of the globin-chains. Hb C is the second most frequently variant of hemoglobin found in Brazil. The laboratory diagnosis of hemoglobinopathies, including thalassemias, is growing in importance, particularly because of an increasing requirement for neonatal diagnosis of abnormal hemoglobins. Screening tests were carried out using alkaline and acid electrophoresis, globin-chain analysis by cellulose acetate in alkaline pH, isoelectric focusing and HPLC. The molecular characterization was made by PCR-ASO for Hb C and beta thalassemia mutants. Large-scale screening and discriminative methodologies must provide information about the hemoglobin polymorphisms in Brazilian population. HPLC is a powerful tool in these cases. Molecular characterization is important to genetic counseling and clinical management, in particular for the Brazilian population that have an intense racial admixture, with great variability of hemoglobins. In this paper an association between Hb C and beta thalassemia (IVS-II-654 in a black family from Brazil was described.

  15. Prevalência de talassemias e hemoglobinas variantes em pacientes com anemia não ferropênica Prevalence of thalassemias and variant hemoglobins in patients with non-ferropenic anemia

    Directory of Open Access Journals (Sweden)

    Sandrine C. Wagner

    2005-03-01

    Full Text Available Para estabelecer a freqüência de hemoglobinopatias e talassemias em pacientes com anemia não ferropênica foram estudados 58 casos de pacientes comprovadamente com anemia não ferropênica e 235 controles obtidos de pessoas sem anemia. Todas as amostras foram obtidas do Hospital de Clínicas de Porto Alegre (HCPA, RS, Brasil. As técnicas realizadas foram eletroforese em acetato de celulose, pH alcalino, pesquisa citológica de Hb H, HPLC, hemograma e ferritina. A análise dos dados realizada no grupo de pacientes com anemia não ferropênica demonstrou que 63,8% eram portadores de alguma forma de anemia hereditária: 25,9% de talassemia alfa heterozigota, 32,8% de talassemia beta heterozigota, 3,4% de heterozigose para hemoglobina S (Hb AS e 1,7% de homozigose para hemoglobina C (Hb CC. No grupo dos controles, foram identificados 14,1% de anemias hereditárias, sendo destas 11,5% de talassemia alfa, 0,9% de talassemia beta, 1,3% de heterozigose para hemoglobina S (Hb AS e 0,4% de heterozigose para hemoglobina C (Hb AC. Os resultados obtidos permitem concluir que a prevalência de talassemias e hemoglobinas variantes no grupo controle é coincidente com a descrita na literatura. Entretanto, a excepcional prevalência dessas hemopatias hereditárias em pessoas com anemia não ferropênica deve ser divulgada entre médicos e serviços de saúde dada a sua importância no diagnóstico definitivo de anemia e dos corretos procedimentos terapêuticos.To establish the frequency of hemoglobinopathies and thalassemias in patients with non-ferropenic anemia, 58 patients with confirmed non-ferropenic anemia and 235 non-anemic individuals (control group were studied. All samples were obtained from the Hospital de Clínicas de Porto Alegre (HCPA, Rio Grande do Sul, Brazil. The techniques used were Alkaline pH cellulose acetate electrophoresis and cytological screening of Hb, Hl, HPLC, hemogram and ferritin. The data analysis showed that 63% of the

  16. Stress analysis of the HFIR HB-2 and HB-3 beam tube nozzles

    International Nuclear Information System (INIS)

    Williams, P.T.

    1998-08-01

    The results of three-dimensional linear elastic stress analyses of the HFIR HB-2 and HB-3 nozzles are presented in this report. Finite element models were developed using the PATRAN pre-processing code and translated into ABAQUS input file format. A scoping analysis using simple geometries with internal pressure loading was carried out to assess the capabilities of the ABAQUS/Standard code to calculate maximum principal stress distributions within cylinders with and without holes. These scoping calculations were also used to provide estimates for the variation in tangential stress around the rim of a nozzle using the superposition of published closed-form solutions for the stress around a hole in an infinite flat plate under uniaxial tension. From the results of the detailed finite element models, peak stress concentration factors (based on the maximum principal stresses in tension) were calculated to be 3.0 for the HB-2 nozzle and 2.8 for the HB-3 nozzle. Submodels for each nozzle were built to calculate the maximum principal stress distribution in the weldment region around the nozzle, where displacement boundary conditions for the submodels were automatically calculated by ABAQUS using the results of the global nozzle models. Maximum principal stresses are plotted and tabulated for eight positions around each nozzle and nozzle weldment

  17. Characterization of a Novel Anti-Human HB-EGF Monoclonal Antibody Applicable for Paraffin-Embedded Tissues and Diagnosis of HB-EGF-Related Cancers.

    Science.gov (United States)

    Iwamoto, Ryo; Takagi, Mika; Akatsuka, Jun-Ichi; Ono, Ken-Ichiro; Kishi, Yoshiro; Mekada, Eisuke

    2016-04-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that bind to and activate the EGF receptor (EGFR/ErbB1) and ErbB4. HB-EGF plays pivotal roles in pathophysiological processes, including cancer. Thus, monoclonal antibodies (mAbs) for HB-EGF detection could be an important tool in the therapeutic diagnosis of HB-EGF-related cancers and other diseases. However, few mAbs, especially those applicable for immunohistochemistry (IHC), have been established to date. In this study, we generated a clone of hybridoma-derived mAb 2-108 by immunizing mice with recombinant human HB-EGF protein expressed by human cells. The mAb 2-108 specifically bound to human HB-EGF but not to mouse HB-EGF and was successful in immunoblotting, even under reducing conditions, immunoprecipitation, and immunofluorescence for unfixed as well as paraformaldehyde-fixed cells. Notably, this mAb was effective in IHC of paraffin-embedded tumor specimens. Epitope mapping analysis showed that mAb 2-108 recognized the N-terminal prodomain in HB-EGF. These results indicate that this new anti-HB-EGF mAb 2-108 would be useful in the diagnosis of HB-EGF-related cancers and would be a strong tool in both basic and clinical research on HB-EGF.

  18. Beyond HbA1c.

    Science.gov (United States)

    Bloomgarden, Zachary

    2017-12-01

    It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience. The diaTribe Foundation convened a meeting on the topic of glycemic outcomes beyond HbA1c on 21 July 2017, in Bethesda (MD, USA), focusing on potential uses of continuous glucose monitoring (CGM). Understanding patterns of glycemia in people with diabetes has long been a focus of approaches to improving treatment, and over the past few years this has become an available modality for clinical practice. Glucose levels are not the only biologic parameters affecting HbA1c levels; HbA1c changes with anemia or, more subtly, with changes in rates of erythrocyte turnover not reflected in hemoglobin levels outside the normal range. Renal disease often is associated with lower HbA1c than would be predicted based on an individual's glycemic levels. Furthermore, HbA1c levels tend to increase with age and are higher in some ethnic groups; for example, people of African ethnicity have higher HbA1c levels than people of Northern European descent. Indeed, we have argued that even as a measure of mean glycemia HbA1c is inherently imprecise. Overall, for some 20% of people with diabetes, HbA1c levels are substantially higher, or substantially lower, than those that would be predicted from mean blood glucose levels. If one recognizes that HbA1c is, at best, a partial measure of mean glycemic exposure, one must surely accept that HbA1c does not reflect variability within a day, from day to day, and from period to period. Many glucose-lowering medicines, particularly the sulfonylureas and insulin, cause hypoglycemia, with consequent negative effects on quality of life and patient-reported outcomes, as well as association with weight gain and adverse macrovascular outcome; hypoglycemia will, of course, not be captured by HbA1c measurement. Based on these

  19. Detection of CTX-M-15 Among Uropathogenic Escherichia coli Isolated from Five Major Hospitals in Tripoli, Libya.

    Science.gov (United States)

    Zorgani, Abdulaziz; Almagatef, Asma; Sufya, Najib; Bashein, Abdulla; Tubbal, Abdullatif

    2017-07-01

    Multidrug resistance (MDR) and emergence of extended-spectrum β-lactamases (ESBLs) among uropathogenic Escherichia coli have been reported worldwide, but there was no information on the detection of bla CTX-M-15 in major teaching hospitals in Libya. The aim of the study was to investigate the occurrence of CTX-M-15 β-lactamases producers isolated from five teaching hospitals in Tripoli, Libya. A total of 346 urine samples were collected from hospitalized patients in five teaching hospitals with a diagnosis of urinary tract infection (UTI). Phenotypic confirmation of ESBLs was confirmed by E-test strip; all ESBL-producing E. coli isolates were screened for the bla CTX-M-15 gene. The distribution of ESBL-producing E. coli varied among the five hospitals. The highest proportion was identified in Tripoli Medical Centre (67.6%). There were extremely high proportions of isolates resistant to ceftriaxone, cefepime, and ceftazidime (93.0-100.0%) among ESBL producers compared to non-ESBL producers (2.2-4.7%). MDR was detected in 22.2% of isolates. The majority of isolates (85.9%) in which bla CTX-M-15 was identified were ESBL producers. There was a correlation ( p < 0.001) between expression of CTX-M-15 and resistance to ceftazidime. The isolation of MDR ESBL-producing uropathogens expressing the CTX-M-15 gene will limit the choices clinicians have to treat their patients with UTIs. Continued surveillance and implementation of efficient infection control measures are required.

  20. Neutrons and gamma transport in atmosphere by Tripoli-2 code. Energy deposit and electron current time function

    International Nuclear Information System (INIS)

    Vergnaud, T.; Nimal, J.C.; Ulpat, J.P.; Faucheux, G.

    1988-01-01

    The Tripoli-2 computer code has been adapted to calculate, in addition to energy deposit in matter by neutrons (Kerma) the energy deposit by gamma produced in neutronic impacts and the induced recoil electron current. The energy deposit conduces at air ionization, consequently at a conductibility. This knowledge added at that of electron current permit to resolve the Maxwell equations of electromagnetic field. The study is realized for an atmospheric explosion 100 meters high. The calculations of energy deposit and electron current have been conducted as far as 2.5km [fr

  1. PCSK9 genetic variants and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Schmidt, Amand F; Swerdlow, Daniel I; Holmes, Michael V

    2017-01-01

    used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using...... diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we...... a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL...

  2. Automated importance generation and biasing techniques for Monte Carlo shielding techniques by the TRIPOLI-3 code

    International Nuclear Information System (INIS)

    Both, J.P.; Nimal, J.C.; Vergnaud, T.

    1990-01-01

    We discuss an automated biasing procedure for generating the parameters necessary to achieve efficient Monte Carlo biasing shielding calculations. The biasing techniques considered here are exponential transform and collision biasing deriving from the concept of the biased game based on the importance function. We use a simple model of the importance function with exponential attenuation as the distance to the detector increases. This importance function is generated on a three-dimensional mesh including geometry and with graph theory algorithms. This scheme is currently being implemented in the third version of the neutron and gamma ray transport code TRIPOLI-3. (author)

  3. Simultaneous dual syringe electrospinning system using benign solvent to fabricate nanofibrous P(3HB-co-4HB)/collagen peptides construct as potential leave-on wound dressing

    International Nuclear Information System (INIS)

    Vigneswari, S.; Murugaiyah, V.; Kaur, G.; Abdul Khalil, H.P.S.; Amirul, A.A.

    2016-01-01

    The main focus of this study is the incorporation of collagen peptides to fabricate P(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] nano-fiber construct to further enhance surface wettability and support cell growth while harbouring desired properties for biodegradable wound dressing. Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen peptides construct was carried out using dual syringe system. The wettability of the constructs increased with the increase in 4HB molar fraction from 20 mol% 4HB [53.2°], P(3HB-co-35 mol%4HB)[48.9°], P(3HB-co-50 mol%4HB)[44.5°] and P(3HB-co-82 mol%4HB) [37.7°]. In vitro study carried out using mouse fibroblast cells (L929) grown on nanofiber P(3HB-co-4HB)/collagen peptides construct showed an increase in cell proliferation. In vivo study using animal model (Sprague Dawley rats) showed that nanofibrous P(3HB-co-4HB)/collagen peptides construct had a significant effect on wound contractions with the highest percentage of wound closure of 79%. Hence, P(3HB-co-4HB)/collagen peptides construct suitable for wound dressing have been developed using nano-fabrication technique. - Highlights: • Nano-fiber construct to enhance surface wettability and cell growth, harbouring desired properties as biodegradable wound dressing. • Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen construct using dual syringe system. • Nanofibrous construct accelerated wound healing with efficient cellular organization.

  4. Simultaneous dual syringe electrospinning system using benign solvent to fabricate nanofibrous P(3HB-co-4HB)/collagen peptides construct as potential leave-on wound dressing

    Energy Technology Data Exchange (ETDEWEB)

    Vigneswari, S. [Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM, MOSTI, 11700 Penang (Malaysia); Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu (Malaysia); Murugaiyah, V. [School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11700 Penang (Malaysia); Kaur, G. [Institute of Research in Molecular Medicine, Universiti Sains Malaysia, 11700 Penang (Malaysia); Abdul Khalil, H.P.S. [School of Industrial Technology, Universiti Sains Malaysia, 11700 Penang (Malaysia); Amirul, A.A., E-mail: amirul@usm.my [Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM, MOSTI, 11700 Penang (Malaysia); School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang (Malaysia); Centre of Chemical Biology, Universiti Sains Malaysia, 11900 Penang (Malaysia)

    2016-09-01

    The main focus of this study is the incorporation of collagen peptides to fabricate P(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] nano-fiber construct to further enhance surface wettability and support cell growth while harbouring desired properties for biodegradable wound dressing. Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen peptides construct was carried out using dual syringe system. The wettability of the constructs increased with the increase in 4HB molar fraction from 20 mol% 4HB [53.2°], P(3HB-co-35 mol%4HB)[48.9°], P(3HB-co-50 mol%4HB)[44.5°] and P(3HB-co-82 mol%4HB) [37.7°]. In vitro study carried out using mouse fibroblast cells (L929) grown on nanofiber P(3HB-co-4HB)/collagen peptides construct showed an increase in cell proliferation. In vivo study using animal model (Sprague Dawley rats) showed that nanofibrous P(3HB-co-4HB)/collagen peptides construct had a significant effect on wound contractions with the highest percentage of wound closure of 79%. Hence, P(3HB-co-4HB)/collagen peptides construct suitable for wound dressing have been developed using nano-fabrication technique. - Highlights: • Nano-fiber construct to enhance surface wettability and cell growth, harbouring desired properties as biodegradable wound dressing. • Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen construct using dual syringe system. • Nanofibrous construct accelerated wound healing with efficient cellular organization.

  5. Convergence acceleration in the Monte-Carlo particle transport code TRIPOLI-4 in criticality

    International Nuclear Information System (INIS)

    Dehaye, Benjamin

    2014-01-01

    Fields such as criticality studies need to compute some values of interest in neutron physics. Two kind of codes may be used: deterministic ones and stochastic ones. The stochastic codes do not require approximation and are thus more exact. However, they may require a lot of time to converge with a sufficient precision.The work carried out during this thesis aims to build an efficient acceleration strategy in the TRIPOLI-4. We wish to implement the zero variance game. To do so, the method requires to compute the adjoint flux. The originality of this work is to directly compute the adjoint flux directly from a Monte-Carlo simulation without using external codes thanks to the fission matrix method. This adjoint flux is then used as an importance map to bias the simulation. (author) [fr

  6. Drugs affecting HbA1c levels

    Directory of Open Access Journals (Sweden)

    Ranjit Unnikrishnan

    2012-01-01

    Full Text Available Glycated hemoglobin (HbA1c is an important indicator of glycemic control in diabetes mellitus, based on which important diagnostic and therapeutic decisions are routinely made. However, there are several situations in which the level of HbA1c may not faithfully reflect the glycemic control in a given patient. Important among these is the use of certain non-diabetic medications, which can affect the HbA1c levels in different ways. This review focuses on the non-diabetic medications which can inappropriately raise or lower the HbA1c levels, and the postulated mechanisms for the same.

  7. [About the HbA1c in the elderly].

    Science.gov (United States)

    Farcet, Anaïs; Delalande, Géraldine; Oliver, Charles; Retornaz, Frédérique

    2016-03-01

    HbA1c product of non enzymatic glycation of HbA increases in relation with the mean blood glucose level during the former 2-3 months. HbA1c levels are correlated with the development of diabetic complications and HbA1c assessment is now the gold standard for evaluation of diabetes control. HbA1c level should not be higher than 7% to avoid these complications. However, in aged peoples, the objectives of diabetes control vary according to their health status. It must be good with HbA1c lower than 7-7.5% in healthy subjects and more relax in subjects with symptoms of frailty and risks of non perceived and self corrected hypoglycemia. Under these conditions, HbA1c values lower than 8 to 9% are advised. Nevertheless, hypoglycemia episodes may occur in patients with high HbA1c and capillary glucose follow-up is necessary for detection of such complications.

  8. Influence of semisynthetic modification of the scaffold of a contact domain of HbS on polymerization: role of flexible surface topology in polymerization inhibition.

    Science.gov (United States)

    Sonati, Srinivasulu; Bhutoria, Savita; Prabhakaran, Muthuchidambaran; Acharya, Seetharama A

    2018-02-01

    A new variant of HbS, HbS-Einstein with a deletion of segment α 23-26 in the B-helix, has been assembled by semisynthetic approach. B-helix of the α chain of cis αβ-dimer of HbS plays dominant role in the quinary interactions of deoxy HbS dimer. This B-helix is the primary scaffold that provides the orientation for the side chains of contact residues of this intermolecular contact domain. The design of HbS-Einstein has been undertaken to map the influence of perturbation of molecular surface topology and the flexibility of surface residues in the polymerization. The internal deletion exerts a strong inhibitory influence on Val-6 (β)-dependent polymerization, comparable to single contact site mutations and not for complete neutralization of Val-6(β)-dependent polymerization. The scaffold modification in cis-dimer is inhibitory, and is without any effect when present on the trans dimer. The flexibility changes in the surface topology in the region of scaffold modification apparently counteracts the intrinsic polymerization potential of the molecule. The inhibition is close to that of Le Lamentin mutation [His-20 (α) → Gln] wherein a mutation engineered without much change in flexibility of the contact domain. Interestingly, the chimeric HbS with swine-human chimeric α chain with multiple non-conservative mutations completely inhibits the Val-6(β)-dependent polymerization. The deformabilities of surface topology of chimeric HbS are comparable to HbS in spite of the multiple contact site mutations in the α-chain. We conclude that the design of antisickling Hbs for gene therapy of sickle cell disease should involve multiple mutations of intermolecular contact sites.

  9. Envisioning a Post-Conflict Tripoli: The Inclusive Urban Strategy and Action Plan for Bab Al-Tabbaneh and Jebel Mohsen

    Directory of Open Access Journals (Sweden)

    Fabiano Micocci

    2017-02-01

    Full Text Available The Inclusive Urban Strategy and Action Plan is a study conducted by a multi-disciplinary international team focused on the post-conflict area of Tripoli, the second largest city of Lebanon. The project includes the neighbourhoods of Bab Al-Tabbaneh and Jebel Mohsen and the conflict zone in between where hostilities ended thanks to the implementation of a security plan in 2014. The aim of the proposal is to initiate and foster peace and reconciliation between the conflicting communities, while addressing spatial, social and economic segregations by a holistic and tactical urban approach.The strategy results from a deep study and understanding of the actual fragile conditions in Tripoli, and derives its guidelines from the fractures and the intrinsic resources of the place. It is structured in three main layers (urban armature, functional injections and placemaking and envisions the possibility to establish new relations and synergies inside the hugely fragmented environment.Instead of proposing concrete solutions, the strategy aims at initially generating the necessary conditions to trigger processes of recovery and therefore development, encountering positive outcomes and opportunities as well as possible threats. Adaptability and retrofitting thus became keywords in developing a realistic strategy that can take into consideration the difficulty of programming and making decisions in the context of post-conflict reconstruction.

  10. Detection of Hb Constant Spring (HBA2: c.427T>C) Heterozygotes in Combination with β-Thalassemia or Hb E Trait by Capillary Electrophoresis.

    Science.gov (United States)

    Pornprasert, Sakorn; Saoboontan, Supansa; Punyamung, Manoo

    2015-01-01

    Hb Constant Spring (Hb CS; HBA2: c.427T>C) is often missed by routine laboratory testing as its mRNA as well as gene product are unstable and presented at a low level in peripheral blood. This study aimed to analyze the efficacy of capillary electrophoresis (CE) for detecting and quantifying of Hb CS in β-thalassemia (β-thal) trait or Hb E (HBB: c.79G>A) trait samples with reduced β-globin chain expression. Thalassemia diagnostic data were reviewed in 2524 blood samples that were submitted to the laboratory of the Associated Medical Sciences Clinical Service Center, Chiang Mai, Thailand for hemoglobinopathy and thalassemia diagnosis. DNA analysis for Hb CS was performed in 322 β-thal trait and 397 Hb E trait samples using the amplification refractory mutation system (ARMS). The CE electropherogram of Hb CS at zone 2 was observed in all five samples with β-thal trait and nine samples with Hb E trait with levels varying from 0.1-2.8 and 0.1-2.3%, respectively. Thus, the CE method proved useful for screening of Hb CS in samples with β-thal trait or Hb E trait, which is essential for providing accurate diagnosis, genetic counseling, prevention and control programs of Hb H-CS disease.

  11. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress.

    Science.gov (United States)

    Annarapu, Gowtham K; Singhal, Rashi; Peng, Yuandong; Guchhait, Prasenjit

    2016-01-01

    Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions.

  12. Detection of CTX-M-15 Among Uropathogenic Escherichia coli Isolated from Five Major Hospitals in Tripoli, Libya

    Directory of Open Access Journals (Sweden)

    Abdulaziz Zorgani1*,

    2017-07-01

    Full Text Available Objectives: Multidrug resistance (MDR and emergence of extended-spectrum β-lactamases (ESBLs among uropathogenic Escherichia coli have been reported worldwide, but there was no information on the detection of blaCTX-M-15 in major teaching hospitals in Libya. The aim of the study was to investigate the occurrence of CTX-M-15 β-lactamases producers isolated from five teaching hospitals in Tripoli, Libya. Methods: A total of 346 urine samples were collected from hospitalized patients in five teaching hospitals with a diagnosis of urinary tract infection (UTI. Phenotypic confirmation of ESBLs was confirmed by E-test strip; all ESBL-producing E. coli isolates were screened for the blaCTX-M-15 gene. Results: The distribution of ESBL-producing E. coli varied among the five hospitals. The highest proportion was identified in Tripoli Medical Centre (67.6%. There were extremely high proportions of isolates resistant to ceftriaxone, cefepime, and ceftazidime (93.0–100.0% among ESBL producers compared to non-ESBL producers (2.2–4.7%. MDR was detected in 22.2% of isolates. The majority of isolates (85.9% in which blaCTX-M-15 was identified were ESBL producers. There was a correlation (p < 0.001 between expression of CTX-M-15 and resistance to ceftazidime. Conclusions: The isolation of MDR ESBL-producing uropathogens expressing the CTX-M-15 gene will limit the choices clinicians have to treat their patients with UTIs. Continued surveillance and implementation of efficient infection control measures are required.

  13. Neutron dose rate in the upper part of a PWR containment. Comparison between measurements and TRIPOLI-2 calculations

    International Nuclear Information System (INIS)

    Vergnaud, T.; Bourdet, L.; Gonnord, J.; Nimal, J.C.; Champion, G.

    1984-01-01

    Conception of a reactor building requires large openings in the primary concrete shield for a postulated loss-of-coolant accident. Through these openings neutrons escape and produce dose rates in several parts of the reactor building. Some calculations using ANISN, DOT and essentially TRIPOLI-2 codes allow to compute the neutron dose rates at several places such as reactor containment operating floor and containment annulus. Some complementary shields are provided and the instrumentations are placed in area where the dose rate is lower. Comparisons are presented between measurements and calculations

  14. Radio-ligand immunoassay for human hemoglobin variants

    International Nuclear Information System (INIS)

    Javid, J.; Pettis, P.K.; Miller, J.E.

    1981-01-01

    A quantitative method is described for the individual assay of human hemoglobin variants occurring singly or in mixture. The hemoglobin to be assayed is bound to specific antibody; the immune complex is attached to protein A-containing S. aureus and removed from the mixture. The hemoglobin thus isolated is quantified by its ability to bind radiolabeled haptoglobin. The technique is accurate and distinguishes among the 4 hemoglobins tested, namely Hb A, S, C and F. It has the advantage over conventional radioimmunoassay that a single probe, radiolabeled haptoglobin, is needed for the specific assay of any hemoglobin. (Auth.)

  15. Pregnancy outcome in patients with sickle cell disease in the UK--a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease.

    Science.gov (United States)

    Oteng-Ntim, Eugene; Ayensah, Benjamin; Knight, Marian; Howard, Jo

    2015-04-01

    We describe the findings from a national study of maternal and fetal outcomes of pregnancy in women with sickle cell disease (SCD). Data were collected via the United Kingdom Obstetric Surveillance System between 1 February 2010 and 31 January 2011 from 109 women, of whom 51 (46·8%) had HbSS and 44 (40·4%) had HbSC. Data included antenatal, maternal and fetal outcomes. Comparisons were made between women with HbSS and HbSC. Incidence of complications were acute pain (57%), blood transfusion (26%), urinary tract infection (UTI; 12%) and critical care unit admission (23%) and these were all more common in women with HbSS than HbSC. There was no difference in the incidence of acute chest syndrome, hypertension and venous thromboembolism between HbSS and HbSC. Women with HbSS were more likely to deliver at pregnancy. © 2014 John Wiley & Sons Ltd.

  16. Hb D/Talassemia beta associada à anemia crônica Hb D/ Beta thalassaemia associated with chronic anaemia

    Directory of Open Access Journals (Sweden)

    Paulo C. Naoum

    2002-03-01

    Full Text Available We describe a case of Hb D/Beta thalassemia associated with chronic anemia. Hematological analyses performed in a patient with chronic anemia demonstrating microcytosis and hypochromic in his erythrocytes. Specific laboratory diagnosis performed by alkaline and acid electrophoresis, and fetal determination by alkali resistance, indicated it to be Hb D associated with beta thalassemia. Analyses carried out on his family (father, mother and brother confirmed the suspected diagnosis. Hb D/Beta thalassemia is a very rare interaction in the Brazilian population, and its determination required specific laboratorial techniques and hematological analyses.

  17. الحركة الفكرية في طرابلس الغرب عهد بني خزرون Intellectual Movement in Tripoli (Bani Khozron era

    Directory of Open Access Journals (Sweden)

    Dr. Firas Salim Hayawi أ.د.فراس سليم حياوي

    2017-01-01

    Full Text Available Bani Khozronis a family it's Pedigree to the tribe Zenata, ruled Tripoli over one hundred and fifty years began at filfle bin Said in 391 AH / 1000 AD and ended by Mohammed bin Khozron Last princes and who was expelled from the city of Tripoli in 540 AH / 1146 AD, which had cleared to them of the atmosphere when left Muizzledineallah al Fatimid to Egypt so the independing Tripoli and overpowering as between them and the Fatimids of difficulties. The Zenata succession of Umayyad in Andalusia and with prejudiceSaeed bin khazer Ben Vlfol sided to Sanhaja so honor by Beijing bin zirivery honor and made him rule Tunbh and closer links to link their clan by marriage, so as to marry one of the daughters Saeed bin khazer has successive events in Morocco and that made Pepper worried about the intentions of Sanhaja It is reluctant to cooperate with the Badis, and then the war between him and the Addis year 389 AH / 999 AD onwards Vofelt him pepper to the realms of the plug, and there I turned around Zenata, offering Bjmuah and occupied Tripoli in 390 AH / 1000 AD, and the foundations of the state fluctuated her life between the ebb and flow due to the conflict with Sanhaja so that was the end, as we mentioned in 540 AH / 1146 AD. On the whole, this study sheds light on the history of intellectual movement in the city of Tripoli during the reign of BaniKhozron in the political, intellectual and economic aspects. And it proceeded to study novels relevant to the subject of research and discussion analysis.

  18. Pemphigus : A clinical study of 109 cases from Tripoli, Libya

    Directory of Open Access Journals (Sweden)

    Shafi M

    1994-01-01

    Full Text Available From 1981 to 1992, 109 cases (90 females and 19 males of pemphigus were seen in the Department of Dermatology, Central Hospital Tripoli, Libya. Age of onset of the disease varied from 17 to 85 years, while duration of the disease at the time of presentation varied from 3 days to 13 days. On the basis of clinical features and routine histological findings the cases were divided into various subtypes as : pemphigus foliaceus 65 cases, pemphigus vulgaris 34 patients, pemphigus erythematosus 5, herpetiform pemphigus 3 and vegetans type 2 cases. Three of our patients had diabetes mellitus preceding pemphigus, while 12 patients developed steroid induced diabetes. Significant secondary bacterial infection occurred in all cases at some stage of the disease while oral candidiasis occurred in 15 cases. Eczema herpeticum was seen in 4 patients, while 2 had extensive tinea corporis. One of 4 patients of pemphigus vulgaris had complete shedding of nail and 1 female patient had alternate phases of pemphigus foliaceus and generalized pustular psoriasis. The features in our cases of pemphigus foliaceus were somewhat similar to Brazilian pemphigus foliaceus and we had more cases of pemphigus foliaceus, almost exclusively affecting females.

  19. HB-Line Plutonium Oxide Data Collection Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, R. [Savannah River Nuclear Solutions; Varble, J. [Savannah River Nuclear Solutions; Jordan, J. [Savannah River Nuclear Solutions

    2015-05-26

    HB-Line and H-Canyon will handle and process plutonium material to produce plutonium oxide for feed to the Mixed Oxide Fuel Fabrication Facility (MFFF). However, the plutonium oxide product will not be transferred to the MFFF directly from HB-Line until it is packaged into a qualified DOE-STD-3013-2012 container. In the interim, HB-Line will load plutonium oxide into an inner, filtered can. The inner can will be placed in a filtered bag, which will be loaded into a filtered outer can. The outer can will be loaded into a certified 9975 with getter assembly in compliance with onsite transportation requirement, for subsequent storage and transfer to the K-Area Complex (KAC). After DOE-STD-3013-2012 container packaging capabilities are established, the product will be returned to HB-Line to be packaged into a qualified DOE-STD-3013-2012 container. To support the transfer of plutonium oxide to KAC and then eventually to MFFF, various material and packaging data will have to be collected and retained. In addition, data from initial HB-Line processing operations will be needed to support future DOE-STD-3013-2012 qualification as amended by the HB-Line DOE Standard equivalency. As production increases, the volume of data to collect will increase. The HB-Line data collected will be in the form of paper copies and electronic media. Paper copy data will, at a minimum, consist of facility procedures, nonconformance reports (NCRs), and DCS print outs. Electronic data will be in the form of Adobe portable document formats (PDFs). Collecting all the required data for each plutonium oxide can will be no small effort for HB-Line, and will become more challenging once the maximum annual oxide production throughput is achieved due to the sheer volume of data to be collected. The majority of the data collected will be in the form of facility procedures, DCS print outs, and laboratory results. To facilitate complete collection of this data, a traveler form will be developed which

  20. Small Sample Reactivity Measurements in the RRR/SEG Facility: Reanalysis using TRIPOLI-4

    Energy Technology Data Exchange (ETDEWEB)

    Hummel, Andrew [Idaho National Lab. (INL), Idaho Falls, ID (United States); Palmiotti, Guiseppe [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-08-01

    This work involved reanalyzing the RRR/SEG integral experiments performed at the Rossendorf facility in Germany throughout the 1970s and 80s. These small sample reactivity worth measurements were carried out using the pile oscillator technique for many different fission products, structural materials, and standards. The coupled fast-thermal system was designed such that the measurements would provide insight into elemental data, specifically the competing effects between neutron capture and scatter. Comparing the measured to calculated reactivity values can then provide adjustment criteria to ultimately improve nuclear data for fast reactor designs. Due to the extremely small reactivity effects measured (typically less than 1 pcm) and the specific heterogeneity of the core, the tool chosen for this analysis was TRIPOLI-4. This code allows for high fidelity 3-dimensional geometric modeling, and the most recent, unreleased version, is capable of exact perturbation theory.

  1. A method comparison study between two hemoglobinometer models (Hemocue Hb 301 and Hb 201+) to measure hemoglobin concentrations and estimate anemia prevalence among women in Preah Vihear, Cambodia.

    Science.gov (United States)

    Rappaport, A I; Karakochuk, C D; Whitfield, K C; Kheang, K M; Green, T J

    2017-02-01

    Hemoglobin (Hb) concentration is often measured in global health and nutrition surveys to determine anemia prevalence using a portable hemoglobinometer such as the Hemocue® Hb 201+. More recently, a newer model was released (Hemocue Hb 301) utilizing slightly different methods to measure Hb as compared to the older model. The objective was to measure bias and concordance between Hb concentrations using the Hemocue Hb 301 and Hb 201+ models in a rural field setting. Hemoglobin (Hb) concentration was measured using one finger prick of blood (approximately 10 μL) from 175 Cambodian women (18-49 years) using three Hemocue Hb 201+ and three Hb 301 machines. Bias and concordance were measured and plotted. Overall, mean ± SD Hb concentration was 116 ± 13 g/L using the Hb 201+ and 118 ± 12 g/L using the Hb 301; and anemia prevalence (Hb < 120 g/L) was 58% (n = 102) and 58% (n = 101), respectively. Overall bias ± SD was 2.0 ± 10.5 g/L and concordance (95% CI) was 0.63 (0.54, 0.72). Despite the 2 g/L bias detected between models, anemia prevalence was very similar in both models. The two models measured anemia prevalence comparably in this population of women in rural Cambodia. © 2016 John Wiley & Sons Ltd.

  2. Current Status of HbA1c Biosensors

    Science.gov (United States)

    Lin, Hua; Yi, Jun

    2017-01-01

    Glycated hemoglobin (HbA1c) is formed via non-enzymatic glycosylation reactions at the α–amino group of βVal1 residues in the tetrameric Hb, and it can reflect the ambient glycemic level over the past two to three months. A variety of HbA1c detection methods, including chromatography, immunoassay, enzymatic measurement, electrochemical sensor and capillary electrophoresis have been developed and used in research laboratories and in clinics as well. In this review, we summarize the current status of HbA1c biosensors based on the recognition of the sugar moiety on the protein and also their applications in the whole blood sample measurements. PMID:28777351

  3. A general, three-dimensional Monte Carlo program: TRIPOLI-01

    International Nuclear Information System (INIS)

    Katz, Shlomo; Nimal, J.-C.

    1976-09-01

    TRIPOLI 01 is a general, three-dimensional Monte-Carlo program, which treats the slowing down and diffusion of neutrons in source problems. This version is essentially devoted to reactor shielding studies. The geometry is described as a combination of volumes, bounded by portions of first or second degree surfaces. The space orientation of these volumes is quite arbitrary. Geometries repeated by translation, symmetry, or rotation can be treated. The program can itself control the consistency of geometry data. The nuclear constants are presently represented in a multigroup mode, with a number of groups as large as necessary. Multigroup data are derived from a library tape (LINDA) containing point wise data taken from the UKNDL (73) library and completed by certain data from UNC (GENDA). The neutron energy is followed in a continuous way; the program takes into account: elastic collision with any anisotropy order, (n,n') and (n,2n) reactions, and absorption; in this version, thermal neutrons are treated as a single energy group. The program can solve deep penetration problems by utilizing variance reduction techniques based on exponential transform, and biasing of angular scattering laws. The distribution of sources can be any arbitrary function of space, energy and direction. The program calculates spectra and activities averaged in specified volumes or areas. Further exploitation of results is possible by using the FORTRI routine [fr

  4. Study of cold neutron sources: Implementation and validation of a complete computation scheme for research reactor using Monte Carlo codes TRIPOLI-4.4 and McStas

    International Nuclear Information System (INIS)

    Campioni, Guillaume; Mounier, Claude

    2006-01-01

    The main goal of the thesis about studies of cold neutrons sources (CNS) in research reactors was to create a complete set of tools to design efficiently CNS. The work raises the problem to run accurate simulations of experimental devices inside reactor reflector valid for parametric studies. On one hand, deterministic codes have reasonable computation times but introduce problems for geometrical description. On the other hand, Monte Carlo codes give the possibility to compute on precise geometry, but need computation times so important that parametric studies are impossible. To decrease this computation time, several developments were made in the Monte Carlo code TRIPOLI-4.4. An uncoupling technique is used to isolate a study zone in the complete reactor geometry. By recording boundary conditions (incoming flux), further simulations can be launched for parametric studies with a computation time reduced by a factor 60 (case of the cold neutron source of the Orphee reactor). The short response time allows to lead parametric studies using Monte Carlo code. Moreover, using biasing methods, the flux can be recorded on the surface of neutrons guides entries (low solid angle) with a further gain of running time. Finally, the implementation of a coupling module between TRIPOLI- 4.4 and the Monte Carlo code McStas for research in condensed matter field gives the possibility to obtain fluxes after transmission through neutrons guides, thus to have the neutron flux received by samples studied by scientists of condensed matter. This set of developments, involving TRIPOLI-4.4 and McStas, represent a complete computation scheme for research reactors: from nuclear core, where neutrons are created, to the exit of neutrons guides, on samples of matter. This complete calculation scheme is tested against ILL4 measurements of flux in cold neutron guides. (authors)

  5. Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available BACKGROUND: Previous studies have identified that variants in peroxisome proliferator-activated receptor PPAR-δ (PPARD, a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations. This current study sought to determine (1 whether the genetic associations of PPARD variants with type 2 diabetes and its related traits could be replicated in Chinese Han population, and (2 whether the associations would be modified by the effect of vitamin D status. METHODS AND FINDINGS: We genotyped 9 tag single nucleotide polymorphisms (SNPs that cover the gene of PPARD (rs2267664, rs6902123, rs3798343, rs2267665, rs2267668, rs2016520, rs2299869, rs1053049, and rs9658056 and tested their associations with type 2 diabetes risk and its related traits, including fasting glucose, insulin and HbA1c in 3,210 Chinese Hans. Among the 9 PPARD tag SNPs, rs6902123 was significantly associated with risk of type 2 diabetes (odds ratio 1.75 [95%CI 1.22-2.53]; P = 0.0025 and combined type 2 diabetes and impaired fasting glucose (IFG (odds ratio 1.47 [95%CI 1.12-1.92]; P = 0.0054. The minor C allele of rs6902123 was associated with increased levels of fasting glucose (P = 0.0316 and HbA1c (P = 0.0180. In addition, we observed that vitamin D modified the effect of rs6902123 on HbA1c (P for interaction = 0.0347. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that common variants in PPARD contribute to the risk of type 2 diabetes in Chinese Hans, and provided suggestive evidence of interaction between 25(OHD levels and PPARD-rs6902123 on HbA1c.

  6. HB D Los Angeles in a Brazilian family Hb D Los Angeles em família brasileira

    Directory of Open Access Journals (Sweden)

    Guilherme G. Leoneli

    2001-09-01

    Full Text Available Inherited disorders of hemoglobin, the most common monogenic disease, are now well understood at the molecular level, knowledge, which has led to considerable improvements in their control and management. The Brazilian population is multiethnic, and the correct characterization of the Hb D is important, mainly because the method available for detection of abnormal hemoglobins, present a migration in the same zone at alkaline pH, for Hb S, D, and G for example. In this paper we studied a family with an abnormal hemoglobin like S in alkaline electrophoresis, by appropriated methods including HPLC and molecular analysis, characterized as hemoglobin D Los Angeles.As doenças hereditária da hemoglobina são as mais comuns doenças monogênicas e atualmente bem conhecidas do ponto de vista molecular, fato este que propiciou um avanço no seu controle e manuseio. A população brasileira caracteriza-se pela multiplicidade étnica e a caracterização da Hb D torna-se importante por este dado, associado ao fato de que os métodos de detecção das hemoglobinopatias comumente não identificam esta fração anormal que apresenta a peculiaridade de migração eletroforéticia em pH alcalino na mesma zona observada nas Hb S e G. Neste relato é apresentado um estudo familiar no qual é empregada metodologia adequada, o HLPC, que permite a identificação da Hb D.

  7. Transfusion Associated Peak in Hb HPLC Chromatogram – a Case Report

    Science.gov (United States)

    Jain, Sonal; Dass, Jasmita; Pati, Hara Prasad

    2012-01-01

    High performance liquid chromatography (HPLC) and electrophoresis are commonly used to diagnose various hemoglobinopathies. However, insufficient information about the transfusion history can lead to unexpected and confusing results. We are reporting a case of Juvenile myelomonocytic leukemia (JMML) in which HbHPLC was done to quantify fetal hemoglobin (HbF). The chromatogram showed elevated HbF along with a peak in the HbD window. A transfusion acquired peak was suspected based on the unexpectedly low percentage of HbD and was subsequently confirmed using parental HbHPLC. PMID:22348188

  8. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion.

    Science.gov (United States)

    Shimura, Takaya; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2012-05-30

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation

  9. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    International Nuclear Information System (INIS)

    Shimura, Takaya; Higashiyama, Shigeki; Joh, Takashi; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi

    2012-01-01

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P < 0.01). The growth of wt-HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for

  10. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Science.gov (United States)

    2012-01-01

    Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Conclusions Both the function of HB-EGF as an EGFR ligand

  11. How does CKD affect HbA1c?

    Science.gov (United States)

    Bloomgarden, Zachary; Handelsman, Yehuda

    2018-04-01

    HOW DOES CHRONIC KIDNEY DISEASE AFFECT HBA1C?: A number of factors determine HbA1c other than the level of glucose exposure alone. In an subset analysis of the Atherosclerosis Risk in Communities study of 941 diabetic people with varying degrees of chronic kidney disease (CKD), as well as 724 who did not have CKD, and mean age in the eighth decade, Jung et al. ask whether HbA1c is reliable as an indicator of glycemia in people with kidney disease (CKD) to the same degree as in those not having kidney disease, and, if not, whether measures of glycated serum proteins may be more useful. The only available measure of glycemia for comparison was a single fasting glucose level, and the authors acknowledge that this gives an incomplete measure, particularly in people with relatively mild diabetes, whose mean HbA1c was 6.4%, with most having levels of 7.5% or lower. In patients of this sort, postprandial glucose levels may better explain variations in mean HbA1c. Recognizing that the dataset may be limited, Jung et al. nevertheless give an intriguingly negative answer to the first question, of the reliability of HbA1c with kidney disease. Using Deming regression analysis, Jung et al. showed that the correlation between HbA1c and fasting glucose weakens as renal function worsens, and, moreover, that this appears particularly to be the case in people with anemia (hemoglobin men and women, respectively), confirming earlier observations. Among those diabetic people with neither anemia nor CKD, the correlation coefficient between HbA1c and fasting glucose was r = 0.70, compared with r = 0.35 among those with both anemia and very severe CKD (estimated glomerular filtration rate [eGFR] perform SMBG to more adequately interpret HbA1c results. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  12. Balanced scorecard: application in the General Panarcadian Hospital of Tripolis, Greece.

    Science.gov (United States)

    Koumpouros, Yiannis

    2013-01-01

    The purpose of this paper is to discuss the application of the balanced scorecard (BSC) in the Greek public health sector. The basic balanced scorecard theory has been adopted in the characteristics and individualities of the Greek public health system. The theoretical model developed was applied in the General Panarcadian Hospital of Tripolis (GPHT) in Greece. GPHT is a representative paradigm of a big regional Greek public hospital. It has about 300 beds and many clinics and specialties (internal medicine, cardiology, general surgery, intensive care unit, artificial kidney unit, etc.). Strategic management was performed for almost three years. The BSC model was formulated in an appropriate software program. The problems (both technical and managerial) faced during a three-year period along with the results of this management approach are presented in the current paper. The paper highlights some important gaps in the Greek public health system, while proposing actions to be taken. The BSC theory can be very successful under certain conditions. Special attention is given to the peculiarities of the Greek public health situation. The paper presents for the first time a real life example of applying BSC in the Greek public health sector.

