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Sample records for thalassaemia major resistant

  1. Thalassaemia major and the heart

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    J. Malcolm Walker

    2013-03-01

    Full Text Available Disorders of haemoglobin synthesis are the commonest monogenetic disorders worldwide. When first described, thalassaemia was universally fatal in childhood, but after the adoption of regular blood transfusion survival until early teenage and adulthood was to be expected. At that stage in the life of these affected individuals organ failure followed, due to accumulated iron, for which the human has no excretory capacity. Principal amongst the tissues affected by iron overload is the heart and even to the present day, heart disease accounts for the overwhelming majority of premature deaths in this population. Managing transfusion derived iron overload was the next hurdle for clinicians and the families of the patients. For nearly four decades the only available treatment was the demanding regime of parenteral chelation therapy, required on a daily basis, to achieve growth, development and survival with limited or no organ damage. Despite the adoption of these treatment strategies the outlook for thalassaemia patients remained poor, with a 30% to 40% mortality occurring between late teenage and 30 years of age, even in well organised health care systems, such as in the UK, where regular transfusion and desferioxamine treatment were readily available. This dreadful early mortality, largely as a consequence of myocardial iron overload, (1,2 is now improving so that in the UK and other developed nations, heart failure in thalassaemic patients has become uncommon and premature death a much rarer tragedy. This editorial reviews, from a personal viewpoint of a cardiologist involved in the care of these patients for the last 20 years, the progress in the management of the cardiovascular complications of thalassaemia major (TM, which has followed better techniques of identifying those thalassaemic individuals at greatest risk, improved chelation strategies making best use of the three chelating agents that are now available and improved co

  2. Minerals in thalassaemia major patients: An overview.

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    Ozturk, Zeynep; Genc, Gizem Esra; Gumuslu, Saadet

    2017-05-01

    Thalassaemia major (TM) is a hereditary blood disease characterised by reduced or absent production of beta globin chains. Erythrocyte transfusions are given to raise the haemoglobin level in patients with thalassaemia major. However, transfusions have been related to increased risk of iron overload and tissue damage related to excess iron. Both elevated oxidative stress due to iron overload and increased hemolysis lead to over utilisation of minerals required for antioxidant enzymes activities. Iron chelators have been used to prevent iron overload in thalassaemia major patients, but these chelators have the possibility of removing minerals from the body. Thalassaemia patients are more at risk for mineral deficiency because of increased oxidative stress and iron chelation therapies. Growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis are the complications of thalassaemia. Minerals may play a particular role to prevent these complications. In the current review, we provide an overview of minerals including zinc (Zn), copper (Cu), selenium (Se), magnesium (Mg) and calcium (Ca) in thalassaemia major patients. We, also, underline that some complications of thalassaemia can be caused by an increased need for minerals or lack of the minerals. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Anaesthesia for a patient with beta thalassaemia major ...

    African Journals Online (AJOL)

    Presented here is a case report of a 32-year-old gentleman with beta thalassaemia major presenting for elective laparoscopic cholecystectomy and splenectomy, followed by a discussion of the literature. Keywords: anaemia, anaesthesia, beta thalassaemia, iron overload, laparoscopic cholecystectomy, splenectomy ...

  4. Osteoporosis Syndrome in Thalassaemia Major: An Overview

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    Meropi Toumba

    2010-01-01

    Full Text Available Osteoporosis in thalassaemia major (TM represents a prominent cause of morbidity. The mechanism of pathogenesis of bone disease (BD in TM is multifactorial and complicated. Peak bone mass is achieved shortly after completion of puberty and normally remains stable until the third decade of life when age-related bone mass begins. Growth hormone (GH and sex steroids play a crucial role in bone remodeling and in the maintenance of skeletal architecture during adult life. GH and insulin growth factors (IGFs have anabolic effect in bone formation. Sex steroids act probably by increasing the expression of RANKL by osteoblastic cells and alterations in the RANK/RANKL/OPG system in favor of osteoclasts. Impaired GH secretion and lack of sex steroids in thalassemic patients due to pituitary damage, contribute to failure of achieving optimal peak bone mass. Other endocrine complications such as hypoparathyroidism and vitamin D deficiency have also a detrimental role on bones in TM. It is still questionable whether the international criteria for defining osteopenia and osteoporosis are relevant to patients with TM; also a question arises for the diagnostic methods such as DEXA scan and management of osteoporosis with known treatment protocols, in the thalassaemic patient.

  5. Trace elements status in children with B-thalassaemia major

    International Nuclear Information System (INIS)

    Moawad, A.T.

    2005-01-01

    This study was conducted on 30 children suffering from ft-thalassaemia major (15 males and 15 females) with mean age of 10.3 ± 5.1 years and 17 apparently healthy children with the same age and sex and served as controls. Patients as well as controls were subjected to careful history, clinical examination and laboratoiy investigations. Patients with jB-thalassaemia major had low body mass index (BMI) of 15.6± 3.5 compared to 19.5± 3.7 for the control (P<0.05). Hematological profile revealed that the mean This study was conducted on 30 children suffering from ft-thalassaemia major (15 males and 15 females) with mean age of 10.3 ± 5.1 years and 17 apparently healthy children with the same age and sex and served as controls. Patients as well as controls were subjected to careful history, clinical examination and laboratoiy investigations. Patients with jB-thalassaemia major had low body mass index (BMI) of 15.6± 3.5 compared to 19.5 ± 3.7 for the control (P<0.05). Hematological profile revealed that the mean

  6. Diagnosis of Beta-thalassaemia major in previously transfused patients

    International Nuclear Information System (INIS)

    Ahmed, S.; Rehman, Z.; Karamat, K.A.

    2003-01-01

    Objective: The study was conducted to evaluate the effects of blood transfusion(s) on the haematological picture of beta-thalassaemia major. Results: Out of the 280 patients 109 (39%) had received one or more blood transfusions (cases). The remaining 171 patients who did not receive any transfusion served as controls. The mean MCV, MCH and Hb-F in cases were significantly higher than in the controls (p 4 transfusions (17%) (p=0.016). In the occasionally transfused patients Hb-F level was directly related to the time since last transfusion. In 44/109 (40%) transfused patients (Hb-F>30%) the diagnosis of thalassaemia was not difficult. In 54/109 (50%) patients (Hb-:5-30%) the diagnosis was aided by parent's study, while PCR for thalassaemia mutation was required in 11/109 (10%) patients (Hb-F <5%). Conclusion: In most transfused patients of thalassaemia major MCV and MCH were significantly higher while Hb-F was lower than in the un-transfused patients. There was a linear correlation between Hb-F level and time since last transfusion in the occasionally transfused patients. However, the reduction in Hb-F level was more marked and sustained in multipally transfused patients. Parent's study and PCR are useful aids in establishing the correct diagnosis in these patients. (author)

  7. Prevalence of diabetes mellitus in Chinese children with thalassaemia major.

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    Liang, Yuzhen; Bajoria, Rekha; Jiang, Yan; Su, Hongwei; Pan, Hongfei; Xia, Ning; Chatterjee, Ratna; Lai, Yongrong

    2017-06-01

    Diabetes mellitus is a common endocrinopathy in patients with β-thalassaemia major (β-TM), which is high prevalent in southern China. This study aimed to determine the cause and prevalence of glycaemic disorders in Chinese children with β-TM. In this prospective study, fasting glucose and insulin (FINS) levels were assessed in 267 β-TM and 80 non-TM control children. Homeostatic model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI) were evaluated. Iron overload was assessed by serum ferritin (SF), total units of blood transfused and cardiac T2*. β-TM had higher FPG (P 10 years (OR 6.5; 95% CI 3.7-11.4; P 2500 μg/l (OR 4.8; 95% CI 2.1-11.1; P 50 IU/l (OR 2.1; 95% CI 1.2-3.7; P < 0.05) and cardiac T2* of <20 ms (OR 3.3; 95% CI 1.7-6.6; P < 0. 01). The children on deferiprone (DFP) had a reduced incidence of glycaemic aberrations than those on other chelating agents (OR 0.4; 95% CI 0.23-0.8; P < 0.05). Our data suggest that IFG occurred in 30% of β TM children, perhaps due to insulin resistance secondary to iron overload. Deferiprone-containing chelating agent may have a protective effect. © 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  8. Splenectomy for people with thalassaemia major or intermedia.

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    Easow Mathew, Manu; Sharma, Akshay; Aravindakshan, Rajeev

    2016-06-14

    Thalassaemia is a genetic disease of the haemoglobin protein in red blood cells. It is classified into thalassaemia minor, intermedia and major, depending on the severity of the disease and the genetic defect. Thalassaemia major and intermedia require frequent blood transfusions to compensate for the lack of well-functioning red blood cells, although this need is significantly less in thalassaemia intermedia.Damaged or defective red blood cells are normally eliminated in the spleen. In people with thalassaemia there is a large quantity of defective red blood cells which results in an enlarged hyperfunctioning spleen (splenomegaly). Removal of the spleen may thus prolong red blood cell survival by reducing the amount of red blood cells removed from circulation and may ultimately result in the reduced need for blood transfusions. To assess the efficacy and safety of splenectomy in people with beta-thalassaemia major or intermedia. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from searches of electronic databases and the handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the most recent search: 25 April 2016. We included randomised controlled studies and quasi-randomised controlled studies of people of any age with thalassaemia major or intermedia, evaluating splenectomy in comparison to conservative treatment (transfusion therapy and iron chelation) or other forms of splenectomy compared to each other (laparoscopic, open, radio-frequency). Two authors independently selected and extracted data from the single included study using a customised data extraction form and assessed the risk of bias. One study, including 28 participants was included in the review; the results were described, primarily, in a narrative manner. The study assessed the feasibility of splenectomy using laparoscopy in comparison to open

  9. Liver volume in thalassaemia major: relationship with body weight, serum ferritin, and liver function

    International Nuclear Information System (INIS)

    Chan Yuleung; Law Manyee; Howard, Robert; Li Chikong; Chik Kiwai

    2005-01-01

    It is not known whether body weight alone can adjust for the volume of liver in the calculation of the chelating dose in β-thalassaemia major patients, who frequently have iron overload and hepatitis. The hypothesis is that liver volume in children and adolescents suffering from β-thalassaemia major is affected by ferritin level and liver function. Thirty-five β-thalassaemia major patients aged 7-18 years and 35 age- and sex-matched controls had liver volume measured by MRI. Serum alanine aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia major patients. Body weight explained 65 and 86% of the change in liver volume in β-thalassaemia major patients and age-matched control subjects, respectively. Liver volume/kilogram body weight was significantly higher (P 3 /kg) than control subjects (mean 23.4±3.6 cm 3 /kg) and patients with normal ALT levels (mean 27.4±3.6 cm 3 /kg). Body weight is the most important single factor for liver-volume changes in thalassaemia major patients, but elevated ALT also has a significant role. Direct liver volume measurement for chelation dose adjustment may be advantageous in patients with elevated ALT. (orig.)

  10. Heart rate variability in β-thalassaemia major with or without cardiac siderosis.

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    Alp, A; Ozdogan, O; Guloglu, C C; Turker, M; Atabay, B

    2014-04-01

    Iron cardiomyopathy remains the major cause of death in β-thalassaemia major. Excessive iron loading could lead to cardiac dysfunction and arrhythmias. Reduced heart rate variability is associated with a higher risk of arrhythmia and sudden death after myocardial infarction and heart failure. Previous data have reported on reduced heart rate variability in patients with marked cardiac iron accumulation. In this study, we compared heart rate variability among β-thalassaemia major (TM) patients with or without cardiac siderosis. Out of 70 β-thalassaemia major patients with preserved ejection fractions, 38 patients with cardiac T2* magnetic resonance imaging assessment were included in our study. Time domain heart rate variability parameters were analysed from 24-hour recorded electrocardiograms and were compared with the control group. The mean T2* magnetic resonance imaging value was 22.9 ± 13.3 (4.7-47.5). In 21 patients with β-thalassaemia major, the T2* magnetic resonance imaging values were greater than 20 ms and these patients were considered to be in the early stage of the disease. When we compare these patients with control subjects, the standard deviation of all NN intervals was still significantly lower (133.0 ± 32.2 versus 162.8 ± 32.9, p = 0.001) in β-thalassaemia major patients despite normal T2* magnetic resonance imaging values. On the contrary, the standard deviation of all NN intervals was not correlated with haemoglobin levels in these patients (p > 0.05). Heart rate variability parameters were reduced even in β-thalassaemia major patients without evident cardiac siderosis, as specified by magnetic resonance imaging data. The results of this study show that reduction of heart rate variability may start before cardiac iron loading is demonstrated by T2* magnetic resonance imaging in β-thalassaemia major.