  13. Effects of α-Thalassemia on HbA1c Measurement.

    Science.gov (United States)

    Xu, Anping; Ji, Ling; Chen, Weidong; Xia, Yong; Zhou, Yu

    2016-11-01

    α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes α-thalassemia on HbA 1c measurement. A total of 189 samples from nondiabetic patients were analyzed. HbA 1c analysis was performed by ion-exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis. Fasting glucose, fructosamin, and HbA 2 were also performed. All samples were confirmed by genotyping for thalassemia. In patients with two or three functional α-genes, HbA 1c values were not significantly different from those of controls (P > 0.05); however, in individuals with α-thalassemia with one functional α-gene (i.e., HbH disease), HbA 1c levels were significantly different from those of controls (P 0.05). In this study, HbA 1c values in samples from individuals with two or three functional α-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not. © 2016 Wiley Periodicals, Inc.

  14. Investigation on the possible interconnection between Kanata sinkhole, on the high plateau of Tripolis, and springs of Argos area

    Energy Technology Data Exchange (ETDEWEB)

    Leontiadis, I.; Dimitroulas, C.; Zouridakis, N.; Dounas, A.; Morfis, A.; Paraskevopoulou, P.

    1984-07-01

    /sup 51/Cr-EDTA has been used as tracer for the investigation of possible interconnection between the sinkhole Kanata, on the high Plateau of Tripolis, and springs of the areas of Argos, Achladokambos and Kinouria. By this experiment, the interconnection between the sinkhole and the submarine spring of Kiveri, as well as the springs of Xovrios Achladokambos river, is proved. Furthermore, the percentage of connection between the sinkhole and the springs, the mean transit time of the water from the sinkhole to the springs, the volume of the underground reservoir feeding the springs, etc., have been calculated.

  15. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Directory of Open Access Journals (Sweden)

    Shimura Takaya

    2012-05-01

    Full Text Available Abstract Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C, translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF and mutated HB-EGF (HB-EGF-mC, which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 % and in the cytoplasm only in 25 cases (26.0 %. The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P  Conclusions Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  16. Hb Oegstgeest [alpha104(G11)Cys-->Ser (alpha1)]. A new hemoglobin variant associated with a mild alpha-thalassemia phenotype

    NARCIS (Netherlands)

    Harteveld, Cornelis L.; Rozendaal, Lieke; Blom, Nico A.; Lo-A-Njoe, Shirley; Akkerman, Nicole; Arkestijn, Sandra; van Delft, Peter; Giordano, Piero C.

    2005-01-01

    A microcytic hypochromic anemic state was observed in an 8-year old Black female of Surinam origin during pre-operative Hb S [beta6(A3)Glu-->Val] screening. Her high zinc protoporphyrin (ZPP) level suggested a chronic iron depletion but, in contrast, the high red blood cell (RBC) count (5.85 x

  17. The optical emission from the supernova remnant HB 3

    Science.gov (United States)

    Fesen, R. A.; Gull, T. R.

    1983-01-01

    The supernova remnant HB 3 was first detected as a radio source by Brown and Hazard (1953). On the basis of subsequent radio studies, it was concluded that the object was a supernova remnant (SNR). HB 3 is located at the far western edge of the H II region/molecular cloud complex W3-W4-W5 (IC 1795-1805-1848). However, a physical association of HB 3 with this complex is uncertain. In the present investigation, attention is called to the probability that HB 3 exhibits a more extensive optical emission structure than previously realized, and one which agrees well with both the position and morphology of the radio emission. It is found that narrow-passband optical images strongly suggest an almost complete optical emission shell for HB 3. Spectroscopic observations are, however, required to confirm that this emission is characteristic of a SNR.

  18. Pre-treatment of desalination feed seawater by Jordanian Tripoli, Pozzolana and Feldspar: batch experiments

    Directory of Open Access Journals (Sweden)

    AIMAN E. AL-RAWAJFEH

    2011-06-01

    Full Text Available In this research, composites of layered double hydroxide (LDH with three Jordanian natural raw materials: Tripoli (T, Pozzolana (P and Feldspar (F were prepared by co-precipitation and have been used for feed seawater pre-treatment. The data reveals that percent adsorption decreased with increase in initial concentration, but the actual amount of adsorbed ions per unit mass of LDH/T-P-F increased with increase in metal ion concentrations. The values of ΔG were negative and within 21 to 26 kJ/mol, while the values of and ΔS were positive, with ΔH within the range of 0.1 to 25 kJ/mol. The values of ΔH, ΔS and ΔG indicate the favorability of physisorption and show that the LDH/T-P-F composites have a considerable potential as adsorbents for the removal of ions from seawater.

  19. Standardization of method for determining glycosylated hemoglobin (Hb A1c by cation exchange high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Marina Venzon Antunes

    2009-12-01

    Full Text Available Hemoblobin A1c is the most important parameter for the monitoring of metabolic control of patients with diabetes mellitus. The purpose of this study was to adapt the Mono S method to a conventional HPLC system, allowing highly selective HbA1c determination without the acquisition of kits or the use of dedicated systems The results obtained were compared to the Tinaquant® immune turbidimetric method and the Bio-Rad Variant® chromatographic method. The developed method presented intra-study precision (C.V. % of 1.39-3.65 and inter-study precision (C.V. % of 2.80-3.02%. The determination coefficients among methods were: HPLC Mono S x Tinaquant®: r²: 0.9856 (n=60 and HPLC Mono S x HPLC Bio-Rad Variant®: r²: 0.9806 (n=16. A conversion equation between HPLC Mono S and Bio-Rad Variant® was calculated allowing yielding comparable and interchangeable values. The HPLC Mono-S is a precise, low-cost method which yields similar values to the Bio-Rad Variant® method on conventional HPLC equipment.A hemoglobina A1c é o parâmetro laboratorial mais importante no monitoramento do controle metabólico de pacientes portadores de diabetes melito. Dentre as metodologias existentes para a quantificação desta fração de hemoglobina, a cromatografia líquida de alta eficiência (CLAE baseada em troca catiônica apresenta a melhor precisão, sendo o método de escolha. O objetivo deste trabalho foi adaptar o método Mono S a um sistema de CLAE convencional permitindo a disponibilidade da determinação altamente seletiva de Hb A1c sem a aquisição de kits e comparar os resultados obtidos com o método imunoturbidimétrico Tinaquant® (Roche® e com o método de cromatografia líquida Bio-Rad Variant®. O método desenvolvido apresentou precisão intra-ensaio de 1,39-3,65% e inter-ensaio de 2,80-3,02%. Os coeficientes de determinação entre os métodos foram: CLAE Mono S x Tinaquant®: r² = 0,9856 (n=60 e CLAE Mono S x Bio-Rad Variant®: r² = 0,9806 (n=16

  20. Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long-term HbA1c and HbA1c variability.

    Science.gov (United States)

    Walker, G S; Chen, J Y; Hopkinson, H; Sainsbury, C A R; Jones, G C

    2018-06-01

    Previous evidence has demonstrated that participation in the Dose Adjustment for Normal Eating (DAFNE) education programme can reduce HbA 1c and severe hypoglycaemia in people with Type 1 diabetes. In a number of studies, increased HbA 1c variability has been associated with higher diabetic morbidity and mortality. No studies have examined the impact of structured education on HbA 1c variability in Type 1 diabetes. People with Type 1 diabetes who had attended DAFNE were identified for inclusion from the Scottish Care Information-Diabetes dataset. HbA 1c median and variability, expressed as coefficient of variation (CV) before and after DAFNE was calculated. Some 1061 individuals participated in DAFNE education and 687 met the inclusion criteria. A significant median reduction in HbA 1c [-3.5 mmol/mol (-0.3%)] was seen at 12 months with a significant reduction [-1.5 mmol/mol (-0.1%)] still seen at 60 months of follow-up. HbA 1c variability as measured by CV was significantly lower during the post-DAFNE period: 0.08 (IQR 0.05-0.12) reduced to 0.07 (IQR 0.05-0.10); P = 0.002. The data confirm that DAFNE participation improves glycaemic control in Type 1 diabetes with benefits being sustained for 5 years. This study is the first to demonstrate reduced HbA 1c variability after completion of structured education. This is new evidence of the beneficial impact of DAFNE on glycaemic profile. © 2018 Diabetes UK.

  1. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach

    International Nuclear Information System (INIS)

    Hoskins, J.T.; Zhou, Z.; Harding, P.A.

    2008-01-01

    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser 108/121 , HB-EGF-Cys/Ser 116/132 , and HB-EGF-Cys/Ser 134/143 ) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with M r of 6.5, 21 and 24 kDa were observed from lysates of HB-EGF and each HB-EGF disulfide analogue. HB-EGF immunohistochemical analyses of each HB-EGF stable cell line demonstrated ubiquitous protein expression except HB-EGF-Cys/Ser 108/121 and HB-EGF-Cys/Ser 116/132 stable cell lines which exhibited accumulated expression immediately outside the nucleus. rHB-EGF, HB-EGF, and HB-EGF 134/143 proteins competed with 125 I-EGF in an A431 competitive binding assay, whereas HB-EGF-Cys/Ser 108/121 and HB-EGF-Cys/Ser 116/132 failed to compete. Each HB-EGF disulfide analogue lacked the ability to stimulate tyrosine phosphorylation of the 170 kDa EGFR. These results suggest that HB-EGF-Cys/Ser 134/143 antagonizes EGFRs

  2. Complex Interaction of Hb Q-Thailand (HBA1: c.223G>C) with β-Thalassemia/Hb E (HBB: c.79G>A) Disease.

    Science.gov (United States)

    Panyasai, Sitthichai; Satthakarn, Surada; Pornprasert, Sakorn

    2018-01-01

    Hb Q-Thailand [α74(EF3)Asp→His (α1), GAC>CAC, HBA1: c.223G>C] is an abnormal hemoglobin (Hb) frequently found in Thailand and Southeast Asian countries. The association of the α Q-Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report how to diagnose the coinheritance of Hb Q-Thailand with β-thalassemia (β-thal)/Hb E disease in four Thai samples from high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) testing results. Understanding of the HPLC chromatogram and CE electropherogram patterns of this complex mutation is important for interpretation of testing results and providing genetic counseling.

  3. The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release

    Energy Technology Data Exchange (ETDEWEB)

    Prince, Robin N.; Schreiter, Eric R.; Zou, Peng; Wiley, H. S.; Ting, Alice Y.; Lee, Richard T.; Lauffenburger, Douglas A.

    2010-07-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGFlike domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane proform from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HBEGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling.

  4. The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin Cutoff Points in Double Heterozygous Hb E/- -SEA α-Thalassemia-1 Carriers are Dependent on Hemoglobin Levels.

    Science.gov (United States)

    Leckngam, Prapapun; Limweeraprajak, Ektong; Kiewkarnkha, Tiemjan; Tatu, Thanusak

    2017-01-01

    Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- - SEA (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of - - SEA and -α 3.7 (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0-11.9 g/dL. Finally, in the group having Hb levels ≥12.0 g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to screen for the double heterozygous Hb E/- - SEA anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.

  5. Is insulin the preferred treatment for HbA1c >9%?

    Science.gov (United States)

    Bloomgarden, Zachary

    2017-09-01

    The algorithms and guidelines of the American Association of Clinical Endocrinologists and the American Diabetes Association recommend that insulin administration be strongly considered for people with type 2 diabetes (T2D) with HbA1c levels exceeding 9.0% and 10%, respectively. Although the caveat is given in both sets of recommendations that this is particularly appropriate when patients are "symptomatic," referring to urinary frequency with increased thirst and appetite, weight loss, and ketosis, the clinical definition of such presentations may be ill-defined, and it is noteworthy that both documents consider insulin to offer particular benefit under such circumstances. However, with multiple options for glycemic treatment, it is of interest to reconsider this argument for insulin use. It should be recalled that in the UK Prospective Diabetes Study, diet alone was associated with a reduction in HbA1c from 9% to 7%. Drug-naïve people with T2D do often show surprisingly strong reductions in HbA1c with metformin-based dual-agent oral treatment approaches; a recent report showed that even with baseline HbA1c >11%, the combination of metformin with a sulfonylurea, pioglitazone, or sitagliptin was associated with reduction in HbA1c from 11.6% to 6.0%. A 32-week study of the combination of rosiglitazone with metformin in patients with mean baseline HbA1c 8.9% showed a mean HbA1c reduction of 2.3%, and an open-label cohort with baseline HbA1c 11.8% had a reduction in HbA1c to 7.8%. With metformin plus sitagliptin, a mean placebo-adjusted HbA1c reduction of 2.1% from a baseline of 8.8% was reported, with those patients with baseline HbA1c >9% having a 2.6% reduction in HbA1c, and an open-label cohort with baseline HbA1c 11.2% having a 2.9% reduction in HbA1c. Similar 2% HbA1c reductions from baseline levels of 9.1% were seen with metformin in initial combination with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin. Although such dual oral agent

  6. Formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blodgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical property

    International Nuclear Information System (INIS)

    Yin Fan; Shin, Hoon-Kyu; Kwon, Young-Soo

    2006-01-01

    The formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blotgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical properties were studied in this paper. This method ensured better electrode activity because almost no protein was adsorbed onto electrode surface before depositing Hb-ODA monolayer onto electrode surface. The optimum equilibrium time of Hb interacted with ODA layer, the optimum protein amount spread onto subphase's interface and the optimum ionic strength and pH of subphase were obtained from the experimental results. The compressibility analyses of Hb-ODA films showed that the surface pressure of this film from liquid-expanded to liquid-condensed state ranged between 16 and 40 mN/m. Direct electron transfer of Hb immobilized on gold electrode by LB technique was observed by cyclic voltammetry. Results showed that Hb molecules still kept their electrochemical activity. The electrode with Hb-ODA LB film displayed the fastest electron transfer rate when the film transferred under the surface pressure of 35 mN/m

  7. Formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blodgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical property

    Energy Technology Data Exchange (ETDEWEB)

    Yin Fan [Department of Electrical Engineering, Dong-A University, Busan 604-714 (Korea, Republic of); Department of Chemistry, Changshu Institute of Technology, Changshu, 215500 (China); Shin, Hoon-Kyu [Department of Electrical Engineering, Dong-A University, Busan 604-714 (Korea, Republic of); Kwon, Young-Soo [Department of Electrical Engineering, Dong-A University, Busan 604-714 (Korea, Republic of)]. E-mail: yskwon@daunet.donga.ac.kr

    2006-03-21

    The formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blotgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical properties were studied in this paper. This method ensured better electrode activity because almost no protein was adsorbed onto electrode surface before depositing Hb-ODA monolayer onto electrode surface. The optimum equilibrium time of Hb interacted with ODA layer, the optimum protein amount spread onto subphase's interface and the optimum ionic strength and pH of subphase were obtained from the experimental results. The compressibility analyses of Hb-ODA films showed that the surface pressure of this film from liquid-expanded to liquid-condensed state ranged between 16 and 40 mN/m. Direct electron transfer of Hb immobilized on gold electrode by LB technique was observed by cyclic voltammetry. Results showed that Hb molecules still kept their electrochemical activity. The electrode with Hb-ODA LB film displayed the fastest electron transfer rate when the film transferred under the surface pressure of 35 mN/m.

  8. Use of Fructosyl Peptide Oxidase for HbA1c Assay

    Science.gov (United States)

    Yonehara, Satoshi; Inamura, Norio; Fukuda, Miho; Sugiyama, Koji

    2015-01-01

    ARKRAY, Inc developed the world’s first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay “CinQ HbA1c” with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent. PMID:25633966

  9. The Long and Winding Road to Optimal HbA1c Measurement

    Science.gov (United States)

    Little, Randie R.; Rohlfing, Curt

    2016-01-01

    The importance of hemoglobin A1c (HbA1c) as an indicator of mean glycemia and risks for complications in patients with diabetes mellitus was established by the results of long-term clinical trials, most notably the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), published in 1993 and 1998 respectively. However, clinical application of recommended HbA1c targets that were based on these studies was difficult due to lack of comparability of HbA1c results among assay methods and laboratories. Thus, the National Glycohemoglobin Standardization Program (NGSP) was initiated in 1996 with the goal of standardizing HbA1c results to those of the DCCT/UKPDS. HbA1c standardization efforts have been highly successful; however, a number of issues have emerged on the “long and winding road” to better HbA1c, including the development of a higher-order HbA1c reference method by the International Federation of Clinical Chemistry (IFCC), recommendations to use HbA1c to diagnose as well as monitor diabetes, and point-of-care (POC) HbA1c testing. Here, we review the past, present and future of HbA1c standardization and describe the current status of HbA1c testing, including limitations that healthcare providers need to be aware of when interpreting HbA1c results. PMID:23318564

  10. The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Vanelli Maurizio

    2011-03-01

    Full Text Available Abstract Background The protein tyrosine phosphatase nonreceptor type 2 (PTPN22 has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c, glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab in children during the first year after diagnosis of type 1 diabetes. Methods The C1858T variant was genotyped in an international cohort of children (n = 257 patients with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association of this variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset. Results A repeated measurement model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03 for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002, which did not influence the association between PTPN22 and proinsulin (est.: 1.28, p = 0.03. Conclusions The T allele of the C1858T variant is positively associated with proinsulin levels during the first 12 months in newly diagnosed type 1 diabetes children.

  11. Recent Progress in Electrochemical HbA1c Sensors: A Review

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    Baozhen Wang

    2015-03-01

    Full Text Available This article reviews recent progress made in the development of electrochemical glycated hemoglobin (HbA1c sensors for the diagnosis and management of diabetes mellitus. Electrochemical HbA1c sensors are divided into two categories based on the detection protocol of the sensors. The first type of sensor directly detects HbA1c by binding HbA1c on the surface of an electrode through bio-affinity of antibody and boronic acids, followed by an appropriate mode of signal transduction. In the second type of sensor, HbA1c is indirectly determined by detecting a digestion product of HbA1c, fructosyl valine (FV. Thus, the former sensors rely on the selective binding of HbA1c to the surface of the electrodes followed by electrochemical signaling in amperometric, voltammetric, impedometric, or potentiometric mode. Redox active markers, such as ferrocene derivatives and ferricyanide/ferrocyanide ions, are often used for electrochemical signaling. For the latter sensors, HbA1c must be digested in advance by proteolytic enzymes to produce the FV fragment. FV is electrochemically detected through catalytic oxidation by fructosyl amine oxidase or by selective binding to imprinted polymers. The performance characteristics of HbA1c sensors are discussed in relation to their use in the diagnosis and control of diabetic mellitus.

  12. Transcriptional regulation of Hb-α and Hb-β through nuclear factor E2-related factor-2 (Nrf2) activation in human vaginal cells: A novel mechanism of cellular adaptability to oxidative stress.

    Science.gov (United States)

    Saha, Debarchana; Koli, Swanand; Reddy, Kudumula Venkata Rami

    2017-06-01

    Hemoglobin (Hb), a major protein involved in transport of oxygen (O 2 ), is expressed by erythroid lineages. Until recently, it was not known whether non-erythroid cells express Hb. The objective was to evaluate the expression and functional significance of Hb-α and Hb-β in human primary vaginal epithelial cells (hPVECs) and decipher downstream signaling. RT-PCR, qRT-PCR, flow cytometry, Western blot, immunofluorescence were used to evaluate the expression of Hb-α, Hb-β, and nuclear factor E2-related factor-2(Nrf2) after hydrogen peroxide (H 2 O 2 ) induction. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were used to determine the binding efficiency of Nrf2 on the Hb-α promoter. Stimulation of hPVECs and human vaginal epithelial cell line, VK2/E6E7 with H 2 O 2 augmented the expression of Hb-α, Hb-β, Nrf2, heme oxygenase-1 (HO-1), and reactive oxygen species (ROS). Treatment of these cells with Nrf2 inhibitor, trigonelline (Trig) inhibited Hb-α and Hb-β expressions. Hb-α and Hb-β overexpression downregulated H 2 O 2 -induced ROS. The presence of Nrf2 binding domain was demonstrated within Hb-α promoter. The results revealed for the first time that Hb-α and Hb-β were induced by oxidative stress through the activation of Nrf2. Overexpression of Hb-α and Hb-β ameliorated H 2 O 2 -induced oxidative stress, indicating one of the possible mechanism(s) to protect hPVECS from oxidative stress. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Ferulic acid modification enhances the anti-oxidation activity of natural Hb in vitro.

    Science.gov (United States)

    Qi, Donglai; Li, Qian; Chen, Chen; Wang, Xiang

    2018-03-13

    During the development of artificial red blood cell (RBC) substitutes, oxidation side reaction is one of the major factors that hinder the application of haemoglobin (Hb)-based oxygen carriers (HBOCs). In order to avoid oxidation toxicity, we designed and prepared natural Hb conjugated with ferulic acid (FA) via simple chemical modification. In addition, the thiol groups on Hb surface were increased via the reaction of Hb with 2-iminothiolane (2-IT) and then modified with FA for the study of anti-oxidant ability. It was showed that Hb modified with FA (FA-Hb) had similar oxygen-binding capacity to natural Hb. Moreover, the anti-oxidant ability of FA-Hb in vitro in different systems was superior to natural Hb and in proportion to the degree of modification of FA. The results indicate that FA-Hb might have the potential to serve as a novel oxygen carrier with the capacity to reduce oxidative side reaction.

  14. Stat5 phosphorylation is responsible for the excessive potency of HB-EGF.

    Science.gov (United States)

    Heo, Jeongyeon; Kim, Jae Geun; Kim, Sunghwan; Kang, Hara

    2017-12-23

    Heparin-binding EGF-like growth factor (HB-EGF) is a potent growth factor involved in wound healing and tumorigenesis. Despite the sequence similarity between HB-EGF and EGF, HB-EGF induces cellular proliferation and migration more potently than EGF. However, the differential regulation by HB-EGF and EGF has not been thoroughly elucidated. In this study, we compared signaling pathways activated by HB-EGF and EGF to understand the details of the molecular mechanism of the high potency induced by HB-EGF. HB-EGF specifically induced the phosphorylation of EGFR-Y1045 and activated Stat5, which is responsible for promoting cell proliferation, and migration. The competition of phosphorylated EGFR-Y1045 inhibited Stat5 activation and consequently lowered the effect of HB-EGF on cell proliferation, suggesting that the phosphorylation of EGFR-Y1045 is essential for the activation of Stat5. The phosphorylation of EGFR-Y1045 and Stat5 induced by HB-EGF was prevented by sequestering the heparin-binding domain, suggesting that the heparin-binding domain is critical for HB-EGF-mediated signaling and cellular responses. In conclusion, the heparin-binding domain of HB-EGF was responsible for EGFR-mediated Stat5 activation, resulting in a more potent cellular proliferation, and migration than that mediated by EGF. This molecular mechanism is useful for understanding ligand-specific EGFR signaling and developing biomedicines for wound healing or cancer therapy. © 2017 Wiley Periodicals, Inc.

  15. A targetable HB-EGF-CITED4 axis controls oncogenesis in lung cancer.

    Science.gov (United States)

    Hsieh, C-H; Chou, Y-T; Kuo, M-H; Tsai, H-P; Chang, J-L; Wu, C-W

    2017-05-25

    Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells. We observed that, upon HB-EGF induction, CITED4 was induced through a signal transducer and activator of transcription 3 (STAT3)-dependent pathway, regulating cell proliferation. CITED4 interacted with MYC and potentiated MYC-mediated transactivation of the CCND1 promoter, leading to cell cycle progression. Correlation analysis revealed that HB-EGF and CITED4 were significantly positively associated in primary lung tumors, and expression of HB-EGF predicted a poor survival outcome in patients. In vitro and in vivo experiments revealed that pharmacological inhibition of HB-EGF with CRM197 significantly attenuated tumor cell growth. Thus, CITED4 functions as a molecular switch in HB-EGF-induced growth control, and HB-EGF provides a novel therapeutic target for lung cancer intervention.

  16. Mechanosensitive promoter region in the human HB-GAM gene

    DEFF Research Database (Denmark)

    Liedert, Astrid; Kassem, Moustapha; Claes, Lutz

    2009-01-01

    Mechanical loading is essential for maintaining bone mass in the adult skeleton. However, the underlying process of the transfer of the physical stimulus into a biochemical response, which is termed mechanotransduction is poorly understood. Mechanotransduction results in the modulation of gene...... cells. Analysis of the human HB-GAM gene upstream regulatory region with luciferase reporter gene assays revealed that the upregulation of HB-GAM expression occurred at the transcriptional level and was mainly dependent on the HB-GAM promoter region most upstream containing three potential AP-1 binding...

  17. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus

    Science.gov (United States)

    Shim, Joon W.; Sandlund, Johanna; Hameed, Mustafa Q.; Blazer-Yost, Bonnie; Zhou, Feng C.; Klagsbrun, Michael; Madsen, Joseph R.

    2016-01-01

    Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus. PMID:27243144

  18. Predictors of HbA1c levels in patients initiating metformin.

    Science.gov (United States)

    Martono, Doti P; Hak, Eelko; Lambers Heerspink, Hiddo; Wilffert, Bob; Denig, Petra

    2016-12-01

    The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. We conducted a cohort study including type 2 diabetes patients who received their first metformin prescription between 2007 and 2013 in the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was HbA1c level at follow-up adjusted for baseline HbA1c; the secondary outcome was failing to achieve the target HbA1c level of 53 mmol/mol. Associations were analyzed by linear and logistic regression. Multiple imputation was used for missing data. Additional analyses stratified by dose and adherence level were conducted. The cohort included 6050 patients initiating metformin. Baseline HbA1c at target consistently predicted better HbA1c outcomes. Longer diabetes duration and lower total cholesterol level at baseline were predictors for higher HbA1c levels at 6 months. At 18 months, cholesterol level was not a predictor. Longer diabetes duration was also associated with not achieving the target HbA1c at follow-up. The association for longer diabetes duration was especially seen in patients starting on low dose treatment. No consistent associations were found for comorbidity and comedication. Diabetes duration was a relevant predictor of HbA1c levels after 6 and 18 months of follow-up in patients initiating metformin treatment. Given the study design, no causal inference can be made. Our study suggests that prompt treatment intensification may be needed in patients who have a longer diabetes duration at treatment initiation.

  19. Effect of once-weekly dulaglutide on glycated haemoglobin (HbA1c) and fasting blood glucose in patient subpopulations by gender, duration of diabetes and baseline HbA1c.

    Science.gov (United States)

    Gallwitz, Baptist; Dagogo-Jack, Samuel; Thieu, Vivian; Garcia-Perez, Luis-Emilio; Pavo, Imre; Yu, Maria; Robertson, Kenneth E; Zhang, Nan; Giorgino, Francesco

    2018-02-01

    To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in patients with type 2 diabetes by subgroups of gender, duration of diabetes and baseline glycated haemoglobin (HbA1c) in the dulaglutide clinical development programme (AWARD-1 to -6 and -8 clinical trials). Change in HbA1c was analysed by gender, duration of diabetes (baseline HbA1c (baseline in weight, hypoglycaemia and gastrointestinal adverse events were evaluated for individual trials. In the pooled analysis of patients treated with dulaglutide 1.5 mg at 6 months, the reductions in HbA1c from baseline were similar across gender (men: least squares [LS] mean -1.26% [95% confidence interval {CI} -1.36, -1.16]; women: LS mean -1.33% [95% CI -1.43, -1.24]) and among duration of diabetes subgroups (baseline HbA1c ≥8.5% had greater HbA1c reductions than patients with baseline HbA1c baseline HbA1c subgroups, respectively; women had a numerically greater weight loss or less weight gain than men with both dulaglutide doses. There was no clinically meaningful difference in hypoglycaemia trends by gender or duration of diabetes. Hypoglycaemia incidence and rate were generally lower in patients with baseline HbA1c ≥8.5% than in those with baseline HbA1c, with greater HbA1c and FBG reductions in patients with a higher baseline HbA1c. Dulaglutide was well tolerated, with a safety profile similar to other glucagon-like peptide-1 receptor agonists. © 2017 John Wiley & Sons Ltd.

  20. Prevalence and Risk Factors for Intestinal Protozoan Infections with Cryptosporidium, Giardia, Blastocystis and Dientamoeba among Schoolchildren in Tripoli, Lebanon.

    Science.gov (United States)

    Osman, Marwan; El Safadi, Dima; Cian, Amandine; Benamrouz, Sadia; Nourrisson, Céline; Poirier, Philippe; Pereira, Bruno; Razakandrainibe, Romy; Pinon, Anthony; Lambert, Céline; Wawrzyniak, Ivan; Dabboussi, Fouad; Delbac, Frederic; Favennec, Loïc; Hamze, Monzer; Viscogliosi, Eric; Certad, Gabriela

    2016-03-01

    Intestinal protozoan infections are confirmed as major causes of diarrhea, particularly in children, and represent a significant, but often neglected, threat to public health. No recent data were available in Lebanon concerning the molecular epidemiology of protozoan infections in children, a vulnerable population at high risk of infection. In order to improve our understanding of the epidemiology of intestinal pathogenic protozoa, a cross-sectional study was conducted in a general pediatric population including both symptomatic and asymptomatic subjects. After obtaining informed consent from the parents or legal guardians, stool samples were collected in January 2013 from 249 children in 2 schools in Tripoli, Lebanon. Information obtained from a standard questionnaire included demographic characteristics, current symptoms, socioeconomic status, source of drinking water, and personal hygiene habits. After fecal examination by both microscopy and molecular tools, the overall prevalence of parasitic infections was recorded as 85%. Blastocystis spp. presented the highest infection rate (63%), followed by Dientamoeba fragilis (60.6%), Giardia duodenalis (28.5%) and Cryptosporidium spp. (10.4%). PCR was also performed to identify species and genotypes of Cryptosporidium, subtypes of Blastocystis, and assemblages of Giardia. Statistical analysis using a logistic regression model showed that contact with family members presenting gastrointestinal disorders was the primary risk factor for transmission of these protozoa. This is the first study performed in Lebanon reporting the prevalence and the clinical and molecular epidemiological data associated with intestinal protozoan infections among schoolchildren in Tripoli. A high prevalence of protozoan parasites was found, with Blastocystis spp. being the most predominant protozoans. Although only 50% of children reported digestive symptoms, asymptomatic infection was observed, and these children may act as unidentified

  1. Modeling Single-Phase PV HB-ZVR Inverter Connected to Grid

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Zhu, Jieqiong

    2011-01-01

    PLECS is used to model the PV H-bridge zero voltage rectifier (HB-ZVR) inverter connected to grid and good results are obtained. First, several common topologies of PV inverters are introduced. Then the unipolar PWM control strategy is described for PV HB-ZVR inverter. Third, PLECS is briefly...... introduced. Fourth, the modeling of PV HB-ZVR inverter is presented with PLECS. Finally, a series of simulations are carried out. The simulation results tell us PLECS is very powerful tool to real power circuits and it is very easy to simulate LCL filter. They have also verified that the unipolar PWM control...... strategy is feasible to control the PV HB-ZVR inverter....

  2. HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma.

    Science.gov (United States)

    Xie, Shumin; Wang, Xiaoli; Ren, Hongmiao; Liu, Xiaoyu; Ren, Jihao; Liu, Wei

    2017-08-01

    The heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays an essential role in the development and invasiveness of cholesteatoma. This study may help to realize the molecular mechanisms underlying the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug intervention of cholesteatoma. To detect HB-EGF expression in human surgical specimens of acquired middle ear cholesteatoma and analyze its functional role as a regulator of epithelial keratinocytes hyperproliferation. A total of 34 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. The mRNA and protein expression of HB-EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was investigated by real-time quantitative reverse-transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining, and western blot. The correlation between bone resorption degree and HB-EGF expression was also analyzed. On average, compared with normal postauricular skin, expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32-fold by western blot. Positive HB-EGF immunostaining observed in the basal and suprabasal layers of cholesteatoma epithelium was significantly stronger than in normal postauricular skin. Meanwhile, an obviously positive correlation between HB-EGF protein expression and bone resorption degree was discovered.

  3. Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?

    Science.gov (United States)

    Jones, Angus G.; Lonergan, Mike; Henley, William E.; Pearson, Ewan R.; Hattersley, Andrew T.; Shields, Beverley M.

    2016-01-01

    Aims Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c. Methods We assessed the relationship between baseline HbA1c and glycaemic response in 257 participants treated with GLP-1R agonists and assessed whether it reflected measurement error and regression to the mean using duplicate ‘pre-baseline’ HbA1c measurements not included in the response variable. In this cohort and an additional 2659 participants treated with sulfonylureas we assessed the relationship between covariates associated with baseline HbA1c and treatment response with and without baseline adjustment, and with a bias correction using pre-baseline HbA1c to adjust for the effects of error in baseline HbA1c. Results Baseline HbA1c was a major predictor of response (R2 = 0.19,β = -0.44,pHbA1c were associated with response, however these associations were weak or absent after adjustment for baseline HbA1c. Bias correction did not substantially alter associations. Conclusions Adjustment for the baseline HbA1c measurement is a simple and effective way to reduce bias in studies of predictors of response to glucose lowering therapy. PMID:27050911

  4. Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III).

    Science.gov (United States)

    Grimsby, Jonna L; Porneala, Bianca C; Vassy, Jason L; Yang, Quanhe; Florez, José C; Dupuis, Josée; Liu, Tiebin; Yesupriya, Ajay; Chang, Man-Huei; Ned, Renee M; Dowling, Nicole F; Khoury, Muin J; Meigs, James B

    2012-04-27

    Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality. We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.

  5. ERGEBNISSE DER UNTERSUCHUNG VON HB-AL BEI 94 PATIENTEN MIT NIERENINSUFFIZIENZ

    Directory of Open Access Journals (Sweden)

    A

    1983-05-01

    Full Text Available We have qua nt i t a l ed Hb- Al ~n 125 patients . 74 pa t ient s had chronic Renal Failure . 20 of them had Diabetes wi th Renal Fai lure , 21 Diabetics and 10 patients were evaluat ed as control. We have divided the patients with Renal Failure i n 3 groups according to t heir serum c reatin i ne . Hb-Al in a ll groups "as not correlated wi th serum creat i ne. Hb-Al in Diabetic gr oup was highe r than Diabetic patients with Renal Failure . This group a lso had mor e HbA1 than t he gr oup with Renal ~ailure a nd no Diabetes ,and control group . , Hb-Al was correlated with Blood suger i n all pa t i e nt s s o we can u se"nal Failure the me a sureme nt of Hb-Al i n pati ents with Renunder Dial ys i s with gl ucose solution fo r evalua t i o n of sugar meta boli s m.  

  6. GENETIC FACTORS INFLUENCING HEMOGLOBIN F LEVEL IN β-THALASSEMIA/HB E DISEASE.

    Science.gov (United States)

    Ruangrai, Waraporn; Jindadamrongwech, Sumalee

    2016-01-01

    Genetic factors influencing Hb F content in adult red blood cells include β-thalassemia genotypes, co-inheritance of α-thalassemia traits and single nucleotide polymorphisms (SNPs). Genotyping of α- and β-thalassemia and five SNPs in β-globin gene cluster previously identified in genome-wide association studies as being markers of elevated Hb F in β-thalassemia were performed in 81 subjects diagnosed with β-thalassemia/Hb E. Hb F levels are higher (0.9-7.1 g/dl) in subjects (n = 57) with the severe compared to mild β-thalassemia (0.8-2.5 g/ dl) (n = 4) genotypes, and are similarly low (0.7-3.5 g/dl) in those (n = 15) with α-thalassemia co-inheritance. Hb F levels in non-thalassemia controls (n = 150) range from 0 to 0.15 g/dl. The presence of homozygous minor alleles of the 5 SNPs are significant indicators of β-thalassemia/Hb E individuals with high Hb F (> 4 g/dl), independent of their thalassemia genotypes. Given that re-activation of γ-globin genes leads to amelioration of β-thalassemia severity, understanding how genetic factors up-regulate Hb F production may lead to possible therapeutic interventions, genetically or pharmacologically, of this debilitating disease in the not too distant future.

  7. Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes

    DEFF Research Database (Denmark)

    Skriver, Mette Vinther; Sandbæk, Annelli; Kristensen, Jette Kolding

    2015-01-01

    OBJECTIVE: We assessed the relationship of mortality with glycated hemoglobin (HbA1c) variability and with absolute change in HbA1c. DESIGN: A population-based prospective observational study with a median follow-up time of 6 years. METHODS: Based on a validated algorithm, 11 205 Danish individua...

  8. Dermatophytes and other fungi associated with skin mycoses in Tripoli, Libya.

    Science.gov (United States)

    Ellabib, M S; Khalifa, Z; Kavanagh, K

    2002-04-01

    This study sought to determine the prevalence of skin infections and their causative agents in the Libyan population. Samples were collected from 2224 patients attending the Dermatology Clinics of the Tripoli Medical Centre (TMC) between August 1997 and December 1999 and were submitted to a mycology laboratory for analysis. Diagnosis was confirmed by microscopic examination in 1180 cases (53.1%) and the causative agent was isolated and cultured in 1160 cases (52.2%). Dermatophytes, Malassezia furfur and Candida albicans were the most common etiological agents isolated. Tinea corporis accounted for 45.9% of cases (85% of cases occurred in children below 15 years of age). The frequency of the other clinical types in descending order was pityriasis versicolor 27.8% (322 cases), candidiosis 13.4% (156 cases), tinea pedis 8.1% (94 cases), tinea manuum 2.6% (30 cases) and tinea barbae 2.2% (26 cases). Trichophyton violaceum was the most common etiological agent, responsible for 44% (300 cases) of dermatophyte infections. Malassezia furfur was ranked the second most frequent causative agent being found in 27.8% of cases, followed by Trichophyton rubrum 13.8% (160 cases) and Candida albicans 10% (116 cases). Other species isolated included Microsporum canis 8.1% (94 cases), Epidermophyton floccosum 6.6% (76 cases) and Trichophyton mentagrophytes 3.1% (36 cases).

  9. Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular Neovascularization.

    Science.gov (United States)

    Inoue, Yuki; Shimazawa, Masamitsu; Nakamura, Shinsuke; Takata, Shinsuke; Hashimoto, Yuhei; Izawa, Hiroshi; Masuda, Tomomi; Tsuruma, Kazuhiro; Sakaue, Tomohisa; Nakayama, Hironao; Higashiyama, Shigeki; Hara, Hideaki

    2018-01-01

    The incidence of blindness is increasing because of the increase in abnormal ocular neovascularization. Anti-VEGF (vascular endothelial growth factor) therapies have led to good results, although they are not a cure for the blindness. The purpose of this study was to determine what role HB-EGF (heparin-binding epidermal growth factor-like growth factor) plays in ocular angiogenesis. We examined the role played by HB-EGF in ocular neovascularization in 2 animal models of neovascularization: laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy. We also studied human retinal microvascular endothelial cells in culture. Our results showed that the neovascularization was decreased in both the CNV and oxygen-induced retinopathy models in HB-EGF conditional knockout mice compared with that in wild-type mice. Moreover, the expressions of HB-EGF and VEGF were increased after laser-induced CNV and oxygen-induced retinopathy, and their expression sites were located around the neovascular areas. Exposure of human retinal microvascular endothelial cells to HB-EGF and VEGF increased their proliferation and migration, and CRM-197 (cross-reactive material-197), an HB-EGF inhibitor, decreased the HB-EGF-induced and VEGF-induced cell proliferation and migration. VEGF increased the expression of HB-EGF mRNA. VEGF-dependent activation of EGFR (epidermal growth factor receptor)/ERK1/2 (extracellular signal-regulated kinase 1/2) signaling and cell proliferation of endothelial cells required stimulation of the ADAM17 (a disintegrin and metalloprotease) and ADAM12. CRM-197 decreased the grades of the fluorescein angiograms and size of the CNV areas in marmoset monkeys. These findings suggest that HB-EGF plays an important role in the development of CNV. Therefore, further investigations of HB-EGF are needed as a potential therapeutic target in the treatment of exudative age-related macular degeneration. © 2017 American Heart Association, Inc.

  10. HB KURDISTAN [ALPHA-47(CE5)ASP-]TYR], A NEW ALPHA-CHAIN VARIANT IN COMBINATION WITH BETA-THALASSEMIA

    NARCIS (Netherlands)

    GIORDANO, PC; HARTEVELD, CL; STRENG, H; Oosterwijk, Jan; HEISTER, JGAM; AMONS, R; BERNINI, LF

    1994-01-01

    We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish; family. The clinical and hematological investigation of eight individuals have shown that the a variant is associated with a beta degrees-thalassemia mutation (nonsense codon 39). The tryptic peptide map

  11. The immunogenicity and safety of the new, Indonesian DTwP-HB-Hib vaccine compared to the DTwP/HB vaccine given with the Hib vaccine

    Directory of Open Access Journals (Sweden)

    Novilia Sjafri Bachtiar

    2017-06-01

    Full Text Available Background Haemophilus influenzae type b (Hib causes infection with predominant manifestations of pneumonia, meningitis, and other invasive diseases, occurring primarily in children aged under 2 years, particularly in infants.  The World Health Organization (WHO and Indonesian Technical Advisory Group for Immunization recommend to include the Hib vaccine into the national immunization program. The newly developed DTwP-HB-Hib combination vaccine is anticipated to be the preferred choice for Hib vaccine introduction; it is efficient, simple, and has higher coverage. Objective To evaluate the immunogenicity and safety of a new, combined Bio Farma DTwP-HB-Hib vaccine, compared to the registered Hib monovalent vaccine given simultaneously with the local DTwP-HB vaccine, when used as the primary vaccination of Indonesian infants. Methods A prospective, randomized, open-label, phase II study was conducted on the DTwP-HB-Hib vaccine compared to the Hib (registered vaccine given simultaneously with the DTwP-HB vaccine, in Bandung from July 2011 to January 2012. Infants were serially vaccinated at 6-11, 10-15, and 14-19 weeks. Serological assessments were done prior to the first vaccine dose and 28 days after the third dose. Safety was assessed from the time of first injection until 1 month after the last injection. Results Of 220 healthy infants enrolled, 211 completed the study, with 105 receiving the combined vaccine and 106 the two separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were considered to be related to the vaccines. In the DTwP-HB-Hib primary-vaccination group, at least 98% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines while 96% in the control group. Conclusion The DTwP-HB-Hib combined vaccine is immunogenic and safe, as well as

  12. A Monte-Carlo Benchmark of TRIPOLI-4® and MCNP on ITER neutronics

    Science.gov (United States)

    Blanchet, David; Pénéliau, Yannick; Eschbach, Romain; Fontaine, Bruno; Cantone, Bruno; Ferlet, Marc; Gauthier, Eric; Guillon, Christophe; Letellier, Laurent; Proust, Maxime; Mota, Fernando; Palermo, Iole; Rios, Luis; Guern, Frédéric Le; Kocan, Martin; Reichle, Roger

    2017-09-01

    Radiation protection and shielding studies are often based on the extensive use of 3D Monte-Carlo neutron and photon transport simulations. ITER organization hence recommends the use of MCNP-5 code (version 1.60), in association with the FENDL-2.1 neutron cross section data library, specifically dedicated to fusion applications. The MCNP reference model of the ITER tokamak, the `C-lite', is being continuously developed and improved. This article proposes to develop an alternative model, equivalent to the 'C-lite', but for the Monte-Carlo code TRIPOLI-4®. A benchmark study is defined to test this new model. Since one of the most critical areas for ITER neutronics analysis concerns the assessment of radiation levels and Shutdown Dose Rates (SDDR) behind the Equatorial Port Plugs (EPP), the benchmark is conducted to compare the neutron flux through the EPP. This problem is quite challenging with regard to the complex geometry and considering the important neutron flux attenuation ranging from 1014 down to 108 n•cm-2•s-1. Such code-to-code comparison provides independent validation of the Monte-Carlo simulations, improving the confidence in neutronic results.

  13. Heterozygote Hemoglobin G-Coushatta as the Cause of a Falsely Decreased Hemoglobin A1C in an Ion-Exchange HPLC Method

    Directory of Open Access Journals (Sweden)

    Kurtoğlu Ayşegül Uğur

    2017-09-01

    Full Text Available Glycated hemoglobin (HbA1c is used for the assessment of glycemic control in patients with diabetes. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA1c measurement. Here, we report two cases of Hemoglobin G-Coushatta (HBB:c.68A>C variant that interferes in the measurement of HbA1c by a cation-exchange HPLC (CE-HPLC method. HbA1c was measured by a CE-HPLC method in a Tosoh HLC-723 G7 instrument. The HbA1c levels were 2.9% and 4%. These results alerted us to a possible presence of hemoglobinopathy. In the hemoglobin variant analysis, HbA2 levels were detected as 78.3% and 40.7% by HPLC using the short program for the Biorad Variant II. HbA1c levels were measured by an immunoturbidimetric assay in a Siemens Dimension instrument. HbA1c levels were reported as 5.5% and 5.3%. DNA mutation analysis was performed to detect the abnormal hemoglobin variant. Presence of Hemoglobin G-Coushatta variant was detected in the patients. The Hb G-Coushatta variants have an impact on the determination of glycated hemoglobin levels using CEHPLC resulting in a false low value. Therefore, it is necessary to use another measurement method.

  14. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach

    OpenAIRE

    Hoskins, J.T.; Zhou, Z.; Harding, P.A.

    2008-01-01

    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser108/121, HB-EGF-Cys/Ser116/132, and HB-EGF-Cys/Ser134/143) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with Mr of 6.5, 21 and 24kDa were observed from lys...

  15. Posterior transverse interarch discrepancy on HbE β thalassemia patients

    Directory of Open Access Journals (Sweden)

    Yuniar Zen

    2011-03-01

    Full Text Available Background: One of the symptoms that often arises on thalassemia patients is disharmony dentofacial, class II skeletal malocclusion, as a result of the malrelation of maxilla and mandible. This malrelation can be affected by either maxillary bone position, dentoalveolar maxillary position, mandibular bone position, dentoalveolar mandibular position, or combinations of those components. Purpose: The study was aimed to examine whether there is posterior transverse interarch discrepancy on the HbE β thalassemia patients or not. Methods: This study is an observational research with cross-sectional design. The sample consisted of 33 HbE β thalassemia patients and 33 non-thalassemia patients as a control group aged 12–14 years. Lateral cephalogram was carried out and dental casts of maxillary and mandibular dental arches were also taken in all of those patients. Results: There was no difference between the maxillary intermolar width of the HbE β thalassemia patients and that of the normal ones, but the mandibular intermolar width of the HbE β thalassemia patients was significantly smaller than that of the normal ones. Beside that, posterior transverse interarch discrepancy of of the HbE β thalassemia patients was significantly greater than that of the normal ones, which showed great difference between maxillary and mandibular intermolar widths. Conclusion: Posterior transverse interarch discrepancy of the HbE β thalassemia patients was different from that of the normal ones. The dentofacial abnormalities on the HbE β thalassemia patients aged 12–14 years primarily was due to disporposional dentofacial growth in the vertical, sagittal, and transversal directions, especially in the posterior region.Latar belakang: Salah satu akibat yang sering timbul pada penderita talasemia adalah disharmoni dentofasial berupa maloklusi skeletal kelas II yang merupakan kelainan hubungan maksila dan mandibula. Malrelasi ini dapat dipengaruhi oleh posisi

  16. Nota sobre antígeno relacionado à hepatite (HB Ag e anticorpo (HB Ab em população do território Federal do Amapá

    Directory of Open Access Journals (Sweden)

    Hermann G. Schatzmayr

    1974-04-01

    Full Text Available 53 amostras de soro, provenientes de Ferreira Gomes, no Amapá, foram testados para antígeno HB Ag e anticorpo HB Ab, com uma positividade de 3,7% para HB Ag, sub-tipo D. Os autores acentuam a necessidade de inquéritos em populações brasileiras a fim de estabelecer os sub-tipos associados à hepatite.3,7% of 53 serum samples from healthy inhabitants of Ferreira Gomes, Amapá, were positive for HB Ag, subtype D. The authors síress the needs of surveys to deteet the prevalent types of antigens associated with viral hepatitis in different areas of Brazil.

  17. HbA1c, fasting plasma glucose and the prediction of diabetes

    DEFF Research Database (Denmark)

    Soulimane, Soraya; Simon, Dominique; Shaw, Jonathan

    2012-01-01

    With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases.......With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases....

  18. Trichophyton violaceum is the dominant cause of tinea capitis in children in Tripoli, Libya: results of a two year survey.

    Science.gov (United States)

    Ellabib, Mohamed S; Agaj, Muna; Khalifa, Zinab; Kavanagh, Kevin

    2002-01-01

    The causative agents of tinea capitis in Libyan nationals attending the out patient Dermatology Clinic of the Tripoli Medical Centre over the period December 1997 to December 1999 were investigated. Samples (hair and scalp scrapings) were taken from 940 patients who presented with suspected tinea capitis. The etiological agents were identified in 584 cases. Trichophyton violaceum was found to be the most prevalent organism isolated being responsible for 64.4% (376/584) of culture positive cases, followed by Microsporum canis at 24.7% (144/584) and T. mentagrophytes at 5.5% (32/584). The majority of infections (380/584) occurred in females and in children with ages less than 12 years (554/584).

  19. Cell model for the study of receptor and regulatory functions of human proHB-EGF

    Directory of Open Access Journals (Sweden)

    N. V. Korotkevych

    2014-08-01

    Full Text Available Developing of new models and approaches, particularly with fluorescent techniques, for investigation of intracellular transport of proHB-EGF and its ligand-receptor complexes is strongly required. In order to create a model for studying proHB-EGF functions the genetic construction pEGFP-N1-proHB-EGF, encoding proHB-EGF-EGFP which is fluorescent-labeled form of proHB-EGF with enhanced green fluorescent protein EGFP in the cytoplasmic terminus of the molecule, was obtained. Eukaryotic cells expressing fusion protein proHB-EGF-EGFP on the cell surface were obtained by transfection with pEGFP-N1-proHB-EGF. Expressed in the Vero cells proHB-EGF-EGFP could bind fluorescent derivative of nontoxic receptor-binding subunit B of diphtheria toxin mCherry-SubB. After stimulation of transfected cells with TPA (12-O-Tetradecanoylphorbol-13-acetate, proHB-EGF-EGFP formed a fluorescentl-labeled C-terminal fragment of the molecule – CTF-EGFP. Thus, the obtained genetic construction pEGFP-N1-proHB-EGF could be helpful in visualization of molecules proHB-EGF and CTF in cells, may open new possibilities for the studying of their functions, such as receptor function of proHB-EGF for diphtheria toxin, intracellular translocation of CTF and provide possibilities for natural proHB-EGF ligands search.

  20. Impact of Mean Cell Hemoglobin on Hb A1c-Defined Glycemia Status.

    Science.gov (United States)

    Rodriguez-Segade, Santiago; Garcia, Javier Rodriguez; García-López, José M; Gude, Francisco; Casanueva, Felipe F; Rs-Alonso, Santiago; Camiña, Félix

    2016-12-01

    Several hematological alterations are associated with altered hemoglobin A 1c (Hb A 1c ). However, there have been no reports of their influence on the rates of exceeding standard Hb A 1c thresholds by patients for whom Hb A 1c determination is requested in clinical practice. The initial data set included the first profiles (complete blood counts, Hb A 1c , fasting glucose, and renal and hepatic parameters) of all adult patients for whom such a profile was requested between 2008 and 2013 inclusive. After appropriate exclusions, 21844 patients remained in the study. Linear and logistic regression models were adjusted for demographic, hematological, and biochemical variables excluded from the predictors. Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated negatively with Hb A 1c . Fasting glucose, MCH, and age emerged as predictors of Hb A 1c in a stepwise regression that discarded sex, hemoglobin, MCV, mean corpuscular hemoglobin concentration (MCHC), serum creatinine, and liver disease. Mean Hb A 1c in MCH interdecile intervals fell from 6.8% (51 mmol/mol) in the lowest (≤27.5 pg) to 6.0% (43 mmol/mol) in the highest (>32.5 pg), with similar results for MCV. After adjustment for fasting glucose and other correlates of Hb A 1c , a 1 pg increase in MCH reduced the odds of Hb A 1c -defined dysglycemia, diabetes and poor glycemia control by 10%-14%. For at least 25% of patients, low or high MCH or MCV levels are associated with increased risk of an erroneous Hb A 1c -based identification of glycemia status. Although causality has not been demonstrated, these parameters should be taken into account in interpreting Hb A 1c levels in clinical practice. © 2016 American Association for Clinical Chemistry.

  1. HbA1c for diagnosis and prognosis of gestational diabetes mellitus.

    Science.gov (United States)

    Kwon, Soon Sung; Kwon, Ja-Young; Park, Yong-Won; Kim, Young-Han; Lim, Jong-Baeck

    2015-10-01

    HbA1c is a widely used marker in diagnosing type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational diabetes mellitus (GDM) is not established. Here, we evaluated the clinical usefulness of HbA1c in diagnosing GDM and predicting the risk of future type 2 DM development among GDM patients. This retrospective, cross-sectional study included 321 subjects who underwent 100-g oral glucose tolerance tests (OGTT) during pregnancy. HbA1c and other variables were analyzed to evaluate their diagnostic performance for GDM. To evaluate the clinical usefulness of HbA1c in predicting future type 2 DM development, we classified GDM subjects who had more than 3 months of follow-up data into two subgroups: those who developed postpartum type 2 DM (PDM) and those who did not. HbA1c was significantly higher in the GDM group than in the normal control group. With the 100-g OGTT as reference, HbA1c showed 91.3% sensitivity and 62% specificity at a cut-off value of 5.05% (32 mmol/mol) for GDM diagnosis. At a cut-off value of 5.25% (34 mmol/mol), sensitivity was 73.6% and specificity was 77.2%. HbA1c levels during pregnancy were higher in those with PDM than in those without PDM (5.91 [41 mmol/mol] vs. 5.44% [36 mmol/mol], p<0.001). The prognostic value of HbA1c for PDM was evaluated by ROC curve analysis, with sensitivity of 78.6% and specificity of 72.5% at a cut-off value of 5.55% (37 mmol/mol). HbA1c showed high sensitivity with relatively low specificity for diagnosis of GDM in pregnant women and was a potential predictor of PDM. HbA1c may be able to be used as a simple and less invasive alternative screening test for OGTT in GDM patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Analysis of HbA1c on an automated multicapillary zone electrophoresis system.

    Science.gov (United States)

    Rollborn, Niclas; Åkerfeldt, Torbjörn; Nordin, Gunnar; Xu, Xiao Yan; Mandic-Havelka, Aleksandra; Hansson, Lars-Olof; Larsson, Anders

    2017-02-01

    Hemoglobin A1c (HbA1c) is a frequently requested laboratory test and there is thus a need for high throughput instruments for this assay. We evaluated a new automated multicapillary zone electrophoresis instrument (Capillarys 3 Tera, Sebia, Lisses, France) for analysis of HbA1c in venous samples. Routine requested HbA1c samples were analyzed immunologically on a Roche c6000 instrument (n = 142) and then with the Capillarys 3 Tera instrument. The Capillarys 3 Tera instrument performed approximately 70 HbA1c tests/hour. There was a strong linear correlation between Capillarys 3 Tera and Roche Tina-Quant HbA1c Gen 3 assay (y = 1.003x - 0.3246 R 2  = .996). The total CV for the 12 capillaries varied between 0.8 and 2.2% and there was a good agreement between duplicate samples (R 2  = .997). In conclusion, the Capillarys 3 Tera instrument has a high assay capacity for HbA1c. It has a good precision and agreement with the Roche Tina-Quant HbA1c method and is well suited for high volume testing of HbA1c.

  3. Dynamics of α-Hb chain binding to its chaperone AHSP depends on heme coordination and redox state.

    Science.gov (United States)

    Kiger, Laurent; Vasseur, Corinne; Domingues-Hamdi, Elisa; Truan, Gilles; Marden, Michael C; Baudin-Creuza, Véronique

    2014-01-01

    AHSP is an erythroid molecular chaperone of the α-hemoglobin chains (α-Hb). Upon AHSP binding, native ferric α-Hb undergoes an unprecedented structural rearrangement at the heme site giving rise to a 6th coordination bond with His(E7). Recombinant AHSP, WT α-Hb:AHSP and α-Hb(HE7Q):AHSP complexes were expressed in Escherichia coli. Thermal denaturation curves were measured by circular dichroism for the isolated α-Hb and bound to AHSP. Kinetics of ligand binding and redox reactions of α-Hb bound to AHSP as well as α-Hb release from the α-Hb:AHSP complex were measured by time-resolved absorption spectroscopy. AHSP binding to α-Hb is kinetically controlled to prevail over direct binding with β-chains and is also thermodynamically controlled by the α-Hb redox state and not the liganded state of the ferrous α-Hb. The dramatic instability of isolated ferric α-Hb is greatly decreased upon AHSP binding. Removing the bis-histidyl hexacoordination in α-HbH58(E7)Q:AHSP complex reduces the stabilizing effect of AHSP binding. Once the ferric α-Hb is bound to AHSP, the globin can be more easily reduced by several chemical and enzymatic systems compared to α-Hb within the Hb-tetramer. α-Hb reduction could trigger its release from AHSP toward its final Hb β-chain partner producing functional ferrous Hb-tetramers. This work indicates a preferred kinetic pathway for Hb-synthesis. The cellular redox balance in Hb-synthesis should be considered as important as the relative proportional synthesis of both Hb-subunits and their heme cofactor. The in vivo role of AHSP is discussed in the context of the molecular disorders observed in thalassemia. © 2013 Elsevier B.V. All rights reserved.

  4. Investigation on the possible interconnection of the Kanata sinkhole, on the high plateau of Tripolis, and the springs of Argos areas (Peloponnese, Greece)

    International Nuclear Information System (INIS)

    Leontiadis, Ioannis L.; Dimitroulas, Christos; Zouridakis, N.; Dounas, Athanasios; Morfis, A.; Paraskevopoulou, P.

    1984-07-01

    51 Cr-EDTA has been used as tracer for the investigation of the possible interconnection of the Kanata sinkhole, on the high plateau of Tripolis, and the springs of the Argos areas Achladokampos and Kinouria. By this experiment the interconnection of the sinkhole and the submarine spring of Kiveri, as well as the springs of Xovrios river (Achladokampos) is proved. Furthermore, the percentage of connection between the sinkhole and the springs, the mean transit time of the water from the sinkhole to the springs, the volume of the underground reservoir feeding the springs, etc. have been calculated. (author)

  5. Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)

    Science.gov (United States)

    2012-01-01

    Background Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality. Methods We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. Results RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p HbA1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04) and MA (β = 0.021, p = 0.005) but not NHB (β = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71). Conclusion At many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality. PMID:22540250

  6. The isolation of the γ subunit of fetal hemoglobin (HbF) and its use in a radioimmunoassay for HbF

    International Nuclear Information System (INIS)

    James, R.F.L.; Shuster, J.; Freedman, S.O.; Gold, P.

    1980-01-01

    A method is described for the purification, from fetal hemoglobin (HbF), of the fetal specific globin chain (γ chain) in its native state. In the absence of α chain (the globin chain common to all adult human hemoglobins) γ chain, when used as an immunogen, is able to express its unique antigenicity. Here, a specific, high titer antiserum raised against γ chain has been used to establish a sensitive radioimmunoassay for HbF. This approach may be applicable to the measurement of other normal and abnormal hemoglobins. (Auth.)

  7. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Vani Chandrashekar

    2016-01-01

    Full Text Available Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman’s rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders.

  8. HB+ prepares for insertion into the CMS solenoid

    CERN Multimedia

    Dave Barney, CERN

    2006-01-01

    With calibration of the first half of the barrel Hadron Calorimeter (HB+) complete (using a radioactive source), preparations begin for its insertion into the solenoid for the Magnet Test and Cosmic Challenge (MTCC). It was moved out of its alcove at the beginning of March - a non-trivial (but completely successful) operation due to the proximity of one of the barrel yoke rings (YB+1). The other half of the barrel Hadron Calorimeter (HB-) and one of the endcaps (HE+) should also be calibrated before the MTCC.

  9. HB+ inserted into the CMS Solenoid

    CERN Multimedia

    Tejinder S. Virdee, CERN

    2006-01-01

    The first half of the barrel hadron calorimeter (HB+) has been inserted into the superconducting solenoid of CMS, in preparation for the magnet test and cosmic challenge. The operation went smoothly, lasting a couple of days.

  10. Serum levels of antioxidant vitamins in foetal haemoglobin (HbF ...

    African Journals Online (AJOL)

    Background: sickle cell anaemia (SCA) is one of the commonest health problems of Nigerian children. Method: The serum levels of antioxidant vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) were determined in foetal haemogbobin persistent sickle cell anaemic (Hb SS + F), sickle cell anaemic (Hb SS) and ...

  11. Prevalence and predictors of the sub-target Hb level in children on dialysis

    DEFF Research Database (Denmark)

    van Stralen, Karlijn J; Krischock, Leah; Schaefer, Franz

    2012-01-01

    Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level.......Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level....

  12. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.

    Directory of Open Access Journals (Sweden)

    Eleanor Wheeler

    2017-09-01

    Full Text Available Glycated hemoglobin (HbA1c is used to diagnose type 2 diabetes (T2D and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits or glycemic (associated with other glucose-related traits. In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E or glycemic variants (GS-G were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241. Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29; whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60. In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in

  13. A Family with γ-Thalassemia and High Hb A2 Levels.

    Science.gov (United States)

    Parmeggiani, Giulia; Gualandi, Francesca; Selvatici, Rita; Rimessi, Paola; Bigoni, Stefania; Taddei Masieri, Marina; Dolcini, Bernadetta; Venturoli, Anna; Cappabianca, Maria P; Ferlini, Alessandra; Ravani, Anna

    2016-06-01

    We describe a family carrying a γ-globin gene deletion associated with an increase of Hb A2 level beyond the normal range. The family included the proband, his sister and their father, all with increased Hb A2 and normal Hb F levels. The proband and his sister showed borderline values of mean corpuscular volume (MCV) and reduced values of mean corpuscular hemoglobin (Hb) (MCH). The proband was referred to our Medical Genetics Service for preconception counseling together with his partner, a typical β-thalassemia (β-thal) carrier. The results were negative for the most frequent α-thalassemia (α-thal) mutations, and had no significant sequence variations of the coding sequences and promoter of the β- and δ-globin genes. Quantitative analysis by multiplex ligation-dependent probe amplification (MPLA) of the β-globin gene cluster detected a heterozygous deletion, ranging between 2.1 and 4.7 kb, in the proband, his sister and the father. The deletion involved the (G)γ gene and (G)γ-(A)γ intergenic region, whereas the 3' region of the (A)γ gene was preserved. A subsequent gap-polymerase chain reaction (gap-PCR) showed that a hybrid (GA)γ fusion gene was present. The deletion segregated with the elevation of Hb A2. The MLPA analysis of the β-globin gene cluster in 150 control alleles excluded a common polymorphism. Despite stronger evidence being needed, the described family suggests a possible role of this γ-globin gene deletion in contributing to Hb A2 elevation, possibly by altering the transcription regulation of the cluster. We propose γ-globin gene dosage analysis to be performed in patients with unexplained elevated Hb A2 levels.

  14. HbA1c measurements from dried blood spots : validation and patient satisfaction

    NARCIS (Netherlands)

    Fokkema, Margaretha; Bakker, Andries J; de Boer, Fokje; Kooistra, Jeltsje; de Vries, Sifra; Wolthuis, Albert

    2009-01-01

    Background: This study evaluates HbA1c measurements from dried blood spots collected on filter paper and compares HbA1c from filter paper (capillary blood) with HbA1c measured in venous blood. Methods: Patient satisfaction was evaluated using a questionnaire. The performance with the filter paper

  15. Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli.

    Science.gov (United States)

    Taher, Yousef A; Samud, Awatef M; Ratimy, Aya H; Seabe, Areeje M

    2012-01-01

    The effect of sleep difficulties has achieved a great deal of attention recently, with university students considered as a homogenized population, particularly affected by sleep habits. The objective of this study was to investigate whether Libyan college students experience sleep disturbance during their academic programmes. A cross-sectional survey was conducted in the college of Pharmacy, Tripoli University, during February 2010. A total of 201 students, including 179 females (89.05%) and 22 males (10.95%), were recruited from different academic levels. Data were collected using a structured questionnaire and included a number of life-style variables. Epworth Sleepiness Scale (ESS) was used for the assessment of daytime sleepiness. This study showed that the total sleep time (TST) on a weeknight was 6.40 h and 67 students reported napping during daytime. The TST plus naps totalled 7.39 h. Out of eight possible dozing situations, we found that the mean score for ESS was 8.78. In addition, 79 students showed an ESS score of >10. Furthermore, our results showed that the majority of students (>92%) reported poor sleep satisfaction with quality and duration of sleep hours. Thinking about difficulty of study but not increasing education programs or tea/coffee consumption is associated with sleep difficulties reported. Moreover, 77.6% of students reported an irregular sleep-wake schedule. These findings indicate that students experienced excessive daytime sleepiness. The TST of pharmaceutical students in Libya, as in other developing countries, is less than those reported by Western students. Students experienced various environmental demands during their college years and, their quality of sleep was negatively affected.

  16. Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli

    Directory of Open Access Journals (Sweden)

    Yousef A. Taher

    2012-10-01

    Full Text Available Background: The effect of sleep difficulties has achieved a great deal of attention recently, with university students considered as a homogenized population, particularly affected by sleep habits. Aim: The objective of this study was to investigate whether Libyan college students experience sleep disturbance during their academic programmes. Methods: A cross-sectional survey was conducted in the college of Pharmacy, Tripoli University, during February 2010. A total of 201 students, including 179 females (89.05% and 22 males (10.95%, were recruited from different academic levels. Data were collected using a structured questionnaire and included a number of life-style variables. Epworth Sleepiness Scale (ESS was used for the assessment of daytime sleepiness. Results: This study showed that the total sleep time (TST on a weeknight was 6.40 h and 67 students reported napping during daytime. The TST plus naps totalled 7.39 h. Out of eight possible dozing situations, we found that the mean score for ESS was 8.78. In addition, 79 students showed an ESS score of >10. Furthermore, our results showed that the majority of students (>92% reported poor sleep satisfaction with quality and duration of sleep hours. Thinking about difficulty of study but not increasing education programs or tea/coffee consumption is associated with sleep difficulties reported. Moreover, 77.6% of students reported an irregular sleep–wake schedule. Conclusion: These findings indicate that students experienced excessive daytime sleepiness. The TST of pharmaceutical students in Libya, as in other developing countries, is less than those reported by Western students. Students experienced various environmental demands during their college years and, their quality of sleep was negatively affected.

  17. Hb Presbyterian (HBB: c.327C>G) in a Nicaraguan Family.

    Science.gov (United States)

    Pernudy-Ubau, Allan; Salinas-Molina, Jaslyn; Requenez, Yaneris; Ortiz-Lopez, Marianela; Puller, Ann-Christin; García-Rosales, Kenia; Rodríguez-Estrada, Anaishelle; Rodríguez-Romero, Walter; Mejía-Baltodano, Gerardo; Luo, Hong-Yuan; Chui, David H K

    2017-01-01

    Hemoglobin (Hb) is the protein responsible for oxygen transportation. It is a tetrameric protein comprising two α- and two β-globin subunits. In the literature, a large number of mutations in the α- and β-globin genes have been documented. Among these mutations, Hb Presbyterian (HBB: c.327 C>G), is a naturally occurring mutant exerting low oxygen affinity. The C to G exchange (AAC>AAG) at codon 108 of the β-globin gene results in the substitution of asparagine by lysine. Here, we document the identification of HBB: c.327 C>G in a 6-year-old female patient and her father from Nicaragua and Cuba, respectively. The presence of the abnormal Hb was confirmed by cellulose acetate electrophoresis, high performance liquid chromatography (HPLC) and genomic DNA sequencing. The β-globin gene sequences for both, father and daughter, disclosed the heterozygous mutation at codon 108 to be Hb Presbyterian or HBB: c.327 C>G. The mutant Hb was previously reported in four families from North America, Germany, Japan and Spain, respectively. This is the fifth family carrying HBB: c.327 C>G described to date and the first report from Latin America.

  18. Characterization and Expression of the Lucina pectinata Oxygen and Sulfide Binding Hemoglobin Genes

    Science.gov (United States)

    López-Garriga, Juan; Cadilla, Carmen L.

    2016-01-01

    The clam Lucina pectinata lives in sulfide-rich muds and houses intracellular symbiotic bacteria that need to be supplied with hydrogen sulfide and oxygen. This clam possesses three hemoglobins: hemoglobin I (HbI), a sulfide-reactive protein, and hemoglobin II (HbII) and III (HbIII), which are oxygen-reactive. We characterized the complete gene sequence and promoter regions for the oxygen reactive hemoglobins and the partial structure and promoters of the HbI gene from Lucina pectinata. We show that HbI has two mRNA variants, where the 5’end had either a sequence of 96 bp (long variant) or 37 bp (short variant). The gene structure of the oxygen reactive Hbs is defined by having 4-exons/3-introns with conservation of intron location at B12.2 and G7.0 and the presence of pre-coding introns, while the partial gene structure of HbI has the same intron conservation but appears to have a 5-exon/ 4-intron structure. A search for putative transcription factor binding sites (TFBSs) was done with the promoters for HbII, HbIII, HbI short and HbI long. The HbII, HbIII and HbI long promoters showed similar predicted TFBSs. We also characterized MITE-like elements in the HbI and HbII gene promoters and intronic regions that are similar to sequences found in other mollusk genomes. The gene expression levels of the clam Hbs, from sulfide-rich and sulfide-poor environments showed a significant decrease of expression in the symbiont-containing tissue for those clams in a sulfide-poor environment, suggesting that the sulfide concentration may be involved in the regulation of these proteins. Gene expression evaluation of the two HbI mRNA variants indicated that the longer variant is expressed at higher levels than the shorter variant in both environments. PMID:26824233

  19. Diagnostic accuracy of HbA1c in diabetes between Eastern and Western.

    Science.gov (United States)

    Yan, Shuang; Liu, Siying; Zhao, Yashuang; Zhang, Wencui; Sun, Xiaohui; Li, Jianing; Jiang, Fuli; Ju, Jiaming; Lang, Ning; Zhang, Yingqi; Zhou, Weiyu; Li, Qiang

    2013-07-01

    In 2010, the American Diabetes Association recommended the use of HbA1c as a diagnostic criterion for diabetes. However, HbA1c is not an accepted diagnostic tool for diabetes in Eastern Asia, because genetic differences compromise the standardization of the diagnostic cut-off point. This study evaluated differences in the use of HbA1c for diagnosing diabetes in Eastern and Western populations and investigated whether HbA1c cut-off point of ≥ 6.5% is diagnostic of diabetes in patients from Eastern Asia. Literature was obtained from MEDLINE, EMBASE and Cochrane databases. The pooled sensitivity and specificity of each HbA1c cut-off point were extracted and compared between Western and Eastern populations. Differences in the cut-off point for diagnosing diabetes in each region were compared by examining differences in the area under summary receiver operating characteristic (SROC) curves. Twelve publications from Eastern countries (n = 59,735) and 13 from Western countries (n = 22,954) were included in the analysis. Areas under SROC curves in the Eastern and Western groups were 0.9331 and 0.9120, respectively (P = 0.98). The cut-off point of the highest Youden index was 6.0%. At the HbA1c cut-off point of 6.5%, the pooled sensitivity and specificity were 58.7% and 98.4% for Eastern countries and 65.5% and 98.1% for Western countries, respectively. HbA1c exhibits the same diagnostic value for diabetes in Eastern and Western populations. In both populations, HbA1c levels > 6.0% identify the population at high risk of diabetes, and HbA1c > 6.5% is diagnostic of clinically established diabetes. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  20. HB-EGF is necessary and sufficient for Müller glia dedifferentiation and retina regeneration

    Science.gov (United States)

    Wan, Jin; Ramachandran, Rajesh; Goldman, Daniel

    2011-01-01

    Summary Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that proHB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals. PMID:22340497

  1. Role of HbA1c in predicting risk for congenital malformations.

    Science.gov (United States)

    Hammouda, Sahar Ali Ibrahim; Hakeem, Rubina

    2015-12-01

    Association between conventionally identified hyperglycemias and rates of congenital abnormalities is known; however there is less information about role of HbA1c in determining gestational hyperglycemias and associated risks. This study tried to explore the association between HbA1c in women without known diabetes at first antenatal visit and risk of congenital malformations (CM) among Saudi women living at Al-Madinah Al-Monawarah. Eleven hundred and eighty (1180), healthy, first-trimester pregnant Saudi females without known diabetes, were selected from various antenatal care clinics of Al-Madinah Al-Monawarah city. General clinical and biochemical data was collected for this study by researchers at first visit and the time of delivery. Nearly one fifth (19.6%) of mothers had above normal HbA1c (>5.7) at first visit. Rates of CM had significant positive association with level of HbA1c. Rate of CM among those who had HbA1c in diabetes range, pre-diabetes range or normal range was 27.8%, 9.8% and 3.0%, respectively. The difference was significant between normal and pre-diabetes at the level P=0.000 and between pre-diabetes and diabetes at level P=0.038. In this study HbA1c is found to be a valuable predictor of risk of congenital malformations. This observation calls for further studies and establishment of policies for care of pregnant mothers having higher than normal HbA1c at first visit. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  2. Baseline Report on HB2320

    Science.gov (United States)

    State Council of Higher Education for Virginia, 2015

    2015-01-01

    Staff provides this baseline report as a summary of its preliminary considerations and initial research in fulfillment of the requirements of HB2320 from the 2015 session of the General Assembly. Codified as § 23-7.4:7, this legislation compels the Education Secretary and the State Council of Higher Education for Virginia (SCHEV) Director, in…

  3. Continuous-energy adjoint flux and perturbation calculation using the iterated fission probability method in Monte-Carlo code TRIPOLI-4 and underlying applications

    International Nuclear Information System (INIS)

    Truchet, G.; Leconte, P.; Peneliau, Y.; Santamarina, A.

    2013-01-01

    The first goal of this paper is to present an exact method able to precisely evaluate very small reactivity effects with a Monte Carlo code (<10 pcm). it has been decided to implement the exact perturbation theory in TRIPOLI-4 and, consequently, to calculate a continuous-energy adjoint flux. The Iterated Fission Probability (IFP) method was chosen because it has shown great results in some other Monte Carlo codes. The IFP method uses a forward calculation to compute the adjoint flux, and consequently, it does not rely on complex code modifications but on the physical definition of the adjoint flux as a phase-space neutron importance. In the first part of this paper, the IFP method implemented in TRIPOLI-4 is described. To illustrate the efficiency of the method, several adjoint fluxes are calculated and compared with their equivalent obtained by the deterministic code APOLLO-2. The new implementation can calculate angular adjoint flux. In the second part, a procedure to carry out an exact perturbation calculation is described. A single cell benchmark has been used to test the accuracy of the method, compared with the 'direct' estimation of the perturbation. Once again the method based on the IFP shows good agreement for a calculation time far more inferior to the 'direct' method. The main advantage of the method is that the relative accuracy of the reactivity variation does not depend on the magnitude of the variation itself, which allows us to calculate very small reactivity perturbations with high precision. It offers the possibility to split reactivity contributions on both isotopes and reactions. Other applications of this perturbation method are presented and tested like the calculation of exact kinetic parameters (βeff, Λeff) or sensitivity parameters

  4. 2,3-DPG-Hb complex: a hypothesis for an asymmetric binding.

    Science.gov (United States)

    Pomponi, M; Bertonati, C; Fuglei, E; Wiig, O; Derocher, A E

    2000-05-15

    This study was undertaken to test the symmetry of 2,3-diphosphoglycerate (2,3-DPG) binding site in hemoglobin (Hb). From Arnone's study [A. Arnone, Nature (London) 237 (1972) 146] the 2,3-DPG binding site is located at the top of the cavity, that runs through the center of the deoxy-Hb molecule. However, it is possible that this symmetry reported by Arnone, for crystals of 2,3-DPG-Hb complex, might not be conserved in solution. In this paper, we report the 31P nuclear magnetic resonances of the 2,3-DPG interaction with Hb. The 2,3-DPG chemical shifts of the P2 and P3 resonance are both pH- and hemoglobin-dependent [protein from man, polar bear (Ursus maritimus), Arctic fox (Alopex lagopus) and bovine]. 2,3-DPG binds tightly to deoxyhemoglobin and weakly, nevertheless significantly, to oxyhemoglobin. In particular, our results suggest similar spatial position of the binding site of 2,3-DPG in both forms of Hb in solutions. However, the most unexpected result was the apparent loss of symmetry in the binding site, which might correlate with the ability of the hemoglobin to modulate its functional behavior. The different interactions of the phosphate groups indicate small differences in the quaternary structure of the different deoxy forms of hemoglobin. Given the above structural perturbation an asymmetric binding in the complex could justify, at least in part, different physiological properties of Hb. Regardless, functionally relevant effects of 2,3-DPG seem to be measured and best elucidated through solution studies.

  5. Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III

    Directory of Open Access Journals (Sweden)

    Grimsby Jonna L

    2012-04-01

    Full Text Available Abstract Background Hemoglobin A1c (HbA1c levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1 HbA1c-associated risk allele frequencies (RAFs for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2 association of SNPs with HbA1c and 3 association of SNPs with mortality. Methods We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. Results RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p 1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04 and MA (β = 0.021, p = 0.005 but not NHB (β = 0.007, p = 0.39. The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71. Conclusion At many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.

  6. Decontamination and decommissioning of the MTR-603 HB-2 cubicle

    International Nuclear Information System (INIS)

    Smith, D.L.

    1987-01-01

    The decontamination and decommissioning (D and D) of the MTR-603 HB-2 cubicle located at the Idaho National Engineering Laboratory (INEL) are described. The HP-2 cubicle became radioactively contaminated during out-of-pile circulating water loop experiments conducted in the Materials Testing Reactor in the 1950s and 1960s. The work performed to accomplish the D and D objectives of reducing the high radiation fields caused by contamination inside the cubicle, preventing future contamination spread, and making about 1400 ft 2 of floor space available for reuse are discussed. Decommissioning of the HB-2 cubicle consisted of total dismantlement of the cubicle and its contents and was performed without disrupting ongoing laboratory work being conducted in areas surrounding the HB-2 cubicle

  7. Isolation and characterization of atrazine mineralizing Bacillus subtilis strain HB-6.

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    Full Text Available Atrazine is a widely used herbicide with great environmental concern due to its high potential to contaminate soil and waters. An atrazine-degrading bacterial strain HB-6 was isolated from industrial wastewater and the 16S rRNA gene sequencing identified HB-6 as a Bacillus subtilis. PCR assays indicated that HB-6 contained atrazine-degrading genes trzN, atzB and atzC. The strain HB-6 was capable of utilizing atrazine and cyanuric acid as a sole nitrogen source for growth and even cleaved the s-triazine ring and mineralized atrazine. The strain demonstrated a very high efficiency of atrazine biodegradation with a broad optimum pH and temperature ranges and could be enhanced by cooperating with other bacteria, suggesting its huge potential for remediation of atrazine-contaminated sites. To our knowledge, there are few Bacillus subtilis strains reported that can mineralize atrazine, therefore, the present work might provide some new insights on atrazine remediation.

  8. HbA2 measurements in β-thalassemia and in other conditions

    Directory of Open Access Journals (Sweden)

    Giovanni Ivaldi

    2014-09-01

    Full Text Available Quite a few papers have been written on the significance of elevated hemoglobin (Hb A2 as a parameter for the diagnosis of β-thalassemia trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors reducing or elevating the expression of HbA2 and last but not least on the need for reliable measurement methods and precise calibrations with accurate standards. However, little has been published on the causes that elevate or reduce the HbA2 levels in β- and a-thalassemia and in other conditions. For a better understanding of the value of a precise measurement of this parameter we summarize and elucidate in this review the direct and indirect mechanisms that cause the variations in HbA2 expression and that influence the value of this parameter in particular conditions. We conclude by explaining the advantages and disadvantages of trusting on a precise measurement in the complete diagnostic contest.

  9. The changing relationship between HbA1c and FPG according to different FPG ranges.

    Science.gov (United States)

    Guan, X; Zheng, L; Sun, G; Guo, X; Li, Y; Song, H; Tian, F; Sun, Y

    2016-05-01

    Since the American Diabetes Association included hemoglobin A1c (HbA1c) in the diagnostic criteria for diabetes in 2010, the clinical use of HbA1c has remained controversial. We explored the use of HbA1c for diagnosing diabetes and intermediate hyperglycemia in comparison with fasting plasma glucose (FPG). We screened 3710 adult subjects (mean age = 55.24 years) comprising 1704 males and 2006 females. We drew an receiver operating characteristic (ROC) curve to evaluate the ability of HbA1c to diagnose diabetes and intermediate hyperglycemia according to FPG. We used Kappa coefficient and Pearson's correlation coefficient to evaluate the relationship between HbA1c and FPG in different FPG ranges. The areas under ROC curve to diagnose diabetes and intermediate hyperglycemia were 0.859 (95 % CI 0.827-0.892) and 0.633 (95 % CI 0.615-0.651). The kappa coefficients between FPG and HbA1c for diagnosis of diabetes and intermediate hyperglycemia were 0.601 (P HbA1c was 0.640 (P HbA1c and FPG changed according to the different FPG ranges. When FPG was higher, the relationship was stronger. HbA1c and FPG were highly consistent in diagnosing diabetes, but they were not in predicting intermediate hyperglycemia.

  10. Hb and dyslipidaemia as predicting markers of serum alanine aminotransferase elevation in Chinese adolescents.

    Science.gov (United States)

    Chao, Kuo-Ching; Chang, Chun-Chao; Owaga, Eddy; Bai, Chyi-Huey; Huang, Tzu-chieh; Pan, Wen-Harn; Chang, Jung-Su

    2016-04-01

    Fe is an essential element for erythropoiesis and Hb synthesis. High Hb levels affect the blood's viscosity and are associated with cardiovascular dysfunction. The aim of the present study was to examine relationships of Hb and cardiometabolic abnormalities with the risk of alanine aminotransferase (ALT) elevation in adolescents. A population-based, cross-sectional study. National Nutrition and Health Survey in Taiwan (2010-2011, adolescents). Healthy adolescents aged 13-18 years. In total, 1941 adolescents (963 boys and 978 girls) were entered in the study. The mean age was 15·3 (sd 0·1) years (boys, 15·3 (sd 0·1) years; girls, 15·2 (sd 0·1) years). ALT tertile cut-off points for boys were 11 and 16 U/l, and for girls were 9 and 12 U/l. Girls without dyslipidaemia and presenting in the highest quartile (Q1) of Hb (>13·6 g/dl) were 1·89 and 3·76 times more likely to have raised serum ALT (9 and >12 U/l, respectively) than the reference (lowest quartile of Hb (Q1), 12 U/l) than the reference (Q1 of Hb, 15·4 g/dl), who were 7·40 times more likely to have elevated serum ALT of >16 U/l than the reference (Q1 of Hb, Hb level is a predictor of elevated serum ALT in adolescent girls with dyslipidaemia. Our study also highlights the importance of further research to establish cut-off points for Hb and its utility in diagnosing and preventing the onset of dyslipidaemia in adolescents.

  11. HbA1c as a predictor of diabetes after gestational diabetes mellitus.

    Science.gov (United States)

    Claesson, Rickard; Ignell, Claes; Shaat, Nael; Berntorp, Kerstin

    2017-02-01

    We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36mmol/mol) were associated with a 5.5-fold increased risk of diabetes. Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

  13. Complex structure of the supernova remnant HB 3

    Science.gov (United States)

    Leahy, D. A.; Venkatesan, D.; Long, K. S.; Naranan, S.

    1985-01-01

    HB 3 is an old, large (84 pc diameter) supernova remnant associated with the W3 H II region/molecular cloud complex. Observations of the imaging proportional counter (IPC) onboard the Einstein X-ray astronomy satellite have been reprocessed to yield a contour map of X-ray brightness and spectra of various regions of this remnant. The measured IPC flux is 2.4 x 10 to the -11th ergs per sq cm per s, giving a 0.2-4 keV luminosity of 1.6 x 10 to the 35th ergs/s for a column densityof 6 x 10 to the 21st per sq cm. The measured X-ray temperatures reveal a decrease from center to limb of the remnant of 1-0.3 keV. HB 3 is in the late adiabatic blast-wave phase of evolution, 30,000 to 50,000 yr old and with an initial blast energy of 3 x 10 to the 50th ergs. The X-ray map is compared with available radio and optical images. In X-rays, HB 3 has two components - a diffuse emission inside the 84 pc radio remnant and a ring of emission at the center of 30 pc in diameter. The diffuse emission is similar to that from other supernova remnants which are moderately obscured (column density, nH approximately 10 to the 22nd per sq cm). Three possibilities for the origin of the ring are explored: (1) a second supernova remnant, (2) a shocked shell in the interstellar medium surrounding HB 3, and (3) reverse-shock heated ejecta. There is no hot neutron star within the remnant.

  14. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.

    Science.gov (United States)

    Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole

    2017-01-27

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2 Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

  15. Identification of diphtheria toxin R domain mutants with enhanced inhibitory activity against HB-EGF.

    Science.gov (United States)

    Suzuki, Keisuke; Mizushima, Hiroto; Abe, Hiroyuki; Iwamoto, Ryo; Nakamura, Haruki; Mekada, Eisuke

    2015-05-01

    Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a ligand of EGF receptor, is involved in the growth and malignant progression of cancers. Cross-reacting material 197, CRM197, a non-toxic mutant of diphtheria toxin (DT), specifically binds to the EGF-like domain of HB-EGF and inhibits its mitogenic activity, thus CRM197 is currently under evaluation in clinical trials for cancer therapy. To develop more potent DT mutants than CRM197, we screened various mutant proteins of R domain of DT, the binding site for HB-EGF. A variety of R-domain mutant proteins fused with maltose-binding protein were produced and their inhibitory activity was evaluated in vitro. We found four R domain mutants that showed much higher inhibitory activity against HB-EGF than wild-type (WT) R domain. These R domain mutants suppressed HB-EGF-dependent cell proliferation more effectively than WT R domain. Surface plasmon resonance revealed their higher affinity to HB-EGF than WT R domain. CRM197(R460H) carrying the newly identified mutation showed increased cell proliferation inhibitory activity and affinity to HB-EGF. These results suggest that CRM197(R460H) or other recombinant proteins carrying newly identified mutation(s) in the R domain are potential therapeutics targeting HB-EGF. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  16. Registration of a High Yielding Malt Barley Variety HB1454 for the ...

    African Journals Online (AJOL)

    else

    Bayeh and Berhane 2011). Even though Ethiopia has favorable environment and .... malting profile for HB1454 is better than Beka for kernel weight, plump kernels, hectoliter weight and grain protein. HB1454 has shown relatively low percentage.