  11. Liver volume in thalassaemia major: relationship with body weight, serum ferritin, and liver function

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    Chan Yuleung; Law Manyee; Howard, Robert [Chinese University of Hong Kong, Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, Hong Kong (China); Li Chikong; Chik Kiwai [Chinese University of Hong Kong, Department of Paediatrics, Prince of Wales Hospital, Hong Kong (China)

    2005-02-01

    It is not known whether body weight alone can adjust for the volume of liver in the calculation of the chelating dose in {beta}-thalassaemia major patients, who frequently have iron overload and hepatitis. The hypothesis is that liver volume in children and adolescents suffering from {beta}-thalassaemia major is affected by ferritin level and liver function. Thirty-five {beta}-thalassaemia major patients aged 7-18 years and 35 age- and sex-matched controls had liver volume measured by MRI. Serum alanine aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia major patients. Body weight explained 65 and 86% of the change in liver volume in {beta}-thalassaemia major patients and age-matched control subjects, respectively. Liver volume/kilogram body weight was significantly higher (P<0.001) in thalassaemia major patients than in control subjects. There was a significant correlation between ALT level and liver volume/kilogram body weight (r=0.55, P=0.001). Patients with elevated ALT had significantly higher liver volume/kilogram body weight (mean 42.9{+-}12 cm{sup 3}/kg) than control subjects (mean 23.4{+-}3.6 cm{sup 3}/kg) and patients with normal ALT levels (mean 27.4{+-}3.6 cm{sup 3}/kg). Body weight is the most important single factor for liver-volume changes in thalassaemia major patients, but elevated ALT also has a significant role. Direct liver volume measurement for chelation dose adjustment may be advantageous in patients with elevated ALT. (orig.)

  12. Prevalence of dentofacial abnormalities in children and adolescents with β-thalassaemia major

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    Arun Elangovan

    2013-01-01

    Full Text Available Background: β-thalassaemia major is a hereditary hemolytic anemia and the patients often experience growth retardation, protrusive maxilla, and depressed nasal bride leading to various degrees of malocclusion. Aim: The purpose of this investigation is to find the prevalence of dentofacial abnormalities in β-thalassaemia major patients. Subjects and Methods: Seventy-two patients between 6 and 18 years of age diagnosed with β-thalassaemia major were examined for extraoral abnormalities, malocclusion, oral hygiene, and dental caries. Data obtained were tabulated and statistically analyzed using Chi-square and paired t-test. Results: Thirty-nine (54.2% were males and 33 (45.8% were females. Prominent extraoral abnormalities were found in 41 (56.9% of the individuals. Study population predominantly had class I occlusion (59.7% followed by class II occlusion (23.6% and no class III occlusion. Mean oral hygiene index-simplified score was 2.43 ± 1.24, mean decayed missing filled teeth (DMFT score was 7.10 ± 3.92, and deft was 5.68 ± 3.12. Conclusion: Despite starting regular blood transfusion at an early age, β-thalassaemia major patients showed marked facial abnormalities. When compared with individuals with no systemic disease, oral hygiene status was similar, but the caries experience was higher in β-thalassaemia major patients. Therefore, emphasis to educate these patients in the prevention and control of dental caries and maintenance of good oral hygiene should be considered.

  13. Diabetes and thalassaemia

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    Maria Barnard

    2013-03-01

    Full Text Available Diabetes is a significant complication of b-thalassaemia major. The aetiology includes iron overload causing b-cell destruction, autoimmunity, insulin resistance secondary to liver disease and development of type 1 or 2 diabetes. There are specific issues for patients with diabetes and thalassaemia which will be discussed here. Impaired carbohydrate metabolism must be detected early, to allow intensification of iron chelation. As life expectancy in thalassaemia rises, diabetic complications are seen. Optimising blood glucose and cardiovascular risk factor control is essential. Insulin remains critical for severely symptomatic patients. With milder hyperglycaemia, oral antidiabetic drugs are increasingly used. At Whittington Hospital, we wanted to address these issues. In 2005, we developed a unique Joint Diabetes Thalassaemia Clinic, where patients are reviewed jointly by specialist teams, including Consultant Diabetologist and Haematologist. The Joint Clinic aims to optimise diabetes, endocrine and thalassaemia care, while supporting patient self-management. A retrospective audit of the Joint Clinic (2005-09, showed improvement in glycaemic control, (Fructosamine falling from 344 umol/l to 319 umol/l. We compared our cohort to the National Diabetes Audit for England (2007-08. Patients attending the Joint Clinic achieved better glycaemic control (target reached: 73% Joint Clinic vs. 63% Nationally, blood pressure control (target reached: 58% Joint Clinic vs. 30% Nationally and cholesterol control (target reached: 81% Joint Clinic vs. 78% Nationally. 22.7% of our patients had ≥1 microvascular complication. A significant proportion had endocrinopathies (86% hypogonadism, 23% hypoparathyroidism, 18% hypothyroidism. Managing diabetes is one of the greatest challenges a person with thalassaemia can face. Training people to self-manage their diabetes and providing support from specialist teams working together are critical. The unique partnership

  14. Effect of hcv infection on hepatic fibrosis in patients of thalassaemia major

    International Nuclear Information System (INIS)

    Anwar, M.; Nadeem, A.; Ayyub, M.; Jamal, S.; Dilawar, M.; Ali, W.; Aziz, S.; Ashraf, T.; Khalilullah; Ahmed, P.; Khan, B.; Husain, T.; Hussain, S.

    2006-01-01

    Objective: To investigate the effect of HCV infection on hepatic fibrosis in patients of thalassaemia major with iron overload in order to modify Pesaro criteria for classification into prognostic groups for allogenic haemopoietic stem cell transplant in these patients. Design: Cross-sectional comparative study. Place and Duration of Study: Armed Forces Institute of Pathology, Armed Forces Bone Marrow Transplant Center and Departments of Pediatrics of Military Hospital and Combined Military Hospital, Rawalpindi, from July 2003 to June 2004. Subjects and Methods: Twenty eight HCV- and 18 HCV+ patients of thalassaemia major, who were prospective recipients of allogeneic bone marrow transplant, were included in the study. Serum ferritin was estimated by chemiluminescent immunoassay. Degree of fibrosis in liver biopsy was scored using Knodell's scoring system. Correlation between the two was evaluated statistically through Pearson's correlation coefficient. Results: Mean serum ferritin was lower and degree of hepatic fibrosis was less in hepatitis C negative patients of TM. The correlation between serum ferritin and the degree of hepatic fibrosis was much stronger in hepatitis C negative patients with 'r' value of 0.507 and 'p' value of 0.006, which was statistically significant. Conclusion: A strong correlation between serum ferritin and degree of hepatic fibrosis was observed in patients of thalassaemia major not infected with hepatitis C infection. Serum ferritin levels alone are, therefore, not sufficient to assess degree of fibrosis in HCV positive patients of TM. (author)

  15. Evidence of abnormal left ventricular function in patients with thalassaemia major: an echocardiography based study

    International Nuclear Information System (INIS)

    Sohail, M.; Hyder, S.N.

    2009-01-01

    Thalassaemia represent one of the most common single gene disorder causing a major public health problem in Pakistan. Nearly 100,000 people are born worldwide with this severe blood disorder every year. Over the last 3 decades, the development of regular transfusion therapy and iron chelation has dramatically improved the quality of life and transformed thalassaemia from a rapidly fatal disease to a chronic disease compatible with prolonged survival. Objective of this observational cross sectional study was to determine the effects of chronic anaemia and transfusional iron overload on the left ventricular function using Doppler echocardiography. This study was conducted in the Department of Paediatric Cardiology, The Children's Hospital and Institute of Child Health, Lahore, Pakistan from first April 2006 to September 30, 2007. The study comprised of 50 consecutive cases of beta-Thalassaemia major and 30 controls with normal haemoglobin and electrophoresis pattern. beta- Thalassaemia major patients were diagnosed on the basis of haemoglobin electrophoresis. Patients with any congenital or acquired heart disease, concurrent infective disorder and with history of cardiac surgery were excluded from the study. 2-D, M-mode and Doppler echocardiography was performed in all the study cases and controls. Statistical comparison of study cases and controls was conducted by using unpaired t-test. The age of the patients ranged from 2 years to 25 years with mean age of 9.65 years. Males were 34 (68%) and females were 16 (32%). None of the study cases was on regular chelation programme while 31 (62%) patients were on irregular chelation with single dose of intravenous desferrioxamine only at the time of blood transfusion. 19 (38%) of the patients had LV dysfunction in the form of isolated systolic dysfunction in 2 (4%), isolated diastolic dysfunction in 15 (30%) while global dysfunction in 2 (4%) of the patients. Left ventricular dimensions, stroke volume and E/A ratio were

  16. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease

    International Nuclear Information System (INIS)

    Narayana, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K.

    2016-01-01

    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition.

  17. Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial

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    Maggio, Aurelio; Vitrano, Angela; Capra, Marcello

    2009-01-01

    A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8-1...

  18. Psychological therapies for thalassaemia.

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    Anie, Kofi A; Massaglia, Pia

    2014-03-06

    Thalassaemia is a group of genetic blood disorders characterised by the absence or reduction in the production of haemoglobin. Severity is variable from less severe anaemia, through thalassaemia intermedia, to profound severe anaemia (thalassaemia major). In thalassaemia major other complications include growth retardation, bone deformation, and enlarged spleen. Blood transfusion is required to treat severe forms of thalassaemia, but this results in excessive accumulation of iron in the body (iron overload), removed mostly by a drug called desferrioxamine through 'chelation therapy'. Non-routine treatments are bone marrow transplantation (which is age restricted), and possibly hydroxyurea, designed to raise foetal haemoglobin level, thus reducing anaemia. In addition, psychological therapies seem appropriate to improving outcome and adherence to medical treatment. To examine the evidence that in people with thalassaemia, psychological treatments improve the ability to cope with the condition, and improve both medical and psychosocial outcomes. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Searches on the Internet were also performed.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 11 November 2013. All randomised or quasi-randomised controlled trials comparing the use of psychological intervention to no (psychological) intervention in people with thalassaemia. No trials of psychological therapies have been found in the literature for inclusion in this review. There are currently no results to be reported. As a chronic disease with a considerable role for self-management, psychological support seems appropriate for managing thalassaemia. However, from the information currently available, no conclusions

  19. The spectrum of beta-globin gene mutations in children with beta-thalassaemia major from Kota Kinabalu, Sabah, Malaysia.

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    Thong, M K; Soo, T L

    2005-07-01

    Beta-thalassaemia major is one of the commonest genetic disorders in South East Asia. The strategy for the community control of beta-thalassaemia major requires the characterisation of the spectrum of beta-globin gene mutations in any multi-ethnic population. There is only a single report of mutation analyses of the beta-globin gene in an isolated Kadazandusun community in Kota Belud, Sabah, Malaysia, which showed the presence of a common 45 kb deletion. To confirm the observation that this large deletion is the commonest beta-globin gene mutation among the Kadazandusun and other indigenous populations in Sabah, Malaysia, we performed polymerase chain reaction (PCR) analysis of the beta-globin gene in ten children with beta-thalassaemia major attending the Thalassaemia Centre, Queen Elizabeth Hospital, the major paediatric referral centre in Kota Kinabalu, Sabah. The 45 kb deletion was confirmed to be the commonest mutation found in the Kadazandusun, Bajau and Murut populations, whereby it was detected in 19 out of the 20 (95 percent) alleles analysed. The other mutation was due to an IVS-1 position 1 G > T mutation. This finding confirmed the deletion in the homozygous state was associated with a severe phenotype. The reason for the predominance of this mutation in Kota Kinabalu is most likely to be due to founder effects and possibly intermarriages between the various ethnic groups. Prenatal diagnosis using PCR for this common mutation is feasible in this community. Medical workers and scientists at molecular diagnostic centres serving large South East Asian populations should incorporate a diagnostic strategy for this deletion in the appropriate population. Future studies on these indigenous ethnic groups in other areas and other groups in Sabah are required.

  20. MRI evaluation of tissue iron burden in patients with {beta}-thalassaemia major

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    Argyropoulou, Maria I.; Astrakas, Loukas [University of Ioannina, Radiology Department, Medical School, Ioannina (Greece)

    2007-12-15

    {beta}-Thalassaemia major is a hereditary haemolytic anaemia that is treated with multiple blood transfusions. A major complication of this treatment is iron overload, which leads to cell death and organ dysfunction. Chelation therapy, used for iron elimination, requires effective monitoring of the body burden of iron, for which serum ferritin levels and liver iron content measured in liver biopsies are used as markers, but are not reliable. MRI based on iron-induced T2 relaxation enhancement can be used for the evaluation of tissue siderosis. Various MR protocols using signal intensity ratio and mainstream relaxometry methods have been used, sometimes with discrepant results. Relaxometry methods using multiple echoes achieve better sampling of the time domain in which relaxation mechanisms take place and lead to more precise results. In several studies the MRI parameters of liver siderosis have failed to correlate with those of other affected organs, underlining the necessity for MRI iron evaluation in individual organs. Most studies have included children in the evaluated population, but MRI data on very young children are lacking. Wider application of relaxometry methods is indicated, with the establishment of universally accepted MRI protocols, and further studies, including young children, are needed. (orig.)