  17. To establish trimester-specific reference ranges for glycated haemoglobin (HbA1c) in pregnancy

    LENUS (Irish Health Repository)

    O'Connor, CM

    2011-09-01

    Background and aims: Diabetes in Pregnancy imposes additional risks to both mother and infant. These poor outcomes are considered to be primarily related to glycaemic control which is monitored longitudinally through pregnancy by means of HbA1c. The correlation between HbA1c levels with clinical outcomes emphasises the need to measure HbA1c accurately, precisely and for data interpretation comparison to appropriately defined reference intervals. From July 1st 2010, the HbA1c assay in Irish laboratories became fully metrologically traceable to the IFCC standard, permitting HbA1c to be reported in IFCC units (mmol\\/mol) and derived DCCT\\/NGSP units (%) using the IFCC-DCCT\\/NGSP master equation (DCCT = Diabetes Control and Complications Trial, NGSP = National Glycohemoglobin standardisation program). The aim of this project is to establish trimester-specific reference ranges in pregnancy for IFCC standardised HbA1c in non-diabetic Caucasian women. This will allow us to define the goal for HbA1c during pregnancy complicated by diabetes.\\r\

  18. Electrochemical sensor based on magnetic molecularly imprinted nanoparticles modified magnetic electrode for determination of Hb.

    Science.gov (United States)

    Sun, Binghua; Ni, Xinjiong; Cao, Yuhua; Cao, Guangqun

    2017-05-15

    A fast and selective electrochemical sensor for determination of hemoglobin (Hb) was developed based on magnetic molecularly imprinted nanoparticles modified on the magnetic glassy carbon electrode. The nanoparticles Fe 3 O 4 @SiO 2 with a magnetic core and a molecularly imprinted shell had regular structures and good monodispersity. Hb could be determined directly by electrochemical oxidization with the modified electrode. A magnetic field increased electrochemical response to Hb by two times. Imprinting Hb on the surface of Fe 3 O 4 @SiO 2 shortened the response time within 7min. Under optimum conditions, the imprinting factor toward the non-imprinted sensor was 2.8, and the separation factor of Hb to horseradish peroxidase was 2.6. The oxidation peak current had a linear relationship with Hb concentration ranged from 0.005mg/ml to 0.1mg/ml with a detection limit (S/N =3) of 0.0010mg/ml. The sensors were successfully applied to analysis of Hb in whole blood samples with recoveries between 95.7% and 105%. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Effects of a healthier snack on snacking habits and glycated Hb (HbA1c): a 6-week intervention study.

    Science.gov (United States)

    Yan, Mary R; Parsons, Andrew; Whalley, Gillian A; Rush, Elaine C

    2016-12-01

    Dietary behaviour modification may change eating habits and reduce the impact of poor nutrition. This study aimed to evaluate the effects of daily consumption of a healthier snack bar on snacking habits and glycated Hb (HbA1c) within a 6-week intervention. In all, twenty-eight participants were randomly allocated to two groups to either consume the bars as the main snack for 6 weeks (n 14) or receipt of the bars was delayed for 6 weeks (n 14) following a stepped-wedge design. All participants had HbA1c concentrations measured at weeks -1, 0, 4, 6, 10 and 12. A short dietary habits questionnaire was self-completed at weeks 0, 6 and 12. Participants consumed the bars they received instead of other snacks, and found that the healthier snack bar was acceptable as part of their daily dietary pattern. Over the 12 weeks, there was a significant reduction in intake of biscuits, cakes and pies (approximately 2 servings/week, Psnack intervention and a trend towards a favourable effect on glucose homoeostasis. Habitual snacking behaviour has the potential to be improved through changes in the food supply, and in the longer term may reduce the impact of poor nutrition on public health.

  20. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    OpenAIRE

    Chandrashekar, Vani

    2016-01-01

    Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman's rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to st...

  1. Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease.

    Science.gov (United States)

    Akinbami, Anthony O; Campbell, Andrew D; Han, Zeqiu J; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H

    2016-01-01

    Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)γ-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)γ- and (G)γ-globin gene promoters in cis [(G)γ(A)γ(β(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F.

  2. Hemoglobin A1c (HbA1c) Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/hemoglobina1chba1ctest.html Hemoglobin A1c (HbA1c) Test To use the sharing features on this page, please enable JavaScript. What is a hemoglobin A1c (HbA1c) test? A hemoglobin A1c (HbA1c) test measures ...

  3. Elevated HbA1c and Fasting Plasma Glucose in Predicting Diabetes Incidence Among Older Adults

    Science.gov (United States)

    Lipska, Kasia J.; Inzucchi, Silvio E.; Van Ness, Peter H.; Gill, Thomas M.; Kanaya, Alka; Strotmeyer, Elsa S.; Koster, Annemarie; Johnson, Karen C.; Goodpaster, Bret H.; Harris, Tamara; De Rekeneire, Nathalie

    2013-01-01

    OBJECTIVE To determine which measures—impaired fasting glucose (IFG), elevated HbA1c, or both—best predict incident diabetes in older adults. RESEARCH DESIGN AND METHODS From the Health, Aging, and Body Composition study, we selected individuals without diabetes, and we defined IFG (100–125 mg/dL) and elevated HbA1c (5.7–6.4%) per American Diabetes Association guidelines. Incident diabetes was based on self-report, use of antihyperglycemic medicines, or HbA1c ≥6.5% during 7 years of follow-up. Logistic regression analyses were adjusted for age, sex, race, site, BMI, smoking, blood pressure, and physical activity. Discrimination and calibration were assessed for models with IFG and with both IFG and elevated HbA1c. RESULTS Among 1,690 adults (mean age 76.5, 46% men, 32% black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of diabetes were 6.2 (95% CI 4.4–8.8) in those with IFG (versus those with fasting plasma glucose [FPG] HbA1c (versus those with HbA1c HbA1c were considered together, odds ratios were 3.5 (1.9–6.3) in those with IFG only, 8.0 (4.8–13.2) in those with elevated HbA1c only, and 26.2 (16.3–42.1) in those with both IFG and elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated HbA1c to the model with IFG resulted in improved discrimination and calibration. CONCLUSIONS Older adults with both IFG and elevated HbA1c have a substantially increased odds of developing diabetes over 7 years. Combined screening with FPG and HbA1c may identify older adults at very high risk for diabetes. PMID:24135387

  4. Changing from glucose to HbA1c for diabetes diagnosis

    DEFF Research Database (Denmark)

    Nielsen, Aneta Aleksandra; Petersen, Per Hyltoft; Green, Anders

    2014-01-01

    BACKGROUND: In Denmark, the use of HbA1c in the diagnosis of diabetes was adopted from March 2012. We evaluated the change in the number of diabetes cases diagnosed by haemoglobin A1c (HbA1c) versus fasting venous plasma glucose (FPG), and estimated the influence of analytical variation and bias ...

  5. Source convergence diagnostics using Boltzmann entropy criterion application to different OECD/NEA criticality benchmarks with the 3-D Monte Carlo code Tripoli-4

    International Nuclear Information System (INIS)

    Dumonteil, E.; Le Peillet, A.; Lee, Y. K.; Petit, O.; Jouanne, C.; Mazzolo, A.

    2006-01-01

    The measurement of the stationarity of Monte Carlo fission source distributions in k eff calculations plays a central role in the ability to discriminate between fake and 'true' convergence (in the case of a high dominant ratio or in case of loosely coupled systems). Recent theoretical developments have been made in the study of source convergence diagnostics, using Shannon entropy. We will first recall those results, and we will then generalize them using the expression of Boltzmann entropy, highlighting the gain in terms of the various physical problems that we can treat. Finally we will present the results of several OECD/NEA benchmarks using the Tripoli-4 Monte Carlo code, enhanced with this new criterion. (authors)

  6. Antibacterial activity of a modified unfilled resin containing a novel polymerizable quaternary ammonium salt MAE-HB.

    Science.gov (United States)

    Huang, Li; Yu, Fan; Sun, Xiang; Dong, Yan; Lin, Ping-Ting; Yu, Hao-Han; Xiao, Yu-Hong; Chai, Zhi-Guo; Xing, Xiao-Dong; Chen, Ji-Hua

    2016-09-23

    Resins with strong and long-lasting antibacterial properties are critical for the prevention of secondary dental caries. In this study, we evaluated the antibacterial effect and the underlying mechanism of action of an unfilled resin incorporating 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB) against Streptococcus mutans UA159 (S. mutans UA159). MAE-HB was added into unfilled resin at 10 mass%, and unfilled resin without MAE-HB served as the control. Bacterial growth was inhibited on 10%-MAE-HB unfilled resin compared with the control at 1 d, 7 d, 30 d, or 180 d (P  0.05). No significant differences in the antibacterial activities of eluents from control versus 10%-MAE-HB unfilled resins were observed at any time point (P > 0.05). The number of bacteria attached to 10%-MAE-HB unfilled resin was considerably lower than that to control. Fe-SEM and CLSM showed that 10%-MAE-HB unfilled resin disturbed the integrity of bacterial cells. Expression of the bacterial glucosyltransferases, gtfB and gtfC, was lower on 10%-MAE-HB unfilled resin compared to that on control (P HB confers unfilled resin with strong and long-lasting antibacterial effects against S. mutans.

  7. Comparação de metodologia utilizada para a detecção de Hemoglobina S (Hb S em doadores de sangue

    Directory of Open Access Journals (Sweden)

    Prudêncio Brígida C. A. B.

    2000-01-01

    Full Text Available O Brasil apresenta alta prevalência de hemoglobina S, com nítidas diferenças regionais marcadas pelos processos de miscigenação da população. A presença desta hemoglobina tem sido objeto de estudo, não só em pacientes com anemia falciforme (homozigotos para hemoglobina S - Hb SS, mas também em portadores desta variante de hemoglobina em heterozigose (Hb AS. As complicações clínicas dos portadores são influenciadas por fatores genéticos e ambientais. De acordo com a portaria 1376 de 19 de novembro de 1993 para Normas técnicas de coleta, processamento e transfusão de sangue, componentes e derivados, do Ministério da Saúde, deve ser realizada a detecção de hemoglobinas anormais em doadores de sangue. Diante desta normatização e às taxas de hemoglobina S em nossa população, objetivamos no presente trabalho a identificação da hemoglobina S, utilizando técnicas de triagem utilizadas na rotina de Bancos de Sangue, como o kit de identificação para hemoglobina S da Diamed, comercializado pela designação ID-Hb S, e o teste de solubilidade. Os casos que apresentaram positividade nesta triagem foram posteriormente confirmados em eletroforese em pH alcalino e ácido. Do total de 5.416 doadores de sangue analisados pelo teste de triagem (ID - Hb S Diamed e solubilidade, 50 (0,92% apresentaram hemoglobina S. Após confirmação eletroforética evidenciamos a compatibilidade das técnicas em 100 % dos casos analisados. O teste da Diamed apresenta custo de R$ 1,20 por doador e o de solubilidade R$ 0,14. Pelos resultados obtidos sugerimos o uso do teste de solubilidade como de escolha, para triagem de hemoglobina S em bancos de sangue, não só pela eficácia e praticidade, como também pelo baixo custo.

  8. Changes in proHB-EGF expression after functional activation of the immune system cells

    Directory of Open Access Journals (Sweden)

    T. O. Chudina

    2017-12-01

    Full Text Available The level of proHB-EGF expression on J774, Raji, KG-1 cells derived from different types of human and mouse immune system cells under the standard in vitro culture conditions and during functional activation of these cells was investigated. Changes in the proHB-EGF expression on the cell surface were found to depend on the density of cell population, the content of fetal bovine serum in the culture medium, the effect of mitogenic factors – bacterial lipopolysaccharide, an inactive full-size form of diphtheria toxin (CRM197 and recombinant soluble HB-EGF – rsHB-EGF. The results obtained are important for the understanding of the functional role of proHB-EGF receptor on the surface of macrophage-like cells and B lymphocytes and indicate the involvement of this receptor in immune response regulation in an organism.

  9. Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A).

    Science.gov (United States)

    Boucher, Maria O; Chui, David H K; Woda, Bruce A; Newburger, Peter E

    2016-06-01

    We report an infant with a compound heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A) and a phenotype of mild microcytic anemia with target cell morphology but without overt hemolysis.

  10. An alternative approach to modelling HbA1c trajectories in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    McEwan, Phil; Bennett, Hayley; Qin, Lei; Bergenheim, Klas; Gordon, Jason; Evans, Marc

    2017-05-01

    Time-dependent HbA1c trajectories in health economic models of type 2 diabetes mellitus (T2DM) are typically informed by the UK Prospective Diabetes Study (UKPDS). However, this approach may not accurately predict HbA1c progression in patients who do not conform to the demographic profile of the original UKPDS cohort. This study aimed to develop an alternative mathematical model (MM) to simulate HbA1c progression in T2DM. A systematic literature review identified studies, published between 2005 and 2015, that reported HbA1c in adult T2DM patients over a minimum duration of 18 months. Pooled data from eligible studies were used to develop an alternative MM equation for HbA1c progression, which was then contrasted with the UKPDS 68 progression equation in illustrative scenarios. A total of 68 studies were eligible for data extraction (mean follow-up time 4.1 years). HbA1c progression was highly heterogeneous across studies, varying with baseline HbA1c, treatment group and patient age. The MM equation was fitted with parameters for mean baseline HbA1c (8.3%), initial change in HbA1c (-0.62%) and upper quartile of maximum observed HbA1c (9.3%). Differences in HbA1c trajectories between the MM and UKPDS approaches altered the timing of therapy escalation in illustrative scenarios. The MM represents an alternative approach to simulate HbA1c trajectories in T2DM models, as UKPDS data may not adequately reflect the heterogeneity of HbA1c profiles observed in clinical studies. However, the choice of approach should ultimately be determined by the characteristics of individual patients under consideration and the clinical face validity of the modelled trajectories. © 2016 John Wiley & Sons Ltd.

  11. NEAR-IR PHOTOMETRIC PROPERTIES OF HB, MSTO, AND SGB FOR METAL POOR GALACTIC GLOBULAR CLUSTERS

    Directory of Open Access Journals (Sweden)

    J.-W. Kim

    2007-03-01

    Full Text Available We report photometric features of the HB, MSTO, and SGB for a set of metal-poor Galactic globular clusters on the near-IR CMDs. The magnitude and color of the MSTO and SGB are measured on the fiducial normal points of the CMDs by applying a polynomial fit. The near-IR luminosity functions of horizontal branch stars in the classical second parameter pair M3 and M13 indicate that HB stars in M13 are dominated by hot stars that are rotatively faint in the infrared, whereas HB stars in M3 are brighter than those in M13. The luminosity functions of HB stars in the observed bulge clusters, except for NGC 6717, show a trend that the fainter hot HB stars are dominated in the relatively metal-poor clusters while the relatively metal-rich clusters contain the brighter HB stars. It is suggestive that NGC 6717 would be an extreme example of the second-parameter phenomenon for the bulge globular clusters.

  12. Association of plasma PCB levels and HbA1c concentration in Iran.

    Science.gov (United States)

    Eftekhari, Sahar; Aminian, Omid; Moinfar, Zeinab; Schettgen, Thomas; Kaifie, Andrea; Felten, Michael; Kraus, Thomas; Esser, André

    2018-01-01

    The rapid increase in prevalence of diabetes mellitus over the last decades warrants more attention to the effects of environmental and occupational exposures on glucose metabolism. Our study aimed to assess the association between the plasma levels of various congeners of polychlorinated biphenyls (PCBs) and the serum concentration of glycated haemoglobin (HbA1c). Our study population consisted of 140 Iranian adults from seven different occupational groups and a group of non-occupationally exposed female participants. The plasma concentration of PCBs were determined at the laboratory of occupational toxicology at RWTH Aachen University, Germany. We considered an HbA1c concentration of 5.7% and more as indicating a disturbed glucose metabolism. Logistic regression was used to assess the association between quartiles of concentrations of PCB congeners and serum HbA1c. Participants with an increased HbA1c value had higher plasma levels of PCB 138, 153, 180 and the PCB sum, although this association was statistically not significant. There was no significant difference between the levels of PCB 138, 153, 180, the sum of these congeners, and PCB 118 in their quartiles when comparing with HbA1c concentrations. For our cohort, we could not demonstrate a significant association between PCB and HbA1c concentrations indicating a disturbance of glucose metabolism.

  13. HbA1c, systolic blood pressure variability and diabetic retinopathy in Asian type 2 diabetics.

    Science.gov (United States)

    Foo, Valencia; Quah, Joanne; Cheung, Gemmy; Tan, Ngiap Chun; Ma Zar, Kyi Lin; Chan, Choi Mun; Lamoureux, Ecosse; Tien Yin, Wong; Tan, Gavin; Sabanayagam, Charumathi

    2017-02-01

    The aim of the present study was to examine the association between variability in HbA1c or systolic blood pressure (SBP) and diabetes-specific moderate retinopathy in Asians with type 2 diabetes (T2D). A retrospective study was conducted of 172 cases of moderate diabetic retinopathy (DR) cases and 226 controls without DR, matched for age, sex, and ethnicity. Serial HbA1c and SBP (range 3-6 readings) over the 2 years prior to photographic screening of DR were collected. Intrapersonal mean and SD values for HbA1c (iM-HbA1c and iSD-HbA1c) and SBP (iM-SBP and iSD-SBP) were derived. Moderate DR was assessed from digital retinal photographs and defined as levels >43 using the Early Treatment Diabetic Retinopathy Study scale. Cases of moderate DR had higher iM-HbA1c (8.2 % vs 7.3 %; P = 0.001), iSD-HbA1c (1.22 vs 0.64; P = 0.001), iM-SBP (136.8 vs 129.6 mmHg; P = 0.001) and iSD-SBP (13.3 vs 11.1; P = 0.002) than controls. In the multivariate regression model adjusted for age, gender, ethnicity, duration of diabetes, SBP, and HbA1c, iM-HbA1c and iM-SBP were significantly associated with moderate DR (odds ratio [OR] 1.80, 95 % confidence interval [CI] 1.37-2.36; and OR 1.03, 95 % CI 1.01-1.05, respectively). Neither iSD-HbA1c nor iSD-SBP were associated with moderate DR. When stratified by HbA1c HbA1c levels and SBP, but not their variability, were associated with moderate DR. Among those with good glycemic control, wider variability of SBP is associated with moderate DR. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  14. Analytical verification and quality assessment of the Tosoh HLC-723GX HbA1c analyzer

    Directory of Open Access Journals (Sweden)

    Marko Ris

    2017-04-01

    Full Text Available Objectives: Ion-exchange high-performance liquid chromatography (IE-HPLC has long been used as a reproducible and versatile analytical tool for HbA1c measurement.In this study, we performed analytical verification and quality assessment of the recently introduced small IE-HPLC Tosoh HLC-723GX HbA1c analyzer, and a comparison of results to immunoassay (IA and capillary electrophoresis (CE. Design and methods: The total imprecision of Tosoh HLC-723GX was verified according to CLSI EP15-A2 protocol using commercial control materials (C-QC and pooled human whole blood samples (HWB. The Sigma metric was used for the evaluation of quality targets. HbA1c results were compared to automated CE (MiniCap Flex Piercing, Sebia, France and IA (Tina-quant HbA1c Gen 2, Cobas Integra 400+, Roche Diagnostics, USA procedures. Results: The total imprecision of Tosoh HLC-723GX-HbA1c for IFCC(mmol/mol and NGSP(% units was: 1.91/1.25% (HbA1c=31 mmol/mol/5.0% and 0.51/0.63% (HbA1c=84 mmol/mol/9.8% for C-QC, and 0.39/0.2% (HbA1c=47 mmol/mol/6.5% and 0.77/0.46% (HbA1c=94 mmol/mol/10.8% in HWB samples, respectively. Bland-Altman analysis did not reveal any deviation of the results between Tosoh HLC-723GX and CE: mean difference 0.0% (95%CI: −0.02927 to 0.02653%, while the mean HbA1c difference against IA was −0.07% (95%CI: −0.1039 to −0.02765. At the selected HbA1c clinical decision level (48 mmol/mol/6,5%, six sigma analysis gave σ value of 3.91, within a desirable classification of performance. Conclusion: The analytical performance of the Tosoh HLC-723GX complies with the rigorous quality criteria for clinical use of HbA1c, with the results comparable to the CE procedure. Tosoh HLC-723GX provides a plausible analytical choice for reliable HbA1c measurement in low-volume laboratories. Keywords: HbA1c, Quality targets, Six sigma, Tosoh HLC-723GX analyzer

  15. HB-Line Dissolution of Glovebox Floor Sweepings

    International Nuclear Information System (INIS)

    Gray, J.H.

    1998-02-01

    Two candidate flowsheets for dissolving glovebox floor sweepings in the HB-Line Phase I geometrically favorable dissolver have been developed.Dissolving conditions tested and modified during the laboratory program were based on the current processing scheme for dissolving high-fired Pu-238 oxide in HB-Line. Subsequent adjustments made to the HB-Line flowsheet reflected differences in the dissolution behavior between high-fired Pu-238 oxide and the MgO sand/PuF 4 /PuO 2 mixture in glovebox floor sweepings. Although both candidate flowsheets involved two separate dissolving steps and resulted incomplete dissolution of all solids, the one selected for use in HB-Line will require fewer processing operations and resembles the initial flowsheet proposed for dissolving sand, slag, and crucible material in F-Canyon dissolvers. Complete dissolution of glovebox floor sweepings was accomplished in the laboratory by initially dissolving between 55 and 65 degree in a 14 molar nitric acid solution. Under these conditions, partial dissolution of PuF 4 and complete dissolution of PuO 2 and MgO sand were achieved in less than one hour. The presence of free fluoride in solution,uncomplexed by aluminum, was necessary for complete dissolution of the PuO 2 .The remaining PuF 4 dissolved following addition of aluminum nitrate nonahydrate (ANN) to complex the fluoride and heating between 75 and 85 degree C for an additional hour. Precipitation of magnesium and/or aluminum nitrates could occur before, during, and after transfer of product solutions. Both dilution and/or product solution temperature controls may be necessary to prevent precipitation of these salts. Corrosion of the dissolver should not be an issue during these dissolving operations. Corrosion is minimized when dissolving at 55-65 degree C for one to three hours at a maximum uncomplexed free fluoride concentration of 0.07 molar and by dissolving at 75-85 degree C at a one to one aluminum to fluoride mole ratio for another

  16. Association of fibrinogen with HbA1C in diabetic foot ulcer

    Science.gov (United States)

    Pase, M. A.; Gatot, D.; Lindarto, D.

    2018-03-01

    Fibrinogen is one of the inflammatory markers of vascular changes and endothelial dysfunction in diabetic patients. The aim of this study to associate serum fibrinogen levels with HbA1C in diabetic foot ulcer (DFU). This study was cross-sectional and retrospective in DFU patients from January to July 2017 in Haji Adam Malik Central General Hospital. The patients enrolled in the study were T2DM with DFU as a complication. The grading of DFU was evaluated according to the Wagner’s Classification. Serum fibrinogen level, HbA1C and ankle-brachial index (ABI) were carried out directly in the patients. Fibrinogen serum levels were found significantly with HbA1C (P=0.001, r=0.387) and ABI (P=0.008, r=-0.454). Fibrinogen serum levels in DFU patients were positively correlated with HbA1C and significantly higher in patients with poor glycemic control.

  17. Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia.

    Science.gov (United States)

    Sheehan, Vivien A; Crosby, Jacy R; Sabo, Aniko; Mortier, Nicole A; Howard, Thad A; Muzny, Donna M; Dugan-Perez, Shannon; Aygun, Banu; Nottage, Kerri A; Boerwinkle, Eric; Gibbs, Richard A; Ware, Russell E; Flanagan, Jonathan M

    2014-01-01

    Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in Spalt-like transcription factor, or SALL2, was associated with higher final HbF in this second independent replication sample and SALL2 represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA.

  18. Trajectories of HbA1c Levels in Children and Youth with Type 1 Diabetes

    Science.gov (United States)

    Pinhas-Hamiel, Orit; Hamiel, Uri; Boyko, Valentina; Graph-Barel, Chana; Reichman, Brian; Lerner-Geva, Liat

    2014-01-01

    Purpose To illustrate the distribution of Hemoglobin A1c (HbA1c) levels according to age and gender among children, adolescents and youth with type 1 diabetes (T1DM). Methods Consecutive HbA1c measurements of 349 patients, aged 2 to 30 years with T1DM were obtained from 1995 through 2010. Measurement from patients diagnosed with celiac disease (n = 20), eating disorders (n = 41) and hemoglobinopathy (n = 1) were excluded. The study sample comprised 4815 measurements of HbA1c from 287 patients. Regression percentiles of HbA1c were calculated as a function of age and gender by the quantile regression method using the SAS procedure QUANTREG. Results Crude percentiles of HbA1c as a function of age and gender, and the modeled curves produced using quantile regression showed good concordance. The curves show a decline in HbA1c levels from age 2 to 4 years at each percentile. Thereafter, there is a gradual increase during the prepubertal years with a peak at ages 12 to 14 years. HbA1c levels subsequently decline to the lowest values in the third decade. Curves of females and males followed closely, with females having HbA1c levels about 0.1% (1.1 mmol/mol) higher in the 25th 50th and 75th percentiles. Conclusion We constructed age-specific distribution curves for HbA1c levels for patients with T1DM. These percentiles may be used to demonstrate the individual patient's measurements longitudinally compared with age-matched patients. PMID:25275650

  19. Biochemical and molecular investigations on qualitative and quantitative Hb polymorphism in the river buffalo (Bubalus bubalis L. population reared in Southern Italy

    Directory of Open Access Journals (Sweden)

    Mario Iorio

    2004-01-01

    Full Text Available On 398 river buffalo samples, randomly collected in distinct breeding areas of the Campania region, high-resolution analytical systems were used to identify both qualitative and quantitative variations of the Hb phenotype. Polyacrylamide gel isoelectric focusing and HPLC were used to determine the ratio between HBA1 and HBA2 globin chains; restriction endonuclease analysis was performed to assess whether quantitative variations in Hb bands were related to an unusual number of a-globin genes. In the two buffalo subpopulations, allele frequencies of the alpha and beta globin systems were calculated, and F statistics (FIS, FIT and FST were estimated as parameters of genetic diversity. The results suggest that: i as shown by RFLP analysis, only a couple of associated a globin genes account for the quantitative variations recorded at the phenotypic level; ii as expected, in the a globin gene system (HBA, the frequency of haplotype B (HBA-B largely exceeded that of haplotype A (HBA-A (95.1% vs 4.9%; iii the frequency of the usual allele at the beta locus is 0.6, as opposed to 0.4 of the slow variant; iiii the most significant component of variation of the genetic system of hemoglobin is between individuals within the same location.

  20. Empirically establishing blood glucose targets to achieve HbA1c goals.

    Science.gov (United States)

    Wei, Nancy; Zheng, Hui; Nathan, David M

    2014-04-01

    OBJECTIVE To determine the average fasting, postprandial, and bedtime self-monitored blood glucose (SMBG) concentrations associated with specified HbA1c levels using data from the A1c-Derived Average Glucose (ADAG) study. RESEARCH DESIGN AND METHODS The ADAG study was a multicenter observational study that used continuous glucose monitoring and SMBG testing to determine the relationship between mean average glucose and HbA1c. We used the SMBG data from 470 of the ADAG study participants (237 with type 1 diabetes and 147 with type 2 diabetes) to determine the average fasting, premeal, 90-min postmeal, and bedtime blood glucose (BG) for predefined target HbA1c groups between 5.5 and 8.5% (37-69 mmol/mol). t Tests were used to compare mean BG values between type 1 and type 2 diabetes groups. RESULTS The average fasting BG needed to achieve predefined HbA1c target levels of 5.5-6.49% (37-47 mmol/mol), 6.5-6.99% (48-52 mmol/mol), 7.0-7.49% (52-58 mmol/mol), 7.5-7.99% (58-64 mmol/mol), and 8.0-8.5% (64-69 mmol/mol) were 122 mg/dL with 95% CI 117-127, 142 mg/dL (135-150), 152 mg/dL (143-162), 167 mg/dL (157-177), and 178 mg/dL (164-192), respectively. Postmeal BG to achieve the HbA1c level of 6.5-6.99% (48-52 mmol/mol) and 7.0-7.49% (52-58 mmol/mol) were 139 mg/dL (134-144) and 152 mg/dL (147-157), respectively. Bedtime BG was 153 mg/dL (145-161) and 177 mg/dL (166-188), respectively. CONCLUSIONS We have determined the average BG at premeal, postmeal, and bedtime to achieve a variety of HbA1c targets. These results, based on empirical data, will help patients and providers set realistic day-to-day SMBG targets to achieve individualized HbA1c goals.

  1. Decontamination and decommissioning of the MTR [Materials Testing Reactor]-603 HB-2 cubicle

    International Nuclear Information System (INIS)

    Smith, D.L.

    1987-10-01

    This paper describes the decontamination and decommissioning (D and D) of the MTR-603 HB-2 cubicle located at the Idaho National Engineering Laboratory (INEL). The HB-2 cubicle became radioactively contaminated during out-of-pile circulating water loop experiments conducted in the Materials Testing Reactor in the 1950s and 1960s. This paper describes work performed to accomplish the D and D objectives of reducing the high radiation fields caused by contamination inside the cubicle, preventing future contamination spread, and making about 1400 ft 2 of floor space available for reuse. Decommissioning of the HB-2 cubicle consisted of total dismantlement of the cubicle and its contents and was performed without disrupting ongoing laboratory work being conducted in areas surrounding the HB-2 cubicle. 3 refs., 7 figs., 4 tabs

  2. Fetal Anemia and Hydrops Fetalis Associated with Homozygous Hb Constant Spring (HBA2: c.427T > C).

    Science.gov (United States)

    He, Yi; Zhao, Ying; Lou, Ji-Wu; Liu, Yan-Hui; Li, Dong-Zhi

    2016-01-01

    Hb Constant Spring (Hb CS, HBA2: c.427T > C) is a common nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at the termination codon of the α2-globin gene. Homozygosity for Hb CS (α(CS)α/α(CS)α) is relatively rare, and generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. In this report we present a fetus with cardiomegaly, pericardial effusion, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 24 weeks' gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 4.8 g/dL] and Hb H (β4) disease-like hematological findings with Hb Bart's (γ4) level of 17.9%. DNA sequencing of the α-globin genes found that both partners were Hb CS carriers and the fetus was an Hb CS homozygote. Therefore, this was a rare case of homozygous Hb CS which demonstrated an unusual and serious anemia and hydrops fetalis in utero.

  3. HbA1c Identifies Subjects With Prediabetes and Subclinical Left Ventricular Diastolic Dysfunction.

    Science.gov (United States)

    Di Pino, Antonino; Mangiafico, Sarah; Urbano, Francesca; Scicali, Roberto; Scandura, Salvatore; D'Agate, Veronica; Piro, Salvatore; Tamburino, Corrado; Purrello, Francesco; Rabuazzo, Agata Maria

    2017-10-01

    Prediabetes is associated with subclinical cardiac changes associated with heart failure development. We investigated diastolic function and its association with markers of glycation and inflammation related to cardiovascular disease in patients with prediabetes. We focused on individuals with prediabetes identified only by glycated hemoglobin A1c [HbA1c; 5.7% to 6.4% and normal fasting glucose (NFG) and normal glucose tolerance (NGT) after an oral glucose tolerance test (OGTT)]. Cross-sectional study. Departments of Clinical and Experimental Medicine and Cardiology, University of Catania, Catania, Italy. HbA1c, OGTT, Doppler echocardiography, soluble receptor for advanced glycation end products (sRAGEs), and endogenous secretory RAGE (esRAGE) were evaluated. We recruited 167 subjects with NFG/NGT who were stratified according to HbA1c level: controls (HbA1c prediabetes (HbA1c 5.7% to 6.4%). Patients with HbA1c prediabetes (n = 106) showed a lower peak mitral inflow in early diastole (E wave) to late diastolic atrial filling velocity (A wave) ratio (E/A ratio) than controls (n = 61) (1.10 ± 0.24 vs 1.18 ± 0.23; P prediabetes exhibited subclinical cardiac alterations associated with sRAGE, esRAGE, and HbA1c. These subjects would not have been classified as having prediabetes on the basis of fasting glycemia or post-OGTT values. Copyright © 2017 Endocrine Society

  4. Decontamination and decommissioning of the MTR-603 HB-2 cubicle. Final report

    International Nuclear Information System (INIS)

    Smith, D.L.

    1985-12-01

    This report describes the decontamination and decommissioning (D and D) of the MTR-603 HB-2 cubicle located at the Idaho National Engineering Laboratory (INEL). The HB-2 cubicle became radioactively contaminated during out-of-pile circulating water loop experiments conducted in the Materials Testing Reactor in the 1950s and 1960s. This report describes work performed to accomplish the D and D objectives of reducing the high radiation fields caused by contamination inside the cubicle, preventing future contamination spread, and making about 1400 ft 2 of floor space available for reuse. D and D of the HB-2 cubicle consisted of total dismantlement of the cubicle and its contents

  5. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Keywords. Aminophospholipids; fluorescence; Hb variant; kinetics of heme loss; Soret absorption. Abstract. We report studies on loss of heme at or below pH 3.0 from two clinically important hemoglobin variants, HbE and HbS, in the presence and absence of phopholipid membranes. The kinetics of heme loss has been ...

  6. HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

    Science.gov (United States)

    Vijayakumar, Pavithra; Nelson, Robert G; Hanson, Robert L; Knowler, William C; Sinha, Madhumita

    2017-01-01

    Long-term data validating glycated hemoglobin (HbA 1c ) in assessing the risk of type 2 diabetes in children are limited. HbA 1c , fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA 1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA 1c , FPG, and 2hPG in predicting diabetes within 10 years were compared. During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA 1c ≥5.7% as in those with HbA 1c ≤5.3%-greater rate ratios than experienced by adults in the same HbA 1c categories. Analyses of ROCs revealed no significant differences between HbA 1c , FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. HbA 1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. © 2017 by the American Diabetes Association.

  7. Impact of Disease Management Programs on HbA1c Values in Type 2 Diabetes Patients in Germany.

    Science.gov (United States)

    Kostev, Karel; Rockel, Timo; Jacob, Louis

    2017-01-01

    The aim was to analyze the impact of disease management programs on HbA1c values in type 2 diabetes mellitus (T2DM) patients in Germany. This study included 9017 patients followed in disease management programs (DMPs) who started an antihyperglycemic treatment upon inclusion in a DMP. Standard care (SC) patients were included after individual matching (1:1) to DMP cases based on age, gender, physician (diabetologist versus nondiabetologist care), HbA1c values at baseline, and index year. The main outcome was the share of patients with HbA1c HbA1c level as a dependent variable and the potential predictor (DMP versus SC). The mean age was 64.3 years and 54.7% of the patients were men. The mean HbA1c level at baseline was equal to 8.7%. In diabetologist practices, 64.7% of DMP patients and 55.1% of SC patients had HbA1c levels HbA1c levels HbA1c levels HbA1c levels HbA1c levels lower than 7.5% or 6.5% after 6 months of therapy in both diabetologist and general care practices. The present study indicates that the enrollment of T2DM patients in DMPs has a positive impact on HbA1c values in Germany.

  8. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  9. Significance of HbA1c and its measurement in the diagnosis of diabetes mellitus: US experience.

    Science.gov (United States)

    Juarez, Deborah Taira; Demaris, Kendra M; Goo, Roy; Mnatzaganian, Christina Louise; Wong Smith, Helen

    2014-01-01

    The 2014 American Diabetes Association guidelines denote four means of diagnosing diabetes. The first of these is a glycosylated hemoglobin (HbA1c) >6.5%. This literature review summarizes studies (n=47) in the USA examining the significance, strengths, and limitations of using HbA1c as a diagnostic tool for diabetes, relative to other available means. Due to the relatively recent adoption of HbA1c as a diabetes mellitus diagnostic tool, a hybrid systematic, truncated review of the literature was implemented. Based on these studies, we conclude that HbA1c screening for diabetes has been found to be convenient and effective in diagnosing diabetes. HbA1c screening is particularly helpful in community-based and acute care settings where tests requiring fasting are not practical. Using HbA1c to diagnose diabetes also has some limitations. For instance, HbA1c testing may underestimate the prevalence of diabetes, particularly among whites. Because this bias differs by racial group, prevalence and resulting estimates of health disparities based on HbA1c screening differ from those based on other methods of diagnosis. In addition, existing evidence suggests that HbA1c screening may not be valid in certain subgroups, such as children, women with gestational diabetes, patients with human immunodeficiency virus, and those with prediabetes. Further guidelines are needed to clarify the appropriate use of HbA1c screening in these populations.

  10. Evaluation of risk factors in acute myocardial infarction patients admitted to the coronary care unit, Tripoli Medical Centre, Libya.

    Science.gov (United States)

    Abduelkarem, A R; El-Shareif, H J; Sharif, S I

    2012-04-01

    The aim of this study was to provide an overview of the risk factors for acute myocardial infarction in patients attending Tripoli Medical Centre, Libya. Records were reviewed for 622 patients with a mean age of 58.3 (SD 12.9) years. Diabetes mellitus (48.2%), hypertension (35.7%) and smoking (50.6%) were among the risk factors reported. There were 110 patients (17.7%) who died during hospitalization, mainly suffering cardiogenic shock (48.0%). The rate of use of thrombolytic therapy was low in patients who were female (40.4% versus 58.4% for males), older age (31.6% for those > 85 years versus 63.3% for patients < 55 years), diabetics (45.3% versus 62.0% for non-diabetic patients) and hypertensives (47.3% versus 57.8% for non-hypertensive patients). Prevention strategies should be implemented in order to improve the long-term prognosis and decrease overall morbidity and mortality from coronary artery disease in Libyan patients.

  11. Evaluation of a next generation direct whole blood enzymatic assay for hemoglobin A1c on the ARCHITECT c8000 chemistry system.

    Science.gov (United States)

    Teodoro-Morrison, Tracy; Janssen, Marcel J W; Mols, Jasper; Hendrickx, Ben H E; Velmans, Mathieu H; Lotz, Johannes; Lackner, Karl; Lennartz, Lieselotte; Armbruster, David; Maine, Gregory; Yip, Paul M

    2015-01-01

    The utility of HbA1c for the diagnosis of type 2 diabetes requires an accurate, precise and robust test measurement system. Currently, immunoassay and HPLC are the most popular methods for HbA1c quantification, noting however the limitations associated with some platforms, such as imprecision or interference from common hemoglobin variants. Abbott Diagnostics has introduced a fully automated direct enzymatic method for the quantification of HbA1c from whole blood on the ARCHITECT chemistry system. Here we completed a method evaluation of the ARCHITECT HbA1c enzymatic assay for imprecision, accuracy, method comparison, interference from hemoglobin variants and specimen stability. This was completed at three independent clinical laboratories in North America and Europe. The total imprecision ranged from 0.5% to 2.2% CV with low and high level control materials. Around the diagnostic cut-off of 48 mmol/mol, the total imprecision was 0.6% CV. Mean bias using reference samples from IFCC and CAP ranged from -1.1 to 1.0 mmol/mol. The enzymatic assay also showed excellent agreement with HPLC methods, with slopes of 1.01 and correlation coefficients ranging from 0.984 to 0.996 compared to Menarini Adams HA-8160, Bio-Rad Variant II and Variant II Turbo instruments. Finally, no significant effect was observed for erythrocyte sedimentation or interference from common hemoglobin variants in patient samples containing heterozygous HbS, HbC, HbD, HbE, and up to 10% HbF. The ARCHITECT enzymatic assay for HbA1c is a robust and fully automated method that meets the performance requirements to support the diagnosis of type 2 diabetes.

  12. The use of sustainable architectural methods in designing a dwelling unit in Tripoli-Libya

    International Nuclear Information System (INIS)

    Almansouri, A. A.; El-Menghawi, F.

    2006-01-01

    The new urban built environment is considered as the most energy consuming theme as the industrial and technical devices have been applied without realising their side effects. Therefore, building started to function depending mostly on the mechanical equipment deemed to provide a comfortable atmosphere. As a consequence, this has led to, firstly, many ecological problems such as: the over and misuse of the energy resources, pollution, pollution and diseases. Secondly, an ignorance of the importance of the local climatic conditions, which contribute in defining an identity related specifically to every climatic region. This will result in having a typicality that makes buildings have the same features all around the world regardless the cultural, social and physical differences. In Libya, some issues related to this subject are neglected or rarely studied. This paper, therefore, aims to highlight some architectural solutions that contribute extremely in reducing building's energy consumption as well as creating an architecture related to the local environment. In this paper. an overview of the general architecture principles and a study of the components of the environmental treatments for different climatic zones will be given. A proposal model of a house for a Libyan family lives in Tripoli will be shown in order to give an idea about the application of some architectural treatments for sustainable buildings taking into consideration the physical, cultural and social differences.(Author)

  13. Evaluation of high performance liquid chromatography (HPLC) pattern and prevalence of beta-thalassaemia trait among sickle cell disease patients in Lagos, Nigeria.

    Science.gov (United States)

    Adeyemo, Titilope; Ojewunmi, Oyesola; Oyetunji, Ajoke

    2014-01-01

    Sickle cell disease (SCD) is the most common inherited disorder of haemoglobin worldwide. This study evaluated the chromatographic patterns and red blood cell indices of sickle cell patients to determine the co-inheritance of other haemoglobin(Hb) variants and β-thalassaemia trait. Red cell indices, blood film, sickle solubility test, Hb electrophoresis using alkaline cellulose acetate membrane, and chromatographic patterns using Bio Rad HPLC Variant II were evaluated for 180 subjects. Based on low MCV 4.0% on HPLC and Hb variants eluting outside the S and C windows, at least four haemoglobin phenotypes (SS: 87.7%; SC: 1.1%; SD Punjab: 0.6%; Sβ-thalassemia: 10.6%) were identified. Mean Hb F% was 8.1±5.1 (median 7.65) for Hb SS and 6.03±5.2 (median 3.9) for Hb Sβ-thalassemia trait. Majority of Hb SS (69.1%) had Hb F% less than 10 while 27.6% had 10-19.9 and 3.2% had ≥ 20. Mean Hb F% was higher in female Hb SS (9.55±5.09; mean age 7.4±3.8 years) than the males (7.63±4.80; mean age 6.9±3.8 years) (P=0.02). A borderline significant negative correlation between age and Hb F levels among Hb SS subjects (r= -0.169 P=0.038) was also observed. Our data suggests that α and β- thalassaemia traits, and other haemoglobin variants co-exist frequently with SCD in our population.

  14. Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in Patients with Haemodialysis.

    Science.gov (United States)

    Rasche, Franz Maximilian; Ebert, Thomas; Beckmann, Julia; Busch, Volker; Barinka, Filip; Rasche, Wilma Gertrud; Lindner, Tom H; Schneider, Jochen G; Schiekofer, Stephan

    2017-06-01

    HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin α (n=48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of ΔHbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Change in Sedentary Time, Physical Activity, Bodyweight, and HbA1c in High-Risk Adults.

    Science.gov (United States)

    McCarthy, Matthew; Edwardson, Charlotte L; Davies, Melanie J; Henson, Joseph; Gray, Laura; Khunti, Kamlesh; Yates, Thomas

    2017-06-01

    In recent years, there has been a migration toward the use of glycated hemoglobin (HbA1c) in determining glycemic control. This study aimed to quantify the associations between changes in body weight, sedentary time, and moderate to vigorous physical activity (MVPA) time with HbA1c levels for a 3-yr period among adults at high risk of type 2 diabetes. This study reports baseline and 3-yr follow-up data from the Walking Away from Type 2 Diabetes study. ActiGraph GT3X accelerometers captured sedentary time and MVPA. Linear regression examined the independent associations of changes in sedentary time, MVPA, and body weight with HbA1c between baseline and 3-yr follow-up. The sample composed of 489 participants (mean age = 64.2 ± 7.3 yr, body mass index = 31.7 ± 5.1, 63.4% male) with valid baseline and follow-up accelerometer, body weight, and HbA1c data. After adjustment for known confounders, an increase in MVPA time (per 30 min·d) was associated with a decrease in HbA1c percentage (β = -0.11 [-0.18 to -0.05], P = 0.001), and an increase in body weight (per 6 kg) was associated with an increase in HbA1c percentage (β = 0.08 [0.04-0.12], P HbA1c ≥ 6.0%) strengthened these associations (P HbA1c after adjustment for change in MVPA time. Increases in MVPA and body weight were associated with a reduction and increase in HbA1c, respectively, particularly in those with dysglycemia. Quantifying the effect that health behavior changes have on HbA1c can be used to inform prevention programs.

  16. Serum testosterone levels of HbSS (sickle cell disease male subjects in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Adediran Adewumi

    2011-08-01

    Full Text Available Abstract Background Infertility is a major problem in sickle cell disease patients, especially in males. In addition to low serum testosterone, other abnormalities involving the accessory sex organs, such as the seminal vesicles and the prostate gland, as well as marked decrease in ejaculate volume may be observed in male HbSS patients. Hence, the need to study the role of sex hormones as a cause of infertility in male HbSS patients. Methods An unmatched case-control study was performed using seventy-five consenting subjects from Lagos University Teaching Hospital. These included 47 patients with haemoglobin phenotype SS from the Sickle cell clinic and 28 volunteered medical students and members of staff with haemoglobin phenotype AA. Demographic data were obtained using a self-administered questionnaire. A total of 5 mls of blood was collected from each subject between 9.00 am & 11.am, and assayed for serum testosterone concentration. Results The concentrations of serum testosterone in HbSS patients ranged from 0.2 to 4.3 ng/ml with a mean of 1.28 ± 0.72 ng/ml whilst the values in HbAA controls ranged from 1.2 to 6.9 ng/ml with a mean of 2.63 ± 1.04 ng/ml. Seven (25.0% of the 28 controls had serum testosterone concentration lower than the quoted reference (normal range whereas 44 (93.6% of the 47 HbSS subjects had serum testosterone concentration lower than the reference range. Conclusion Overall, subjects with HbSS have significantly lower mean serum testosterone than HbAA controls.

  17. HB 1347 and Its Relationship to Foodservice Outsourcing in Illinois Public Schools

    Science.gov (United States)

    Brashear, Gary L.

    2012-01-01

    This study examined foodservice outsourcing in the State of Illinois. School administrators currently outsourcing foodservice were surveyed about their perceptions of HB1347 and its components. This study looked at HB1347 in Illinois, and its effects on outsourcing in school districts. Data for this study was collected from a survey sent to 100%…

  18. High maternal HbA1c is associated with overweight in neonates

    DEFF Research Database (Denmark)

    Mikkelsen, Maria R.; Nielsen, Sigrid Bruun; Stage, E

    2011-01-01

    The aims of this study were to determine the prevalence of women with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal range (= 5.6%) before delivery and to examine whether elevated HbA1c values are associated with an increased risk of large for gestational age (LGA) infa...

  19. PEGYLATION OF αα-Hb USING SUCCINIMIDYL PROPIONIC ACID PEG 5K

    Science.gov (United States)

    Meng, Fantao; Tsai, Amy G.; Intaglietta, Marcos; Acharya, Seetharama A.

    2014-01-01

    PEGylation of intramolecularly crosslinked Hb has been studied here to overcome the limitation of dissociation of Hb tetramers. New hexa and deca PEGylated low oxygen affi nity PEG-αα-Hbs have been generated. Infl uence of PEG conjugation chemistry and the PEG shell structure on the functional properties as well as PEGylation induced plasma expander like properties of the protein has been delineated. The results have established that in the design of PEG-Hbs as oxygen therapeutics, the infl uence of conjugation chemistry and the PEG shell structure on the oxygen affi nity of Hb needs to be optimized independently besides optimizing the PEG shell structure for inducing resuscitation fluid like properties. PMID:24597567

  20. HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix

    Science.gov (United States)

    Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki

    2016-01-01

    Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

  1. Prevalence and molecular characterization of abnormal hemoglobin in eastern Guangdong of southern China.

    Science.gov (United States)

    Lin, M; Wang, Q; Zheng, L; Huang, Y; Lin, F; Lin, C P; Yang, L Y

    2012-02-01

    Abnormal hemoglobins (Hbs) are the most commonly inherited disorders in humans. Their frequency and types change considerably with geographic location and ethnic group. To investigate the molecular epidemiological characterization of abnormal Hbs in eastern Guangdong of southern China, a total of 11,450 'healthy' subjects were subjected to hemoglobin electrophoresis screening. Samples of EDTA-K(2) blood with abnormal Hbs were analyzed by CELL-DYN1700 blood analyzer; thalassemia genotypes and Hb E variant were identified by gap-PCR and/or reverse dot blot (RDB). The genotypes of Hb variants were detected by PCR and sequencing. The incidence of abnormal Hbs was 0.358%(41/11,450) in Chaozhou, including 12.2% (5/41) Hb J, 4.9% (2/41) Hb K, 9.7% (4/41) Hb Q, 31.7% (13/41) Hb G/D and 41.5% (17/41) Hb E. Eight types of Hb variants were found, including 3 cases of Hb J-Bangkok, 2 cases of Hb J-Wenchang-Wuming, 2 cases of Hb New York, 4 cases of Hb Q-Thailand, 5 cases of Hb G-Waimanalo, 4 cases of Hb Ottawa, 4 cases of Hb G-Chinese and 17 cases of Hb E. In comparison with other areas of Guangdong, Chaozhou had a different pattern of abnormal Hbs with a high prevalence of Hb G/D. This study describes the prevalence and molecular characterization of abnormal Hbs in eastern Guangdong. © 2011 John Wiley & Sons A/S.

  2. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Paula Breitenbach Renz

    Full Text Available Gestational diabetes mellitus (GDM is a prevalent and potentially serious condition which may put both mothers and neonates at risk. The current recommendation for diagnosis is the oral glucose tolerance test (OGTT. This study aimed to determine the usefulness of HbA1c test as a diagnostic tool for GDM as compared to the traditional criteria based on the OGTT.This was a diagnostic test accuracy study. We performed OGTT and HbA1c test in women attending prenatal visits at a tertiary hospital. GDM was defined according to WHO1999 or ADA/WHO 2013 criteria. ROC curve was used to evaluate the diagnostic performance of HbA1c. Sensitivity, specificity and likelihood ratios for different HbA1c cut-off points were calculated.Of the 262 women in the third trimester of gestation enrolled in the study, 86 (33% were diagnosed with GDM. Only five of these women presented HbA1c ≥48 mmol/mol (6.5%. This cut-off point presented 100% specificity but very low sensitivity (7%. Based on ROC curve, and considering OGTT as the reference criterion, HbA1c ≥40 mmol/mol (5.8% showed adequate specificity in diagnosing GDM (94.9% but low sensitivity (26.4%. Unlike, HbA1c values of 31 mmol/mol (5.0% presented adequate sensitivity (89.7% but low specificity (32.6% to detect GDM. For women with HbA1c ≥40 mmol/mol (5.8%, the positive and negative likelihood ratios were 5.14 (95%CI 2.49-10.63 and 0.78 (0.68-0.88, respectively. The post-test probability of GDM was about 40%, representing a 4.0-fold increase in the mean pre-test probability. This cut-off point could eliminate the need for the unpleasant and laborious OGTT tests in almost one third of cases, as 38% of patients with GDM may be diagnosable by HbA1c test alone.Our results show that combined HbA1c and OGTT measurements may be useful in diagnosing GDM.

  3. Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c

    Science.gov (United States)

    Jeon, Ja Young; Ko, Seung-Hyun; Kwon, Hyuk-Sang; Kim, Nan Hee; Kim, Jae Hyeon; Kim, Chul Sik; Song, Kee-Ho; Won, Jong Chul; Lim, Soo; Choi, Sung Hee; Jang, Myoung-jin; Kim, Yuna; Oh, Kyungwon

    2013-01-01

    Background Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests. Methods Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%. Results When we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5%) and 19.3% (men, 23.8%; women, 14.9%), respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4%) and 38.3% (men, 41%; women, 35.7%), respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate. Conclusion We concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes. PMID:24199164

  4. Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c

    Directory of Open Access Journals (Sweden)

    Ja Young Jeon

    2013-10-01

    Full Text Available BackgroundDue to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG level only or the combination of FPG and HbA1c tests.MethodsData from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%.ResultsWhen we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5% and 19.3% (men, 23.8%; women, 14.9%, respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4% and 38.3% (men, 41%; women, 35.7%, respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate.ConclusionWe concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes.

  5. [Assays of HbA1c and Amadori products in human biology].

    Science.gov (United States)

    Gillery, P

    2014-09-01

    Different Amadori products, formed during the early steps of the non-enzymatic glycation of proteins, may be assayed in current practice in human biology. The most important marker is HbA1c, resulting from the binding of glucose to the N-terminal extremity of HbA beta chains. HbA1c may be evaluated by various techniques (ion exchange or affinity high performance liquid chromatography, capillary electrophoresis, immunoassay, enzymatic technique) and is considered the best marker of diabetic patient survey. Due to its irreversible and cumulative formation, it provides a retrospective information on the glycemic balance over the four to eight weeks preceding blood collection. It benefits from an international standardization, based on a reference method using liquid chromatography coupled to capillary electrophoresis or mass spectrometry, maintained by an international network of reference laboratories. When HbA1c assay cannot be used (anemia, hemolysis, hemoglobinopathy) or when a shorter period of glycemic equilibrium must be evaluated (child and adolescent, pregnancy, therapeutic changes), other Amadori products may be assayed, like plasma fructosamine (all plasma glycated proteins) or glycated albumin. Nevertheless, these assays are less used in practice, because their semiological value has been less evidenced. Besides, fructosamine assay lacks specificity, and glycated albumin assay has been described recently. An expanding use of HbA1c assay is expected, especially for the diagnosis of diabetes mellitus and the evaluation of other risks, especially cardiovascular ones. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Benchmarking by HbA1c in a national diabetes quality register--does measurement bias matter?

    Science.gov (United States)

    Carlsen, Siri; Thue, Geir; Cooper, John Graham; Røraas, Thomas; Gøransson, Lasse Gunnar; Løvaas, Karianne; Sandberg, Sverre

    2015-08-01

    Bias in HbA1c measurement could give a wrong impression of the standard of care when benchmarking diabetes care. The aim of this study was to evaluate how measurement bias in HbA1c results may influence the benchmarking process performed by a national diabetes register. Using data from 2012 from the Norwegian Diabetes Register for Adults, we included HbA1c results from 3584 patients with type 1 diabetes attending 13 hospital clinics, and 1366 patients with type 2 diabetes attending 18 GP offices. Correction factors for HbA1c were obtained by comparing the results of the hospital laboratories'/GP offices' external quality assurance scheme with the target value from a reference method. Compared with the uncorrected yearly median HbA1c values for hospital clinics and GP offices, EQA corrected HbA1c values were within ±0.2% (2 mmol/mol) for all but one hospital clinic whose value was reduced by 0.4% (4 mmol/mol). Three hospital clinics reduced the proportion of patients with poor glycemic control, one by 9% and two by 4%. For most participants in our study, correcting for measurement bias had little effect on the yearly median HbA1c value or the percentage of patients achieving glycemic goals. However, at three hospital clinics correcting for measurement bias had an important effect on HbA1c benchmarking results especially with regard to percentages of patients achieving glycemic targets. The analytical quality of HbA1c should be taken into account when comparing benchmarking results.

  7. Evaluation of the HB&L System for the Microbiological Screening of Storage Medium for Organ-Cultured Corneas.

    Science.gov (United States)

    Camposampiero, D; Grandesso, S; Zanetti, E; Mazzucato, S; Solinas, M; Parekh, M; Frigo, A C; Gion, M; Ponzin, D

    2013-01-01

    Aims. To compare HB&L and BACTEC systems for detecting the microorganisms contaminating the corneal storage liquid preserved at 31°C. Methods. Human donor corneas were stored at 4°C followed by preservation at 31°C. Samples of the storage medium were inoculated in BACTEC Peds Plus/F (aerobic microorganisms), BACTEC Plus Anaerobic/F (anaerobic microorganisms), and HB&L bottles. The tests were performed (a) after six days of storage, (b) end of storage, and (c) after 24 hours of preservation in deturgescent liquid sequentially. 10,655 storage and deturgescent media samples were subjected to microbiological control using BACTEC (6-day incubation) and HB&L (24-hour incubation) systems simultaneously. BACTEC positive/negative refers to both/either aerobic and anaerobic positives/negatives, whereas HB&L can only detect the aerobic microbes, and therefore the positives/negatives depend on the presence/absence of aerobic microorganisms. Results. 147 (1.38%) samples were identified positive with at least one of the two methods. 127 samples (134 identified microorganisms) were positive with both HB&L and BACTEC. 14 HB&L+/BACTEC- and 6 BACTEC+/HB&L- were identified. Sensitivity (95.5%), specificity (99.8%), and positive (90.1%) and negative predictive values (99.9%) were high with HB&L considering a 3.5% annual contamination rate. Conclusion. HB&L is a rapid system for detecting microorganisms in corneal storage medium in addition to the existing methods.

  8. Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance.

    Science.gov (United States)

    Pappas, Colleen; Andel, Ross; Infurna, Frank J; Seetharaman, Shyam

    2017-02-01

    As the ageing population grows, it is important to identify strategies to moderate cognitive ageing. We examined glycated haemoglobin (HbA1c) and diabetes in relation to level and change in episodic memory in older adults with and without diabetes. Data from 4419 older adults with (n=950) and without (n=3469) diabetes participating in a nationally representative longitudinal panel study (the Health and Retirement Study) were examined. Average baseline age was 72.66 years and 58% were women. HbA1c was measured in 2006 and episodic memory was measured using immediate and delayed list recall over 4 biennial waves between 2006 and 2012. Growth curve models were used to assess trajectories of episodic memory change. In growth curve models adjusted for age, sex, education, race, depressive symptoms and waist circumference, higher HbA1c levels and having diabetes were associated with poorer baseline episodic memory (p=0.036 and HbA1c on episodic memory decline was smaller than the effect of age. The results were stronger for women than men and were not modified by age or race. When the main analyses were estimated for those with and without diabetes separately, HbA1c was significantly linked to change in episodic memory only among those with diabetes. Higher HbA1c and diabetes were both associated with declines in episodic memory, with this relationship further exacerbated by having diabetes and elevated HbA1c. HbA1c appeared more important for episodic memory performance among women than men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Trimester-specific reference intervals for haemoglobin A(1c) (HbA(1c)) in pregnancy.

    LENUS (Irish Health Repository)

    O'Connor, Catherine

    2011-11-26

    Abstract Background: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA(1c)). The correlation of HbA(1c) with clinical outcomes emphasises the need to measure HbA(1c) accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA(1c) assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA(1c) in non-diabetic Caucasian women. Methods: The authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol\\/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13-27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term. Results: The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol\\/mol (Diabetes Control and Complications Trial; DCCT: 4.8%-5.5%), T1: 24-36 mmol\\/mol (DCCT: 4.3%-5.4%), T2: 25-35 mmol\\/mol (DCCT: 4.4%-5.4%) and T3: 28-39 mmol\\/mol (DCCT: 4.7%-5.7%). HbA(1c) was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. Conclusions: HbA(1c) trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.

  10. Radioisotope Characterization of HB Line Low Activity Waste

    International Nuclear Information System (INIS)

    Snyder, S.J.

    1999-01-01

    The purpose of this document is to provide a physical, chemical, hazardous and radiological characterization of Low-Level Waste (LLW) generated in HB-Line as required by the 1S Manual, Savannah River Site Waste Acceptance Criteria Manual

  11. Impact of demographics and disease progression on the relationship between glucose and HbA1c.

    Science.gov (United States)

    Claussen, Anetta; Møller, Jonas B; Kristensen, Niels R; Klim, Søren; Kjellsson, Maria C; Ingwersen, Steen H; Karlsson, Mats O

    2017-06-15

    Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012). To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model. Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, BMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component. Participants included 47% females and 20% above 65years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races. Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model. The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship. Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Discordance in the diagnosis of diabetes: Comparison between HbA1c and fasting plasma glucose.

    Science.gov (United States)

    Ho-Pham, Lan T; Nguyen, Uyen D T; Tran, Truong X; Nguyen, Tuan V

    2017-01-01

    HbA1c has been introduced as a complementary diagnostic test for diabetes, but its impact on disease prevalence is unknown. This study evaluated the concordance between HbA1c and fasting plasma glucose (FPG) in the diagnosis of diabetes in the general population. The study was designed as a population based investigation, with participants being sampled from the Ho Chi Minh City, Vietnam. Blood samples were collected after overnight fasting and analyzed within 4 hours after collection. HbA1c was measured with high pressure liquid chromatography (Arkray Adams, Japan). FPG was measured by the hexokinase method (Advia Autoanalyzer; Bayer Diagnostics, Germany). Diabetes was defined as HbA1c ≥ 6.5% or FPG ≥ 7.0 mmol/L. Prediabetes was classified as HbA1c between 5.7% and 6.4%. The study included 3523 individuals (2356 women) aged 30 years and above. Based on the HbA1c test, the prevalence of diabetes and prediabetes was 9.7% (95%CI, 8.7-10.7%; n = 342) and 34.6% (33.0-36.2; n = 1219), respectively. Based on the FPG test, the prevalence of diabetes and prediabetes was 6.3% (95%CI, 5.5-7.2%; n = 223) and 12.1% (11.1-13.2; n = 427). Among the 427 individuals identified by FPG as "pre-diabetes", 28.6% were classified as diabetes by HbA1c test. The weighted kappa statistic of concordance between HbA1c and FPG was 0.55, with most of the discordance being in the prediabetes group. These data indicate that there is a significant discordance in the diagnosis of diabetes between FPG and HbA1c measurements, and the discordance could have significant impact on clinical practice. FPG appears to underestimate the burden of undiagnosed diabetes.

  13. HB-Line Material Control and Accountability Measurements at SRS

    International Nuclear Information System (INIS)

    Casella, V.R.

    2003-01-01

    Presently, HB-Line work at the Savannah River Site consists primarily of the stabilization and packaging of nuclear materials for storage and the characterization of materials for disposition in H-Area. In order to ensure compliance with Material Control and Accountability (MC and A) Regulations, accountability measurements are performed throughout the HB-Line processes. Accountability measurements are used to keep track of the nuclear material inventory by constantly updating the amount of material in the MBAs (Material Balance Area) and sub-MBAs. This is done by subtracting the amount of accountable material that is added to a process and by adding the amount of accountable material that is put back in storage. A Physical Inventory is taken and compared to the ''Book Value'' listed in the Nuclear Material Accounting System. The difference (BPID) in the Book Inventory minus the Physical Inventory of a sub-account for bulk material must agree within the measurement errors combined in quadrature to provide assurance that nuclear material is accounted for. This work provides an overview of HB-Line processes and accountability measurements. The Scrap Recovery Line and Neptunium-237/Plutonium-239 Oxide Line are described and sampling and analyses for Phase II are provided. Recommendations for improvements are provided to improve efficiency and cost effectiveness

  14. Glutathione Redox System in β-Thalassemia/Hb E Patients

    Directory of Open Access Journals (Sweden)

    Ruchaneekorn W. Kalpravidh

    2013-01-01

    Full Text Available β-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH/glutathione disulfide (GSSG and also to evaluate glutathione-related responses to oxidation in β-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 β-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body’s first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores.

  15. Defining a glycated haemoglobin (HbA1c) level that predicts increased risk of penile implant infection.

    Science.gov (United States)

    Habous, Mohamad; Tal, Raanan; Tealab, Alaa; Soliman, Tarek; Nassar, Mohammed; Mekawi, Zenhom; Mahmoud, Saad; Abdelwahab, Osama; Elkhouly, Mohamed; Kamr, Hatem; Remeah, Abdallah; Binsaleh, Saleh; Ralph, David; Mulhall, John

    2018-02-01

    To re-evaluate the role of diabetes mellitus (DM) as a risk factor for penile implant infection by exploring the association between glycated haemoglobin (HbA1c) levels and penile implant infection rates and to define a threshold value that predicts implant infection. We conducted a multicentre prospective study including all patients undergoing penile implant surgery between 2009 and 2015. Preoperative, perioperative and postoperative management were identical for the entire cohort. Univariate analysis was performed to define predictors of implant infection. The HbA1c levels were analysed as continuous variables and sequential analysis was conducted using 0.5% increments to define a threshold level predicting implant infection. Multivariable analysis was performed with the following factors entered in the model: DM, HbA1C level, patient age, implant type, number of vascular risk factors (VRFs), presence of Peyronie's disease (PD), body mass index (BMI), and surgeon volume. A receiver operating characteristic (ROC) curve was generated to define the optimal HbA1C threshold for infection prediction. In all, 902 implant procedures were performed over the study period. The mean patient age was 56.6 years. The mean HbA1c level was 8.0%, with 81% of men having a HbA1c level of >6%. In all, 685 (76%) implants were malleable and 217 (24%) were inflatable devices; 302 (33.5%) patients also had a diagnosis of PD. The overall infection rate was 8.9% (80/902). Patients who had implant infection had significantly higher mean HbA1c levels, 9.5% vs 7.8% (P HbA1c level, we found infection rates were: 1.3% with HbA1c level of 9.5% (P HbA1c level, whilst a high-volume surgeon had a protective effect and was associated with a reduced infection risk. Using ROC analysis, we determined that a HbA1c threshold level of 8.5% predicted infection with a sensitivity of 80% and a specificity of 65%. Uncontrolled DM is associated with increased risk of infection after penile implant surgery

  16. Significance of HbA1c and its measurement in the diagnosis of diabetes mellitus: US experience

    Directory of Open Access Journals (Sweden)

    Juarez DT

    2014-10-01

    Full Text Available Deborah Taira Juarez, Kendra M Demaris, Roy Goo, Christina Louise Mnatzaganian, Helen Wong SmithDaniel K Inouye College of Pharmacy, University of Hawaii at Hilo, Honolulu, HI, USAAbstract: The 2014 American Diabetes Association guidelines denote four means of diagnosing diabetes. The first of these is a glycosylated hemoglobin (HbA1c >6.5%. This literature review summarizes studies (n=47 in the USA examining the significance, strengths, and limitations of using HbA1c as a diagnostic tool for diabetes, relative to other available means. Due to the relatively recent adoption of HbA1c as a diabetes mellitus diagnostic tool, a hybrid systematic, truncated review of the literature was implemented. Based on these studies, we conclude that HbA1c screening for diabetes has been found to be convenient and effective in diagnosing diabetes. HbA1c screening is particularly helpful in community-based and acute care settings where tests requiring fasting are not practical. Using HbA1c to diagnose diabetes also has some limitations. For instance, HbA1c testing may underestimate the prevalence of diabetes, particularly among whites. Because this bias differs by racial group, prevalence and resulting estimates of health disparities based on HbA1c screening differ from those based on other methods of diagnosis. In addition, existing evidence suggests that HbA1c screening may not be valid in certain subgroups, such as children, women with gestational diabetes, patients with human immunodeficiency virus, and those with prediabetes. Further guidelines are needed to clarify the appropriate use of HbA1c screening in these populations.Keywords: diabetes mellitus, diagnosis, glycosylated hemoglobin, USA

  17. Clinical and hematological response to hydroxyurea in a patient with Hb Lepore/beta-thalassemia.

    Science.gov (United States)

    Rigano, P; Manfré, L; La Galla, R; Renda, D; Renda, M C; Calabrese, A; Calzolari, R; Maggio, A

    1997-05-01

    The possibility of increasing Hb F in vivo using drugs like 5-azacytidine, hydroxyurea, and butyrate has been established. However, in many cases this does not entail an increase in total hemoglobin. We report on a patient with Hb Lepore/beta-thalassemia being treated with hydroxyurea (30 mg/Kg/day) because of the presence of erythroid extramedullary masses with severe neurological abnormalities. During therapy the patient showed a remarkable improvement in neurological signs due to the reduction in extra-medullary masses, a significant increase in both total hemoglobin (from 5.8 to 9.7 g/dl) and Hb F (from 4.9 g/dl to 9.1 g/dl). The marked improvement in hemoglobin level in our patient with Hb Lepore/beta-thalassemia suggests gamma-globin gene activation due to the DNA structure determined by the crossover event.

  18. On a New Variance Reduction Technique: Neural Network Biasing-a Study of Two Test Cases with the Monte Carlo Code Tripoli4

    International Nuclear Information System (INIS)

    Dumonteil, E.

    2009-01-01

    Various variance-reduction techniques are used in Monte Carlo particle transport. Most of them rely either on a hypothesis made by the user (parameters of the exponential biasing, mesh and weight bounds for weight windows, etc.) or on a previous calculation of the system with, for example, a deterministic solver. This paper deals with a new acceleration technique, namely, auto-adaptative neural network biasing. Indeed, instead of using any a priori knowledge of the system, it is possible, at a given point in a simulation, to use the Monte Carlo histories previously simulated to train a neural network, which, in return, should be able to provide an estimation of the adjoint flux, used then for biasing the simulation. We will describe this method, detail its implementation in the Monte Carlo code Tripoli4, and discuss its results on two test cases. (author)

  19. The effects of detergent, sodium tripoly-phosphate and ethoxyled oleyl-cetyl alcohol on metabolic parameters of the fungus Trichothecium roseum link

    Directory of Open Access Journals (Sweden)

    Stojanović Jelica

    2011-01-01

    Full Text Available The degradation of detergents that are dispersed in water and soil partially depends on the metabolic activities of fungi. Among the fungi that have this ability, Deuteromycetes are particularly noted for their biochemical characteristics. Taking this into account, it was of interest to analyze the influence of detergent and its main compounds, ethoxyled oleylcetyl alcohol (AOC and sodium tripoly-phosphate (TTP, on the metabolism of the fungus Trichothecium roseum. Our results revealed that both detergent and AOC had an inhibitory effect on the bioproduction of free organic acids, while TTP stimulated their production. Also, detergent inhibited the bioproduction of basic amino acids, with the exception of alanine. In addition, detergent applied at 1% concentration inhibited the bioproduction of proteins and the total biomass of the fungus, while AOC and TTP inhibited the production of proteins, but stimulatedl the production of Trichothecium.

  20. Cation-exchange high-performance liquid chromatography for variant hemoglobins and HbF/A2: What must hematopathologists know about methodology?

    OpenAIRE

    Sharma, Prashant; Das, Reena

    2016-01-01

    Cation-exchange high-performance liquid chromatography (CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It’s versatility, speed, reproducibility and convenience have made CE-HPLC the method of choice to initially screen for hemoglobin disorders. Despite its popularity, several methodological aspects of the technology remain obscure to pathologists and this may have consequences in spec...

  1. Implementation of an approximate zero-variance scheme in the TRIPOLI Monte Carlo code

    Energy Technology Data Exchange (ETDEWEB)

    Christoforou, S.; Hoogenboom, J. E. [Delft Univ. of Technology, Mekelweg 15, 2629 JB Delft (Netherlands); Dumonteil, E.; Petit, O.; Diop, C. [Commissariat a l' Energie Atomique CEA, Gif-sur-Yvette (France)

    2006-07-01

    In an accompanying paper it is shown that theoretically a zero-variance Monte Carlo scheme can be devised for criticality calculations if the space, energy and direction dependent adjoint function is exactly known. This requires biasing of the transition and collision kernels with the appropriate adjoint function. In this paper it is discussed how an existing general purpose Monte Carlo code like TRIPOLI can be modified to approach the zero-variance scheme. This requires modifications for reading in the adjoint function obtained from a separate deterministic calculation for a number of space intervals, energy groups and discrete directions. Furthermore, a function has to be added to supply the direction dependent and the averaged adjoint function at a specific position in the system by interpolation. The initial particle weights of a certain batch must be set inversely proportional to the averaged adjoint function and proper normalization of the initial weights must be secured. The sampling of the biased transition kernel requires cumulative integrals of the biased kernel along the flight path until a certain value, depending on a selected random number is reached to determine a new collision site. The weight of the particle must be adapted accordingly. The sampling of the biased collision kernel (in a multigroup treatment) is much more like the normal sampling procedure. A numerical example is given for a 3-group calculation with a simplified transport model (two-direction model), demonstrating that the zero-variance scheme can be approximated quite well for this simplified case. (authors)

  2. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

    Science.gov (United States)

    Sibmooh, Nathawut; Fucharoen, Suthat

    2017-01-01

    Abstract Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The βE-globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794–813. PMID:27650096

  3. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

    Science.gov (United States)

    Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

    2017-05-10

    Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

  4. Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9.

    Science.gov (United States)

    Ashok, Anushruti; Rai, Nagendra Kumar; Raza, Waseem; Pandey, Rukmani; Bandyopadhyay, Sanghamitra

    2016-11-01

    Chronic cerebral hypoperfusion (CCH) manifests Alzheimer's Disease (AD) neuropathology, marked by increased amyloid beta (Aβ). Besides, hypoxia stimulates Heparin-binding EGF-like growth factor (HB-EGF) mRNA expression in the hippocampus. However, involvement of HB-EGF in CCH-induced Aβ pathology remains unidentified. Here, using Bilateral Common Carotid Artery Occlusion mouse model, we explored the mechanism of HB-EGF regulated Aβ induction in CCH. We found that HB-EGF inhibition suppressed, while exogenous-HB-EGF triggered hippocampal Aβ, proving HB-EGF-dependent Aβ increase. We also detected that HB-EGF affected the expression of primary Aβ transporters, receptor for advanced glycation end-products (RAGE) and lipoprotein receptor-related protein-1 (LRP-1), indicating impaired Aβ clearance across the blood-brain barrier (BBB). An HB-EGF-dependent loss in BBB integrity supported impaired Aβ clearance. The effect of HB-EGF on Amyloid Precursor Protein pathway was relatively insignificant, suggesting a lesser effect on Aβ generation. Delving into BBB disruption mechanism demonstrated HB-EGF-mediated stimulation of Matrix metalloprotease-9 (MMP9), which affected BBB via HB-EGF-ectodomain shedding and epidermal growth factor receptor activation. Examining the intersection of HB-EGF-regulated pathway and hypoxia revealed HB-EGF-dependent increase in transcription factor, Hypoxia-inducible factor-1alpha (HIF1α). Further, via binding to hypoxia-responsive elements in MMP9 gene, HIF1α stimulated MMP9 expression, and therefore appeared as a prominent intermediary in HB-EGF-induced BBB damage. Overall, our study reveals the essential role of HB-EGF in triggering CCH-mediated Aβ accumulation. The proposed mechanism involves an HB-EGF-dependent HIF1α increase, generating MMP9 that stimulates soluble-HB-EGF/EGFR-induced BBB disintegration. Consequently, CCH-mediated hippocampal RAGE and LRP-1 deregulation together with BBB damage impair Aβ transport and clearance

  5. The macrophage scavenger receptor CD163

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Madsen, Mette; Møller, Holger J

    2006-01-01

    CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are subs......CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants...

  6. WALKABILITY IN HISTORIC URBAN SPACES: TESTING THE SAFETY AND SECURITY IN MARTYRS' SQUARE IN TRIPOLI

    Directory of Open Access Journals (Sweden)

    Khairi M. Al-bashir Abdulla

    2017-11-01

    Full Text Available Much of the built environment design literature focuses on a composite of walkable spaces variables such as density, diversity, and destination accessibility.  One of the most effective factors in walkability is “safety and security”. There is an evident gap in understanding the perceived ability of Libyan public spaces to support walkability. This paper aims to investigate the effectiveness of “walkability” in traditional Libyan urban spaces and analyse the relationship between walking, a safe and secure environment, and its impact on a heritage site in Tripoli city centre. The perceived personal safety of 140 users of the heritage site “Martyrs' Square” were measured; this research is studying the quality of environment and users’ interaction with their environmental issues relating to the study area. Mixed methods were used in this research: this study used both quantitative and qualitative methods to gather information; the quantitative took the form of a questionnaire; and the qualitative took the form of observations. Analysis of quantitative data was conducted with SPSS software; the survey was conducted from August 2016 to September 2016. The results of this study are useful for urban planning, to classify the walkable urban space elements, which could improve the level of walkability in Libyan cities and create sustainable and liveable urban spaces.

  7. Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes.

    Science.gov (United States)

    Law, Graham R; Gilthorpe, Mark S; Secher, Anna L; Temple, Rosemary; Bilous, Rudolf; Mathiesen, Elisabeth R; Murphy, Helen R; Scott, Eleanor M

    2017-04-01

    This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA 1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA 1c measurements are applicable to pregnant women with diabetes. CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5-7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA 1c measure. In total, 688 average glucose-HbA 1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA 1c . There was a strong association between HbA 1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA 1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA 1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4-7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA 1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week. The HbA 1c -average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care.

  8. Improving access to HbA1c in sub-Saharan Africa (IA3) cohort: cohort profile.

    Science.gov (United States)

    Balde, Naby; Camara, Alioune; Sobngwi-Tambekou, Joelle; Balti, Eric Vounsia; Tchatchoua, Alain; Fezeu, Leopold; Limen, Serge; Ngamani, Sylvie; Ngapout, Suzanne; Kengne, Andre Pascal; Sobngwi, Eugene

    2017-01-01

    Glycated haemoglobin (HbA1c) is the best surrogate of average blood glucose control in diabetic patients, and lowering HbA1c significantly reduces diabetes complications. Moreover, immediate feedback of HbA1c measurement to patients may improve control. However, HbA1c is unavailable in most parts of Africa, a continent with one of the highest burden of diabetes. To translate these evidences, we are conducting a multicentric project in 10 health care facilities in Guinea and Cameroon to evaluate the feasibility and one-year benefit of affordable HbA1c measurement with immediate feedback to patients on diabetes control and related outcomes. We consecutively enrolled patients with diabetes mellitus independently of the type of disease. We hypothesised an average 1%-decrease in HbA1c in a 1000-patient study population, with a 20% increase in the number of patients reaching treatment goals within 12 months of intervention and follow-up. A total of 1, 349 diabetic patients aged 56.2±12.6 years are enrolled (813 in Cameroon and 536 in Guinea) of whom 59.8% are women. The mean duration of diabetes is 7.4±6.3 years and baseline HbA1c is 9.7±2.6% in Guinea and 8.6±2.5% in Cameroon. To investigate whether the introduction of routine HbA1c measurement with immediate feedback to patients and provision of relevant education would improve diabetes control after one year. The impact of the intervention on diabetes associated-complications and mortality warrant further assessment in the long term.

  9. Oxidized LDL but not total LDL is associated with HbA1c in individuals without diabetes.

    Science.gov (United States)

    Spessatto, Débora; Brum, Liz Marina Bueno Dos Passos; Camargo, Joíza Lins

    2017-08-01

    This study investigates the association between HbA1c, LDL and oxi-LDL in individuals without diabetes (DM). One hundred and ninety-six individuals, without DM, were enrolled and divided into three groups according to HbA1c and fasting plasma glucose values. HbA1c, oxi-LDL, LDL, and other biochemical measurements of lipid profile were also carried out. oxi-LDL levels showed significant differences among all groups and group 3 presented higher values [34U/L (27-46); 44U/L (37-70); and 86U/L (49-136); pHbA1c showed moderate positive associations with oxi-LDL (r=0.431; pHbA1c and TC (r=0.142; p=0.048), triglycerides (r=0.155; p=0.030), LDL (r=0.148; p=0.039), non-HDL (r=0.192; p=0.007) and Apo B (r=0.171, pHbA1c and oxi-LDL, oxi-LDL/HDL and oxi-LDL/LDL ratios remained significant even after adjustment by multiple linear regression analysis for the variables alcohol consumption, use of medicine, BMI, and age. oxi-LDL levels are significantly associated with HbA1c in non-diabetic individuals. However, the levels of traditional atherogenic lipids only showed a weak association with HbA1c levels. Those at high risk of developing DM or cardiovascular disease have higher levels of oxi-LDL. These data favor to the use of HbA1c as a biomarker to identify individuals at risk of developing complications even in non-diabetic glycemic levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community

    Directory of Open Access Journals (Sweden)

    Jae Hyun Kim

    2012-02-01

    Full Text Available BackgroundRecently, the measurement of glycated hemoglobin (HbA1c was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM. In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population.MethodsWe analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes.ResultsThe mean age of the subjects was 56.3±8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5±25.6 and 138.3±67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7±0.9%. There were 8,809 non-DM patients (87.1% and 1,302 DM patients (12.9%. A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%.ConclusionOur results suggest that the optimal HbA1c level for DM screening is 5.95%.

  11. Characterization of Hb Bart's Hydrops Fetalis Caused by - -SEA and a Large Novel α0-Thalassemia Deletion.

    Science.gov (United States)

    He, Sheng; Li, Jihui; Huang, Peng; Zhang, Shujie; Lin, Li; Zuo, Yangjin; Tian, Xiaoxian; Zheng, Chenguang; Qiu, Xiaoxia; Chen, Biyan

    2018-01-01

    Hb Bart's hydrops fetalis is the most severe and generally fatal clinical phenotype of α-thalassemia (α-thal), which is due to the deletion of all four functional α-globin genes of hemoglobin (Hb), resulting in no α-globin chain production (- -/- -). Homozygosity for the - - SEA (Southeast Asian) α-globin gene deletion is the main cause of the Hb Bart's hydrops fetalis in Asia, especially South China. Occasionally, other α 0 -thal deletions can also be found. In this study, we report a case with an atypical form of Hb Bart's hydrops fetalis that was caused by - - SEA and a large novel α 0 -thal deletion (- - GX ) (Guangxi). The fetus with Hb Bart's in our study presented fetal hydrops features in early gestation which was different from that of traditional Hb Bart's hydrops fetalis with a homozygous - - SEA deletion. The early onset of fetal hydrops is attributed to the decreased formation of embryonic Hb Portland (ζ2γ2), which is proposed as a candidate for reactivation in cases of severe α-thal. Our findings indicated that it was important to characterize new or rare mutations, and highlighted the significance of using ultrasonography to identify signs of Hb Bart's hydrops fetalis.

  12. Environmental regulation of lateral root emergence in Medicago truncatula requires the HD-Zip I transcription factor HB1.

    Science.gov (United States)

    Ariel, Federico; Diet, Anouck; Verdenaud, Marion; Gruber, Véronique; Frugier, Florian; Chan, Raquel; Crespi, Martin

    2010-07-01

    The adaptation of root architecture to environmental constraints is a major agricultural trait, notably in legumes, the third main crop worldwide. This root developmental plasticity depends on the formation of lateral roots (LRs) emerging from primary roots. In the model legume Medicago truncatula, the HD-Zip I transcription factor HB1 is expressed in primary and lateral root meristems and induced by salt stress. Constitutive expression of HB1 in M. truncatula roots alters their architecture, whereas hb1 TILLING mutants showed increased lateral root emergence. Electrophoretic mobility shift assay, promoter mutagenesis, and chromatin immunoprecipitation-PCR assays revealed that HB1 directly recognizes a CAATAATTG cis-element present in the promoter of a LOB-like (for Lateral Organ Boundaries) gene, LBD1, transcriptionally regulated by auxin. Expression of these genes in response to abscisic acid and auxin and their behavior in hb1 mutants revealed an HB1-mediated repression of LBD1 acting during LR emergence. M. truncatula HB1 regulates an adaptive developmental response to minimize the root surface exposed to adverse environmental stresses.

  13. Implantation of FRAPCON-2 code in HB computer

    International Nuclear Information System (INIS)

    Silva, C.F. da.

    1987-05-01

    The modifications carried out for implanting FRAPCON-2 computer code in the HB DPS-T7 computer are presented. The FRAPCON-2 code calculates thermo-mechanical response during long period of burnup in stationary state for fuel rods of PWR type reactors. (M.C.K.)

  14. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

    Directory of Open Access Journals (Sweden)

    J. H. Gillis

    2015-01-01

    Full Text Available Acute sickle hepatic crisis (ASHC has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  15. Accurate genotyping across variant classes and lengths using variant graphs

    DEFF Research Database (Denmark)

    Sibbesen, Jonas Andreas; Maretty, Lasse; Jensen, Jacob Malte

    2018-01-01

    of read k-mers to a graph representation of the reference and variants to efficiently perform unbiased, probabilistic genotyping across the variation spectrum. We demonstrate that BayesTyper generally provides superior variant sensitivity and genotyping accuracy relative to existing methods when used...... collecting a set of candidate variants across discovery methods, individuals and databases, and then realigning the reads to the variants and reference simultaneously. However, this realignment problem has proved computationally difficult. Here, we present a new method (BayesTyper) that uses exact alignment...... to integrate variants across discovery approaches and individuals. Finally, we demonstrate that including a ‘variation-prior’ database containing already known variants significantly improves sensitivity....

  16. Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes.

    Science.gov (United States)

    Berthelot, Karine; Lecomte, Sophie; Estevez, Yannick; Zhendre, Vanessa; Henry, Sarah; Thévenot, Julie; Dufourc, Erick J; Alves, Isabel D; Peruch, Frédéric

    2014-01-01

    The biomembrane surrounding rubber particles from the hevea latex is well known for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3) are major components, linked on rubber particles, and they have been shown to be involved in rubber synthesis or quality (mass regulation), but their exact function is still to be determined. In this study we highlighted the different modes of interactions of both recombinant proteins with various membrane models (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles) to mimic the latex particle membrane. We combined various biophysical methods (polarization-modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR-FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber particle protein (SRPP) shows less affinity than rubber elongation factor (REF) for the membranes but displays a kind of "covering" effect on the lipid headgroups without disturbing the membrane integrity. Its structure is conserved in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity with changes in its aggregation properties, the amyloid nature of REF, which we previously reported, is not favored in the presence of lipids. REF binds and inserts into membranes. The membrane integrity is highly perturbed, and we suspect that REF is even able to remove lipids from the membrane leading to the formation of mixed micelles. These two homologous proteins show affinity to all membrane models tested but neatly differ in their interacting features. This could imply differential roles on the surface of rubber particles. © 2013.

  17. Validation and determination of a reference interval for canine HbA1c using an immunoturbidimetric assay.

    Science.gov (United States)

    Goemans, Anne F; Spence, Susanna J; Ramsey, Ian K

    2017-06-01

    Hemoglobin A1c (HbA1c) provides a reliable measure of glycemic control over 2-3 months in human diabetes mellitus. In dogs, presence of HbA1c has been demonstrated, but there are no validated commercial assays. The purpose of the study was to validate a commercially available automated immunoturbidimetric assay for canine HbA1c and determine an RI in a hospital population. The specificity of the assay was assessed by inducing glycosylation in vitro using isolated canine hemoglobin, repeatability by measuring canine samples 5 times in succession, long term inter-assay imprecision by measuring supplied control materials, stability using samples stored at 4°C over 5 days and -20°C over 8 weeks, linearity by mixing samples of known HbA1c in differing proportions, and the effect of anticoagulants with paired samples. An RI was determined using EDTA-anticoagulated blood samples from 60 nondiabetic hospitalized animals of various ages and breeds. Hemoglobin A1c was also measured in 10 diabetic dogs. The concentration of HbA1c increased proportionally with glucose concentration in vitro. For repeat measurements, the CV was 4.08% (range 1.16-6.10%). Samples were stable for 5 days at 4°C. The assay was linear within the assessed range. Heparin- and EDTA-anticoagulated blood provided comparable results. The RI for HbA1c was 9-18.5 mmol/mol. There was no apparent effect of age or breed on HbA1c. In diabetic dogs, HbA1c ranged from 14 to 48 mmol/mol. The assay provides a reliable method for canine HbA1c measurement with good analytic performance. © 2017 American Society for Veterinary Clinical Pathology.