  1. Dynamic dyssynchrony and impaired contractile reserve of the left ventricle in beta-thalassaemia major: an exercise echocardiographic study.

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    Yiu-fai Cheung

    Full Text Available BACKGROUND: Performance of the left ventricle during exercise stress in thalassaemia patients is uncertain. We aimed to explore the phenomenon of dynamic dyssynchrony and assess contractile reserve in patients with beta-thalassaemia major and determine their relationships with myocardial iron load. METHODS AND RESULTS: Thirty-two thalassaemia patients (16 males, aged 26.8 ± 6.9 years, without heart failure and 17 healthy controls were studied. Their left ventricular (LV volumes, ejection fraction, systolic dyssynchrony index (SDI, and myocardial acceleration during isovolumic LV contraction (IVA were determined at rest and during submaximal bicycle exercise testing using 3-dimensional and tissue Doppler echocardiography. Myocardial iron load as assessed by T2* cardiac magnetic resonance in patients were further related to indices of LV dyssynchrony and contractile reserve. At rest, patients had significantly greater LV SDI (p4.6%, control+2SD increased from baseline 25% to 84% in patients. Δ SDI(exercise-baseline correlated with exercise-baseline differences in LV ejection fraction (p<0.001 and stroke volume (p = 0.006. Compared with controls, patients had significantly less exercise-induced increase in LV ejection fraction, cardiac index, and IVA (interaction, all p<0.05 and had impaired contractile reserve as reflected by the gentler IVA-heart rate slope (p = 0.018. Cardiac T2* in patients correlated with baseline LV SDI (r = -0.44, p = 0.011 and IVA-heart rate slope (r = 0.36, p = 0.044. CONCLUSIONS: Resting LV dyssynchrony is associated with myocardial iron load. Exercise stress further unveils LV dynamic dyssynchrony and impaired contractile reserve in patients with beta-thalassaemia major.

  2. Spermatogenesis in young adult patients with beta-thalassaemia major long-term treated with desferrioxamine.

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    De Sanctis, V; Borsari, G; Brachi, S; Govoni, M; Carandina, G

    2008-03-01

    Since the introduction of hypertransfusion and intensive iron chelation therapy, patients with homozygous beta-thalassaemia major (TM) achieve adulthood. Many patients grow and develop normal hoping for marriage and to have a family. Therefore the question of fertility potential in this adult group of TM patients has become paramount. We report the semen parameters, the endocrine functions and serum zinc levels in 12 young adult TM patients. Their mean age was 24.8 years. Six patients (50%) had a normal sperm count, motility and morphology. While the remaining patients had oligospermia (sperm concentration plasma zinc, serum ferritin and seminal parameters. Nevertheless we observed that serum ferritin levels were lower (mean 543 ng/ml) in TM patients with abnormal seminal parameters (count and motility) compared to TM patients with normal seminal parameters (mean serum ferritin 1276 ng/ml; p<0.01). In conclusion, impairment of semen parameters may be a negative effect of intensive chelation therapy. Clearly, further investigations are required to evaluate if these adverse effects can be reduced or prevented, and if the existing spermatogenesis damage is reversible.

  3. Pulmonary dysfunction in thalassaemia major: is there any relationship with body iron stores?

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    Guidotti, Francesca; Piatti, Gioia; Marcon, Alessia; Cassinerio, Elena; Giuditta, Marianna; Roghi, Alberto; Fasano, Valter; Consonni, Dario; Cappellini, Maria Domenica

    2017-01-01

    Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the pathogenetic mechanism is not clear and data are contradictory, probably because of study heterogeneity and the multifactorial nature of the pathogenesis. We retrospectively analysed 73 adult TM patients to evaluate the prevalence of pulmonary dysfunction in adult TM and investigate relationships with iron load. All patients underwent body plethysmography and carbon monoxide diffusion (DLCO) was assessed in 63, in addition to blood tests, echocardiogram and T2* myocardial and liver magnetic resonance imaging. Restrictive lung disease was present in 26 (35·6%) patients. Serum ferritin levels were higher in patients with restrictive pattern (1526 μg/l vs. 975 μg/l, P = 0·05). Restrictive lung disease did not correlate with cardiac or liver iron overload. However, considering only patients with serum ferritin >2500 μg/l, those with restrictive pattern also had heart (T2* 14·28 ± 9·99 ms vs. 31·59 ± 7·43 ms) and liver iron overload (LIC 16·02 ± 8·44 mg vs. 5·02 ± 2·69 mg Fe/g dry weight) compared to those without restrictive pattern. Twenty-five patients (39·7%) had decreased DLCO. No correlation was observed with iron parameters. In our data restrictive pattern was predominant; we observed a relationship with serum ferritin levels suggesting that iron, particularly its chronic effect, could play a role in the pathogenesis of pulmonary disease. © 2016 John Wiley & Sons Ltd.

  4. MRI for the determination of pituitary iron overload in children and young adults with {beta}-thalassaemia major

    Energy Technology Data Exchange (ETDEWEB)

    Christoforidis, Athanasios [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece)]. E-mail: christoforidis@doctors.org.uk; Haritandi, Afroditi [Radiology Department, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki (Greece); Perifanis, Vassilios [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece); Tsatra, Ioanna [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece); Athanassiou-Metaxa, Miranda [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece); Dimitriadis, Athanasios S. [Radiology Department, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki (Greece)

    2007-04-15

    Hypogonadism, resulting from iron-induced pituitary dysfunction, is the most frequently reported complication in patients with {beta}-thalassaemia major. The aim of this study was to evaluate pituitary Magnetic Resonance Imaging (MRI) signal intensity reduction, on T2*-weighted images, as a marker of pituitary iron overload. Thirty patients (13 females and 17 males, mean age: 16.6 {+-} 4.1) with {beta}-thalassaemia major on conventional treatment and 13 healthy volunteers (7 females and 6 males, mean age: 11 {+-} 4.51 years) were studied with T2*-weighted images of the anterior pituitary using a 1.5 T unit. Four thalassaemic patients (2 females and 2 males) had clinical hypogonadism and required hormonal replacement treatment. Results revealed a statistically significant reduction of pituitary signal intensity in the thalassaemia group compared to controls (p < 0.001). Moreover, hypogonadal patients had significantly decreased MRI values compared to thalassaemic patients without hypogonadism (p = 0.017). Relatively decreased adeno-hypophyseal MRI signal intensity was recorded in pubertal thalassaemic patients. A significant negative correlation was observed between pituitary MRI values and age (r = -0.67, r {sup 2} = 0.443, p = 0.001), whereas ferritin levels and pituitary MRI values were moderately correlated (r = -0.56, r {sup 2} = 0.32, p = 0.08) in adult thalassaemic patients. In conclusion, pituitary MRI indices as measured on T2*-weighted images seem to reflect pituitary iron overload and could, therefore, be used for a preclinical detection of patients who are in greater danger of developing hypogonadism.

  5. Patterns of bone diseases in transfusion-dependent homozygous thalassaemia major: predominance of osteoporosis and desferrioxamine-induced bone dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Yu-Leung; Pang, Lai-Man [Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, Shatin (Hong Kong); Chik, Ki-Wai; Li, Chi-Kong [Department of Paediatrics, Prince of Wales Hospital, Chinese University of Hong Kong (Hong Kong); Cheng, Jack C.Y. [Department Orthopaedics and Traumatology, Prince of Wales Hospital, Chinese University of Hong Kong (Hong Kong)

    2002-07-01

    Objective: To study the radiographic skeletal changes in transfusion-dependent homozygous {beta}-thalassaemia. Materials and methods: This was a retrospective review of radiographs of 41 homozygous {beta}-thalassaemic patients over 3 years. These included 55 left hand radiographs for bone age, 37 chest radiographs, 7 scanograms of lower limbs, 8 knee radiographs and 3 skull radiographs. The radiographs were evaluated for the skeletal changes owing to medullary expansion, as well as for the skeletal dysplasia related to desferrioxamine therapy. The combined cortical width of the mid shaft of the second metacarpal was measured on left hand radiographs to assess osteoporosis. Results: Sixteen patients had radiographic evidence of desferrioxamine-induced bone dysplasia. These included metaphyseal sclerosis in long bone (n=16), irregular sclerosis at the costochondral junction (n=3) and platyspondyly (n= 1). Two patients had radiographic evidence of medullary expansion with widening of medulla and marked thinning of cortex in the tubular bones. Osteoporosis, as indicated by thinning of metacarpal cortex, was noted in 17 patients (8 with and 9 without desferrioxamine-induced bone dysplasia). Conclusions: With provision of the modern regime of regular transfusion and desferrioxamine chelation, desferrioxamine-induced bone dysplasia was a much more frequently detected radiographic abnormality in {beta}-thalassaemia major than radiographic features owing to medullary expansion. Osteoporosis, as indicated by thinned metacarpal cortices, remained a frequent feature irrespective of the status of the skeletal dysplasia. (orig.)

  6. A case of selective mutism in an 8-year-old girl with thalassaemia major after bone marrow transplantation.

    Science.gov (United States)

    Plener, P L; Gatz, S A; Schuetz, C; Ludolph, A G; Kölch, M

    2012-01-01

    Selective mutism is rare with a prevalence below 1% in the general population, but a higher prevalence in populations at risk (children with speech retardation, migration). Evidence for treatment strategies is hardly available. This case report provides information on the treatment of selective mutism in an 8-year-old girl with preexisting thalassaemia major. As medications she received penicillin prophylaxis (500000 IE/d) and deferasirox (Exjade; 20-25mg/kg/d), an iron chelator. The preexisting somatic disease and treatment complicated the treatment, as there are no data about pharmacological combination therapy. Psychotherapy in day treatment, supported by the use of the SSRI fluoxetine (10 mg), led to a decrease in the selective mutism score from 33 to 12 points, GAF improved by 21 points. Mean levels of fluoxetine plus norfluoxetine were 287.8 ng/ml without significant level fluctuations. © Georg Thieme Verlag KG Stuttgart · New York.

  7. THALASSAEMIA INTERMEDIA : AN UPDATE

    Directory of Open Access Journals (Sweden)

    Ali Taher

    2009-08-01

    Full Text Available Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with thalassaemia intermedia (TI has substantially increased over the past decade. TI encompasses a wide clinical spectrum of beta-thalassaemia phenotypes. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years of age. A number of clinical complications commonly associated with TI are rarely seen in thalassaemia major, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis and pulmonary hypertension. There are a number of options currently available for managing patients with TI, including transfusion therapy, iron chelation therapy, modulation of foetal haemoglobin production and haematopoietic stem cell transplantation. However, at present, there are no clear guidelines for an orchestrated optimal treatment plan.

  8. Dual energy x-ray absorptiometry (DEXA) in the assessment of liver iron in patients with beta thalassaemia major

    International Nuclear Information System (INIS)

    Chatterton, B.E.; Thomas, C.M.; Schultz, C.G.

    2000-01-01

    Full text: Beta thalassaemia major is a condition in which anaemia from abnormal haemoglobin production causes bone marrow expansion and frequently reduced bone mineral density. These patients have a chronic requirement for transfusion which results in tissue iron overload which may cause organ damage. Increased X-ray attenuation in the liver was noted in patients undergoing whole body DEXA for the assessment of bone density and it was assumed that this was related to liver iron stores. The aim of this study was to determine if useful information about liver iron could be obtained from these studies. Method: Using a Lunar DPXL, whole body scanning was performed in 16 patients (eight male) age 19-32 with Beta Thalassaemia. As well as calculating indices of total body composition, regions of interest were placed over the visualised liver. The 'bone mineral content' (BMC),g and bone mineral density (BMD),g/cm 2 were calculated over the liver regions, with the assumption that the calculation related to mineral in the region of interest. The results were compared with the serum ferritin as an indirect measure of body iron stores. Results showed a highly significant correlation (r=0.85) between 'BMD' in the liver region and ferritin. Conclusion: Despite the known difficulties with equating iron stores and ferritin, and possible confounders on liver density, such as fibrosis, the high correlation suggests that DEXA may have a place in the assessment of iron deposition, and be more cost effective than other technologies such as MRI and CT. Prospective studies with invasive measurements of liver iron will be needed to determine this. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  9. [Anabolic therapy of induced osteoporosis in beta-thalassaemia major: case report and literature review].