  18. Clinical and molecular genetic features of Hb H and AE Bart's diseases in central Thai children.

    Science.gov (United States)

    Traivaree, Chanchai; Boonyawat, Boonchai; Monsereenusorn, Chalinee; Rujkijyanont, Piya; Photia, Apichat

    2018-01-01

    α-Thalassemia, one of the major thalassemia types in Thailand, is caused by either deletion or non-deletional mutation of one or both α-globin genes. Inactivation of three α-globin genes causes hemoglobin H (Hb H) disease, and the combination of Hb H disease with heterozygous hemoglobin E (Hb E) results in AE Bart's disease. This study aimed to characterize the clinical and hematological manifestations of 76 pediatric patients with Hb H and AE Bart's diseases treated at Phramongkutklao Hospital, a tertiary care center for thalassemia patients in central Thailand. Seventy-six unrelated pediatric patients, 58 patients with Hb H disease and 18 patients with AE Bart's disease, were enrolled in this study. Their clinical presentations, transfusion requirement, laboratory findings, and mutation analysis were retrospectively reviewed and analyzed. A total of 76 pediatric patients with Hb H and AE Bart's diseases who mainly lived in central Thailand were included in this study. The clinical severities of patients with non-deletional mutations were more severe than those with deletional mutations. Eighty-six percent of patients with non-deletional AE Bart's disease required more blood transfusion compared to 12.5% of patients with deletional AE Bart's disease. Non-deletional AE Bart's disease also had a history of urgent blood transfusion with the average of 6±0.9 times compared to 1±0.3 times in patients with deletional Hb H disease. The difference was statistically significant. This study revealed the differences in clinical spectrum between patients with Hb H disease and those with AE Bart's disease in central Thailand. The differentiation of α-thalassemia is essential for appropriate management of patients. The molecular diagnosis is useful for diagnostic confirmation and genotype-phenotype correlation.

  19. Thermo-mechanical model optimization of HB-LED packaging

    NARCIS (Netherlands)

    Yuan, C.A.; Erinc, M.; Gielen, A.W.J.; Waal, A. van der; Driel, W. van; Zhang, K.

    2011-01-01

    Lighting is an advancing phenomenon both on the technology and on the market level due to the rapid development of the solid state lighting technology. The efforts in improving the efficacy of high brightness LED's (HB-LED) have concentrated on the packaging architecture. Packaging plays a

  20. The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading.

    Science.gov (United States)

    Beck, Roy W; Connor, Crystal G; Mullen, Deborah M; Wesley, David M; Bergenstal, Richard M

    2017-08-01

    HbA 1c is a v aluable metric for comparing treatment groups in a randomized trial, for assessing glycemic trends in a population over time, or for cross-sectional comparisons of glycemic control in different populations. However, what is not widely appreciated is that HbA 1c may not be a good indicator of an individual patient's glycemic control because of the wide range of mean glucose concentrations and glucose profiles that can be associated with a given HbA 1c level. To illustrate this point, we plotted mean glucose measured with continuous glucose monitoring (CGM) versus central laboratory-measured HbA 1c in 387 participants in three randomized trials, showing that not infrequently HbA 1c may underestimate or overestimate mean glucose, sometimes substantially. Thus, if HbA 1c is to be used to assess glycemic control, it is imperative to know the patient's actual mean glucose to understand how well HbA 1c is an indicator of the patient's glycemic control. With knowledge of the mean glucose, an estimated HbA 1c (eA1C) can be calculated with the formula provided in this article to compare with the measured HbA 1c . Estimating glycemic control from HbA 1c alone is in essence applying a population average to an individual, which can be misleading. Thus, a patient's CGM glucose profile has considerable value for optimizing his or her diabetes management. In this era of personalized, precision medicine, there are few better examples with respect to the fallacy of applying a population average to a specific patient rather than using specific information about the patient to determine the optimal approach to treatment. © 2017 by the American Diabetes Association.

  1. Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes.

    Science.gov (United States)

    Sweeting, Arianne N; Ross, Glynis P; Hyett, Jon; Molyneaux, Lynda; Tan, Kris; Constantino, Maria; Harding, Anna Jane; Wong, Jencia

    2017-01-01

    The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort. Copyright © 2017 by the Endocrine Society

  2. HbA1c Variability as an Independent Correlate of Nephropathy, but Not Retinopathy, in Patients With Type 2 Diabetes

    Science.gov (United States)

    Penno, Giuseppe; Solini, Anna; Bonora, Enzo; Fondelli, Cecilia; Orsi, Emanuela; Zerbini, Gianpaolo; Morano, Susanna; Cavalot, Franco; Lamacchia, Olga; Laviola, Luigi; Nicolucci, Antonio; Pugliese, Giuseppe

    2013-01-01

    OBJECTIVE To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS Serial (3–5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86–8.38) and 0.46% (0.29–0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1–2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3–5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications. PMID:23491522

  3. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

    Science.gov (United States)

    Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

    2017-08-23

    Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

  4. TRIPOLI 01, a three-dimensional polykinetic Monte Carlo program. Pt.2. Constant data input and results obtained for a complex bench-mark example

    International Nuclear Information System (INIS)

    Baur, A.; Bourdet, L.; Gonnord, J.; Nimal, J.C.; Vergnaud, T.

    1977-01-01

    Some properties of the sub-routines included in TRIPOLI for the constant data input are briefly reviewed. The bench-mark example then proposed is a problem of the contour lines of a neutron-opaque shield. The example is derived from activation calculations for the secondary sodium in a fast reactor provided with an integrated shield of Phenix type. The dimensions have been reduced so as the geometry to be simplified, and the constant data load reduced. Besides the rate of 24 Na formation by capture in the exchanger region, the attenuation of various detector responses all along the neutron trajectory was taken into account. The detectors chiefly used were: 103 Rh activation from (n,n') reactions for fast neutron detection, the activation Mn detectors, either bare or under cadmium, for detecting thermal and epithermal neutrons respectively [fr

  5. Enhancing Effect of Hydroxyurea on Hb F in Sickle Cell Disease: Ten-Year Egyptian Experience.

    Science.gov (United States)

    Youssry, Ilham; Abdel-Salam, Amina; Ismail, Rania; Bou-Fakhredin, Rayan; Mohamed Samy, Rania; Ezz El-Deen, Fatma; Taher, Ali T

    Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.

  6. Development of pro-inflammatory phenotype in monocytes after engulfing Hb-activated platelets in hemolytic disorders.

    Science.gov (United States)

    Singhal, Rashi; Chawla, Sheetal; Rathore, Deepak K; Bhasym, Angika; Annarapu, Gowtham K; Sharma, Vandana; Seth, Tulika; Guchhait, Prasenjit

    2017-02-01

    Monocytes and macrophage combat infections and maintain homeostatic balance by engulfing microbes and apoptotic cells, and releasing inflammatory cytokines. Studies have described that these cells develop anti-inflammatory properties upon recycling the free-hemoglobin (Hb) in hemolytic conditions. While investigating the phenotype of monocytes in two hemolytic disorders-paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD), we observed a high number of pro-inflammatory (CD14 + CD16 hi ) monocytes in these patients. We further investigated in vitro the phenotype of these monocytes and found an estimated 55% of CD14 + cells were transformed into the CD14 + CD16 hi subset after engulfing Hb-activated platelets. The CD14 + CD16 hi monocytes, which were positive for both intracellular Hb and CD42b (platelet marker), secreted significant amounts of TNF-α and IL-1β, unlike monocytes treated with only free Hb, which secreted more IL-10. We have shown recently the presence of a high number of Hb-bound hyperactive platelets in patients with both diseases, and further investigated if the monocytes engulfed these activated platelets in vivo. As expected, we found 95% of CD14 + CD16 hi monocytes with both intracellular Hb and CD42b in both diseases, and they expressed high TNF-α. Furthermore our data showed that these monocytes whether from patients or developed in vitro after treatment with Hb-activated platelets, secreted significant amounts of tissue factor. Besides, these CD14 + CD16 hi monocytes displayed significantly decreased phagocytosis of E. coli. Our study therefore suggests that this alteration of monocyte phenotype may play a role in the increased propensity to pro-inflammatory/coagulant complications observed in these hemolytic disorders-PNH and SCD. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

    Science.gov (United States)

    Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  8. Impact of HbA1c Testing at Point of Care on Diabetes Management

    Science.gov (United States)

    Schnell, Oliver; Crocker, J. Benjamin; Weng, Jianping

    2016-01-01

    Diabetes is a highly prevalent disease also implicated in the development of several other serious complications like cardiovascular or renal disease. HbA1c testing is a vital step for effective diabetes management, however, given the low compliance to testing frequency and, commonly, a subsequent delay in the corresponding treatment modification, HbA1c at the point of care (POC) offers an opportunity for improvement of diabetes care. In this review, based on data from 1999 to 2016, we summarize the evidence supporting a further implementation of HbA1c testing at POC, discuss its limitations and propose recommendations for further development. PMID:27898388

  9. Investigation of local heterogeneity of hbO2 and hb in working dog heart in situ under isovolemic hemodilution and critical coronary stenosis

    Science.gov (United States)

    Krug, Alfons; Kessler, Manfred D.; Khuri, Raja; Lust, Robert; Chitwood, Randolph

    1996-12-01

    A tissue spectrophotometer (EMPHO II) working with 70 micrometer micro lightguide sensors enables recording of spectra in the visible wavelength range (500 - 630 nm). During an initial period arterial hypoxia and hyperoxia were induced on working dog heart by mechanical ventilation with oxygen fractions (fiO2) of 0.1 and 0.5. Under these conditions the effects of low and high fiO2 on oxygenation distribution of intracapillary hemoglobin were investigated. In the second part of the experiment the relation between systemic hematocrit, local hemoglobin concentration, local hemoglobin oxygenation and the oxygen regulation mechanism were studied in detail. In the final part of the experiment the effect of critical coronary stenosis on hb and hbO2 was measured. Critical stenosis was achieved by partial clamping of the left anterior coronary artery (LAD).

  10. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang-Keun; Yoon, Joonseon [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of); Choi, Gyung Ja [Screening Division, Korea Research Institute of Chemical Technology, Daejeon 305-600 (Korea, Republic of); Jang, Hyun A; Kwon, Suk-Yoon [Korea Research Institute of Bioscience and Biotechnology, Yusung, Daejeon 305-600 (Korea, Republic of); Choi, Doil, E-mail: doil@snu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of)

    2013-12-06

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense.

  11. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    International Nuclear Information System (INIS)

    Oh, Sang-Keun; Yoon, Joonseon; Choi, Gyung Ja; Jang, Hyun A; Kwon, Suk-Yoon; Choi, Doil

    2013-01-01

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense

  12. Serum Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) as a Biomarker for Primary Ovarian Cancer.

    Science.gov (United States)

    Miyata, Kohei; Yotsumoto, Fusanori; Fukagawa, Satoshi; Kiyoshima, Chihiro; Ouk, Nam Sung; Urushiyama, Daichi; Ito, Tomohiro; Katsuda, Takahiro; Kurakazu, Masamitsu; Araki, Ryota; Sanui, Ayako; Miyahara, Daisuke; Murata, Masaharu; Shirota, Kyoko; Yagi, Hiroshi; Takono, Tadao; Kato, Kiyoko; Yaegashi, Nobuo; Akazawa, Kohei; Kuroki, Masahide; Yasunaga, Shin'ichiro; Miyamoto, Shingo

    2017-07-01

    Ovarian cancer is the most lethal malignancy among gynaecological cancers. Although many anticancer agents have been developed for the treatment of ovarian cancer, it continues to have an extremely poor prognosis. Heparin-binding epidermal growth factor-like grown factor (HB-EGF) has been reported to be a rational therapeutic target for ovarian cancer. Here, we evaluated the clinical significance of serum HB-EGF by examining the association between prognosis and serum HB-EGF levels in patients with primary ovarian cancer. We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease. In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Cellulase variants

    Science.gov (United States)

    Blazej, Robert; Toriello, Nicholas; Emrich, Charles; Cohen, Richard N.; Koppel, Nitzan

    2015-07-14

    This invention provides novel variant cellulolytic enzymes having improved activity and/or stability. In certain embodiments the variant cellulotyic enzymes comprise a glycoside hydrolase with or comprising a substitution at one or more positions corresponding to one or more of residues F64, A226, and/or E246 in Thermobifida fusca Cel9A enzyme. In certain embodiments the glycoside hydrolase is a variant of a family 9 glycoside hydrolase. In certain embodiments the glycoside hydrolase is a variant of a theme B family 9 glycoside hydrolase.

  14. Correlation of same-visit HbA1c test with laboratory-based measurements: A MetroNet study

    Directory of Open Access Journals (Sweden)

    West Patricia A

    2005-07-01

    Full Text Available Abstract Background Glycated hemoglobin (HbA1c results vary by analytical method. Use of same-visit HbA1c testing methodology holds the promise of more efficient patient care, and improved diabetes management. Our objective was to test the feasibility of introducing a same-visit HbA1c methodology into busy family practice centers (FPC and to calculate the correlation between the same-visit HbA1c test and the laboratory method that the clinical site was currently using for HbA1c testing. Methods Consecutive diabetic patients 18 years of age and older having blood samples drawn for routine laboratory analysis of HbA1c were asked to provide a capillary blood sample for same-visit testing with the BIO-RAD Micromat II. We compared the results of the same-visit test to three different laboratory methods (one FPC used two different laboratories. Results 147 paired samples were available for analysis (73 from one FPC; 74 from the other. The Pearson correlation of Micromat II and ion-exchange HPLC was 0.713 (p Conclusion For each of the laboratory methods, the correlation coefficient was lower than the 0.96 reported by the manufacturer. This might be due to variability introduced by the multiple users of the Micromat II machine. The mean HbA1c results were also consistently lower than those obtained from laboratory analysis. Additionally, the amount of dedicated time required to perform the assay may limit its usefulness in a busy clinical practice. Before introducing a same-visit HbA1c methodology, clinicians should compare the rapid results to their current method of analysis.

  15. Efficacy of acarbose and metformin in newly diagnosed type 2 diabetes patients stratified by HbA1c levels.

    Science.gov (United States)

    Zhang, Jin-Ping; Wang, Na; Xing, Xiao-Yan; Yang, Zhao-Jun; Wang, Xin; Yang, Wen-Ying

    2016-07-01

    The aim of the present study was to investigate whether the therapeutic efficacy of acarbose and metformin is correlated with baseline HbA1c levels in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Data for 711 subjects were retrieved from the MARCH (Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment) trial database and reviewed retrospectively. Patients were grouped according to baseline HbA1c levels (8%) and the results for these three groups were compared between acarbose and metformin treatments. Acarbose and metformin treatment significantly improved T2DM-associated parameters (weight, fasting plasma glucose [FPG], postprandial glucose [PPG], glucagon-like peptide-1 [GLP-1], HOMA-IR, and total cholesterol) across all HbA1c levels. Acarbose decreased PPG and HOMA-β significantly more than metformin, but only in subjects with lower baseline HbA1c (PPG in the HbA1c levels (P HbA1c groups (all P HbA1c levels, whereas metformin induced greater reductions in FPG. These results may help guide selection of initial therapy based on baseline HbA1c. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  16. Heparin-Binding EGF-like Growth Factor (HB-EGF) Therapy for Intestinal Injury: Application and Future Prospects

    Science.gov (United States)

    Yang, Jixin; Su, Yanwei; Zhou, Yu; Besner, Gail E.

    2014-01-01

    Throughout the past 20 years, we have been investigating the potential therapeutic roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor family, in various models of intestinal injury including necrotizing enterocolitis (NEC), intestinal ischemia/reperfusion (I/R) injury, and hemorrhagic shock and resuscitation (HS/R). Our studies have demonstrated that HB-EGF acts as an effective mitogen, a restitution-inducing reagent, a cellular trophic factor, an anti-apoptotic protein and a vasodilator, via its effects on various cell types in the intestine. In the current paper, we have reviewed the application and therapeutic effects of HB-EGF in three classic animal models of intestinal injury, with particular emphasis on its protection of the intestines from NEC. Additionally, we have summarized the protective functions of HB-EGF on various target cells in the intestine. Lastly, we have provided a brief discussion focusing on the future development of HB-EGF clinical applications for the treatment of various forms of intestinal injury including NEC. PMID:24345808

  17. Seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in Tripoli-Libya.

    Directory of Open Access Journals (Sweden)

    Mohamed A Daw

    Full Text Available In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population.A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay.A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20-40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection.HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned.

  18. Carbonyl Functionalized Single-Walled Carbon Nanotube-Hb Crosslinked Network: A Novel Platform for Studying Bio-Electrochemistry and Electrocatalysis of Hemoglobin.

    Science.gov (United States)

    Kafi, A K M; Yam, C C L; Azmi, N S; Yusoff, Mashitah M

    2018-04-01

    In this work, the direct electrochemistry of hemoglobin (Hb), which was immobilized on carbonyl functionalized single walled carbon nanotube (SWCNT) and deposited onto a gold (Au) electrode has been described. The synthesis of the network of crosslinked SWCNT/Hb was done with the help of crosslinking agent EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide). The UV-Vis and FTIR spectroscopy of SWCNT/Hb networks showed that Hb maintained its natural structure and kept good stability. In addition with this, scanning electron microscopy (SEM) illustrated that SWCNT/Hb networks had a featured layered structure and Hb being strongly liked with SWCNT surface. Cyclic voltammetry (CV) was used to study and to optimize the performance of the resulting modified electrode. The cyclic voltammetric (CV) responses of SWCNT/Hb networks in pH 7.0 exhibit prominent redox couple for the FeIII/II redox process with a midpoint potential of -0.46 V and -0.34, cathodic and anodic respectively. Furthermore, SWCNT/Hb networks are utilized for the detection of hydrogen peroxide (H2O2). Electrochemical measurements reveal that the resulting SWCNT/Hb electrodes display high electrocatalytic activity to H2O2 with high sensitivity, wide linear range, and low detection limit. Overall, the electrochemical results are due to excellent biocompatibility and excellent electron transport efficiency of CNT as well as high Hb loading and synergistic catalytic effect of the modified electrode toward H2O2.

  19. Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease

    Science.gov (United States)

    Leecharoenkiat, Kamonlak; Tanaka, Yuka; Harada, Yasuko; Chaichompoo, Porntip; Sarakul, Orawan; Abe, Yasunobu; Smith, Duncan Richard; Fucharoen, Suthat; Svasti, Saovaros; Umemura, Tsukuru

    2017-01-01

    In Southeast Asia, particularly in Thailand, β0-thalassemia/hemoglobin E (HbE) disease is a common hereditary hematological disease. It is associated with pathophysiological processes, such as the intramedullary destruction of immature erythroid cells and peripheral hemolysis of mature red blood cells. MicroRNA (miR) sequences, which are short non-coding RNA that regulate gene expression in a suppressive manner, serve a crucial role in human erythropoiesis. In the present study, the plasma levels of the erythroid-expressed miRNAs, miR-451 and miR-155, were analyzed in 23 patients with β0-thalassemia/HbE and 16 control subjects. Reverse transcription-quantitative polymerase chain reaction analysis revealed significantly higher levels of plasma miR-451 and miR-155 in β0-thalassemia/HbE patients when compared to the control subjects. Notably, among the β0-thalassemia/HbE patients, a significant increase in miR-451 levels was detected in severe cases when compared with mild cases. The levels of plasma miR-451 correlated with reticulocyte and platelet counts. The results suggest that increased plasma miR-451 levels may be associated with the degree of hemolysis and accelerated erythropoiesis in β0-thalassemia/HbE patients. In conclusion, miR-451 may represent a relevant biomarker for pathological erythropoiesis associated with β0-thalassemia/HbE. PMID:28447765

  20. MdHB1 down-regulation activates anthocyanin biosynthesis in the white-fleshed apple cultivar 'Granny Smith'.

    Science.gov (United States)

    Jiang, Yonghua; Liu, Cuihua; Yan, Dan; Wen, Xiaohong; Liu, Yanli; Wang, Haojie; Dai, Jieyu; Zhang, Yujie; Liu, Yanfei; Zhou, Bin; Ren, Xiaolin

    2017-02-01

    Coloration in apple (Malus×domestica) flesh is mainly caused by the accumulation of anthocyanin. Anthocyanin is biosynthesized through the flavonoid pathway and regulated by MYB, bHLH, and WD40 transcription factors (TFs). Here, we report that the HD-Zip I TF MdHB1 was also involved in the regulation of anthocyanin accumulation. MdHB1 silencing caused the accumulation of anthocyanin in 'Granny Smith' flesh, whereas its overexpression reduced the flesh content of anthocyanin in 'Ballerina' (red-fleshed apple). Moreover, flowers of transgenic tobacco (Nicotiana tabacum 'NC89') overexpressing MdHB1 showed a remarkable reduction in pigmentation. Transient promoter activation assays and yeast one-hybrid results indicated that MdHB1 indirectly inhibited expression of the anthocyanin biosynthetic genes encoding dihydroflavonol-4-reductase (DFR) and UDP-glucose:flavonoid 3-O-glycosyltransferase (UFGT). Yeast two-hybrid and bimolecular fluorescence complementation determined that MdHB1 acted as a homodimer and could interact with MYB, bHLH, and WD40 in the cytoplasm, consistent with its cytoplasmic localization by green fluorescent protein fluorescence observations. Together, these results suggest that MdHB1 constrains MdMYB10, MdbHLH3, and MdTTG1 to the cytoplasm, and then represses the transcription of MdDFR and MdUFGT indirectly. When MdHB1 is silenced, these TFs are released to activate the expression of MdDFR and MdUFGT and also anthocyanin biosynthesis, resulting in red flesh in 'Granny Smith'. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Estimation of coolant void reactivity for CANDU-NG lattice using DRAGON and validation using MCNP5 and TRIPOLI-4.3

    International Nuclear Information System (INIS)

    Karthikeyan, R.; Tellier, R. L.; Hebert, A.

    2006-01-01

    The Coolant Void Reactivity (CVR) is an important safety parameter that needs to be estimated at the design stage of a nuclear reactor. It helps to have an a priori knowledge of the behavior of the system during a transient initiated by the loss of coolant. In the present paper, we have attempted to estimate the CVR for a CANDU New Generation (CANDU-NG) lattice, as proposed at an early stage of the Advanced CANDU Reactor (ACR) development. We have attempted to estimate the CVR with development version of the code DRAGON, using the method of characteristics. DRAGON has several advanced self-shielding models incorporated in it, each of them compatible with the method of characteristics. This study will bring to focus the performance of these self-shielding models, especially when there is voiding of such a tight lattice. We have also performed assembly calculations in 2 x 2 pattern for the CANDU-NG fuel, with special emphasis on checkerboard voiding. The results obtained have been validated against Monte Carlo codes MCNP5 and TRIPOLI-4.3. (authors)

  2. Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth.

    Science.gov (United States)

    Vehik, Kendra; Cuthbertson, David; Boulware, David; Beam, Craig A; Rodriguez, Henry; Legault, Laurent; Hyytinen, Mila; Rewers, Marian J; Schatz, Desmond A; Krischer, Jeffrey P

    2012-09-01

    The aim of this study was to evaluate HbA(1c) as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects TrialNet Natural History (TrialNet) studies and had an HbA(1c) within 90 days of an OGTT with a 2-h plasma glucose (2-hPG) measure were included. An OGTT of 140-199 mg/dL defined IGT, and an OGTT with 2-hPG ≥200 mg/dL or fasting plasma glucose ≥126 mg/dL defined diabetes. HbA(1c) ≥5.7% defined IGT, and HbA(1c) ≥ 6.5% defined diabetes. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy of HbA(1c) compared with OGTT. There were 587 subjects from DPT-1, 884 from TrialNet, 91 from TEDDY, and 420 from TRIGR. As an indicator for IGT, HbA(1c) sensitivity was very low across the studies (8-42%), and specificity was variable (64-95%). With HbA(1c) ≥6.5% threshold used for T1D diagnosis, the sensitivity was very low and specificity was high (sensitivity and specificity: DPT-1 24 and 98%, TrialNet 28 and 99%, TEDDY 34 and 98%, and TRIGR 33 and 99%, respectively). The positive predictive value of HbA(1c) ≥6.5% for the development of T1D was variable (50-94%) across the four studies. HbA(1c) ≥6.5% is a specific but not sensitive early indicator for T1D in high-risk subjects <21 years of age diagnosed by OGTT or asymptomatic hyperglycemia. Redefining the HbA(1c) threshold is recommended if used as an alternative criterion in diagnosing T1D.

  3. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis

    Directory of Open Access Journals (Sweden)

    Zhenghong Bi

    2016-03-01

    Full Text Available A homolog of MOTHER OF FT AND TFL1 (MFT was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT and TERMINAL FLOWER1 (TFL1-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1 and FRUITFULL (FUL were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species.

  4. Smoking: the influence of carboxyhemoglobin (HbCO) on tumor oxygenation and response to radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, R.P.; Bush, R.S.

    1978-01-01

    The effectiveness of localized x radiation on the transplantable KHT sarcoma was studied in nonanesthetized C3H mice possessing blood carboxyhemoglobin (HbCO) levels similar to those observed in heavy smokers. HbCO values of 10 percent were induced in tumor-bearing animals, either acutely just prior to irradiation or chronically during tumor growth and irradiation, by allowing the mice to breathe gas mixtures containing carbon monoxide (CO) in air. Tumors were irradiated either with single doses of 1500, 2000, or 2500 rad or with seven 500 rad fractions given at 24 hr intervals. Tumor cell survival was determined using an in vivo lung colony or an in vitro agar colony assay. The results with single doses of radiation indicate that under conditions of both acute and chronic exposure, the presence of 10 percent HbCO in the blood of the mice at the time of irradiation increases the survival of tumor cells in the hypoxic region of the survival curve by a factor of 2. During the fractionated irradiation, tumor cell survival in the presence of a 10 percent blood HbCO level (induced either acutely or chronically) was found to be significantly higher than that observed in air breathing mice. The results indicate that HbCO levels, such as are observed in heavy smokers, result in a larger fraction of hypoxic tumor cells. These findings suggest that heavy smoking prior to treatment may worsen the prognosis of patients undergoing radiotherapy

  5. Association between effort-reward imbalance and glycosylated hemoglobin (HbA1c) among Chinese workers: results from SHISO study.

    Science.gov (United States)

    Xu, Weixian; Hang, Juan; Gao, Wei; Zhao, Yiming; Li, Weihong; Wang, Xinyu; Li, Zhaoping; Guo, Lijun

    2012-02-01

    The studies focusing on effort-reward imbalance and diabetes mellitus (DM)/glycosylated hemoglobin (HbA1c) are rare. We sought to examine the association between job stress evaluated by effort-reward imbalance (ERI) model and HbA1c in a Chinese population. We analyzed 680 subjects (465 men and 215 women) without DM or impaired glucose tolerance from the stress and health in Shenzhen workers (SHISO) study. Job stress was evaluated by effort-reward imbalance (ERI) model. HbA1c was measured by an automatic analyzer by means of high-performance liquid chromatography. The association between job stress and HbA1c was explored by variance analysis, partial correlations and multiple linear regression analysis. For women, effort, and ERI were positively associated with HbA1c (r = 0.22, p = 0,003; r = 0.21, p = 0.006, respectively), in contrast, reward was negatively associated with HbA1c (r = -0.17, p = 0.021), after controlling age, BMI and physical exercise in the partial correlation analysis; the similar results were confirmed in the multiple linear regression. No significant correlations between job stress and HbA1c were found for men. Effort and ERI are positively associated with HbA1c, and reward is inversely related to HbA1c among Chinese women. The association is not accounted for by age, BMI, and physical exercise. More efforts should be made to improve the job stress status of Chinese working women for the purpose of DM prevention.

  6. Associations between gestational diabetes mellitus and elevated HbA1c early postpartum in a multi-ethnic population.

    Science.gov (United States)

    Waage, Christin; Jenum, Anne Karen; Mdala, Ibrahimu; Berg, Jens Petter; Richardsen, Kåre; Birkeland, Kåre

    2017-04-01

    To investigate the prevalence of elevated HbA 1c 14 weeks postpartum in different ethnic groups and in women with and without gestational diabetes mellitus (GDM) in the index pregnancy and to explore demographic and biological factors from early pregnancy associated with elevated HbA 1c (HbA 1c ≥5.7% (≥39mmol/mol)) postpartum. From a cohort study in Oslo, Norway, we included 570 pregnant women, examined in gestational week 15, 28, and 14 weeks postpartum. The association between elevated HbA 1c and demographic and biological factors were assessed by logistic regression analyses. The prevalence of elevated HbA 1c postpartum was 23% in the total population, 15% among Western Europeans and 28% among women with ethnic minority background (p<0.01). In ethnic minorities elevated HbA 1c was found in 39% of women with recent GDM diagnosed by the World Health Organization 2013 criteria and in 21% of women without GDM (p<0.01), compared to 22% and 13% in Western Europeans (p=0.11). We found independent associations between elevated HbA 1c and ethnic minority background (OR 2.0, 95% CI 1.27, 3.18), and GDM (OR 2.04, 95% CI 1.35, 3.10) (p<0.01). The prevalence of elevated HbA 1c postpartum was 23%, and significantly higher among women with ethnic minority background irrespective of GDM. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  7. Clinical profile and factors associated with mortality in hospitalized patients with HIV/AIDS: a retrospective analysis from Tripoli Medical Centre, Libya, 2013.

    Science.gov (United States)

    Shalaka, N S; Garred, N A; Zeglam, H T; Awasi, S A; Abukathir, L A; Altagdi, M E; Rayes, A A

    2015-10-02

    In Libya, little is known about HIV-related hospitalizations and in-hospital mortality. This was a retrospective analysis of HIV-related hospitalizations at Tripoli Medical Centre in 2013. Of 227 cases analysed, 82.4% were males who were significantly older (40.0 versus 36.5 years), reported injection drug use (58.3% versus 0%) and were hepatitis C virus co-infected (65.8% versus 0%) compared with females. Severe immunosuppression was prevalent (median CD4 count = 42 cell/μL). Candidiasis was the most common diagnosis (26.0%); Pneumocystis pneumonia was the most common respiratory disease (8.8%), while cerebral toxoplasmosis was diagnosed in 8.4% of patients. Current HAART use was independently associated with low risk of in-hospital mortality (OR 0.33), while central nervous system symptoms (OR 4.12), sepsis (OR 6.98) and low total lymphocyte counts (OR 3.60) were associated with increased risk. In this study, late presentation with severe immunosuppression was common, and was associated with significant in-hospital mortality.

  8. Molecular characterization of HbEREBP2, a jasmonateresponsive ...

    African Journals Online (AJOL)

    Transcription factors of AP2/ERF superfamily are generally involved in defense responses of plants to biotic and abiotic stresses. Although, defense proteins are present in abundance in laticifers of rubber tree, little is known about their transcriptional regulation. In this study, a full length cDNA, referred to as HbEREBP2 was ...

  9. Identifying the independent effect of HbA1c variability on adverse health outcomes in patients with Type 2 diabetes.

    Science.gov (United States)

    Prentice, J C; Pizer, S D; Conlin, P R

    2016-12-01

    To characterize the relationship between HbA 1c variability and adverse health outcomes among US military veterans with Type 2 diabetes. This retrospective cohort study used Veterans Affairs and Medicare claims for veterans with Type 2 diabetes taking metformin who initiated a second diabetes medication (n = 50 861). The main exposure of interest was HbA 1c variability during a 3-year baseline period. HbA 1c variability, categorized into quartiles, was defined as standard deviation, coefficient of variation and adjusted standard deviation, which accounted for the number and mean number of days between HbA 1c tests. Cox proportional hazard models predicted mortality, hospitalization for ambulatory care-sensitive conditions, and myocardial infarction or stroke and were controlled for mean HbA 1c levels and the direction of change in HbA 1c levels during the baseline period. Over a mean 3.3 years of follow-up, all HbA 1c variability measures significantly predicted each outcome. Using the adjusted standard deviation measure for HbA 1c variability, the hazard ratios for the third and fourth quartile predicting mortality were 1.14 (95% CI 1.04, 1.25) and 1.42 (95% CI 1.28, 1.58), for myocardial infarction and stroke they were 1.25 (95% CI 1.10, 1.41) and 1.23 (95% CI 1.07, 1.42) and for ambulatory-care sensitive condition hospitalization they were 1.10 (95% CI 1.03, 1.18) and 1.11 (95% CI 1.03, 1.20). Higher baseline HbA 1c levels independently predicted the likelihood of each outcome. In veterans with Type 2 diabetes, greater HbA 1c variability was associated with an increased risk of adverse long-term outcomes, independently of HbA 1c levels and direction of change. Limiting HbA 1c fluctuations over time may reduce complications. © 2016 Diabetes UK.

  10. HbA1c values calculated from blood glucose levels using truncated Fourier series and implementation in standard SQL database language.

    Science.gov (United States)

    Temsch, W; Luger, A; Riedl, M

    2008-01-01

    This article presents a mathematical model to calculate HbA1c values based on self-measured blood glucose and past HbA1c levels, thereby enabling patients to monitor diabetes therapy between scheduled checkups. This method could help physicians to make treatment decisions if implemented in a system where glucose data are transferred to a remote server. The method, however, cannot replace HbA1c measurements; past HbA1c values are needed to gauge the method. The mathematical model of HbA1c formation was developed based on biochemical principles. Unlike an existing HbA1c formula, the new model respects the decreasing contribution of older glucose levels to current HbA1c values. About 12 standard SQL statements embedded in a php program were used to perform Fourier transform. Regression analysis was used to gauge results with previous HbA1c values. The method can be readily implemented in any SQL database. The predicted HbA1c values thus obtained were in accordance with measured values. They also matched the results of the HbA1c formula in the elevated range. By contrast, the formula was too "optimistic" in the range of better glycemic control. Individual analysis of two subjects improved the accuracy of values and reflected the bias introduced by different glucometers and individual measurement habits.

  11. Polar bear hemoglobin and human Hb A0: same 2,3-diphosphoglycerate binding site but asymmetry of the binding?

    Science.gov (United States)

    Pomponi, Massimo; Bertonati, Claudia; Patamia, Maria; Marta, Maurizio; Derocher, Andrew E; Lydersen, Christian; Kovacs, Kit M; Wiig, Oystein; Bårdgard, Astrid J

    2002-11-01

    Polar bear (Ursus maritimus) hemoglobin (Hb) shows a low response to 2,3-diphosphoglycerate (2,3-DPG), compared to human Hb A0, even though these proteins have the same 2,3-DPG-binding site. In addition, polar bear Hb shows a high response to chloride and an alkaline Bohr effect (deltalog P50/deltapH) that is significantly greater than that of human Hb A0. The difference in sequence Pro (Hb A0)-->Gly (polar bear Hb) at position A2 in the A helix seems to be critical for reduced binding of 2,3-DPG. Our results also show that the A2 position may influence not only the flexibility of the A helix, but that differences in flexibility of the first turn of the A helix may affect the unloading of oxygen for the intrinsic ligand affinities of the alpha and beta chains. However, preferential binding to either chain can only take place if there is appreciable asymmetric binding of the phosphoric effector. Regarding this point, 31P NMR data suggest a loss of symmetry of the 2,3-DPG-binding site in the deoxyHb-2,3-DPG complex.

  12. Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

    Science.gov (United States)

    Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

    2017-07-01

    Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA 1c . Methods HbA 1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA 1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA 1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA 1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

  13. Somatic cancer variant curation and harmonization through consensus minimum variant level data

    Directory of Open Access Journals (Sweden)

    Deborah I. Ritter

    2016-11-01

    Full Text Available Abstract Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG of the Clinical Genome Resource (ClinGen, in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD. MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i reviewing clinical actionability interpretations from institutions participating in the WG, ii conducting extensive literature search of clinical somatic interpretation schemas, and iii survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP, can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of

  14. Association between HbA1c and carotid atherosclerosis among elderly Koreans with normal fasting glucose.

    Directory of Open Access Journals (Sweden)

    Seung Won Lee

    Full Text Available We examined whether glycated haemoglobin (HbA1c is associated to carotid atherosclerosis in an elderly Korean population with normal fasting glucose.Using data from the Korean Urban Rural Elderly study, we conducted a cross-sectional analysis of 1,133 participants (335 men and 798 women with a mean age of 71.8 years. All participants had fasting blood glucose less than 100mg/dL (5.6 mmol/L and HbA1c level below 6.5% (48 mmol/mol. They were also free from a history of cardiovascular disease, known type 2 diabetes mellitus or use of anti-diabetes medications. Carotid atherosclerosis was assessed by intima-media thickness (IMT using ultrasonography. The association between HbA1c and carotid IMT was investigated using multivariable linear regression analysis.HbA1c levels were independently and positively associated with carotid IMT (β = 0.020, p = 0.045 after adjusting for sex, age, body mass index, systolic blood pressure, diastolic blood pressure, triglyceride, LDL cholesterol, smoking and alcohol intake. However, fasting insulin and glucose levels were not associated with carotid IMT.HbA1c levels were positively associated with carotid atherosclerosis, as assessed by carotid IMT, in an elderly population with normoglycemia. Our study suggested that higher HbA1c level is an effective and informative marker of carotid atherosclerosis in an elderly population.

  15. Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis

    Science.gov (United States)

    Freitas, Priscila Aparecida Correa; Gross, Jorge Luiz

    2017-01-01

    Aims/Hypothesis Disparities in HbA1c levels have been observed among ethnic groups. Most studies were performed in patients with diabetes mellitus (DM), which may interfere with results due to the high variability of glucose levels. We conducted a systematic review and meta-analysis to investigate the effect of ethnicity on HbA1c levels in individuals without DM. Methods This is a systematic review with meta-analysis. We searched MEDLINE and EMBASE up to September 2016. Studies published after 1996, performed in adults without DM, reporting HbA1c results measured by certified/standardized methods were included. A random effects model was used and the effect size was presented as weighted HbA1c mean difference (95% CI) between different ethnicities as compared to White ethnicity. Results Twelve studies met the inclusion criteria, totalling data from 49,238 individuals. There were significant differences between HbA1c levels in Blacks [0.26% (2.8 mmol/mol); 95% CI 0.18 to 0.33 (2.0 to 3.6), p HbA1c values are higher in Blacks, Asians, and Latinos when compared to White persons. Although small, these differences might have impact on the use of a sole HbA1c point to diagnose DM in all ethnic populations. PMID:28192447

  16. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis

    NARCIS (Netherlands)

    Wheeler, Eleanor; Leong, Aaron; Liu, Ching-Ti; Hivert, Marie-France; Strawbridge, Rona J; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M; Porneala, Bianca C; Sharp, Stephen J; Jia, Yucheng; Kabagambe, Edmond K; Chang, Li-Ching; Chen, Wei-Min; Elks, Cathy E; Evans, Daniel S; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke-Jan; Hu, Yao; Jackson, Anne U; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing-Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A; Navarro, Pau; Nolte, Ilja M; Sanna, Serena; van der Most, Peter J; Van Vliet-Ostaptchouk, Jana V.; Alizadeh, Behrooz Z; Hartman, Catharina A; Swertz, Morris; Oldehinkel, Albertine J; Snieder, Harold; Wolffenbuttel, Bruce H R

    2017-01-01

    Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

  17. SCREENING CORD BLOOD FOR HEMOGLOBINOPATHIES AND THALASSEMIA BY HPLC

    NARCIS (Netherlands)

    VANDERDIJS, FPL; VANDENBERG, GA; SCHERMER, JG; MUSKIET, FD; LANDMAN, H; MUSKIET, FAJ

    We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta+-thalassemia in babies born on Curacao. During three months, 67.2% of all (748) newborns

  18. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis

    NARCIS (Netherlands)

    Wheeler, Eleanor; Leong, Aaron; Liu, Ching-Ti; Hivert, Marie-France; Strawbridge, Rona J; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M; Porneala, Bianca C; Sharp, Stephen J; Jia, Yucheng; Kabagambe, Edmond K; Chang, Li-Ching; Chen, Wei-Min; Elks, Cathy E; Evans, Daniel S; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke-Jan; Hu, Yao; Jackson, Anne U; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing-Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A; Navarro, Pau; Nolte, Ilja M; Rose, Lynda M; Rybin, Denis V; Sanna, Serena; Shi, Yuan; Stram, Daniel O; Takeuchi, Fumihiko; Tan, Shu Pei; van der Most, Peter J; van Vliet-Ostaptchouk, Jana V; Wong, Andrew; Yengo, Loic; Zhao, Wanting; Goel, Anuj; Martinez Larrad, Maria Teresa; Radke, Dörte; Salo, Perttu; Tanaka, Toshiko; van Iperen, Erik P A; Abecasis, Goncalo; Afaq, Saima; Alizadeh, Behrooz Z; Bertoni, Alain G; Bonnefond, Amelie; Böttcher, Yvonne; Bottinger, Erwin P; Campbell, Harry; Carlson, Olga D; Chen, Chien-Hsiun; Cho, Yoon Shin; Garvey, W Timothy; Gieger, Christian; Goodarzi, Mark O; Grallert, Harald; Hamsten, Anders; Hartman, Catharina A; Herder, Christian; Hsiung, Chao Agnes; Huang, Jie; Igase, Michiya; Isono, Masato; Katsuya, Tomohiro; Khor, Chiea-Chuen; Kiess, Wieland; Kohara, Katsuhiko; Kovacs, Peter; Lee, Juyoung; Lee, Wen-Jane; Lehne, Benjamin; Li, Huaixing; Liu, Jianjun; Lobbens, Stephane; Luan, Jian'an; Lyssenko, Valeriya; Meitinger, Thomas; Miki, Tetsuro; Miljkovic, Iva; Moon, Sanghoon; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nauck, Matthias; Pankow, James S; Polasek, Ozren; Prokopenko, Inga; Ramos, Paula S; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rich, Stephen S; Robertson, Neil R; Roden, Michael; Roussel, Ronan; Rudan, Igor; Scott, Robert A; Scott, William R; Sennblad, Bengt; Siscovick, David S; Strauch, Konstantin; Sun, Shan-Liang; Swertz, Morris a.; Tajuddin, Salman M; Taylor, Kent D; Teo, Yik-Ying; Tham, Yih Chung; Tönjes, Anke; Wareham, Nicholas J; Willemsen, Gonneke; Wilsgaard, Tom; Hingorani, Aroon D; Egan, Josephine; Ferrucci, Luigi; Hovingh, G. Kees; Jula, Antti; Kivimaki, Mika; Kumari, Meena; Njølstad, Inger; Palmer, Colin N A; Serrano Ríos, Manuel; Stumvoll, Michael; Watkins, Hugh; Aung, Tin; Blüher, Matthias; Boehnke, Michael; Boomsma, Dorret I; Bornstein, Stefan R; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der Ida; Chen, Yduan-Tsong; Cheng, Ching-Yu; Cucca, Francesco; de Geus, Eco J C; Deloukas, Panos; Evans, Michele K; Fornage, Myriam; Friedlander, Yechiel; Froguel, Philippe; Groop, Leif; Gross, Myron D; Harris, Tamara B; Hayward, Caroline; Heng, Chew-Kiat; Ingelsson, Erik; Kato, Norihiro; Kim, Bong-Jo; Koh, Woon-Puay; Kooner, Jaspal S; Körner, Antje; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lin, Xu; Liu, YongMei; Loos, Ruth J F; Magnusson, Patrik K E; März, Winfried; McCarthy, Mark I; Oldehinkel, Albertine J; Ong, Ken K; Pedersen, Nancy L; Pereira, Mark A; Peters, Annette; Ridker, Paul M; Sabanayagam, Charumathi; Sale, Michele; Saleheen, Danish; Saltevo, Juha; Schwarz, Peter Eh; Sheu, Wayne H H; Snieder, Harold; Spector, Timothy D; Tabara, Yasuharu; Tuomilehto, Jaakko; van Dam, Rob M; Wilson, James G; Wilson, James F; Wolffenbuttel, Bruce H R; Wong, Tien Yin; Wu, Jer-Yuarn; Yuan, Jian-Min; Zonderman, Alan B; Soranzo, Nicole; Guo, Xiuqing; Roberts, David J; Florez, Jose C; Sladek, Robert; Dupuis, Josée; Morris, Andrew P; Tai, E Shyong; Selvin, Elizabeth; Rotter, Jerome I; Langenberg, Claudia; Barroso, Inês; Meigs, James B

    BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

  19. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis

    NARCIS (Netherlands)

    Wheeler, Eleanor; Leong, Aaron; Liu, Ching Ti; Hivert, Marie France; Strawbridge, Rona J.; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y.; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M.; Porneala, Bianca C.; Sharp, Stephen J.; Jia, Yucheng; Kabagambe, Edmond K.; Chang, Li Ching; Chen, Wei Min; Elks, Cathy E.; Evans, Daniel S.; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke Jan; Hu, Yao; Jackson, Anne U.; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E.; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A.; Navarro, Pau; Nolte, Ilja M.; Rose, Lynda M.; Rybin, Denis V.; Sanna, Serena; Shi, Yuan; Stram, Daniel O.; Takeuchi, Fumihiko; Tan, Shu Pei; van der Most, Peter J.; Van Vliet-Ostaptchouk, Jana V.; Wong, Andrew; Yengo, Loic; Zhao, Wanting; Goel, Anuj; Martinez Larrad, Maria Teresa; Radke, Dörte; Salo, Perttu; Tanaka, Toshiko; van Iperen, Erik P.A.; Abecasis, Goncalo; Afaq, Saima; Alizadeh, Behrooz Z.; Bertoni, Alain G.; Bonnefond, Amelie; Böttcher, Yvonne; Bottinger, Erwin P.; Campbell, Harry; Carlson, Olga D.; Chen, Chien Hsiun; Cho, Yoon Shin; Garvey, W. Timothy; Gieger, Christian; Goodarzi, Mark O.; Grallert, Harald; Hamsten, Anders; Hartman, Catharina A.; Herder, Christian; Hsiung, Chao Agnes; Huang, Jie; Igase, Michiya; Isono, Masato; Katsuya, Tomohiro; Khor, Chiea Chuen; Kiess, Wieland; Kohara, Katsuhiko; Kovacs, Peter; Lee, Juyoung; Lee, Wen Jane; Lehne, Benjamin; Li, Huaixing; Liu, Jianjun; Lobbens, Stephane; Luan, Jian'an; Lyssenko, Valeriya; Meitinger, Thomas; Miki, Tetsuro; Miljkovic, Iva; Moon, Sanghoon; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nauck, Matthias; Pankow, James S.; Polasek, Ozren; Prokopenko, Inga; Ramos, Paula S.; Rasmussen-Torvik, Laura; Rathmann, Wolfgang; Rich, Stephen S.; Robertson, Neil R.; Roden, Michael; Roussel, Ronan; Rudan, Igor; Scott, Robert A.; Scott, William R.; Sennblad, Bengt; Siscovick, David S.; Strauch, Konstantin; Sun, Liang; Swertz, Morris; Tajuddin, Salman M.; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Tönjes, Anke; Wareham, Nicholas J.; Willemsen, Gonneke; Wilsgaard, Tom; Hingorani, Aroon D.; Egan, Josephine; Ferrucci, Luigi; Hovingh, G. Kees; Jula, Antti; Kivimaki, Mika; Kumari, Meena; Njølstad, Inger; Palmer, Colin N.A.; Serrano Ríos, Manuel; Stumvoll, Michael; Watkins, Hugh; Aung, Tin; Blüher, Matthias; Boehnke, Michael; Boomsma, Dorret I.; Bornstein, Stefan R.; Chambers, John C.; Chasman, Daniel I.; Chen, Yii Der Ida; Chen, Yduan Tsong; Cheng, Ching Yu; Cucca, Francesco; de Geus, Eco J.C.; Deloukas, Panos; Evans, Michele K.; Fornage, Myriam; Friedlander, Yechiel; Froguel, Philippe; Groop, Leif; Gross, Myron D.; Harris, Tamara B.; Hayward, Caroline; Heng, Chew Kiat; Ingelsson, Erik; Kato, Norihiro; Kim, Bong Jo; Koh, Woon Puay; Kooner, Jaspal S.; Körner, Antje; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lin, Xu; Liu, Yongmei; Loos, Ruth J.F.; Magnusson, Patrik K.E.; März, Winfried; McCarthy, Mark I.; Oldehinkel, Albertine J.; Ong, Ken K.; Pedersen, Nancy L.; Pereira, Mark A.; Peters, Annette; Ridker, Paul M.; Sabanayagam, Charumathi; Sale, Michele; Saleheen, Danish; Saltevo, Juha; Schwarz, Peter E.H.; Sheu, Wayne H.H.; Snieder, Harold; Spector, Timothy D.; Tabara, Yasuharu; Tuomilehto, Jaakko; van Dam, Rob M.; Wilson, James G.; Wilson, James F.; Wolffenbuttel, Bruce H.R.; Wong, Tien Yin; Wu, Jer Yuarn; Yuan, Jian Min; Zonderman, Alan B.; Soranzo, Nicole; Guo, Xiuqing; Roberts, David J.; Florez, Jose C.; Sladek, Robert; Dupuis, Josée; Morris, Andrew P.; Tai, E. Shyong; Selvin, Elizabeth; Rotter, Jerome I.; Langenberg, Claudia; Barroso, Inês; Meigs, James B.

    2017-01-01

    Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

  20. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

    NARCIS (Netherlands)

    Wheeler, Eleanor; Leong, Aaron; Liu, Ching-Ti; Hivert, Marie-France; Strawbridge, Rona J.; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y.; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M.; Porneala, Bianca C.; Sharp, Stephen J.; Jia, Yucheng; Kabagambe, Edmond K.; Chang, Li-Ching; Chen, Wei-Min; Elks, Cathy E.; Evans, Daniel S.; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke-Jan; Hu, Yao; Jackson, Anne U.; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E.; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing-Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A.; Navarro, Pau; Nolte, Ilja M.; Rose, Lynda M.; Rybin, Denis V.; Sanna, Serena; Shi, Yuan; Stram, Daniel O.; Takeuchi, Fumihiko; Tan, Shu Pei; van der Most, Peter J.; van Vliet-Ostaptchouk, Jana V.; Wong, Andrew; Yengo, Loic; Zhao, Wanting; Goel, Anuj; Martinez Larrad, Maria Teresa; Radke, Dorte; Salo, Perttu; Tanaka, Toshiko; van Iperen, Erik P. A.; Abecasis, Goncalo; Afaq, Saima; Alizadeh, Behrooz Z.; Bertoni, Alain G.; Bonnefond, Amelie; Bottcher, Yvonne; Bottinger, Erwin P.; Campbell, Harry; Carlson, Olga D.; Chen, Chien-Hsiun; Cho, Yoon Shin; Garvey, W. Timothy; Gieger, Christian; Goodarzi, Mark O.; Grallert, Harald; Hamsten, Anders; Hartman, Catharina A.; Herder, Christian; Hsiung, Chao Agnes; Huang, Jie; Igase, Michiya; Isono, Masato; Katsuya, Tomohiro; Khor, Chiea-Chuen; Kiess, Wieland; Kohara, Katsuhiko; Kovacs, Peter; Lee, Juyoung; Lee, Wen-Jane; Lehne, Benjamin; Li, Huaixing; Liu, Jianjun; Lobbens, Stephane; Luan, Jian'an; Lyssenko, Valeriya; Meitinger, Thomas; Miki, Tetsuro; Miljkovic, Iva; Moon, Sanghoon; Mulas, Antonella; Muller, Gabriele; Muller-Nurasyid, Martina; Nagaraja, Ramaiah; Nauck, Matthias; Pankow, James S.; Polasek, Ozren; Prokopenko, Inga; Ramos, Paula S.; Rasmussen-Torvik, Laura; Rathmann, Wolfgang; Rich, Stephen S.; Robertson, Neil R.; Roden, Michael; Roussel, Ronan; Rudan, Igor; Scott, Robert A.; Scott, William R.; Sennblad, Bengt; Siscovick, David S.; Strauch, Konstantin; Sun, Liang; Swertz, Morris; Tajuddin, Salman M.; Taylor, Kent D.; teo, Yik-Ying; Tham, Yih Chung; Tonjes, Anke; Wareham, Nicholas J.; Willemsen, Gonneke; Wilsgaard, Tom; Hingorani, Aroon D.; Egan, Josephine; Ferrucci, Luigi; Hovingh, G. Kees; Jula, Antti; Kivimaki, Mika; Kumari, Meena; Njolstad, Inger; Palmer, Colin N. A.; Serrano Rios, Manuel; Stumvoll, Michael; Watkins, Hugh; Aung, Tin; Bluher, Matthias; Boehnke, Michael; Boomsma, Dorret I.; Bornstein, Stefan R.; Chambers, John C.; Chasman, Daniel I.; Chen, Yii-Der Ida; Chen, Yduan-Tsong; Cheng, Ching-Yu; Cucca, Francesco; de Geus, Eco J. C.; Deloukas, Panos; Evans, Michele K.; Fornage, Myriam; Friedlander, Yechiel; Froguel, Philippe; Groop, Leif; Gross, Myron D.; Harris, Tamara B.; Hayward, Caroline; Heng, Chew-Kiat; Ingelsson, Erik; Kato, Norihiro; Kim, Bong-Jo; Koh, Woon-Puay; Kooner, Jaspal S.; Korner, Antje; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lin, Xu; Liu, Yongmei; Loos, Ruth J. F.; Magnusson, Patrik K. E.; Marz, Winfried; McCarthy, Mark I.; Oldehinkel, Albertine J.; Ong, Ken K.; Pedersen, Nancy L.; Pereira, Mark A.; Peters, Annette; Ridker, Paul M.; Sabanayagam, Charumathi; Sale, Michele; Saleheen, Danish; Saltevo, Juha; Schwarz, Peter Eh; Sheu, Wayne H. H.; Snieder, Harold; Spector, Timothy D.; Tabara, Yasuharu; Tuomilehto, Jaakko; van Dam, Rob M.; Wilson, James G.; Wilson, James F.; Wolffenbuttel, Bruce H. R.; Wong, Tien Yin; Wu, Jer-Yuarn; Yuan, Jian-Min; Zonderman, Alan B.; Soranzo, Nicole; Guo, Xiuqing; Roberts, David J.; Florez, Jose C.; Sladek, Robert; Dupuis, Josee; Morris, Andrew P.; Tai, E.-Shyong; Selvin, Elizabeth; Rotter, Jerome I.; Langenberg, Claudia; Barroso, Ines; Meigs, James B.

    2017-01-01

    Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

  1. Measurement of HbA1c in Gingival Crevicular Blood Using a High Pressure Liquid Chromatography Procedure

    Science.gov (United States)

    Pesce, Michael A.; Strauss, Shiela M.; Rosedale, Mary; Netterwald, Jane; Wang, Hangli

    2016-01-01

    Objectives To validate an ion exchange high-pressure liquid chromatography (HPLC) method for measuring glycated hemoglobin (HbA1c) in gingival crevicular blood (GCB) spotted on filter paper, for use in screening dental patients for diabetes. Methods We collected the GCB specimens for this study from the oral cavities of patients during dental visits, using rigorous strategies to obtain GCB that was as free of debris as possible. The analytical performance of the HPLC method was determined by measuring the precision, linearity, carryover, stability of HbA1c in GCB, and correlation of HbA1c results in GCB specimens with finger-stick blood (FSB) specimens spotted on filter paper. Results The coefficients of variation (CVs) for the inter- and intrarun precision of the method were less than 2.0%. Linearity ranged between 4.2% and 12.4%; carryover was less than 2.0%, and the stability of the specimen was 6 days at 4°C and as many as 14 days at −70°C. Linear regression analysis comparing the HbA1c results in GCB with FSB yielded a correlation coefficient of 0.993, a slope of 0.981, and an intercept of 0.13. The Bland-Altman plot showed no difference in the HbA1c results from the GCB and FSB specimens at normal, prediabetes, and diabetes HbA1c levels. Conclusion We validated an HPLC method for measuring HbA1c in GCB; this method can be used to screen dental patients for diabetes. PMID:26489673

  2. CDKL5 variants

    Science.gov (United States)

    Kalscheuer, Vera M.; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A.; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E.S.; Cobb, Stuart R.

    2017-01-01

    Objective: To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. Methods: We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. Results: The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. Conclusions: These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain. PMID:29264392

  3. Correlation of MMP-9, GA, HbA1c, and adipokines levels with DR

    Directory of Open Access Journals (Sweden)

    Cheng Qian

    2017-12-01

    Full Text Available AIM: To investigate the correlation of matrix metalloproteinase -9(MMP-9, glycated albumin(GA, glycosylated hemoglobin(HbA1cand adipokines(including visfatin, resistin and leptinwith diabetic retinopathy(DR. METHODS: From March 2015 to March 2017, 74 patients with DR were treated in our hospital, including 40 patients(80 eyeswith non proliferative diabetic retinopathy(NPDRand 34 patients(68 eyeswith proliferative diabetic retinopathy(PDR, and diabetes mellitus 40 patients(80 eyeswith non DR(NDRand 40 healthy volunteers(80 eyeswere selected as controls, the levels of MMP-9, GA, HbA1c, visfatin, resistin and leptin in each group were detected. RESULTS: PDR group visfatin was 4.41±0.82ng/mL, was significantly lower than the NPDR group, NDR group and control group(PPPPrs=0.523, 0.461 and 0.414, Prs=-0.433, Prs=0.401 and 0.460, PCONCLUSION: MMP-9, GA, HbA1c, and adipokines may play a role in the development and progression of DR, in which MMP-9 is associated with adipokines, both are not significantly related to the levels of GA and HbA1c.

  4. Measurements of SNAC2 area dosimeters placed in different configurations around the PROSPERO reactor and comparison with TRIPOLI-4 calculations

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, G.; Chambru, L.; Authier, N. [CEA, Centre de Valduc, 21120 Is-sur-Tille, (France)

    2015-07-01

    In the context of criticality accident alarm system tests, several experiments were carried out in 2013 on the PROSPERO reactor to study the response to neutron and gamma of different devices and dosimeters, particularly on the SNAC2 dosimeter. This article presents the results of this criticality dosimeter in different configurations, and compares the experimental measurements with the results of calculation performed with the TRIPOLI-4 Monte-Carlo Neutral Particles transport code. PROSPERO is a metallic critical assembly managed by the Criticality, Neutron Science and Measurement Department located at the French CEA Research Center of Valduc. The core, surrounded by a reflector of depleted uranium, is composed of 2 horizontal cylindrical blocks made of a highly enriched uranium alloy which can be placed in contact, and of 4 depleted uranium control rods which allow the reactor to be driven. This reactor, placed in a cell 10 m x 8 m x 6 m high, with 1.4-meter-thick concrete walls, is used as a fast neutron spectrum source and is operated at stable power level in delayed critical state, which can vary from 3 mW to 3 kW. PROSPERO is extensively used for electronic hardening or to study the effect of the neutrons on various materials. The SNAC2 criticality dosimeter is a zone dosimeter allowing the off line measurement of criticality accident neutron doses. This dosimeter consists of the pile up of seven activation foils embedded into a 23 mm diameter x 21 mm height cadmium container. The activation measurement of each foil, using a gamma spectroscopy technique, gives information about the neutron reaction rates. The SNAC2 software allows the spectrum unfolding from these values, taking into account the hypothesis of a particular spectrum shape, in three components: a Maxwell spectrum component for the thermal range, a 1/E component for the epithermal range, and a Watt spectrum component for the high energy range. Moreover, from the neutron spectrum, the SNAC

  5. Genetic Epidemiology, Hematological and Clinical Features of Hemoglobinopathies in Iran

    OpenAIRE

    Rahimi, Zohreh

    2013-01-01

    There is large variation in the molecular genetics and clinical features of hemoglobinopathies in Iran. Studying structural variants of hemoglobin demonstrated that the ?-chain variants of hemoglobin S and D-Punjab are more prevalent in the Fars (southwestern Iran) and Kermanshah (western Iran) provinces, respectively. Also, ? -chain variants of Hb Q-Iran and Hb Setif are prevalent in western Iran. The molecular basis and clinical severity of thalassemias are extremely heterogenous among Iran...

  6. Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development.

    Science.gov (United States)

    Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G; Graham, Mark J; Berliner, Judith A; Lusis, Aldons J; Cai, Lei; Temel, Ryan E; Rateri, Debra L; Lee, Sangderk

    2017-01-01

    The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting.

  7. Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

    Science.gov (United States)

    Unwin, Nigel; Howitt, Christina; Rose, Angela Mc; Samuels, T Alafia; Hennis, Anselm Jm; Hambleton, Ian R

    2017-12-01

    Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population.

  8. [Detecting HB-1 Expression Level in Bone Marrow of Acute Leukemia Patients by Real-Time Fluorescence Quantitative RT-PCR].

    Science.gov (United States)

    Wang, Qing-Yun; Li, Yuan; Ji, Li; Liang, Ze-Yin; Liu, Wei; Ren, Han-Yun; Qiu, Zhi-Xiang

    2018-02-01

    To investigate the expression level of HB-1 gene in patients with acute lymphoblastic leukemia (ALL) and the significance of HB-1 gene in monitoring of minimal residual disease (MRD). The method of real-time fluorescence quantitative RT-PCR (Taqman probe) was established to detect the expression levels of HB-1 gene; then the sensitivity, specificity and repeatability of this assay were evaluated and verified. The HB-1 gene expression levels in bone marrow of 183 cases of ALL, 70 cases of acute myeloid leukemias (AML), 52 cases of non-malignant hematologic diseases and 24 healthy hematopoietic stem cell donors were detected. The correlation of HB-1 level with diagnosis and relapse was analyzed by detecting bone marrow samples of 33 B-ALL. The sensitivity of this assay reached the 10 -4 level. The coefficient of variation for inter-batch and inter-tube of HB-1 were 6.79% and 4.80%, respectively. It was found that HB-1 gene specifically expressed in acute B lymphoblastic leukemia. The median expression levels of HB-1 gene in newly diagnosed and relapsed B-ALL patients were statistically significantly higher than those in ALL in complete remission(CR), newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases, and healthy hematopoietic stem cell donors(33.0% vs 0.68%, 0.07%, 0.02%, 0.58% and 0, respectively) (P0.05). The expression level of HB-1 gene declined sharply when B-ALL patients reached complete remission (0-7.99%, with median level 0.68%), but increased when relapsed (7.69%, 8.08% and 484.0% in 3 relapsed samples), which was in accordance with results of flow cytometry. HB-1 gene specifically expressed in acute B lymphoblastic leukemia cells. The established real-time fluorescence quantitative RT-PCR assay shows good sensitivity, specificity and repeatability, thus, can be used as a biological marker in the clinical detection, monitoring MRD and predicting of early relapse for B-ALL patients.

  9. Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

    Science.gov (United States)

    Bazo-Alvarez, J C; Quispe, R; Pillay, T D; Bernabé-Ortiz, A; Smeeth, L; Checkley, W; Gilman, R H; Málaga, G; Miranda, J J

    2017-06-01

    Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA 1c . This study explores the relationship between HbA 1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA 1c and FPG was assessed using a Kappa index. At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA 1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA 1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA 1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA 1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. The relationship between HbA 1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA 1c to diagnose diabetes mellitus in this setting. © 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  10. Fermi LAT and WMAP observations of the supernova remnant HB 21

    Energy Technology Data Exchange (ETDEWEB)

    Pivato, G. [Dipartimento di Fisica e Astronomia " G. Galilei," Università di Padova, I-35131 Padova (Italy); Hewitt, J. W. [CRESST, University of Maryland, Baltimore County, Baltimore, MD 21250 (United States); Tibaldo, L. [W. W. Hansen Experimental Physics Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Department of Physics and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Acero, F.; Brandt, T. J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Université Paris Diderot, Service d' Astrophysique, CEA Saclay, F-91191 Gif sur Yvette (France); De Palma, F.; Giordano, F. [Dipartimento di Fisica " M. Merlin" dell' Università e del Politecnico di Bari, I-70126 Bari (Italy); Janssen, G. H. [University of Manchester, Manchester, M13 9PL (United Kingdom); Jóhannesson, G. [Science Institute, University of Iceland, IS-107 Reykjavik (Iceland); Smith, D. A., E-mail: giovanna.pivato@pd.infn.it, E-mail: john.w.hewitt@nasa.gov, E-mail: ltibaldo@slac.stanford.edu [Centre d' Études Nucléaires de Bordeaux Gradignan, IN2P3/CNRS, Université Bordeaux 1, BP120, F-33175 Gradignan Cedex (France)

    2013-12-20

    We present the analysis of Fermi Large Area Telescope γ-ray observations of HB 21 (G89.0+4.7). We detect significant γ-ray emission associated with the remnant: the flux >100 MeV is 9.4 ± 0.8 (stat) ± 1.6 (syst) × 10{sup –11} erg cm{sup –2} s{sup –1}. HB 21 is well modeled by a uniform disk centered at l = 88.°75 ± 0.°04, b = +4.°65 ± 0.°06 with a radius of 1.°19 ± 0.°06. The γ-ray spectrum shows clear evidence of curvature, suggesting a cutoff or break in the underlying particle population at an energy of a few GeV. We complement γ-ray observations with the analysis of the WMAP 7 yr data from 23 to 93 GHz, achieving the first detection of HB 21 at these frequencies. In combination with archival radio data, the radio spectrum shows a spectral break, which helps to constrain the relativistic electron spectrum, and, in turn, parameters of simple non-thermal radiation models. In one-zone models multiwavelength data favor the origin of γ rays from nucleon-nucleon collisions. A single population of electrons cannot produce both γ rays through bremsstrahlung and radio emission through synchrotron radiation. A predominantly inverse-Compton origin of the γ-ray emission is disfavored because it requires lower interstellar densities than are inferred for HB 21. In the hadronic-dominated scenarios, accelerated nuclei contribute a total energy of ∼3 × 10{sup 49} erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ∼1 × 10{sup 49} erg.

  11. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

    DEFF Research Database (Denmark)

    Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta

    2017-01-01

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we...... than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion....... use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype...

  12. Exploring the ϒ (4 S ,5 S ,6 S )→hb(1 P )η hidden-bottom hadronic transitions

    Science.gov (United States)

    Zhang, Yawei; Li, Gang

    2018-01-01

    Recently, the Belle Collaboration has reported the measurement of the spin-flipping transition ϒ (4 S )→hb(1 P )η with an unexpectedly large branching ratio: B (ϒ (4 S )→hb(1 P )η )=(2.18 ±0.11 ±0.18 )×10-3 . Such a large branching fraction contradicts with the anticipated suppression for the spin flip. In this work, we examine the effects induced by intermediate bottomed meson loops and point out that these effects are significantly important. Using the effective Lagrangian approach (ELA), we find the experimental data on ϒ (4 S )→hb(1 P )η can be accommodated with the reasonable inputs. We then explore the decays ϒ (5 S ,6 S )→hb(1 P )η and find that these two channels also have sizable branching fractions. We also calculate these processes in the framework of nonrelativistic effective field theory (NREFT). For the decays ϒ (4 S )→hb(1 P )η , the NREFT results are at the same order of magnitude but smaller than the ELA results by a factor of 2 to 5. For the decays ϒ (5 S ,6 S )→hb(1 P )η , the NREFT results are smaller than the ELA results by approximately 1 order of magnitude. We suggest a future experiment Belle-II to search for the ϒ (5 S ,6 S )→hb(1 P )η decays, which will be helpful for understanding the transition mechanism.

  13. Changes in HbA1c and Weight Following Transition to Continuous Subcutaneous Insulin Infusion Therapy in Adults With Type 1 Diabetes.

    Science.gov (United States)

    Mehta, Sanjeev N; Andersen, Henrik Ullits; Abrahamson, Martin J; Wolpert, Howard A; Hommel, Eva E; McMullen, William; Ridderstråle, Martin

    2017-01-01

    Historically, intensive insulin therapy for type 1 diabetes (T1D) has improved glycemic control at the risk of adverse weight gain. The impact of continuous subcutaneous insulin infusion therapy (CSII) on weight in the current era remains unknown. We assessed changes in hemoglobin A1c (HbA1c) and weight in adults with T1D transitioning to CSII at 2 diabetes centers in Denmark and the United States. Patients with T1D, aged ≥18 years, managed with multiple daily injections (MDI) who transitioned to CSII between 2002 and 2013 were identified using electronic health record data from the Steno Diabetes Center (n = 600) and Joslin Diabetes Center (n = 658). Changes in HbA1c and weight after 1 year was assessed overall and by baseline HbA1c cut points. Multivariate regression assessed correlates of HbA1c reduction. In adults with T1D transitioning to CSII, clinically significant HbA1c reductions were found in patients with baseline HbA1c 8.0-8.9% (Steno, -0.7%; Joslin, -0.4%) and baseline HbA1c ≥9.0% (Steno, -1.1%; Joslin, -0.9%) ( P HbA1c ≥9% at Steno (1.1 ± 0.3 kg, P HbA1c reduction was associated with higher HbA1c, older age, female sex at Steno ( R 2 = .28, P HbA1c at Joslin ( R 2 = .19, P HbA1c without a negative impact on weight 1 year after transitioning from MDI to CSII.

  14. Comparison of 1,5-anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus.

    Science.gov (United States)

    Yamanouchi, T; Akanuma, Y; Toyota, T; Kuzuya, T; Kawai, T; Kawazu, S; Yoshioka, S; Kanazawa, Y; Ohta, M; Baba, S

    1991-01-01

    To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.

  15. HbA1c Measured in Stored Erythrocytes Is Positively Linearly Associated with Mortality in Individuals with Diabetes Mellitus

    Science.gov (United States)

    Sluik, Diewertje; Boeing, Heiner; Montonen, Jukka; Kaaks, Rudolf; Lukanova, Annekatrin; Sandbaek, Annelli; Overvad, Kim; Arriola, Larraitz; Ardanaz, Eva; Saieva, Calogero; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Spijkerman, Annemieke M. W.; van der A, Daphne L.; Beulens, Joline W. J.; van Dieren, Susan; Nilsson, Peter M.; Groop, Leif C.; Franks, Paul W.; Rolandsson, Olov; Bueno-de-Mesquita, Bas; Nöthlings, Ute

    2012-01-01

    Introduction Observational studies have shown that glycated haemoglobin (HbA1c) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA1c measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA1c was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA1c in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results After a median follow-up of 9.3 years, 460 participants died. Higher HbA1c was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity =0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA1c and medication. Conclusion This prospective study showed that persons with lower HbA1c had better survival than those with higher HbA1c. The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA1c appears to be associated with reduced mortality risk. PMID:22719972

  16. Entsymaattisen Abbott Architect c8000 HbA1c -menetelmän validointi

    OpenAIRE

    Karjalainen, Laura

    2013-01-01

    Opinnäytetyö suoritettiin THL:n Tautiriskiyksikön analyyttisen biokemian laboratoriossa (TLAB). Työssä validoitiin uusi entsymaattinen Abbott Architect c8000 HbA1c -menetelmä, jota käytetään diabetekseen liittyvissä tutkimuksissa. Validoinnilla haluttiin varmistaa uuden mittaustekniikaltaan erilaisen menetelmän toimivuus. Menetelmävertailussa komparatiivisena menetelmänä oli laboratoriossa rutiinikäytössä ollut Abbottin immunoturbidimetrinen HbA1c-menetelmä. Uusi entsymaattinen menetelmä peru...

  17. Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya

    Science.gov (United States)

    Daw, Mohamed A.; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A.

    2014-01-01

    Background In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. Methods A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. Results A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20–40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. Conclusion HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned. PMID:24936655

  18. Risk of progression to diabetes from prediabetes defined by HbA1c or fasting plasma glucose criteria in Koreans.

    Science.gov (United States)

    Kim, Chul-Hee; Kim, Hong-Kyu; Kim, Eun-Hee; Bae, Sung-Jin; Choe, Jaewon; Park, Joong-Yeol

    2016-08-01

    To examine the abilities of HbA1c and fasting plasma glucose (FPG) criteria predicting 5-year progression rate to diabetes in Korean adults with prediabetes. Participants included 17,971 Koreans (aged 20-79years) who underwent routine medical check-ups at a mean interval of 5.2years (3.1-6.7years). Prediabetes was defined as FPG 5.6-6.9mmol/l or HbA1c 5.7-6.4% (39-46mmol/mol). Incident diabetes was defined as FPG⩾7.0mmol/l, HbA1c⩾6.5% (48mmol/mol), or initiation of antidiabetic medications. At baseline, the prevalence of prediabetes was 30.6% (n=5495) by FPG and 20.4% (n=3664) by HbA1c criteria. The 5-year progression rate to diabetes was significantly higher in prediabetes identified by HbA1c than by FPG tests (14.7% vs. 10.4%, Pprediabetes by only one test, those by HbA1c alone had a higher risk of progression to diabetes than those diagnosed by FPG alone (6.0% vs. 3.9%, Pprediabetes identified by HbA1c (OR 9.91, 8.24-11.9) than by FPG (OR 7.29, 5.97-8.89) (P=0.026). Although fewer individuals with prediabetes were identified by HbA1c than by FPG criteria, the ability to predict progression to diabetes was stronger for HbA1c than for FPG in Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities

    Science.gov (United States)

    Long, D.L.; Ulici, V.; Chubinskaya, S.; Loeser, R.F.

    2015-01-01

    Objective We determined if the epidermal growth factor receptor ligand HB-EGF is produced in cartilage and if it regulates chondrocyte anabolic or catabolic activity. Methods HB-EGF expression was measured by quantitative PCR using RNA isolated from mouse knee joint tissues and from normal and OA human chondrocytes. Immunohistochemistry was performed on normal and OA human cartilage and meniscus sections. Cultured chondrocytes were treated with fibronectin fragments (FN-f) as a catabolic stimulus and osteogenic protein 1 (OP-1) as an anabolic stimulus. Effects of HB-EGF on cell signaling were analyzed by immunoblotting of selected signaling proteins. MMP-13 was measured in conditioned media, proteoglycan synthesis was measured by sulfate incorporation, and matrix gene expression by quantitative PCR. Results HB-EGF expression was increased in 12-month old mice at 8 weeks after surgery to induce OA and increased amounts of HB-EGF were noted in human articular cartilage from OA knees. FN-f stimulated chondrocyte HB-EGF expression and HB-EGF stimulated chondrocyte MMP-13 production. However, HB-EGF was not required for FN-f stimulation of MMP-13 production. HB-EGF activated the ERK and p38 MAP kinases and stimulated phosphorylation of Smad1 at an inhibitory serine site which was associated with inhibition of OP-1 mediated proteoglycan synthesis and reduced aggrecan (ACAN) but not COL2A1 expression. Conclusion HB-EGF is a new factor identified in OA cartilage that promotes chondrocyte catabolic activity while inhibiting anabolic activity suggesting it could contribute to the catabolic-anabolic imbalance seen in OA cartilage. PMID:25937027

  20. Values of HbCO in 1000 inhabitants of Milan non exposed to occupational absorption of CO

    Energy Technology Data Exchange (ETDEWEB)

    Grisler, R.; Gobbi, A.; Giavardi, C.; Caimmi, G.; Soverini, R.; Botta, A.

    1975-01-01

    Carboxyhemoglobin levels for 1000 non-occupationally exposed inhabitants of Milan were determined. The study group consisted of smokers and non-smokers; among the former, only individuals refraining from smoking for at least 10 hr were tested. The upper limit of the normal range for HbCO values among non-smokers was 2.85%, while among heavy smokers it was 4.59%. Heavy smokers also showed higher HbCO levels than did moderate smokers. Elevated HbCO values were also observed among residents living in carbon monoxide-polluted urban areas as compared with those living in unpolluted rural areas.

  1. Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.

    Science.gov (United States)

    Schernthaner, Guntram; Lavalle-González, Fernando J; Davidson, Jaime A; Jodon, Holly; Vijapurkar, Ujjwala; Qiu, Rong; Canovatchel, William

    2016-11-01

    To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks. Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c HbA1c HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks. www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.

  2. Glycated hemoglobin HbA1c, waist circumference, and waist-to-height ratio in overweight and obese adolescents

    Directory of Open Access Journals (Sweden)

    Elysa Nur Safrida

    2017-04-01

    Full Text Available Background Central obesity has been associated with a high risk of insulin resistance. Waist circumference and waist-to-height ratio are anthropometric indices for determining central obesity and have been associated with increased blood pressure, cholesterol, and insulin levels. In adults, fat distribution around the waist is a valid predictor of glycated hemoglobin (HbA1clevels, and is currently recommended by experts as a diagnostic tool for diabetes. Central obesity measurement has advantages over fasting blood glucose and oral glucose tolerance tests, as it is simple and inexpensive to perform. Objective To assess for correlations between HbA1c level and waist circumference as well as waist-to-height ratio and to assess factors potentially associated with HbA1c levels in overweight and obese adolescents. Methods This cross-sectional study was done in four junior high schools in Yogyakarta, which were obtained by cluster sampling. Overweight and obese students who were generally healthy were included in the study. Subjects underwent waist circumference and waist-to-height ratio measurements, as well as blood tests for HbA1clevels. Results Sixty-seven children participated in the study, with 48 girls (71.6% and 19 boys (28.4%. Waist circumference and HbA1c levels were not significantly associated (r=0.178; P=0.15. However, waist-to-height ratio and HbA1c levels had a weak positive correlation (r=0.21; P=0.04. Linear regression analysis revealed that waist-to-height ratio had a significant association with HbA1c level (P=0.02, but age, sex, and nutritional status did not. Conclusion Waist-to-height ratio is correlated with HbA1c levels in overweight and obese adolescents.

  3. Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

    Science.gov (United States)

    Romain, A J; Letendre, E; Akrass, Z; Avignon, A; Karelis, A D; Sultan, A; Abdel-Baki, A

    2017-04-01

    Aim: Prediabetes and type 2 diabetes are highly prevalent among individuals with serious mental illness and increased by antipsychotic medication. Although widely recommended, many obstacles prevent these patients from obtaining a proper screening for dysglycemia. Currently, glycated hemoglobin (HbA1c), fasting glucose, and 2-hour glucose levels from the oral glucose tolerance test are used for screening prediabetes and type 2 diabetes. The objective of this study was to investigate if HbA1c could be used as the only screening test among individuals with serious mental illness. Methods: Cross sectional study comparing the sensitivity of HbA1c, fasting glucose, and 2-h oral glucose tolerance test to detect dysglycemias in serious mental illness participants referred for metabolic complications. Results: A total of 84 participants (43 female; aged: 38.5±12.8 years; BMI: 35.0±6.8 kg/m²) was included. Regarding prediabetes, 44, 44 and 76% were identified by HbA1c, fasting glucose, and 2 h- oral glucose tolerance test respectively and for type 2 diabetes, 60, 53 and 66% were identified by HbA1c, fasting glucose and 2 h-oral glucose tolerance test. The overlap between the 3 markers was low (8% of participants for prediabetes and 26% for Type 2 diabetes). Sensitivity of HbA1c were moderate (range 40-62.5%), while its specificity was excellent (92-93%). Conclusion: The present study indicates a low agreement between HbA1c, fasting glucose and 2-h oral glucose tolerance test. It appears that these markers do not identify the same participants. Thus, HbA1c may not be used alone to detect all glucose abnormalities among individuals with serious mental illness. © Georg Thieme Verlag KG Stuttgart · New York.

  4. The Haber Bosch-harmful algal bloom (HB-HAB) link

    NARCIS (Netherlands)

    Glibert, P.M.; Maranger, R.; Sobota, D.J.; Bouwman, Lex|info:eu-repo/dai/nl/090428048

    2014-01-01

    Large-scale commercialization of the Haber–Bosch (HB) process is resulting in intensification of nitrogen (N) fertilizer use worldwide. Globally N fertilizer use is far outpacing that of phosphorus (P) fertilizer. Much of the increase in N fertilizers is also now in the form of urea, a reduced form

  5. CLD (chronic liver diseases)-HbA1C as a suitable indicator for estimation of mean plasma glucose in patients with chronic liver diseases.

    Science.gov (United States)

    Koga, Masafumi; Kasayama, Soji; Kanehara, Hideo; Bando, Yukihiro

    2008-08-01

    In patients with chronic liver diseases (CLD), turnover of erythrocytes is increased whereas that of serum albumin is decreased. Thus, glycated hemoglobin (HbA(1C)) and glycated albumin (GA) cannot be used as adequate indicators for chronic plasma glucose control in diabetic patients with CLD. In this investigation, we have proposed CLD-HbA(1C), a novel long-term glycemic control marker by using measured HbA(1C) and GA. We studied 82 patients with CLD in whom glycemic control was regarded as to be stable. Daily plasma glucose profiles were monitored and estimated levels of HbA(1C) were calculated on the conversion formula established by Rohlfing et al. [C.L. Rohlfing, J.D. England, H.M. Wiedmeyer, A. Tennill, R.R. Little, D.E. Goldstein, Defining the relationship between plasma glucose and HbA1c, Diabetes Care 25 (2002) 275-278]. Cholinesterase (ChE) as an indicator for hepatic function was determined at the same time when HbA(1C) and GA levels were measured. CLD-HbA(1C) was defined as the average of measured HbA(1C) and GA/3, based upon the results that among healthy individuals, GA levels were roughly estimated at approximately threefold higher than HbA(1C) levels. While measured HbA(1C) levels in patients with CLD were generally lower than estimated HbA(1C) levels, GA/3 values were generally higher than estimated HbA(1C) levels. Such discrepancies lineally increased in accordance with a decrease in ChE levels. On the other hand, CLD-HbA(1C) levels were highly correlated with estimated HbA(1C) levels (R=0.883), while no significant correlation between CLD-HbA(1C) and ChE was noted. In conclusion, CLD-HbA(1C) has been found a superior chronic glycemic control marker than HbA(1C) or GA in diabetic patients with chronic liver diseases.

  6. The 1-hour post-load glucose level is more effective than HbA1c for screening dysglycemia.

    Science.gov (United States)

    Jagannathan, Ram; Sevick, Mary Ann; Fink, Dorothy; Dankner, Rachel; Chetrit, Angela; Roth, Jesse; Buysschaert, Martin; Bergman, Michael

    2016-08-01

    To assess the performance of HbA1c and the 1-h plasma glucose (PG ≥ 155 mg/dl; 8.6 mmol/l) in identifying dysglycemia based on the oral glucose tolerance test (OGTT) from a real-world clinical care setting. This was a diagnostic test accuracy study. For this analysis, we tested the HbA1c diagnostic criteria advocated by the American Diabetes Association (ADA 5.7-6.4 %) and International Expert Committee (IEC 6.0-6.4 %) against conventional OGTT criteria. We also tested the utility of 1-h PG ≥ mg/dl; 8.6 mmol/l. Prediabetes was defined according to ADA-OGTT guidelines. Spearman correlation tests were used to determine the relationships between HbA1c, 1-h PG with fasting, 2-h PG and indices of insulin sensitivity and β-cell function. The levels of agreement between diagnostic methods were ascertained using Cohen's kappa coefficient (Κ). Receiver operating characteristic (ROC) curve was used to analyze the performance of the HbA1c and 1-h PG test in identifying prediabetes considering OGTT as reference diagnostic criteria. The diagnostic properties of different HbA1c thresholds were contrasted by determining sensitivity, specificity and likelihood ratios (LR). Of the 212 high-risk individuals, 70 (33 %) were identified with prediabetes, and 1-h PG showed a stronger association with 2-h PG, insulin sensitivity index, and β-cell function than HbA1c (P HbA1c criteria 0.1[0.03-0.16] and IEC criteria (0.17[0.04-0.30]). The ROC (AUC[95 % CI]) for HbA1c and 1-h PG were 0.65[0.57-0.73] and 0.79[0.72-0.85], respectively. Importantly, 1-h PG ≥ 155 mg/dl (8.6 mmol/l) showed good sensitivity (74.3 % [62.4-84.0]) and specificity 69.7 % [61.5-77.1]) with a LR of 2.45. The ability of 1-h PG to discriminate prediabetes was better than that of HbA1c (∆AUC: -0.14; Z value: 2.5683; P = 0.01022). In a real-world clinical practice setting, the 1-h PG ≥ 155 mg/dl (8.6 mmol/l) is superior for detecting high-risk individuals compared with HbA1c

  7. Possible discrepancy of HbA1c values and its assessment among patients with chronic renal failure, hemodialysis and other diseases.

    Science.gov (United States)

    Inoue, Kaori; Goto, Atsushi; Kishimoto, Miyako; Tsujimoto, Tetsuro; Yamamoto-Honda, Ritsuko; Noto, Hiroshi; Kajio, Hiroshi; Terauchi, Yasuo; Noda, Mitsuhiko

    2015-12-01

    Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. However, these markers are influenced by alterations in hemoglobin and albumin metabolism. Thus, conditions such as anemia, chronic renal failure, hypersplenism, chronic liver diseases, hyperthyroidism, hypoalbuminemia, and pregnancy need to be considered when interpreting HbA1c or GA values. Using data from patients with normal albumin and hemoglobin metabolism, we previously established a linear regression equation describing the GA value versus the HbA1c value to calculate an extrapolated HbA1c (eHbA1c) value for the accurate evaluation of glycemic control. In this study, we investigated the difference between the measured HbA1c and the eHbA1c values for patients with various conditions. Data sets for a total of 2461 occasions were obtained from 731 patients whose HbA1c and GA values were simultaneously measured. We excluded patients with missing data or changeable HbA1c levels, and patients who had received transfusions or steroids within the previous 3 months. Finally, we included 44 patients with chronic renal failure (CRF), 10 patients who were undergoing hemodialysis (HD), 7 patients with hematological malignancies and a hemoglobin level of less than 10 g/dL (HM), and 12 patients with chronic liver diseases (CLD). In all the groups, the eHbA1c values were significantly higher than the measured HbA1c values. The median difference was 0.75 % (95 % CI 0.40-1.10 %, P for the difference is <0.001) in the CRF group, 0.80 % (95 % CI 0.30-1.65 %, P for the difference is 0.041) in the HD group, 0.90 % (95 % CI 0.90-1.30 %, P for the difference is 0.028) in the HM group, and 0.85 % (95 % CI 0.40-1.50 %, P for the difference is 0.009) in the CLD group. We found that the measured HbA1c values were lower than the eHbA1c values in each of the groups.

  8. Sedimentary facies analysis of a high-frequency, small-scale, peritidal carbonate sequence in the Lower Jurassic of the Tripolis carbonate unit (central western Crete, Greece: Long-lasting emergence and fossil laminar dolocretes horizons

    Directory of Open Access Journals (Sweden)

    Fotini A. Pomoni

    2016-07-01

    Full Text Available The study examines a Lower Jurassic (late Liassic cyclic lagoonal–peritidal stratigraphic unit outcropping in central western Crete (Tripolis unit, which corresponds to the eastern (internal part of the mainland Gavrovo-Tripolis platform, the most significant external platform of the Hellenides. The studied Tripolis carbonate sequence consists of meter-scale, shallowing-upward successions of restricted inner-carbonate platform facies, including cyclically repeated subtidal, intertidal and supratidal facies, that are separated by erosion surfaces (elementary cycles. Each cycle starts with relatively open-marine facies, which are overlain by shallower, more restricted facies (tidal flat progradation. The lithofacies association includes dolomitic intraclastic–peloidal–bioclastic wackestones–packstones/floatstones and grainstones/rudstones dominated by a restricted shallow-marine fauna (bivalves, gastropods, ostracods and seldom benthic foraminifers, representing a shallow subtidal to intertidal, moderately high-energy environment within an inner-platform setting (peritidal environment to restricted lagoon. This lithofacies association has been intermittently subaerially exposed and has undergone diagenetic processes in an inter- or supratidal environment, exhibiting features of vadose diagenesis and pedogenesis due to long-lasting exposure along certain horizons. The peritidal facies are capped by dolocretes controlled by root-activities (laminar dolocretes, peloidal–pisoid dolocretes and massive dolocretes, marking the end of each depositional cycle, and, thus, distinguishing the successive episodes of a prolonged subaerial exposure period and birth of paleosol horizons. Dolocretes consist a diagenetic facies, characterized by several vadose and pedogenic fabrics, including fenestral cavities with geopetal structures, “flower spar” to blocky sparry cement in primary pores, micritic coatings, crudely pelleted walls, alveolar

  9. Solids loading evaluation for HB-line scrap recovery filters

    International Nuclear Information System (INIS)

    Crowder, M.L.