    Science.gov (United States)

    Trotta, A; Corrado, A; Cantatore, F P

    2010-01-01

    Transfusion program and chelating therapy treatment has extended the life expectancy of thalassaemic patient; osteoporosis is considered an important cause of morbidity in adult patients who display increased fracture risk. This is a case report is about a thalassaemic young female with multiple spine fractures (D11, D12 e L2) and lumbar spine DEXA - T score = -3,1 and femoral = -3,4. This was in spite of therapy with alendronate 70 mg/week from January 2006 to September 2007. The patient was subsequentently treated for 18 months with 1-34 recombinant human parathyroid hormone and colecalciferol (100.000 U/monthly). After 4 months of therapy, the patient showed a decrease in spinal pain (Roland and Morris Disability Questionnaire) and an improvement of quality of life (Qualeffo) with normalization of osteocalcin and 25-OHcolecalciferol haematic levels after 6 months. Lumbar spine and femoral DEXA - Tscore, at 18 months, rose respectively to -2,5 and -2,4. Thalassaemia-induced osteoporosis is multifactorial and its management is very difficult. Bone marrow expansion, endocrine dysfunction, iron overload and genetic factors all seem to play important roles in the development of low bone mass in these patients. Bisphosfonates have been used in the management of thalassemia induced osteoporosis but there is no data about fracture risk. Anabolic therapy for thalassemic patients requests additional study on a large scale.

  10. Deferasirox pharmacokinetic and toxicity correlation in β-thalassaemia major treatment.

    Science.gov (United States)

    Allegra, Sarah; De Francia, Silvia; Cusato, Jessica; Pirro, Elisa; Massano, Davide; Piga, Antonio; D'Avolio, Antonio

    2016-11-01

    Deferasirox adverse effects include the following: gastrointestinal disturbance, mild elevations in serum creatinine levels and intermittent proteinuria; these events are dose-dependent and reversible with drug discontinuation, but this solution can lead to an inadequate iron chelation. For these reasons, interindividual variability of drug plasma concentration could help the clinical management of deferasirox dosage. We sought to describe deferasirox plasma exposure in a cohort of 60 adult patients. A fully validated chromatographic method was used to quantify deferasirox concentration in plasma collected from β-thalassaemia adult patients. Samples obtained before and after 2, 4, 6 and 24 h drug administration were evaluated. Associations between variables were tested using the Pearson test. Concerning pharmacokinetic parameters, a higher interindividual variability was shown. A positive correlation was found between deferasirox area under the concentration curve over 24 h and serum creatinine (r = 0.314; P = 0.018) and between area and drug dose (r = 0.311; P = 0.016). Moreover, a negative correlation resulted among area under the concentration curve over 24 h and serum ferritin (r = -0.291; P = 0.026) and among drug half-life and its dose (r = -0.319; P = 0.013). Treatment decision based on the individual characteristics could strongly contribute to minimize toxicity and increase efficacy of deferasirox therapy. © 2016 Royal Pharmaceutical Society.

  11. Anabolic therapy in b-thalassaemia major induced osteoporosis: case report and literature review

    Directory of Open Access Journals (Sweden)

    F.P. Cantatore

    2011-06-01

    Full Text Available Transfusion program and chelating therapy treatment has extended the life expectancy of thalassaemic patient; osteoporosis is considered an important cause of morbidity in adult patients who display increased fracture risk. This is a case report is about a thalassaemic young female with multiple spine fractures (D11, D12 e L2 and lumbar spine DEXA - Tscore = -3,1 and femoral = -3,4. This was in spite of therapy with alendronate 70 mg/week from January 2006 to September 2007. The patient was subsequentently treated for 18 months with 1-34 recombinant human parathyroid hormone and colecalciferol (100.000 U/monthly. After 4 months of therapy, the patient showed a decrease in spinal pain (Roland and Morris Disability Questionnaire and an improvement of quality of life (Qualeffo with normalization of osteocalcin and 25-OHcolecalciferol haematic levels after 6 months. Lumbar spine and femoral DEXA - Tscore, at 18 months, rose respectively to -2,5 and -2,4. Thalassaemia-induced osteoporosis is multifactorial and its management is very difficult. Bone marrow expansion, endocrine dysfunction, iron overload and genetic factors all seem to play important roles in the development of low bone mass in these patients. Bisphosfonates have been used in the management of thalassemia induced osteoporosis but there is no data about fracture risk. Anabolic therapy for thalassemic patients requests additional study on a large scale.

  12. New trend in the epidemiology of thalassaemia.

    Science.gov (United States)

    Li, Chi-Kong

    2017-02-01

    Thalassaemia is the most common monogenic disorder worldwide. It is common in areas with prevalent malaria as thalassaemic red cells provide immunity against the parasite. The incidence of thalassaemia carriers is high in regions such as Mediterranean, Middle East, Indian subcontinent, Southeast Asia and South China. In the past few decades, migrants from the thalassaemia prevalent countries to non-prevalent countries, mainly North America and Central and North Europe, are rapidly increasing in number. The non-prevalent countries may not have established pre-natal screening system for thalassaemia. The genetic subtypes among the different ethnic groups vary; this may pose challenges in prenatal diagnosis. Genetic counselling on the postnatal course of thalassaemia may be affected by the genotype-phenotype correlation and coinheritance of other genetic diseases. New treatment methods improve the survival of patient with thalassaemia major, but some late complications that occur with longer survival have been recently discovered. Copyright © 2016. Published by Elsevier Ltd.

  13. Prevalence of hepatitis C infection among children with β-thalassaemia major in Mid Delta, Egypt: a single centre study.

    Science.gov (United States)

    El-Shanshory, Mohamed R; Kabbash, Ibrahim A; Soliman, Hanan H; Nagy, Hala M; Abdou, Said H

    2013-04-01

    Transfusion dependant patients are at a higher risk of acquiring bloodborne infections even under conditions of safe transfusion. This study was designed to determine sero-prevalence of hepatitis C infection and possible associated risk factors in thalassaemic children. One hundred and twenty five children with β thalassaemia major (β-TM) were recruited from the Haematology/Oncology Unit, Paediatric Department, Tanta University Hospital, Egypt, between April 2010 and October 2011. Patients underwent history taking, full clinical examination, routine investigations and venous blood sampling. Serum was stored at -20°C till tested for hepatitis C (HCV Ab) and B (HBsAg) by ELISA. HCV Ab positive cases were confirmed by PCR. All patients were HBsAg negative. HCV Ab ELISA was positive in 76%, negative in 20% and equivocal in 4%. Fifty patients (40%) had positive PCR for HCV. PCR showed low viraemia in 78%, moderate viraemia in 20% and high viraemia in 2%. A positive family history of HCV, history of minor operative intervention and/or dental procedures were significantly associated with higher frequency of HCV infection in thalassaemic children, while amount and frequency of transfused blood, age at transfusion and chelation state were not. HCV infection is highly prevalent in children with β-TM in Egypt despite strict pre-transfusion blood testing. This should arouse the attention for environmental and community acquired factors. Quality management to insure infection control in minor operative procedures and adding more sensitive tests for blood screening are recommended.

  14. Association of BCL11A genetic variant (rs11886868 with severity in β-thalassaemia major & sickle cell anaemia

    Directory of Open Access Journals (Sweden)

    Sneha Dadheech

    2016-01-01

    Interpretation & conclusions: This study confirms that the T/C variant (rs11886868 of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of β-thalassaemia as well as SCA.

  15. Clinical Pharmacist-Provided Services In Iron-Overloaded Beta-Thalassaemia Major Children: A New Insight Into Patient Care.

    Science.gov (United States)

    Bahnasawy, Salma M; El Wakeel, Lamia M; Beblawy, Nagham El; El-Hamamsy, Manal

    2017-04-01

    Iron-overloaded β-thalassaemia major (BTM) children have high risk of delayed sexual/physical maturation, liver/heart diseases and reduced life expectancy. The lifelong need to use iron chelators, their unpleasant administration, side effects and lack of awareness regarding iron overload risks all hamper BTM patient compliance to iron chelators. This study evaluated the impact of clinical pharmacist-provided services on the outcome of iron-overloaded BTM children. Forty-eight BTM children were randomly assigned to either control group, who received standard medical care, or intervention group, who received standard medical care plus clinical pharmacist-provided services. Services included detection of drug-related problems (DRPs) and their management, patient education regarding disease nature and iron chelators, as well as providing patient-tailored medication charts. After six months of study implementation, there was a highly significant difference between the control and intervention groups in serum ferritin (SF) (mean: 3871 versus 2362, μg/l, p = 0.0042), patient healthcare satisfaction (median: 24.47 versus 90.29, p < 0.0001) and quality of life (QoL) (median: 49.84 versus 63.51, p = 0.0049). The intervention group showed a decline from baseline to the end of study in DRPs (64-4), the number of non-compliant patients (24-3) and mean SF levels (3949-2362 μg/l, p < 0.0001). Clinical pharmacist-provided services can positively impact the outcome of BTM children. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. A time-driven, activity-based costing methodology for determining the costs of red blood cell transfusion in patients with beta thalassaemia major.

    Science.gov (United States)

    Burns, K E; Haysom, H E; Higgins, A M; Waters, N; Tahiri, R; Rushford, K; Dunstan, T; Saxby, K; Kaplan, Z; Chunilal, S; McQuilten, Z K; Wood, E M

    2018-04-10

    To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end-organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. We describe the bottom-up, time-driven, activity-based costing methodology used to develop process maps to provide a step-by-step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. Thirty-one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings. © 2018 British Blood Transfusion Society.

  17. THALASSAEMIA INTERMEDIA : AN UPDATE

    Directory of Open Access Journals (Sweden)

    Maria Domenica Cappellini

    2009-06-01

    Full Text Available

    Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with thalassaemia intermedia (TI has substantially increased over the past decade. TI encompasses a wide clinical spectrum of beta-thalassaemia phenotypes. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years of age. A number of clinical complications commonly associated with TI are rarely seen in thalassaemia major, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis and pulmonary hypertension. There are a number of options currently available for managing patients with TI, including transfusion therapy, iron chelation therapy, modulation of foetal haemoglobin production and haematopoietic stem cell transplantation. However, at present, there are no clear guidelines for an orchestrated optimal treatment plan.

  18. Beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, A.; Main, K.M.; Scheibel, E.

    2002-01-01

    INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among Danish children as a result of immigration. The aim of the study was to estimate the occurrence of beta-thalassemia major in Denmark, analyse the treatment and organ functions, and identify areas for an improved treatment...... strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...... were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin

  19. beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, Anne; Main, Katharina Maria; Scheibel, Elma

    2002-01-01

    INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among Danish children as a result of immigration. The aim of the study was to estimate the occurrence of beta-thalassemia major in Denmark, analyse the treatment and organ functions, and identify areas for an improved treatment...... strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...... were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin

  20. Beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, A.; Main, K.M.; Scheibel, E.

    2002-01-01

    were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin ...INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among Danish children as a result of immigration. The aim of the study was to estimate the occurrence of beta-thalassemia major in Denmark, analyse the treatment and organ functions, and identify areas for an improved treatment...... strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...

  1. Beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, A.; Main, K.M.; Scheibel, E.

    2002-01-01

    strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...... were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin .... An earlier and more effective iron chelation therapy together with improved patient support may reduce growth disturbances and endocrine and cardiac late effects....

  2. beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, Anne; Main, Katharina Maria; Scheibel, Elma

    2002-01-01

    strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...... were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin .... An earlier and more effective iron chelation therapy together with improved patient support may reduce growth disturbances and endocrine and cardiac late effects....

  3. Randomised controlled trials of iron chelators for the treatment of cardiac siderosis in thalassaemia major

    Directory of Open Access Journals (Sweden)

    Arun John Baksi

    2014-09-01

    Full Text Available In conditions requiring repeated blood transfusion or where iron metabolism is abnormal, heart failure may result from accumulation of iron in the heart (cardiac siderosis. Death due to heart failure from cardiac iron overload has accounted for considerable early mortality in β-thalassemia major. The ability to detect iron loading in the heart by cardiovascular magnetic resonance using T2* sequences has created an opportunity to intervene in the natural history of such conditions. However, effective and well tolerated therapy is required to remove iron from the heart. There are currently 3 approved commercially available iron chelators: deferoxamine, deferiprone and deferasirox. We review the high quality randomised controlled trials in this area for iron chelation therapy in the management of cardiac siderosis.

  4. Hydroxyurea appears beneficial in patients with beta-thalassaemia major and intermedia

    Directory of Open Access Journals (Sweden)

    S. F.S.A. Abdul Wahid

    2007-06-01

    Full Text Available Patients with severe inherited β-globin chain disorders may have milder illness if they produce high levels of fetal hemoglobin (HbF. Hydroxyurea (HU has been shown to enhance HbF levels in patients with sickle cell disease and may be useful in β-thalassemias. We administered HU to 13 patients with β-thalassemia intermedia or major, including 6 splenectomized patients. The patients received escalating doses (10 to 25 mg/kg/d of HU for around 2 years (median: 21 months, range: 8 - 55 months. Eleven patients responded with an increase in the pre-transfusion HbF levels, from a base line median of 8.0% (2.5 - 61.3% to 28.0% (6.6 - 49.2% and 40.7% (4.8 - 72.3% at 3 months and 18 months post-HU, respectively. A concomitant increment in median hemoglobin levels was noted at 1, 3 and 18 months of HU therapy. Six of 7 transfusion-dependent patients who had an increment of HbF (one with β-thalassemia major also had reduced transfusion requirement over the 2-year period of HU therapy. Response to HU was also shown by a reduction in spleen size. Apart from oral ulcers that resolved upon dose reduction of HU, no significant toxicity was noted. We conclude that increased HbF production in β-thalassemia patients, with an improvement in erythropoiesis, can be achieved using HU with minimal toxicity. (Med J Indones 2007; 16:78-83 Keywords: fetal hemoglobin (HbF, erythropoiesis, toxicity

  5. Acquired Hypogonadotropic Hypogonadism (AHH) in Thalassaemia Major Patients: An Underdiagnosed Condition?

    Science.gov (United States)

    De Sanctis, Vincenzo; Elsedfy, Heba; Soliman, Ashraf T; Elhakim, Ihab Zaki; Pepe, Alessia; Kattamis, Christos; Soliman, Nada A.; Elalaily, Rania; El Kholy, Mohamed; Yassin, Mohamed

    2016-01-01

    Introduction In males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function, and strength, a worsened sense of well-being and degraded quality of life (QOL). Patients and methods We studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: 34.3 ± 8.8 years) with AHH. Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. All patients were on regular transfusions and iron chelation therapy. Fasting venous blood samples were collected two weeks after transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate). Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*. Bone mineral density was measured at the lumbar spine (L1–L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine. Results The mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH showed azoospermia in 3 and oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml (severe iron load) was significantly higher in AHH patients compared to controls, 5/11 (45

  6. The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

    Directory of Open Access Journals (Sweden)

    Berdoussi Eleni

    2009-06-01

    Full Text Available Abstract Background Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR. Results For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis" assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline. Conclusion With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.

  7. Thalassaemia and pregnancy

    DEFF Research Database (Denmark)

    Luk'yanenko, Viktoriya; Droogh, Marjoes; Overgaard, Ulrik Malthe

    2017-01-01

    Global migration has resulted in a larger geographical spread of people with risk of hereditary anaemias. This leads to an increased incidence of pregnant women with rare diseases, including thalassaemia also in Scandinavia. Thalassaemia can cause severe anaemia and other complications during pre...... pregnancy, like risk of miscarriage, intrauterine fetal death, abruptio, intrauterine growth retardation, hypertension, gestational diabetes and pre-eclampsia. In this article, we focus on the aetiology, assessment, antenatal care and treatment of pregnant women with thalassaemia....

  8. Bone age estimation and prediction of final height in patients with {beta}-thalassaemia major: a comparison between the two most common methods

    Energy Technology Data Exchange (ETDEWEB)

    Christoforidis, Athanasios; Katzos, George; Athanassiou-Metaxa, Miranda [Aristotle University of Thessaloniki, 1st Paediatric Department, Thessaloniki (Greece); Badouraki, Maria [Ippokratio Hospital, Paediatric Radiology Department, Thessaloniki (Greece)

    2007-12-15

    Thalassaemic patients are in need of frequent assessment of bone age because of growth failure and pubertal disorders. To compare the ''rapid'' Greulich and Pyle (G and P) method with the third edition of the Tanner and Whitehouse (TW3) method for determining skeletal maturity and predicting final height in thalassaemic patients. A total of 191 radiographs from 58 patients (28 male, 30 female) were retrospectively evaluated by two investigators, one for each method. In 47 radiographs from 15 patients having attained their adult height, predicted final height was calculated according to each method. The mean bone ages determined by both the G and P and TW3 methods were lower than mean chronological age, although the differences were not statistically significant (10.04 {+-} 3.69 years and 9.98 {+-} 3.39 years vs. 10.78 {+-} 3.96 years, respectively). Both methods had a tendency to over-estimate final height. Overall, the TW3 method seemed to be more accurate than the G and P method (mean absolute error 3.21 {+-} 2.51 years vs. 3.99 {+-} 2.99 years, respectively, P=0.048). The same method should be used when serial assessments are performed, as both methods provide similarly reliable, although not equivalent, results. The TW3 height prediction method seemed to be more accurate in patients with {beta}-thalassaemia major than the G and P method, albeit with a large confidence interval. (orig.)

  9. Assessment and management of iron overload in β-thalassaemia major patients during the 21st century: a real-life experience from the Italian WEBTHAL project.

    Science.gov (United States)

    Piga, Antonio; Longo, Filomena; Musallam, Khaled M; Cappellini, Maria Domenica; Forni, Gian Luca; Quarta, Giovanni; Chiavilli, Francesco; Commendatore, Francesca; Mulas, Sergio; Caruso, Vincenzo; Galanello, Renzo

    2013-06-01

    We conducted a cross-sectional study on 924 β-thalassaemia major patients (mean age 30·1 years) treated at nine Italian centres using the WEBTHAL software, to evaluate real-life application of iron overload assessment and management standards. Serum ferritin 2 years. Patients who never had a cardiac MRI (CMR) T2* measurement were 2 years. Deferoxamine (22·8%) was more commonly used in patients with Hepatitis C Virus or high serum creatinine. Deferiprone (20·6%) was less commonly prescribed in patients with elevated alanine aminotransferase; while a deferoxamine + deferiprone combination (17·9%) was more commonly used in patients with serum ferritin >2500 ng/ml or CMR T2* <20 ms. Deferasirox (38·3%) was more commonly prescribed in patients <18 years, but less commonly used in those with heart disease or high iron intake. These observations largely echoed guidelines at the time, although some practices are expected to change in light of evolving evidence. © 2013 John Wiley & Sons Ltd.

  10. Transfusion-transmitted severe Plasmodium knowlesi malaria in a splenectomized patient with beta-thalassaemia major in Sabah, Malaysia: a case report.

    Science.gov (United States)

    Bird, Elspeth M; Parameswaran, Uma; William, Timothy; Khoo, Tien Meng; Grigg, Matthew J; Aziz, Ammar; Marfurt, Jutta; Yeo, Tsin W; Auburn, Sarah; Anstey, Nicholas M; Barber, Bridget E

    2016-07-12

    Transfusion-transmitted malaria (TTM) is a well-recognized risk of receiving blood transfusions, and has occurred with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. The simian parasite Plasmodium knowlesi is also known to be transmissible through inoculation of infected blood, and this species is now the most common cause of malaria in Malaysia with a high rate of severity and fatal cases reported. No confirmed case of accidental transfusion-transmitted P. knowlesi has yet been reported. A 23-year old splenectomized patient with beta thalassaemia major presented with fever 11 days after receiving a blood transfusion from a pre-symptomatic donor who presented with knowlesi malaria 12 days following blood donation. The infection resulted in severe disease in the recipient, with a parasite count of 84,000/µL and associated metabolic acidosis and multi-organ failure. She was treated with intravenous artesunate and made a good recovery. Sequencing of a highly diverse 649-base pair fragment of the P. knowlesi bifunctional dihydrofolate reductase-thymidylate synthase gene (pkdhfr) revealed that the recipient and donor shared the same haplotype. This case demonstrates that acquisition of P. knowlesi from blood transfusion can occur, and that clinical consequences can be severe. Furthermore, this case raises the possibility that thalassaemic patients, particularly those who are splenectomized, may represent a high-risk group for TTM and severe malaria. With rising P. knowlesi incidence, further studies in Sabah are required to determine the risk of TTM in order to guide screening strategies for blood transfusion services.

  11. Prevalence of Hepatitis C Virus Infection in Multi-transfused Thalassaemia Patients in Bangladesh

    Directory of Open Access Journals (Sweden)

    Belayet Hossain

    2018-01-01

    Full Text Available Background: Thalassaemia is one of the most common hereditary diseases worldwide including Bangladesh. Multitransfused thalassaemia patients may acquire hepatitis C virus infection in spite of currently practicing screening schedule. It is postulated that there are some pitfalls in the currently practicing screening system behind the transmission of HCV in transfusion-dependent thalassaemia patients. Objectives: To find out the prevalence of hepatitis C virus infection in transfusiondependent thalassaemia patients and thereby to see the efficacy of currently practicing screening schedule for hepatitis C virus. Materials and Methods: This cross-sectional study was conducted from 1st December, 2015 to 30th November, 2016 at Dhaka Shishu (Children Hospital Thalassemia Center (DSHTC. Three hundred and twenty patients of multitransfused β-thalassaemia major and Hb E β-thalassaemia aged 3−18 years were enrolled. History was taken and physical examination was done. Blood specimens were collected and sent to the standard laboratory for detection of antibody against hepatits C virus. Results: Among the subjects, 174 (54.3% were male and 146 (45.7% were female. Out of total 320 patients, 75 (23% were β-thalassaemia major and 245 (77% were Hb E β-thalassaemia. Among the 320 thalassaemia cases, 47 were found positive for anti-HCV with an overall prevalence of 14.7%. Conclusion: Despite screening of blood donors by Rapid Device (Strip Method, HCV infection remains an important cause of viral hepatitis infection among multitransfused thalassaemia children.

  12. Efficacy of Deferasirox for the treatment of iron overload in Chinese thalassaemia major patients: results from a prospective, open-label, multicentre clinical trial.

    Science.gov (United States)

    Lai, Y-R; Liu, R-R; Li, C-F; Huang, S-L; Li, Q; Habr, D; Martin, N; Shen, Z-X

    2013-12-01

    To assess the efficacy and safety of deferasirox in Chinese thalassaemia major (TM) patients EPIC (Evaluation of Patients' Iron Chelation with Exjade(®)) was a large multi-national study and, notably, the first clinical trial of an iron chelator registered with the Chinese State Food and Drug Administration. Efficacy and safety of deferasirox were compared in Chinese (n = 117) and non-Chinese (n = 998) TM patients. Deferasirox was initiated at 20 mg kg(-1)  day(-1), with titration increments of 5-10 mg kg(-1) day(-1), based on serum ferritin trends and safety parameters. At baseline, Chinese patients were younger than non-Chinese (mean age 6·8 versus 19·5 years), with higher median serum ferritin (4519 vs 3058 ng mL(-1)). Over 1 year, mean actual deferasirox dose was similar for Chinese and non-Chinese patients (24·6 and 24·0 mg kg(-1)  day(-1), respectively); median serum ferritin did not change significantly from baseline in Chinese patients (+340 ng mL(-1), P = 0·102) and significantly decreased in non-Chinese patients (-220 ng mL(-1); P deferasirox dose 33·6 mg kg(-1)  day(-1)), median serum ferritin decreased (-756 ng mL(-1); P = 0·0397), with a numerically higher reduction in patients aged ≥6 to  deferasirox in Chinese patients was similar to the overall population with respect to clinically-relevant findings. Age and deferasirox exposure influenced study findings, supporting the need for longer-term treatment and dose escalation to ≥30 mg kg(-1)  day(-1) to achieve neutral or negative iron balance in heavily iron overloaded and younger Chinese patients. © 2013 The Authors. Transfusion Medicine © 2013 British Blood Transfusion Society.

  13. Pre-natal diagnosis of thalassaemia in Sri Lanka: A ten year review.

    Science.gov (United States)

    Nanayakkara, Kalinga Khemal; Rodrigo, Undugodage Ganganath; Perera, Kuda Liyanage Nandika; Nanayakkara, Chinthani Deepthi

    2017-10-01

    Thalassaemia is the commonest monogenic disease in Sri Lanka, affecting over 3500 children and half-a-million thalassaemia carriers. This is a review of 82 amniocenteses performed from 2006 to 2016, in the largest prenatal diagnoses study for thalassaemia carried out in Sri Lanka. Amniocenteses were performed between 11 and 12 weeks of ultrasonically confirmed gestation, on mothers with previous thalassaemia major children pregnant for the second time and nulliparous thalassaemia trait women married to trait partners. The Consultant Radiologist, using local analgesia, under ultrasound cover, performed these as an outpatient procedure, at the Teaching Hospital Kandy & Suwasevana Hospital Kandy. The amniotic fluid was analysed by the team of Senior Geneticists, at the Genetech Molecular Diagnostics and School of Gene Technology, Colombo, via the polymerase-chain-reaction based ARMS (Amplification Refractory Mutation Systems) assay. The genetic results indicated the presence of 21% thalassaemia major foetuses, 53% thalassaemia traits and 26% foetuses without thalassaemia mutations. The predominance of the IVS1-5(G-C) mutation in the Sri Lankan population is exemplified, with a low prevalence of HbE thalassaemia. Impact statement Thalassaemia is the commonest monogenic disease in Sri Lanka affecting over 3500 children and half-a-million thalassaemia carriers. Although pre-natal diagnosis by amniocentesis was practised universally for many years, this could not be performed in Sri Lanka as genetic diagnostic facilities were not available until 2005. Therefore, parents with a thalassaemia major child limited their families to one child, by choice or by termination. The results of this study point to a 21% probability of thalassaemia major in the next child, giving the parents a guarded optimism to conceive another child without thalassaemia disease. With siblings being the highest HLA compatibility for Bone Marrow Transplant, that is now being established in Sri Lanka

  14. Public perceptions and attitudes toward thalassaemia: Influencing factors in a multi-racial population.

    Science.gov (United States)

    Wong, Li Ping; George, Elizabeth; Tan, Jin-Ai Mary Anne

    2011-03-30

    Thalassaemia is a common public health problem in Malaysia and about 4.5 to 6% of the Malays and Chinese are carriers of this genetic disorder. The major forms of thalassaemia result in death in utero of affected foetuses (α-thalassaemia) or life-long blood transfusions for survival in β-thalassaemia. This study, the first nationwide population based survey of thalassaemia in Malaysia, aimed to determine differences in public awareness, perceptions and attitudes toward thalassaemia in the multi-racial population in Malaysia. A cross-sectional computer-assisted telephone interview survey of a representative sample of multi-racial Malaysians aged 18 years and above was conducted between July and December 2009. Of a total of 3723 responding households, 2846 (76.4%) have heard of thalassaemia. Mean knowledge score was 11.85 (SD ± 4.03), out of a maximum of 21, with higher scores indicating better knowledge. Statistically significant differences (P culturally acceptable in the reduction of pregnancies with thalassaemia major. The findings provide insights into culturally congruent educational interventions to reach out diverse socio-demographic and ethnic communities to increase knowledge and cultivate positive attitudes toward prevention of thalassaemia.