    2000-01-01

    The HB-Line Scrap Recovery facility uses wire screen filters to remove solids from plutonium-containing solutions transferred from the slab tank dissolvers. At times, the accumulation of solids is large enough to cause blinding (i.e., pluggage) of the filters. If the solids contain undissolved plutonium, significant accumulation of fissile material could impact operations. To address this potential issue, experiments were performed to define the minimum solids required to completely blind a filter. The solids loading experiments were performed by arranging 25- and 10-microm HB-Line filters in series to simulate the equipment in the scrap recovery process. Separate tests were performed using coarse and fine glass frit and cerium oxide powder suspended in 35 wt% sodium nitrate solution using a small turbine mixer. The solution and solids were transferred from a reservoir through the filter housings by vacuum. In each case, the 25-microm filter blinded first and was full of wet cake. After drying and accounting for the sodium nitrate in the filter cake, the following results were obtained. The results of the solids loading tests demonstrated that at least 800 g of solids accumulated in the filter housing before flow stopped. The actual amount of collected material was dependent upon the physical properties of the solids such as density and particle size. The mass of solids collected by the blinded 25-microm filter increased when successively finer solids were used in the experiments. Based on these results, one should anticipate that filters in the HB-Line Scrap Recovery Facility have the potential to collect similar quantities of material before transfer of solution from the dissolvers is severely impacted

  10. Dilution Ratios for HB Line Phase I Eductor System

    International Nuclear Information System (INIS)

    Steimke, J.L.

    2002-01-01

    HB Line Phase I product transfer includes an eductor which transfers liquid from Product Hold Tank (PHT) RT-33 or RT-34 to Tank 11.1. The eductor also dilutes the liquid from the PHT with eductant. Dilution must be reliably controlled because of criticality concerns with H Canyon Tanks. The eductor system, which contains a 1 inch Model 264 Schutte and Koerting eductor, was previously modeled [1] in 1998 and dilution ratios were calculated for different flow restrictors, eductant pressures and densities for the eductant and the contents of the PHT. The previous calculation was performed using spreadsheet software no longer supported at SRS. For the previous work dilution ratio was defined as the volume of eductant consumed divided by volume of PHT contents transferred. Since 1998 HB Line Engineering has changed the definition of dilution ratio to the total volume of liquid, eductant consumed plus the volume of PHT liquid transferred, divided by the volume of PHT liquid transferred. The 1998 base case calculation was for a restrictor diameter of 0.334 inches, an eductant supply pressure of 15 psig, full PHT, an eductant specific gravity of 1.385 and a PHT density of 1.015. The base case dilution ratio calculated in 1998 using the current definition was 3.52. After accounting for uncertainty the minimum dilution ratio decreased to 3.23. In 2001 HB Line Engineering requested that the calculation be repeated for a manganous nitrate solution eductant and also a process water eductant. The other conditions were the same as for the 1998 calculation. The objective of this report is to document the calculations and the results

  11. β-Globin gene sequencing of hemoglobin Austin revises the historically reported electrophoretic migration pattern.

    Science.gov (United States)

    Racsa, Lori D; Luu, Hung S; Park, Jason Y; Mitui, Midori; Timmons, Charles F

    2014-06-01

    Hemoglobin (Hb) Austin was defined in 1977, using amino acid sequencing of samples from 3 unrelated Mexican-Americans, as a substitution of serine for arginine at position 40 of the β-globin chain (Arg40Ser). Its electrophoretic migration on both cellulose acetate (pH 8.4) and citrate agar (pH 6.2) was reported between Hb F and Hb A, and this description persists in reference literature. OBJECTIVES.-To review the clinical features and redefine the diagnostic characteristics of Hb Austin. Eight samples from 6 unrelated individuals and 2 siblings, all with Hispanic surnames, were submitted for abnormal Hb identification between June 2010 and September 2011. High-performance liquid chromatography, isoelectric focusing (IEF), citrate agar electrophoresis, and bidirectional DNA sequencing of the entire β-globin gene were performed. DNA sequencing confirmed all 8 individuals to be heterozygous for Hb Austin (Arg40Ser). Retention time on high-performance liquid chromatography and migration on citrate agar electrophoresis were consistent with that identification. Migration on IEF, however, was not between Hb F and Hb A, as predicted from the report of cellulose acetate electrophoresis. By IEF, Hb Austin migrated anodal to ("faster than") Hb A. Hemoglobin Austin (Arg40Ser) appears on IEF as a "fast," anodally migrating, Hb variant, just as would be expected from its amino acid substitution. The cited historic report is, at best, not applicable to IEF and is probably erroneous. Our observation of 8 cases in 16 months suggests that this variant may be relatively common in some Hispanic populations, making its recognition important. Furthermore, gene sequencing is proving itself a powerful and reliable tool for definitive identification of Hb variants.

  12. Complete dissection of the Hb(64-76) determinant using T helper 1, T helper 2 clones, and T cell hybridomas

    DEFF Research Database (Denmark)

    Evavold, B D; Williams, S G; Hsu, B L

    1992-01-01

    We have generated cloned Th1 cells, Th2 cells, and T cell hybridomas specific for the single immunogenic peptide from the beta-chain of murine hemoglobin (Hb(64-76)). The availability of these various types of T cells provided us an unique opportunity to examine and dissect the T cell response...... to an immunogenic peptide. A panel of altered Hb peptides was made by replacing each amino acid in the Hb peptide (positions 64-76) with a conservative amino acid substitution or an alanine. Although none of the eleven T cell clones and hybridomas tested exhibited the same pattern of reactivity to the substituted...... Hb peptides, some general features were identified for all T cell responses. The primary T cell contact residue of Hb(64-76) was shown to be asparagine 72. For every Hb(64-76) specific T cell, no activation was observed using a peptide containing the conservative substitution of a glutamine...

  13. HbA1c and Glycated Albumin Levels Are High in Gastrectomized Subjects with Iron-Deficiency Anemia.

    Science.gov (United States)

    Inada, Shinya; Koga, Masafumi

    2017-01-01

    We report that glycated albumin (GA) is higher relative to HbA1c in non-diabetic, gastrectomized subjects without anemia, and thus is a sign of oxyhyperglycemia. It is known that gastrectomized subjects are prone to iron-deficiency anemia (IDA), and that the HbA1c levels of subjects with IDA are falsely high. In the present study, the HbA1c and GA levels of gastrectomized subjects with IDA were compared with gastrectomized subjects without anemia. Seven non-diabetic gastrectomized subjects with IDA were enrolled in the present study. Twenty-eight non-diabetic gastrectomized subjects without anemia matched with the subjects with IDA in terms of age, gender, and body mass index were used as the controls. Although there were no significant differences in fasting plasma glucose and OGTT 2-hour plasma glucose (2-h PG) between the two groups, the HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than the controls. For all of the gastrectomized subjects (n=35), ferritin exhibited a significant negative correlation with HbA1c and GA, and a significant positive correlation with 2-h PG. In addition, the HbA1c and GA levels exhibited a significant negative correlation with the mean corpuscular hemoglobin and hemoglobin. The HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than those in controls. The high GA levels are attributed to a tendency in which patients with total gastrectomy, who are prone to IDA, are susceptible to postprandial hyperglycemia and reactive hypoglycemia, which in turn leads to large fluctuations in plasma glucose. © 2017 by the Association of Clinical Scientists, Inc.

  14. Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes

    DEFF Research Database (Denmark)

    Law, Graham R; Gilthorpe, Mark S; Secher, Anna L

    2017-01-01

    AIMS/HYPOTHESIS: This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measureme...

  15. How can point-of-care HbA1c testing be integrated into UK primary care consultations? - A feasibility study.

    Science.gov (United States)

    Hirst, J A; Stevens, R J; Smith, I; James, T; Gudgin, B C; Farmer, A J

    2017-08-01

    Point-of-care (POC) HbA1c testing gives a rapid result, allowing testing and treatment decisions to take place in a single appointment. Trials of POC testing have not been shown to improve HbA1c, possibly because of how testing was implemented. This study aimed to identify key components of POC HbA1c testing and determine strategies to optimise implementation in UK primary care. This cohort feasibility study recruited thirty patients with type 2 diabetes and HbA1c>7.5% (58mmol/mol) into three primary care clinics. Patients' clinical care included two POC HbA1c tests over six months. Data were collected on appointment duration, clinical decisions, technical performance and patient behaviour. Fifty-three POC HbA1c consultations took place during the study; clinical decisions were made in 30 consultations. Five POC consultations with a family doctor lasted on average 11min and 48 consultations with nurses took on average 24min. Five POC study visits did not take place in one clinic. POC results were uploaded to hospital records from two clinics. In total, sixty-three POC tests were performed, and there were 11 cartridge failures. No changes in HbA1c or patient behaviour were observed. HbA1c measurement with POC devices can be effectively implemented in primary care. This work has identified when these technologies might work best, as well as potential challenges. The findings can be used to inform the design of a pragmatic trial to implement POC HbA1c testing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. HbA1c variability in type 2 diabetes is associated with the occurrence of new-onset albuminuria within three years.

    Science.gov (United States)

    Dorajoo, Sreemanee Raaj; Ng, Joceline Shi Ling; Goh, Jessica Hui Fen; Lim, Su Chi; Yap, Chun Wei; Chan, Alexandre; Lee, Joyce Yu Chia

    2017-06-01

    To evaluate the association between HbA1c coefficient of variation (HbA1c-CV) and 3-year new-onset albuminuria risk. A retrospective cohort study involving 716 normoalbuminuric type 2 diabetes patients was conducted between 2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or high variability groups. Multivariate logistic models were constructed and validated. Integrated discrimination (IDI) and net reclassification (NRI) improvement indices were used to quantify the added predictive value of HbA1c-CV. The mean age of our cohort was 56.1±12.9years with a baseline HbA1c of 8.3±1.3%. Over 3-years of follow-up, 35.2% (n=252) developed albuminuria. An incremental risk of albuminuria was observed with moderate (6.68-13.43%) and high (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63 (1.12-2.38) and 3.80 (2.10-6.97) for 3-year new-onset albuminuria, respectively. Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model discrimination (IDI: 0.023, NRI: 0.293, pHbA1c-CV improves 3-year prediction of new-onset albuminuria. Together with mean HbA1c, baseline urine albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new-onset albuminuria prediction may be possible. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The Natural History of Hb S/Hereditary Persistence of Fetal Hemoglobin in 13 Children from the State of Minas Gerais, Brazil.

    Science.gov (United States)

    Belisário, André R; Sales, Rahyssa R; Silva, Célia M; Velloso-Rodrigues, Cibele; Viana, Marcos Borato

    2016-06-01

    Children with Hb S (HBB: c.20A > T)/hereditary persistence of fetal hemoglobin (Hb S/HPFH) have a mild clinical phenotype, but some complications have been reported. The natural history of Hb S/HPFH in children from the State of Minas Gerais, Brazil newborn cohort is described. Clinical and hematological data regarding participants' phenotypes were retrieved from medical records. The HPFH-1, HPFH-2, and HPFH-3 and α-thalassemia (α-thal) deletions were detected by gap-polymerase chain reaction (gap-PCR). Thirteen children were included, nine (69.2%) had the Hb S/HPFH-2 deletion, and four (30.8%) had Hb S/HPFH-1 deletion; 11 children (84.6%) had αα/αα, and two (15.4%) carried the αα/-α(3.7) (rightward) deletion. The mean concentration of total hemoglobin (Hb) and Hb F was 12.52 ± 0.56 g/dL and 42.31% ± 1.97%, respectively. Mild microcytosis and hypochromia were observed. We found acute clinical manifestations of sickle cell disease, such as acute chest syndrome (ACS) and acute pain crisis in four children; nine (69.2%) children were completely asymptomatic during the follow-up period. All children were classified as having low-risk transcranial Doppler (TDC). In conclusion, children with Hb S/HPFH have a mild clinical phenotype of sickle cell disease, although acute clinical manifestations may occur. High Hb F levels and absence of anemia are common hematological characteristics.

  18. Alcohol consumption reduces HbA1c and glycated albumin concentrations but not 1,5-anhydroglucitol.

    Science.gov (United States)

    Inada, Shinya; Koga, Masafumi

    2017-11-01

    Background The effect of alcohol consumption on glycaemic control indicators is not well known. In this study, we studied the effect of alcohol consumption on the plasma glucose and glycaemic control indicators in non-diabetic men. Methods The study enrolled 300 non-diabetic men who received a complete medical checkup (age: 52.8 ± 6.5 years, body mass index: 24.4 ± 2.8 kg/m 2 ). The subjects were divided into four groups by the amount of alcohol consumed, and the plasma glucose, HbA1c, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) concentrations of the groups were compared. Results As the level of alcohol consumption increased, significantly high concentrations of fasting plasma glucose (FPG) were observed, and the oral glucose tolerance test 2-h plasma glucose concentrations tended to rise. While no significant effect of alcohol consumption on HbA1c, 1,5-AG, and the 1,5-AG/FPG ratio was observed, the HbA1c/FPG ratio, GA and the GA/FPG ratio exhibited significantly low values as the level of alcohol consumption increased. In stepwise multivariate regression analysis, alcohol consumption was a significant negative independent variable for HbA1c and GA, but not for 1,5-AG. Conclusions As the level of alcohol consumption increased, the plasma glucose concentrations rose, but the HbA1c and GA concentrations were lower compared with the plasma glucose concentrations. These findings suggest that alcohol consumption may reduce HbA1c and GA concentrations, but not 1,5-AG.

  19. Hydrops Fetalis Associated with Compound Heterozygosity for Hb Zurich-Albisrieden (HBA2: C.178G > C) and the Southeast Asian (- -SEA/) Deletion.

    Science.gov (United States)

    Yang, Xin; Yan, Jin-Mei; Li, Jian; Xie, Xing-Mei; Zhou, Jian-Ying; Li, Yan; Li, Dong-Zhi

    2016-09-01

    Hb Zurich-Albisrieden [HBA2: c.178G > C; α59(E8)Gly→Arg (α2)] is a rare nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at codon 59 of the α2-globin gene. In this report, we present a fetus with cardiomegaly, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 25 weeks' gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 5.5 g/dL] and Hb H (β4) disease-like hematological findings with Hb Bart's (γ4) level of 30.7%. Molecular analysis of the family found that the father was an Hb Zurich-Albisrieden carrier, the mother heterozygous for the - - SEA α 0 -thal deletion, and the fetus was a compound heterozygote for Hb Zurich-Albisrieden and the - - SEA α 0 -thal deletion. Therefore, this was a rare case of Hb Bart's hydrops fetalis associated with Hb Zurich Albisrieden.

  20. Diabetes distress is more strongly associated with HbA1c than depressive symptoms in adolescents with type 1 diabetes

    DEFF Research Database (Denmark)

    Hagger, Virginia; Hendrieckx, Christel; Cameron, Fergus

    2018-01-01

    BACKGROUND: Glycated hemoglobin (HbA1c) is higher during adolescence than at any other life stage. Some research among adolescents indicates that depressive symptoms are associated with suboptimal HbA1c. However, research among adults suggests diabetes distress is a stronger predictor of HbA1c th...

  1. HbA1c Outcomes in Patients Treated With Canagliflozin Versus Sitagliptin in US Health Plans.

    Science.gov (United States)

    Thayer, Sarah; Aguilar, Richard; Korrer, Stephanie; Chow, Wing

    2017-10-01

    Clinical trial evidence supports greater glycemic control with canagliflozin than with sitagliptin. The objective of this study was to provide real-world evidence comparing outcomes in routine clinical practice among patients initiating each medication. With the use of a health care administrative database, patients initiating canagliflozin were compared with patients initiating sitagliptin (first prescription fill as index date). Baseline (6 months before index date) demographic and clinical (eg, comorbidities and diabetes-related complications) characteristics were compared, and propensity score matching was used to control for baseline differences between cohorts. Outcomes included change in glycosylated hemoglobin (HbA 1c ) and persistence with medication over a 9-month period after index date. Before matching, the canagliflozin cohort (N = 3993) was younger than the sitagliptin cohort (N = 12,153) and was composed of fewer women and Medicare Advantage enrollees, with lower mean baseline comorbidity scores (all p < 0.001). Before matching, the canagliflozin cohort (valid n = 1482) had a significantly (p < 0.001) higher baseline HbA 1c (8.60) than the sitagliptin cohort (valid n = 3697; HbA 1c , 8.32). After matching (n = 1472 per cohort), patients were well balanced on baseline characteristics, and HbA 1c values were not significantly different (p = 0.634) between the cohorts. Patients initiating canagliflozin had greater reductions in HbA 1c than patients in the sitagliptin cohort (-0.93% versus -0.57%, respectively; p = 0.004), with similar mean (median) time from index date to follow-up HbA 1c of 185.4 (199.0) and 184.3 (190.5) days, respectively (p = 0.802). Only 29.8% of canagliflozin patients discontinued during follow-up compared with 41.5% of sitagliptin patients (p < 0.001); the average days of persistence on index therapy was longer for canagliflozin patients (152 days) than for sitagliptin patients (139 days; p < 0.001). In this observational study

  2. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    Science.gov (United States)

    Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-08-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

  3. Cutoff value of HbA1c for predicting diabetes and prediabetes in a Chinese high risk population aged over 45.

    Science.gov (United States)

    Zhang, Ruyi; Wang, Jiao; Luo, Jinhua; Yang, Xiaoyan; Yang, Rui; Cai, Dehong; Zhang, Hua

    2015-01-01

    To evaluate the cutoff value of HbA1c for predicting diabetes and prediabetes in a Chinese high risk population aged over 45. A total of 619 people aged over 45 without diabetes were randomly recruited to complete Finnish Diabetes Risk Score (FINDRISC) questionnaire. 208 high-risk individuals (defined by Diabetes Risk Score >=9) had OGTT and HbA1c determined at the same time. In a Chinese population aged over 45, the best cutoff value of HbA1c for detecting diabetes and prediabetes was 5.8% and 5.4% respectively. The area under the receiver operating characteristic (AUROC) curve of HbA1c for detecting diabetes was 0.85 (95% CI: 0.80-0.90) and prediabetes was 0.62 (95% CI: 0.54-0.70). The combined use of HbA1c and fasting blood glucose (FPG) had larger AUROC than HbA1c alone (0.88, 95%CI: 0.83-0.92 in detecting diabetes vs 0.75, 95% CI: 0.67-0.82 in prediabetes), and had a higher sensitivity in predicting diabetes and higher specificity and positive predictive value (PPV) in predicting prediabetes. However, the AUROC between HbA1c alone and combined use in predicting diabetes was not significantly different (p=0.173). FINDRISC is feasible tool to screen people who are at high risk of diabetes. The cutoff values of HbA1c to diagnose diabetes and prediabetes in a Chinese high risk population aged over 45 were 5.8% and 5.4%, respectively. The sensitivity and specificity of HbA1c for detecting diabetes and prediabetes was relatively low, so that the combined use of HbA1c and FPG may be more effective in prediction.

  4. The relationships among iron supplement use, Hb concentration and linear growth in young children: Ethiopian Demographic and Health Survey.

    Science.gov (United States)

    Mohammed, Shimels Hussien; Esmaillzadeh, Ahmad

    2017-11-01

    Growth faltering and anaemia remain unacceptably high among infants and young children in Ethiopia. In this study, we investigated the relationships among Fe supplement use (ISU), Hb concentration and linear growth, hypothesising positive relationships between ISU and Hb, ISU and linear growth and Hb and linear growth. We used a nationally representative data of 2400 children aged 6-24 months from the Ethiopian Demographic and Health Survey (EDHS) 2011, conducted following a stratified, two-stage cluster sampling. We examined the links by Pearson's correlation, bivariate and multivariate linear regression analyses and reported adjusted estimates. We found that ISU was not significantly associated with either Hb (β=1·09; 95 % CI -2·73, 5·01, P=0·567) or linear growth (β=0·07; 95 % CI -0·06, 0·21, P=0·217). We found a positive, however, weak, correlation between Hb and linear growth (r 0·09; 95 % CI 0·06, 0·11, PHb predicted linear growth independent of a variety dietary and non-dietary factors (β=0·08; 95 % CI 0·04, 0·11, PHb; age, birth type, size at birth, sex, breast-feeding duration, dietary diversity and deworming were independently associated with linear growth, indicating that Hb and linear growth are multifactorial with both nutritional and non-nutritional factors implicated. Further studies, with better design and exposure assessment, are warranted on the relation of ISU with Hb or linear growth.

  5. The Stricter the Better? The Relationship between Targeted HbA1c Values and Metabolic Control of Pediatric Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Braun, Marcin; Tomasik, Bartlomiej; Wrona, Ewa; Fendler, Wojciech; Jarosz-Chobot, Przemyslawa; Szadkowska, Agnieszka; Zmysłowska, Agnieszka; Wilson, Jayne; Mlynarski, Wojciech

    2016-01-01

    It remains unclear how HbA1c recommendations influence metabolic control of paediatric patients with type 1 diabetes mellitus. To evaluate this we compared reported HbA1c with guideline thresholds. We searched systematically MEDLINE and EMBASE for studies reporting on HbA1c in children with T1DM and grouped them according to targeted HbA1c obtained from regional guidelines. We assessed the discrepancies in the metabolic control between these groups by comparing mean HbA1c extracted from each study and the differences between actual and targeted HbA1c. We included 105 from 1365 searched studies. The median (IQR) HbA1c for the study population was 8.30% (8.00%-8.70%) and was lower in "6.5%" than in "7.5%" as targeted HbA1c level (8.20% (7.85%-8.57%) versus 8.40% (8.20%-8.80%); p = 0.028). Median difference between actual and targeted HbA1c was 1.20% (0.80%-1.70%) and was higher in "6.5%" than in "7.5%" (1.70% (1.30%-2.07%) versus 0.90% (0.70%-1.30%), resp.; p HbA1c levels being closer to the therapeutic goal, but the actual values are still higher than those observed in the "6.5%" group. A meta-analysis of raw data from national registries or a prospective study comparing both approaches is warranted as the next step to examine this subject further.

  6. 77 FR 5566 - Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County...

    Science.gov (United States)

    2012-02-03

    ...] Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County, New Mexico... Statement (Final EIS) for the HB In-Situ Solution Mine Project, and by this notice is announcing its... the Federal Register. ADDRESSES: Copies of the HB In-Situ Solution Mining EIS are available for public...

  7. KADAR HbA1c DAN RASIO LIPID PADA WANITA DEWASA DENGAN OBESITAS SENTRAL

    Directory of Open Access Journals (Sweden)

    Lisa Sudaryanto

    2016-06-01

    Full Text Available Central obesity was accumulation of fat in the abdominal region. Many studies showed correlations between central obesity and cardiovascular diseases, e.g. diabetes and dyslipidemia.  This study was conducted to know the difference between HbA1c and lipid profil between the women with and without central obesity. This study was an analytic observational study with cross-sectional design. Subjects of 52 respondents were healthy adult women staff in campus I, II, III Sanata Dharma University in Yogyakarta and selected using purposive sampling technique. The data of waist circumference, pelvic/hip circumference, HbA1c and lipid profile were collected among the subjects and analyzed with computer with 95% confidence interval. The results of this study showed HbA1c levels and lipid profile were different between the women with and without central obesity, although the difference was not statistically significant.

  8. HbA1c monitoring interval in patients on treatment for stable type 2 diabetes. A ten-year retrospective, open cohort study.

    Science.gov (United States)

    Ohde, Sachiko; Deshpande, Gautam A; Yokomichi, Hiroshi; Takahashi, Osamu; Fukui, Tsuguya; Yamagata, Zentaro

    2018-01-01

    [Aims] This study aims to suggest an informative interval for HbA1c in DM patients with stable glycemic control, based on test characteristics of the HbA1C assay using the signal-to-noise ratio method. [Methods] This was a retrospective, open cohort study. Data were collected between January 2005 to December 2014 at a tertiary-level community hospital in Japan. All adult patients aged under 75 years, with stable glycemic control on a first pharmaceutical regimen for Type II diabetes, and at least two HbA1c measurements after they achieved glycemic stability, were included in the analysis. We defined stable glycemic control as HbA1c HbA1c. The screening interval for HbA1c was defined as informative when the signal-to-noise ratio exceeded 1. [Results] Among 1066 adults with diabetes, 639 patients (18.5%) were identified as achieving stable glycemic control (511 male (67.3%)), with a mean HbA1c (SD) of 6.4 (0.4)% (46 mmol/mol). Patients with stable glycemic control increase their HbA1c 0.27% (3 mmol/mol) every year while HbA1c has 0.32% (3.5 mmol/mol) noise, as testing characteristics. Signal exceeds noise after 1.2 years (95%CI: 0.9-1.6). [Conclusion] Once patients achieve stable glycemic control at their HbA1c goal, an informative interval for HbA1c monitoring is once every year. Current guidelines, which suggest testing every six months, may contribute to substantial over-testing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Use of HbA1c to diagnose type 2 diabetes mellitus among high risk Sri Lankan adults.

    Science.gov (United States)

    Herath, H M M; Weerarathna, T P; Dahanayake, M U; Weerasinghe, N P

    Even though, glycosylated hemoglobin (HbA1c) was found to be effective in predicting diabetes especially in Caucasians there is limited evidence of its diagnostic utility in high risk Sri Lankan adults. This study aimed to determine the optimal HbA1c cut-off points for detecting diabetes in a high risk population in Sri Lanka. This community based study consisted of 254 previously healthy adults with history of diabetes in one or more first-degree relatives. Fasting plasma glucose (FPG) , glucose tolerance test (GTT) and HbA1c were measured in all and GTT was used as a reference to diagnose diabetes. Receiver operating characteristic curve was created to find the optimum HbA1c cut-off value to predict diabetes. Prevalence of diabetes was 12.2% (n=31) with FPG and 16.1% (n=41) with GTT. Prevalence rose to 27.6% (PHbA1c with cut-off of ≥6.5% was used as the diagnostic test. The ROC curves showed the HbA1c threshold of 6.3% provided the optimum balance between sensitivity (80.5%) and specificity (79%). In compared to GTT, FPG had only a modest sensitivity (65%) in diagnosing diabetes in this high risk population. Our study showed that optimum HbA1C cut-off for detecting diabetes was 6.3% and it had better sensitivity, but lower specificity than FPG. This study further showed that the prevalence of diabetes would become double if HbA1c is used over FPG to screen this high risk population. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  10. One-Hour Postload Hyperglycemia Confers Higher Risk of Hepatic Steatosis to HbA1c-Defined Prediabetic Subjects.

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Andreozzi, Francesco; Mannino, Gaia Chiara; Pedace, Elisabetta; Perticone, Maria; Sciacqua, Angela; Perticone, Francesco; Sesti, Giorgio

    2016-11-01

    Individuals with glycated hemoglobin (HbA1c)-defined prediabetes (HbA1c value of 5.7-6.4%) and 1-hour plasma glucose ≥155 mg/dL during an oral glucose tolerance test have an increased risk of developing type 2 diabetes. To evaluate the degree to which HbA1c-defined prediabetes and 1-hour postload glucose ≥155 mg/dL individually and jointly associate with hepatic steatosis and related biomarkers. A cross-sectional analysis was performed on 1108 White individuals. Ambulatory care. Anthropometric and metabolic characteristics including hepatic steatosis assessed by ultrasonography. Compared with the normal group (HbA1c prediabetic and diabetic individuals exhibit higher values of fasting, 1-hour, and 2-hour postload glucose; fasting and 2-hour postload insulin; triglycerides; uric acid; homeostasis model of assessment for insulin resistance; liver insulin resistance index; liver enzymes; and inflammatory biomarkers; and lower levels of high-density lipoprotein cholesterol and IGF-1. Prediabetic and diabetic subjects have increased risk of hepatic steatosis (1.5- and 2.46-fold, respectively). Stratifying participants according to HbA1c and 1-hour postload glucose, we found that individuals with HbA1c-defined prediabetes and 1-hour postload glucose ≥155 mg/dL have significantly higher risk of hepatic steatosis as compared with individuals with HbA1c-defined prediabetes but 1-hour postload glucose prediabetes and 1-hour postload glucose ≥155 mg/dL exhibit higher values of liver enzymes; fasting, 1-hour, and 2-hour postload glucose; insulin; triglycerides; uric acid; and inflammatory biomarkers; and lower levels of high-density lipoprotein and IGF-1. These data suggest that a value of 1-hour postload glucose ≥155 mg/dL may be helpful to identify a subset of individuals within HbA1c-defined glycemic categories at higher risk of hepatic steatosis.

  11. HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Zhu, Bing; Bu, Le; Zhang, Manna; Gusdon, Aaron M.; Zheng, Liang; Rampersad, Sharvan; Li, Jue; Qu, Shen

    2016-01-01

    Ketosis in patients with type 2 diabetes mellitus (T2DM) is overlooked due to atypical symptoms. The objective of this study is to evaluate the value of hemoglobin A1c (HbA1c) as a screening tool for ketosis in T2DM patients. This retrospective study consisted of 253 T2DM patients with ketosis at Shanghai 10th People’s Hospital during a period from January 1, 2011 to June 30, 2015. A control group consisted of 221 T2DM patients without ketosis randomly selected from inpatients during the same period. Receiver operating characteristic curve (ROC) analysis was used to examine the sensitivity and specificity of HbA1c as an indicator for ketosis. Higher HbA1c levels were correlated with ketosis. In patients with newly diagnosed T2DM, the area under the curve (AUC) was 0.832, with 95% confidence interval (CI) 0.754–0.911. The optimal threshold was 10.1% (87 mmol/mol). In patients with previously diagnosed T2DM, the AUC was 0.811 (95% CI: 0.767–0.856), with an optimal threshold of 8.6% (70 mmol/mol). HbA1c is a potential screening tool for ketosis in patients with T2DM. Ketosis is much more likely with HbA1c values at ≥10.1% in patients with newly diagnosed T2DM and HbA1c values at ≥8.6% in patients with previously diagnosed T2DM. PMID:28009017

  12. Genetic Variants in CPA6 and PRPF31 are Associated with Variation in Response to Metformin in Individuals with Type 2 Diabetes.

    Science.gov (United States)

    Rotroff, Daniel M; Yee, Sook Wah; Zhou, Kaixin; Marvel, Skylar W; Shah, Hetal S; Jack, John R; Havener, Tammy M; Hedderson, Monique M; Kubo, Michiaki; Herman, Mark A; Gao, He; Mychaleckyi, Josyf C; McLeod, Howard L; Doria, Alessandro; Giacomini, Kathleen M; Pearson, Ewan R; Wagner, Michael J; Buse, John B; Motsinger-Reif, Alison A

    2018-04-12

    Metformin is the first line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to identify common and rare variants associated with HbA1c response to metformin treatment, and followed up these findings in four replication cohorts. Common variants in PRPF31 and CPA6 , were associated with worse and better metformin response, respectively (p<5×10 -6 ), and meta-analysis in independent cohorts displayed similar associations with metformin response (p=1.2×10 -8 and p=0.005, respectively). Previous studies have shown that PRPF31 (+/-) knockout mice have increased total body fat (p=1.78×10 -6 ) and increased fasted circulating glucose (p=5.73×10 -6 ). Furthermore, rare variants in STAT3 associated with worse metformin response( q <0.1). STAT3 is a ubiquitously expressed pleiotropic transcriptional activator that participates in the regulation of metabolism and feeding behavior. Here we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D. © 2018 by the American Diabetes Association.

  13. Ethnic dependent differences in diagnostic accuracy of glycated hemoglobin (HbA1c) in Canadian adults.

    Science.gov (United States)

    Booth, Ronald A; Jiang, Ying; Morrison, Howard; Orpana, Heather; Rogers Van Katwyk, Susan; Lemieux, Chantal

    2018-02-01

    Previous studies have shown varying sensitivity and specificity of hemoglobin A1c (HbA1c) to identify diabetes and prediabetes, compared to 2-h oral glucose tolerance testing (OGTT) and fasting plasma glucose (FPG), in different ethnic groups. Within the Canadian population, the ability of HbA1c to identify prediabetes and diabetes in First Nations, Métis and Inuit, East and South Asian ethnic groups has yet to be determined. We collected demographic, lifestyle information, biochemical results of glycemic status (FPG, OGTT, and HbA1c) from an ethnically diverse Canadian population sample, which included a purposeful sampling of First Nations, Métis, Inuit, South Asian and East Asian participants. Sensitivity and specificity using Canadian Diabetes Association (CDA) recommended cut-points varied between ethnic groups, with greater variability for identification of prediabetes than diabetes. Dysglycemia (prediabetes and diabetes) was identified with a sensitivity and specificity ranging from 47.1% to 87.5%, respectively in Caucasians to 24.1% and 88.8% in Inuit. Optimal HbA1c ethnic-specific cut-points for dysglycemia and diabetes were determined by receiver operating characteristic (ROC) curve analysis. Our sample showed broad differences in the ability of HbA1c to identify dysglycemia or diabetes in different ethnic groups. Optimal cut-points for dysglycemia or diabetes in all ethnic groups were substantially lower than CDA recommendations. Utilization of HbA1c as the sole biochemical diagnostic marker may produce varying degrees of false negative results depending on the ethnicity of screened individuals. Further research is necessary to identify and validate optimal ethnic specific cut-points used for diabetic screening in the Canadian population. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. Diagnosis of common hemoglobinopathies among South East Asian population using capillary isoelectric focusing system.

    Science.gov (United States)

    Srivorakun, H; Fucharoen, G; Sanchaisuriya, K; Fucharoen, S

    2017-02-01

    We have evaluated an automated capillary isoelectric focusing (cIEF)-based Hb analyzer in diagnosis of hemoglobinopathies commonly found among South East Asian population. Study was performed on a cohort of 665 adult Thai subjects and 13 fetal blood specimens obtained at routine thalassemia diagnostic laboratory. Hb analysis was performed using the cIEF system. Thalassemia genotypes were defined by DNA analysis. The system revealed satisfactorily within-run and between-run precision for quantitation of Hb A 2 and Hb E (CV: 0.02-0.09%). The reference ranges of Hb A 2 and Hb E were 2.6-4.0% and 25.7-33.1%, respectively. The system identified the cases of β-thalassemia and Hb E disorders correctly. Several thalassemia genotypes and Hb variants were identifiable. However, Hb Constant Spring was separated closely to Hb A 2 and Hbs Bart's and H were relatively difficult to be reported due to interfering peaks separating at the same regions. Prenatal diagnosis by fetal blood analysis was found to be accurate for Hb Bart's hydrops fetalis and Hb E-β 0 -thalassemia disease. The cIEF system could accurately diagnose β-thalassemia and Hb E carriers and demonstrate many Hb variants found in the region. The system cannot report Hb A 2 in the presence of Hb E whereas Hbs Lepore and F are comigrated. Diagnosis of α-thalassemia disease based on Hb H and Hb Bart's might be difficult. © 2016 John Wiley & Sons Ltd.

  15. HbA1c in relation to incident diabetes and diabetes-related complications in non-diabetic adults at baseline.

    Science.gov (United States)

    Metcalf, Patricia Anne; Kyle, Cam; Kenealy, Tim; Jackson, Rod T

    2017-05-01

    We compared the utility of glycated hemoglobin (HbA 1c ) and oral glucose tolerance (oGTT) in non-diabetic patients for identifying incident diabetes; all-cause mortality; cardiovascular disease (CVD) mortality; CVD, coronary heart disease (CHD), and ischemic stroke events; and diabetes microvascular complications. Data from a New Zealand community setting were prospectively linked to hospitalization, mortality, pharmaceutical and laboratory test results data. After applying exclusion criteria (prior laboratory diagnosis or history of drug treatment for diabetes or hospitalization for diabetes or CVD event), there were 31,148 adults who had an HbA 1c and 2-h 75g oGTT. HbA 1c was measured by ion-exchange high-performance liquid chromatography, and glucose using a commercial enzymatic method. We compared glycemic measures and outcomes using multivariable Cox proportional hazards regression. The median follow-up time was 4years (range 0 to 13). The mean age was 57·6years and 53·0% were male. After adjusting for other glycemic measures (fasting glucose, 2-h glucose and/or HbA 1c where relevant) in addition to age, sex, ethnicity and smoking habit, the hazard ratios for incident diabetes and diabetes complications of retinopathy and nephropathy were highest for 2-h glucose levels, followed by HbA 1c and lastly by fasting glucose. However, all-cause mortality and CHD were significantly associated with HbA 1c concentrations only, and ischemic stroke and CVD events with 2-h glucose only. Circulatory complications showed a stronger association with HbA 1c . Apart from neuropathy, HbA 1c showed stronger associations with outcomes compared to fasting glucose and provides a convenient alternative to an oGTT. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The Value of HbA1c and hs-CRP Combined Detection in Diagnosis of Diabetic Retinopathy%HbA1c、hs-CRP 联合检测诊断糖尿病视网膜病变的价值

    Institute of Scientific and Technical Information of China (English)

    李孝才; 孙学芬; 吴建霞; 马雪燕

    2016-01-01

    目的:探讨糖化血红蛋白(HbA1c)和高敏 C 反应蛋白(hs-CRP)联合检测诊断糖尿病视网膜病变的价值。方法:选择正常体检者(A 组)、糖尿病无视网膜病变者(B 组)、糖尿病视网膜病变者(C 组)各72例,采用离子交换液相层析法和胶乳增强免疫比浊法测定 HbA1c 及 hs-CRP。结果:无视网膜病变组和视网膜病变组的 HbA1c 和 hs-CRP(mg/L)含量均比健康对照组高,具有统计学意义(P0.05);但是 HbA1c +Hs-CRP 诊断糖尿病视网膜病变的特异为90.3%,分别与 HbA1c 和 hs-CRP 存在明显差异(P 0.05); but specific to the HbA1c of hs CRP in the diagnosis of diabetic retinopathy was 90.3%, respectively and hs CRP and HbA1c exist significant difference (P< 0.05). Conclusion:The detection of HBA1c and Hs-CRPis helpful to early detection of diabetic retinopathy, which can be used asmonitoring indicators for progress and treatment effect in type 2 diabetes mellitus patients.

  17. Simulation and Comparison of the Calorimeters Measuring the Nuclear Heating in the OSIRIS Reactor, with the TRIPOLI-4R Monte-Carlo Code

    International Nuclear Information System (INIS)

    Peron, A.; Malouch, F.; Diop, C.M.

    2013-06-01

    Two calorimeter devices are used in the OSIRIS MTR reactor (CEA-Saclay center) for the nuclear heating measurements. The first one is a fixed five-stage calorimeter device. The second one is an innovative mobile probe called 'CALMOS'. The design of these devices is different (in particular their geometry), implying modifications on the local neutron and photon fluxes and hence on nuclear heating measured values. The measurements performed by the two calorimeter devices cannot directly be compared; this requires perfect irradiation conditions in the reactor core, especially for the core loading and the control element positions. Simulation is here a good help to perform a fully relevant comparison. In this paper, differences between calorimeter devices in terms of nuclear heating and particle fluxes are evaluated using the TRIPOLI-4 Monte-Carlo code. After a description of the OSIRIS reactor and the design of the two calorimeter devices, the nuclear heating calculation scheme used for simulation will be introduced. Different simulations and results will be detailed and analyzed to determine the calorimeter geometry impact on the measured nuclear heating. (authors)

  18. Acute viral hepatitis in adults. Comparison of the radioimmunoassay and counterimmunoelectrophoresis methods of detecting HB/sub s/Ag

    International Nuclear Information System (INIS)

    Wenzel, R.P.; Teates, C.D.; Galapon, Q.; Barczak, R.; Ling, C.M.; Overby, L.R.

    1975-01-01

    The radioimmunoassay (RIA) and counterimmunoelectrophoretic (CIE) methods were compared in detecting hepatitis B antigen (HB/sub s/Ag) in 407 acute and 336 convalescent sera of adults with viral hepatitis. The CIE method demonstrated that 41 percent of acute and 28 percent of 14- to 17-day serum specimens were HB/sub s/Ag-positive. The RIA method demonstrated seropositivity in 60 percent of acute and 56 percent of convalescent specimens (P less than .001). Eighty-four percent of coded specimens initially positive for HB/sub s/Ag by RIA were found to have subtype antigenic determinants d or y; 92 percent of the HB/sub s/Ag-negative controls were negative for subtype antigens, confirming the specificity of the RIA test. RIA subtyping data corroborated earlier work with immunodiffusion techniques. (U.S.)

  19. Zinc-Associated Variant in SLC30A8 Gene Interacts With Gestational Weight Gain on Postpartum Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes Mellitus.

    Science.gov (United States)

    Wang, Tiange; Liu, Huikun; Wang, Leishen; Huang, Tao; Li, Weiqin; Zheng, Yan; Heianza, Yoriko; Sun, Dianjianyi; Leng, Junhong; Zhang, Shuang; Li, Nan; Hu, Gang; Qi, Lu

    2016-12-01

    Zinc transporter 8 genetic variant SLC30A8 has been associated with postpartum risk of type 2 diabetes among women with gestational diabetes mellitus (GDM). Gestational weight gain is one of the strongest risk factors for postpartum hyperglycemia. We assessed the interaction between type 2 diabetes-associated SLC30A8 rs13266634 and gestational weight gain on 1-5 years of postpartum glycemic changes in 1,071 women with prior GDM in a longitudinal study. Compared with gestation of 26-30 weeks, postpartum levels of fasting glucose, oral glucose tolerance test 2-h glucose, and hemoglobin A 1c (HbA 1c ) increased across rs13266634 TT, CT, and CC genotypes in women with excessive gestational weight gain, whereas opposite genetic associations were found in women with inadequate or adequate gestational weight gain. Postpartum changes in fasting glucose per additional copy of the C allele were -0.18, -0.04, and 0.12 mmol/L in women with inadequate, adequate, and excessive gestational weight gain, respectively (P for interaction = 0.002). We also found similar interactions for changes in 2-h glucose and HbA 1c (P for interaction = 0.003 and 0.005, respectively). Our data indicate that gestational weight gain may modify SLC30A8 variant on long-term glycemic changes, highlighting the importance of gestational weight control in the prevention of postpartum hyperglycemia in women with GDM. © 2016 by the American Diabetes Association.

  20. Muscle pathology in lower motor neuron paraplegia and h-b FES

    Directory of Open Access Journals (Sweden)

    Ugo Carraro

    2010-03-01

    Full Text Available After complete Spinal Cord Injury (SCI, causing complete disconnection between the muscle fibers and the nervous system, the denervated muscles become unexcitable with commercial electrical stimulators within several months and undergo severe atrophy and disorganization of contractile apparatus after 1-3 years. Years after the injury the surviving and regenerated myofibers are substituted with adipocytes and collagen. To counteract the progressive changes transforming muscle into an unexcitable tissue, we developed a novel therapy concept for paraplegic patients with complete lower motor neuron (LMN denervation of the lower extremities. The new stimulators for home-based functional electrical stimulation (h-b FES have been designed to reverse longstanding and severe atrophy of LMN denervated muscles by delivering high-intensity (up to 2,4 J and long-duration impulses (up to 150 ms able to elicit contractions of denervated skeletal muscle fibers in absence of nerve. Concurrent to the development of the stimulation equipment, specific clinical assessments and training strategies were developed at the Wilhelminenspital Wien, Austria. Main results of our clinical study on 20 patients, which completed a 2 years h-b FES program are: 1. significant +33% increase of muscle size and +75% of the mean diameter of muscle fibers, with striking improvements of the ultra-structural organization of contractile material; 2. recovery of the tetanic contractility with significant increase in muscle force output during electrical stimulation; 3. five subjects performed FES-assisted stand-up and stepping-in-place exercises;. 4. data from ultrastructural analyses indicating that the shorter the time span between SCI and the beginning of h-b FES, the larger were the number and the size of recovered fibers. The study demonstrates that h-b FES of permanent LMN denervated muscle is an effective home therapy that results in rescue of muscle mass, function and perfusion