  15. Genetic counselling in the beta-thalassaemias

    Directory of Open Access Journals (Sweden)

    Adonis S. Ioannides

    2013-03-01

    Full Text Available The beta-thalassaemias are very important genetic disorders of haemoglobin synthesis and are amongst the commonest monogenic disorders. In view of the severity of beta-thalassaemia major, a number of screening programmes have been developed aimed at reducing the number of individuals born with the condition. Genetic counsellingplays a vital role in this process supporting the successful implementation of screening and delineating available options to at risk individuals. This review assesses the contribution of genetic counsellingat each stage of this process in the context of new diagnostic techniques and therapeutic options and discusses some of the more challenging aspects such as genotype/ phenotype correlation and coinheritance of other genetic conditions or genetic modifiers.

  16. Prevalence and spectrum of thalassaemia in Changsha, Hunan ...

    Indian Academy of Sciences (India)

    JUN HE

    2017-06-17

    Jun 17, 2017 ... transfusion-dependent anaemia. If left untreated with reg- ular blood transfusions, thalassaemia major can lead to death within the first year of life (Van de Velde et al. 2004). To date, Over 200 different β-globin mutations have been identified, with the majority being single nucleotide sub- stitutions, deletions ...

  17. Sample acceptance time criteria, electronic issue and alloimmunisation in thalassaemia.

    Science.gov (United States)

    Trompeter, S; Baxter, L; McBrearty, M; Zatkya, E; Porter, J

    2015-12-01

    To determine the safety of a 1-week acceptance criteria of sample receipt in laboratory to transfusion commencement in transfusion dependent thalassaemia with respect to alloimmunisation. To determine the safety of electronic issue of blood components in such a setting. Retrospective audit of alloimmunisation (1999-2012) and blood exposure in registered thalassaemia patients at a central London thalassaemia centre where the acceptance criteria for the group and save sample from arrival in the laboratory to the time of issue of blood for transfusion for someone who has been transfused in the last 28 days was 1 week, and there was electronic issue protocol for patients who have always had a negative antibody screen (other than temporary positivity in pregnant women receiving prophylactic anti-D or anti Le-a, Anti Le-b and Anti P1 that are no longer detectable). There were 133 patients with thalassemia variants regularly attending UCLH for review. A total of 105 patients had transfusion dependent thalassaemia (TDT) (7 E-beta thalassaemia, 98 beta thalassaemia major). Ten of the 84 patients who received their transfusions at UCLH were alloimmunised. Seven of them had been alloimmunised prior to arrival at UCLH. Only two patients developed antibodies at UCLH during this period. The prevalence of alloantibody formation of 2% in UCLH transfused patients, with presumptive incidence of 0.01 alloantibodies per 100 units or 0·001 immunisations per person per year compares favourably with other reported series and suggests that 1 week interval with appropriate electronic issue is acceptable practice. © 2015 British Blood Transfusion Society.

  18. Alpha thalassaemia in tribal communities of coastal Maharashtra, India

    Directory of Open Access Journals (Sweden)

    Madhav G Deo

    2014-01-01

    Full Text Available Background & objectives: In a routine community health survey conducted in adult Adivasis of the costal Maharashtra, microcytosis and hyprochromia were observed in more than 80 per cent of both males and females having normal haemoglobin levels suggesting the possibility of α-thalassaemia in these communities. We conducted a study in Adivasi students in the same region to find out the magnitude of α-thalessaemia. Methods: The participants (28 girls and 23 boys were 14-17 yr old studying in a tribal school. Fasting venous blood samples (5 ml were subjected to complete blood count (CBC, Hb-HPLC and DNA analysis using gap-PCR for deletion of - α3.7 and - α4.2, the two most common molecular lesions observed in α-thalassaemia in India. Results: Microcytic hypochromic anaemia was observed 50 and 35 per cent girls and boys, respectively. Iron supplementation improved Hb levels but did not correct microcytois and hypochromia. m0 ore than 80 per cent non-anaemic students of both sexes showed microcytois and hypochromia. DNA analysis confirmed that the haematological alterations were due to α-thalassaemia trait characterized by deletion of - α3.7. Majority (> 60% of the affected students had two deletions (-α3.7/-α3.7 genotype α+ thalassaemia. Interpretation & conclusions: This is perhaps the first report on the occurrence of α-thalassaemia in tribal communities of coastal Maharashtra. Very high (78.4% haplotype frequency of -α3.7 suggests that the condition is almost genetically fixed. These preliminary observations should stimulate well planned large scale epidemiological studies on α-thalassaemia in the region.

  19. Alpha thalassaemia in tribal communities of coastal Maharashtra, India.

    Science.gov (United States)

    Deo, Madhav G; Pawar, Prakash V

    2014-08-01

    In a routine community health survey conducted in adult Adivasis of the costal Maharashtra, microcytosis and hyprochromia were observed in more than 80 per cent of both males and females having normal haemoglobin levels suggesting the possibility of α-thalassaemia in these communities. We conducted a study in Adivasi students in the same region to find out the magnitude of α-thalessaemia. The participants (28 girls and 23 boys) were 14-17 yr old studying in a tribal school. Fasting venous blood samples (5 ml) were subjected to complete blood count (CBC), Hb-HPLC and DNA analysis using gap-PCR for deletion of -α3.7 and -α4.2, the two most common molecular lesions observed in α-thalassaemia in India. Microcytic hypochromic anaemia was observed 50 and 35 per cent girls and boys, respectively. Iron supplementation improved Hb levels but did not correct microcytois and hypochromia. m0 ore than 80 per cent non-anaemic students of both sexes showed microcytois and hypochromia. DNA analysis confirmed that the haematological alterations were due to α-thalassaemia trait characterized by deletion of -α3.7. Majority (>60%) of the affected students had two deletions (-α3.7/-α3.7 genotype α+ thalassaemia. This is perhaps the first report on the occurrence of α-thalassaemia in tribal communities of coastal Maharashtra. Very high (78.4%) haplotype frequency of -α3.7 suggests that the condition is almost genetically fixed. These preliminary observations should stimulate well planned large scale epidemiological studies on α-thalassaemia in the region.

  20. Growth hormone therapy for people with thalassaemia.

    Science.gov (United States)

    Ngim, Chin Fang; Lai, Nai Ming; Hong, Janet Yh; Tan, Shir Ley; Ramadas, Amutha; Muthukumarasamy, Premala; Thong, Meow-Keong

    2017-09-18

    Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. To assess the benefits and safety of growth hormone therapy in people with thalassaemia. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Our database and trial registry searches are current to 10 August 2017 and 08 August 2017, respectively. Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity. Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The quality of the evidence was assessed using GRADE criteria. One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes

  1. Treatment of chronic hepatitis C with direct-acting antivirals in patients with β-thalassaemia major and advanced liver disease.

    Science.gov (United States)

    Sinakos, Emmanouil; Kountouras, Dimitrios; Koskinas, John; Zachou, Kalliopi; Karatapanis, Stylianos; Triantos, Christos; Vassiliadis, Themistoklis; Goulis, Ioannis; Kourakli, Alexandra; Vlachaki, Efthymia; Toli, Barbara; Tampaki, Maria; Arvaniti, Pinelopi; Tsiaoussis, Georgios; Bellou, Aristea; Kattamis, Antonis; Maragkos, Konstantinos; Petropoulou, Foteini; Dalekos, George N; Akriviadis, Evangelos; Papatheodoridis, George V

    2017-07-01

    Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with β-thalasaemia major (β-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with β-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology. Five regimens were used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir ± RBV; SOF + daclatasvir ± RBV; ledipasvir/SOF ± RBV and ombitasvir/paritaprevir-ritonavir + dasabuvir ± RBV. Sixty-one patients (median age 43 years) were included. The majority of patients was previously treated for hepatitis C (75%) and had cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22 (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant chelation therapy was a combination of deferoxamine and deferiprone (35%). Overall sustained virological response rates were 90%. All treatment regimens were well tolerated and no major adverse events or drug-drug interactions were observed. Approximately half of the patients who received RBV (7/16, 44%) had increased needs for blood transfusion. Treatment of CHC with DAAs in patients with β-TM and advanced liver disease was highly effective and safe. © 2017 John Wiley & Sons Ltd.

  2. Frequency of hypothyroidism in patients of beta-thalassaemia

    International Nuclear Information System (INIS)

    Malik, S.A.; Syed, S.; Ahmed, N.

    2010-01-01

    To determine the frequency of hypothyroidism in patients suffering from homozygous-thalassaemia. This descriptive study included 70 diagnosed thalassaemia major patients aged 5-14 years. Demographic data as well as history of blood transfusion and chelation therapy was collected. Random blood samples were drawn and thyroid profile (serum thyroxine [T4], triiodothyronine [T3] and thyroid stimulating hormone concentrations [TSH]) was done by enzyme-linked immunosorbent assay (ELISA). Primary hypothyroidism was defined by a TSH level >4 macro IU/ml. Results were analysed by descriptive statistical methods. Primary hypothyroidism was seen in 18 (25.7%) patients. Of these, 17 had normal T4 levels with elevated TSH levels consistent with a diagnosis of compensated primary hypothyroidism whereas only one patient showed a decreased T4 level with elevated TSH (uncompensated primary hypothyroidism). Mean age of hypothyroid patients was 9.2 +- 2.6 years. Frequency of hypothyroidism was associated with increased serum ferritin levels. Primary hypothyroidism occurs in a significant proportion of thalassaemia major patients in the absence of obvious clinical signs of hypothyroidism. Regular follow-up for early detection and timely treatment of such complications could improve the quality of life of these patients (JPMA 60:17; 2010). (author)

  3. Beta-thalassaemia mutations in northern India (Delhi).

    Science.gov (United States)

    Madan, N; Sharma, S; Rusia, U; Sen, S; Sood, S K

    1998-03-01

    The present study was undertaken to define beta-thalassaemia mutations prevalent in northern India (Delhi). Forty six children of beta-thalassaemia major and their families were investigated. DNA was extracted from leucocytes and screened for mutations prevalent in the Indian population. These mutations included 619bp deletion, IVS 1-1 (G-T), IVS 1-5 (G-C), frameshift mutations FS 8/9 (+G), FS 41/42 (-CTTT), Codon 16(-C), Codon 15 (G-A), codon 30 (G-C), IVS 1-110 (G-A) and -88 (C-T). 619 bp deletion mutation was detected directly by amplification of DNA by PCR followed by agarose gel electrophoresis. Other mutations were studied by DNA amplification and dot blot hybridization using synthetic normal and mutant oligonucleotide probes labelled at 5' end with gamma-32 P-ATP. Five mutations accounted for all the chromosomes in 46 patients. 619 bp deletion mutation was found to be the commonest mutation (34.8%) followed by IVS 1-5 (G-C) in 22.8 per cent, IVS 1-1 (G-T) in 19.6 per cent, FS 8/9 (+G) in 13 per cent and FS 41/42 (-CTTT) in 9.8 per cent. Nineteen (41.3%) patients were homozygous and 27 (58.7%) double heterozygous for different beta-thalassaemia mutations. This observation of limited number of mutations is significant and will be useful in planning strategies for prenatal diagnosis of beta-thalassaemia in northern India.

  4. Epidural extramedullary haemopoiesis in thalassaemia

    International Nuclear Information System (INIS)

    Boyacigil, S.; Ali, A.; Ardic, S.; Yuksel, E.

    2002-01-01

    lntrathoracic extramedullary haematopoiesis is a rare condition. Involvement of the spinal epidural space with haematopoietic tissue is rather unusual. A 31-year-old-man with a known diagnosis of β-thalassaemia was referred with focal back pain. Magnetic resonance imaging revealed diffuse bone-marrow changes, thoracic paraspinal masses and lobulated epidural masses, suggesting extramedullary haemopoiesis. The patient was treated with radiotherapy and blood transfusions. Follow-up MRI was performed for evaluation efficacy of the treatment. Copyright (2002) Blackwell Science Pty Ltd

  5. Common Β- Thalassaemia Mutations in

    Directory of Open Access Journals (Sweden)

    P Azarfam

    2005-01-01

    Full Text Available Introduction: β –Thalassaemia was first explained by Thomas Cooly as Cooly’s anaemia in 1925. The β- thalassaemias are hereditary autosomal disorders with decreased or absent β-globin chain synthesis. The most common genetic defects in β-thalassaemias are caused by point mutations, micro deletions or insertions within the β-globin gene. Material and Methods: In this research , 142 blood samples (64 from childrens hospital of Tabriz , 15 samples from Shahid Gazi hospital of Tabriz , 18 from Urumia and 45 samples from Aliasghar hospital of Ardebil were taken from thalassaemic patients (who were previously diagnosed .Then 117 non-familial samples were selected . The DNA of the lymphocytes of blood samples was extracted by boiling and Proteinase K- SDS procedure, and mutations were detected by ARMS-PCR methods. Results: From the results obtained, eleven most common mutations,most of which were Mediterranean mutations were detected as follows; IVS-I-110(G-A, IVS-I-1(G-A ،IVS-I-5(G-C ,Frameshift Codon 44 (-C,( codon5(-CT,IVS-1-6(T-C, IVS-I-25(-25bp del ,Frameshift 8.9 (+G ,IVS-II-1(G-A ,Codon 39(C-T, Codon 30(G-C the mutations of the samples were defined. The results showed that Frameshift 8.9 (+G, IVS-I-110 (G-A ,IVS-II-I(G-A, IVS-I-5(G-C, IVS-I-1(G-A , Frameshift Codon 44(-C , codon5(-CT , IVS-1-6(T-C , IVS-I-25(-25bp del with a frequency of 29.9%, 25.47%,17.83%, 7.00%, 6.36% , 6.63% , 3.8% , 2.5% , 0.63% represented the most common mutations in North - west Iran. No mutations in Codon 39(C-T and Codon 30(G-C were detected. Cunclusion: The frequency of the same mutations in patients from North - West of Iran seems to be different as compared to other regions like Turkey, Pakistan, Lebanon and Fars province of Iran. The pattern of mutations in this region is more or less the same as in the Mediterranean region, but different from South west Asia and East Asia.

  6. Haematopoietic stem cell transplantation for thalassaemia in Chinese patients.

    Science.gov (United States)

    Li, C K; Lee, Vincent; Shing, Matthew M K; Leung, T F

    2009-06-01

    Beta thalassaemia major is a common hereditary haematological disease in southern Chinese. Advances in transfusion and iron chelation improve survival but haematopoietic stem cell transplantation (HSCT) is still the only curative treatment. Due to repeated blood transfusion and iron overload, thalassaemia patients undergoing HSCT are at a higher risk of graft rejection and transplant-related mortality. The prognostic factors identified to be affecting transplant outcome include hepatomegaly, hepatic fibrosis, and compliance to chelation therapy. Patients can be classified into three classes and conditioning regimens are modified according to the risk. Early stage patients have 85 to 90% chance of disease-free survival, whereas advance stage only has 60% disease-free survival. Mixed chimerism is common after HSCT but majority have satisfactory erythropoiesis without need for further transfusion. Sibling cord blood and bone marrow transplantation has similar outcome. Recently alternative donor transplant has been performed in patients without human leukocyte antigen (HLA)-identical siblings. The result of unrelated-donor bone marrow transplantation is in general inferior but extended HLA matching may improve outcome. The use of unrelated cord blood transplant from a single-centre study showed promising result. The survivors require iron depletion to remove excessive iron store and some may require hormonal replacement therapy. Most of the patients have good quality of life after successful HSCT.

  7. Delta-Beta Thalassaemia in a Pathan Family.

    Science.gov (United States)

    Ahmad, Saqib Qayyum; Zafar, Saerah Iffat; Malik, Hamid Saeed; Ahmed, Suhaib

    2017-11-01

    Delta-beta-thalassaemia (δβ-thalassaemia) is a rare type of thalassaemia which mostly results from deletion of δ and β genes with preservation of γ genes. δβ-thalassaemia is classified into (δβ)+ and (δβ)0 types. The (δβ)0-thalassemia is further divided into GγAγ(δβ)0-thalassaemia and Gγ(Aγδβ)0-thalassaemia. In heterozygous state, (δβ)0mutations give rise to phenotype resembling β-thalassaemia trait but with raised Hb-F, ranging from 5 to 20%, without a rise in Hb-A2. In homozygotes, the clinical picture is usually that of thalassaemia intermedia and the patients have 100% Hb-F. Workup of a 1-year child suffering from pallor, chronic ill health, and splenomegaly referred to our laboratory with the suspicion of β-thalassaemia, ultimately resulted in a diagnosis on polymerase chain reaction as having homozygous inversion/deletion Gγ(Aγδβ)0-thalassaemia. Her family members were also investigated.

  8. THALASSAEMIA IS A TROPICAL DISEASE REVIEW ARTICLE

    African Journals Online (AJOL)

    the beta thalassaemia trait (BTT) is low. Under-diagnosis of BTT may arise from the similarity in its clinical manifestation to that of. SCA which is of high prevalence in Nigeria and secondly because the hypochromia and microcytosis associated with it may be misdiagnosed as iron deficiency anaemia. There is therefore the ...

  9. Deferasirox for managing iron overload in people with thalassaemia.

    Science.gov (United States)

    Bollig, Claudia; Schell, Lisa K; Rücker, Gerta; Allert, Roman; Motschall, Edith; Niemeyer, Charlotte M; Bassler, Dirk; Meerpohl, Joerg J

    2017-08-15

    Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed. To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload. We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 12 August 2016.We also searched MEDLINE, Embase, the Cochrane Library, Biosis Previews, Web of Science Core Collection and three trial registries: ClinicalTrials.gov; the WHO International Clinical Trials Registry Platform; and the Internet Portal of the German Clinical Trials Register: 06 and 07 August 2015. Randomised controlled studies comparing deferasirox with no therapy or placebo or with another iron-chelating treatment. Two authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. Sixteen studies involving 1807 randomised participants (range 23 to 586 participants) were included. Twelve two-arm studies compared deferasirox to placebo (two studies) or deferoxamine (seven studies) or deferiprone (one study) or the combination of deferasirox and deferoxamine to deferoxamine alone (one study). One study compared the combination of deferasirox and deferiprone to deferiprone in combination with deferoxamine. Three three-arm studies compared deferasirox to deferoxamine and deferiprone (two studies) or the combination of deferasirox and deferiprone to deferiprone and deferasirox monotherapy respectively (one study). One four-arm study compared two different doses of deferasirox to matching placebo groups.The two studies (a pharmacokinetic and a dose-escalation study

  10. A complex haemoglobinopathy diagnosis in a family with both beta zero- and alpha (zero/+)-thalassaemia homozygosity.

    Science.gov (United States)

    Giordano, P C; Harteveld, C L; Bok, L A; van Delft, P; Batelaan, D; Beemer, F A; Bernini, L F

    1999-01-01

    anaemia. The haematological analysis revealed 9.5 g/dl Hb; 5.4 x 10(12)/I RBC; 0.33 I/I PCV; 61 fl MCV; 17.6 pg MCH and 6.2% of HbA2. The biosynthetic ratio beta:alpha was 1.6 and no HbH fraction was detectable either on electrophoresis or as inclusion bodies. The parents reported no complications during pregnancy, at birth, or in the neonatal period in rural Afghanistan. We presume therefore that the counterbalancing effect induced by the co-existing beta-thalassaemia defect could have modified a potentially severe perinatal HbH disease into a strongly hypochromic but well compensated 'alpha zero-like heterozygous' thalassaemia phenotype. The risk of a severe HbH disease, could have been easily missed in this family which was referred because of a child affected with beta-thalassaemia major.

  11. Red cell deformability, splenic function and anaemia in thalassaemia

    NARCIS (Netherlands)

    Dondorp, A. M.; Chotivanich, K. T.; Fucharoen, S.; Silamut, K.; Vreeken, J.; Kager, P. A.; White, N. J.

    1999-01-01

    Red cell deformability (RCD) was measured in 38 patients with alpha-thalassaemia and 48 patients with beta-thalassaemia, of whom 13 had undergone splenectomy. All splenectomized patients, but none of those with intact spleens, had very rigid erythrocytes with an elongation index <0.45 at a high

  12. α-Thalassaemia in Tunisia: some epidemiological and molecular data

    Indian Academy of Sciences (India)

    The aim of the present work is to acquire further data concerning -thalassaemia prevalence and molecular defects spectrum in Tunisia, by collecting and studying several kinds of samples carrying -thalassaemia. The first survey conducted on 529 cord blood samples using cellulose acetate electrophoresis, have ...

  13. Prevalence and spectrum of thalassaemia in Changsha, Hunan ...

    Indian Academy of Sciences (India)

    JUN HE

    2017-06-17

    Jun 17, 2017 ... disorder worldwide (Joly et al. 2014; Sabath et al. 2015). Thalassaemia has two main ... fetalis syndrome is characterized by severe intrauterine anaemia, and is lethal in utero or soon after birth, due ... of thalassaemia and the molecular characteristics of the inhabitants of Changsha to provide an innovative ...

  14. The role of OMICS research in understanding phenotype variation in thalassaemia: the THALAMOSS project

    Directory of Open Access Journals (Sweden)

    Roberto Gambari

    2014-12-01

    Full Text Available The β-thalassaemias are a group of severe and rare anaemias with monogenic inheritance, a complex systemic phenotype and several treatment-related complications, caused by more than 300 mutations of the β-globin gene. Novel therapeutic protocols, most of which are based on still experimental treatments, show great promise but significant variability of success between patients. These strategies include chemical/ molecular induction of the endogenous β-like g-globin gene or the restoration of clinically relevant β-globin levels by gene therapy. A small number of modifiers with significant impact on disease penetrance, severity and efficacy of treatments are known, but most remain elusive. Improvements of existing treatment regimens and optimization and application of novel treatments will critically depend on the characterization of additional disease modifiers and the stratification of patients for customized treatment regimens. This requires extensive analyses based on “OMICS”, an English-language neologism which refer to different but connected fields in molecular biology and biochemistry, such as genomics, transcriptomics, exomics, proteomics, metabolomics. The major objective of OMICS is a collective characterization of pools of biological molecules (gene sequences, transcripts, proteins and protein domains controlling biological structures, functions and dynamics, including several involved in pathological conditions. One of the most interesting observations of genomics in β-thalassaemias is the association between genomic sequences and high fetal haemoglobin (HbF levels, in consideration of the fact that high HbF levels are usually associated with milder forms of β-thalassaemia. Related to this issue, is the possibility to predict response to different therapeutic protocols on the basis of genomic analyses. For instance, three major loci (Xmn1-HBG2 single nucleotide polymorphism, HBS1L-MYB intergenic region on chromosome 6q, and

  15. Molecular Characterization of α- and β-Thalassaemia among Malay Patients

    Directory of Open Access Journals (Sweden)

    Nur Fatihah Mohd Yatim

    2014-05-01

    Full Text Available Both α- and β-thalassaemia syndromes are public health problems in the multi-ethnic population of Malaysia. To molecularly characterise the α- and β-thalassaemia deletions and mutations among Malays from Penang, Gap-PCR and multiplexed amplification refractory mutation systems were used to study 13 α-thalassaemia determinants and 20 β-thalassaemia mutations in 28 and 40 unrelated Malays, respectively. Four α-thalassaemia deletions and mutations were demonstrated. −−SEA deletion and αCSα accounted for more than 70% of the α-thalassaemia alleles. Out of the 20 β-thalassaemia alleles studied, nine different β-thalassaemia mutations were identified of which βE accounted for more than 40%. We concluded that the highest prevalence of (α- and β-thalassaemia alleles in the Malays from Penang are −−SEA deletion and βE mutation, respectively.

  16. Overview of chelation recommendations for thalassaemia and sickle cell disease

    Directory of Open Access Journals (Sweden)

    Banu Kaya

    2014-12-01

    Full Text Available The long term consequences of iron toxicity are mostly reversible with effective iron chelation therapy. Recommendations for use of chelation therapy in transfusion dependent thalassaemia (TDT, sickle cell disease (SCD and non transfusion dependent thalassaemia (NTDT continue to evolve as our knowledge and clinical experience increases. Improved chelation options including drug combinations and a better understanding of condition specific factors may help to improve efficiency of chelation regimens and meet the needs of patients more effectively.

  17. [Heterocygous beta thalassaemia (author's transl)].

    Science.gov (United States)

    Méndez Aparicio, F

    1978-01-01

    Two girls with an heterocigotic beta-thalassemy are presented in this study. Case 1 has an hypochromic and microtic anaemia with an enormous splenomegaly, increased osmotic resistence of red blood cells in salted solution and increase of A2 hemoglobin. This situation is associated with an increase of the glucolitic intraerythrocitic enzimes. Case 2 showed increase of A2 hemoglobine, but this anomaly was associated with decrease of intraerythrocitic enzimatic rate. First clinical signs of erythrocitic disturbances was an acute hemolytic crisis developed by the supply of the sulphometoxipiridacine. The erythroquinetic study showed a decrease of the average life of the red blood cells in both patients.

  18. Treatment for osteoporosis in people with ß-thalassaemia.

    Science.gov (United States)

    Bhardwaj, Amit; Swe, Kye Mon Min; Sinha, Nirmal K; Osunkwo, Ifeyinwa

    2016-03-10

    difference 0.34 g/cm(2) (95% confidence interval 0.28 to 0.40). The same was true for bone mineral density at the hip after 12 months, mean difference 0.15 g/cm(2) (95% confidence interval 0.11 to 0.19) and after 18 months, mean difference 0.26 g/cm(2) (95% confidence interval 0.21 to 0.31).Fractures were not observed in one trial and not reported in three trials. There were no major adverse effects reported in two of the bisphosphonate trials; in the neridronate trial there was a reduction noted in the use of analgesic drugs and in the reported back pain score in favour of bisphosphonate treatment. Adverse effects were not reported in the trial of different doses of pamidronate or the zinc supplementation trial. There is evidence to indicate an increase in bone mineral density at the femoral neck, lumbar spine and forearm after administration of bisphosphonates and at the lumbar spine and hip after zinc sulphate supplementation. The authors recommend that further long-term randomised control trials on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia and osteoporosis are undertaken.

  19. Glucocorticoid resistance as a major drive in sepsis pathology.

    Science.gov (United States)

    Dendoncker, Karen; Libert, Claude

    2017-06-01

    Sepsis is an acute systemic inflammatory disease. Glucocorticoids (GCs), which function by binding to the GC receptor GR have very powerful anti-inflammatory activities, yet they are hardly useful in sepsis. We can thus consider sepsis as a GC resistant disease. We here review the literature which has investigated this GC resistance, and summarize the mechanisms of GC resistance that have been observed in other diseases and in experimental models. We also discuss the importance of GC resistance in sepsis, in terms of the contribution of this phenomenon to the pathogenesis of sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. [Can anemia be corrected in hemodialysis patients with thalassaemia minor? ].

    Science.gov (United States)

    Di Iorio, B; Guastaferro, P; Gironda, A; Marano, V; Morrongiello, L; Cillo, N; Zito, B; Nigro, F; Frieri, A; Rubino, R; Bellizzi, V

    2002-01-01

    Anemia is an important negative prognostic factor for dialysis patients, whose correction reduces hospitalisation and mortality. Besides, the presence of the thalassaemia minor (Thal-m) in haemodialysed patients causes erythropoietin resistance and more serious anemia. The goal of this study is the correction of anemia (Hb >11 g/dL) in haemodialysed Thal-m patients. Multicentric, prospective and controlled 12-month study for the correction of anemia (up to values ranging from 11 to 12 g/dL) followed by a 12-month observation period. Ten Thal-m patients with inadequate anemia correction were studied after therapy with rHuEPO. Their age at the beginning of the study was 62.8+/-4 years while their dialytic age was 89+/-20 months. During the study we observed no changes in dry weight (p=NS), no increase in interdialytic weight (p=NS), cardiac frequency (p=NS), serum albumin (p=NS), serum aluminium (p=NS), PTH (p=NS), URR (p=NS), flow FAV (p=NS), TSAT (p=NS) and ferritin (p=NS) (maintained at their optimal values by means of intravenous therapy with trivalent iron. The hypotensive therapy (1.6 drug/patient/year) required no modifications during the 24-month study. The rHuEPO dose varied from 200.3+/-94.3 to 286.6+/-116.2, 317.0+/-119.5, 446.9+/-142.3, and 407.0+/-130.5 U/kg/wk (p gradually); moreover, other factors responsible for EPO-resistance must be eliminated (hyperthyroidism, aluminium intoxication, iron overloaded or deficiency).

  1. Attitudes towards prenatal diagnosis and termination of pregnancy for thalassaemia in pregnant Pakistani women in the North of England.

    Science.gov (United States)

    Ahmed, Shenaz; Green, Josephine M; Hewison, Jenny

    2006-03-01

    Most births of children affected with beta-thalassaemia major in the United Kingdom are to parents of Pakistani origin. A popular explanation for this is that Pakistanis decline termination of pregnancy on religious grounds. However, various factors influence people's attitudes towards prenatal diagnosis and termination of pregnancy, which have not been investigated in a UK Pakistani sample. This study is aimed at exploring the attitudes of pregnant Pakistani women towards prenatal diagnosis and termination of pregnancy for beta-thalassaemia major in the North of England. Forty-three pregnant women tested for thalassaemia carrier status were interviewed following receipt of their test results. Interviews were analysed using the grounded theory approach. Findings showed: (1) women's awareness of and attitudes towards prenatal diagnosis; (2) the relationship between attitudes towards prenatal diagnosis and termination of an affected foetus; (3) the relationship between attitudes towards termination of pregnancy and religious beliefs, perceptions of severity of the condition, influence of significant others, and (4) the impact of gestational age at the time of the offer of termination of pregnancy. Pakistani women's attitudes towards prenatal diagnosis and termination of pregnancy are influenced by various factors, and therefore their religion should not be taken as a proxy for their attitudes either for or against termination of pregnancy. 2006 John Wiley & Sons, Ltd.

  2. Health related quality of life in Malaysian children with thalassaemia

    Directory of Open Access Journals (Sweden)

    Jones Georgina L

    2006-07-01

    Full Text Available Abstract Background Health Related Quality of Life (HRQoL studies on children with chronic illness such as thalassaemia are limited. We conducted the first study to investigate if children with thalassaemia have a lower quality of life in the four dimensions as measured using the PedsQL 4.0 generic Scale Score: physical, emotional, social and role (school functioning compared to the healthy controls allowing for age, gender, ethnicity and household income. Methods The PedsQL 4.0 was administered to children receiving blood transfusions and treatments at Hospital Kuala Lumpur, Malaysia using PedsQL 4.0 generic Scale Score. Accordingly, the questionnaire was also administered to a control group of healthy school children. Socio-demographic data were also collected from patients and controls using an interview schedule designed for the study. Results Of the 96 thalassaemia patients approached, 78 gave consent to be interviewed giving a response rate of 81.3%. Out of 235 healthy controls approached, all agreed to participate giving a response rate of 100%. The mean age for the patients and schoolchildren is 11.9 and 13.2 years respectively. The age range for the patients and the schoolchildren is between 5 to 18 years and 7 to 18 years respectively. After controlling for age and demographic background, the thalassaemia patients reported having significantly lower quality of life than the healthy controls. Conclusion Thalassaemia has a negative impact on perceived physical, emotional, social and school functioning in thalassaemia patients which was also found to be worse than the children's healthy counterparts. Continuing support of free desferal from the Ministry of Health should be given to these patients. More understanding and support especially from health authorities, school authorities and the society is essential to enhance their quality of life.

  3. Health Related Quality of Life in Malaysian children with thalassaemia.

    Science.gov (United States)

    Ismail, Adriana; Campbell, Michael J; Ibrahim, Hishamshah Mohd; Jones, Georgina L

    2006-07-02

    Health Related Quality of Life (HRQoL) studies on children with chronic illness such as thalassaemia are limited. We conducted the first study to investigate if children with thalassaemia have a lower quality of life in the four dimensions as measured using the PedsQL 4.0 generic Scale Score: physical, emotional, social and role (school) functioning compared to the healthy controls allowing for age, gender, ethnicity and household income. The PedsQL 4.0 was administered to children receiving blood transfusions and treatments at Hospital Kuala Lumpur, Malaysia using PedsQL 4.0 generic Scale Score. Accordingly, the questionnaire was also administered to a control group of healthy school children. Socio-demographic data were also collected from patients and controls using an interview schedule designed for the study. Of the 96 thalassaemia patients approached, 78 gave consent to be interviewed giving a response rate of 81.3%. Out of 235 healthy controls approached, all agreed to participate giving a response rate of 100%. The mean age for the patients and schoolchildren is 11.9 and 13.2 years respectively. The age range for the patients and the schoolchildren is between 5 to 18 years and 7 to 18 years respectively. After controlling for age and demographic background, the thalassaemia patients reported having significantly lower quality of life than the healthy controls. Thalassaemia has a negative impact on perceived physical, emotional, social and school functioning in thalassaemia patients which was also found to be worse than the children's healthy counterparts. Continuing support of free desferal from the Ministry of Health should be given to these patients. More understanding and support especially from health authorities, school authorities and the society is essential to enhance their quality of life.

  4. Treatment-resistant major depressive disorder and assisted dying

    NARCIS (Netherlands)

    Schuklenk, Udo; van de Vathorst, Suzanne

    2015-01-01

    Competent patients suffering from treatment-resistant depressive disorder should be treated no different in the context of assisted dying to other patients suffering from chronic conditions that render their lives permanently not worth living to them. Jurisdictions that are considering, or that

  5. Hydroxyurea for reducing blood transfusion in non-transfusion dependent beta thalassaemias.

    Science.gov (United States)

    Foong, Wai Cheng; Ho, Jacqueline J; Loh, C Khai; Viprakasit, Vip

    2016-10-18

    Non-transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non-transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.Date of last search: 30 April 2016. Randomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included

  6. Anaesthesia for a patient with beta thalassaemia major

    African Journals Online (AJOL)

    aberration attributable to iron overload. Prior to December 2013, he had no symptoms of liver dysfunction. A MRI done in. December 2013 showed a normal heart, but moderate iron deposition in the liver. He had only one known adverse reaction to blood transfusion, and had no history of blood-borne infections and nothing ...

  7. Internal distribution of excess iron and sources of serum ferritin in patients with thalassaemia

    International Nuclear Information System (INIS)

    Cazzola, M.; Bergamaschi, G.; Dezza, L.; Borgna-Pignatti, C.C.; De Stefano, P.; Bongo, I.G.; Avato, F.

    1983-01-01

    Liver and spleen iron concentrations, serum ferritin level and binding of S-ferritin to concanavalin A (Con A) were measured in 12 patients with thalassaemia major or intermedia at the time of splenectomy. All these subjects had increased liver iron concentration, most of them had hepatic fibrosis but none of them had histological evidence of chronic hepatitis. No patient had ascorbic acid deficiency. Serum ferritin concentration was increased in all cases, ranging from 266 to 5504 μg/l. In all but 2 subjects most of the protein did not bind to Con A, thus behaving as tissue ferritin. There were highly significant correlations between serum ferritin concentration, amount of blood transfused and liver iron concentration. On the avarage, iron concentration in the liver was about 3 times that in the spleen. The findings obtained suggest that in patients with thalassaemia major or intermedia most of the iron is deposited in parenchymal tissues and most of the S-ferritin derives by leakage from the cytosol of iron-loaded parenchymal cells. S-ferritin is a valid index of liver iron overload in thalassaemic patients witout complications such as viral hepatitis and/or ascorbic acid defiency. (author)

  8. Characterisation and confirmation of rare beta-thalassaemia mutations in the Malay, Chinese and Indian ethnic groups in Malaysia.

    Science.gov (United States)

    Tan, Jin Ai Mary Anne; Chin, Pui See; Wong, Yean Ching; Tan, Kim Lian; Chan, Lee Lee; George, Elizabeth

    2006-10-01

    In Malaysia, about 4.5% of the Malay and Chinese populations are heterozygous carriers of beta-thalassaemia. The initial identification of rare beta-globin gene mutations by genomic sequencing will allow the development of simpler and cost-effective PCR-based techniques to complement the existing amplification refractory mutation system (ARMS) and gap-PCR used for the identification of beta-thalassaemia mutations. DNA from 173 beta-thalassaemia carriers and five beta-thalassaemia major patients from the Malay, Chinese and Indian ethnic groups were first analysed by ARMS and gap-PCR. Ninety-five per cent (174/183) of the 183 beta-globin genes studied were characterised using these two techiques. The remaining nine uncharacterised beta-globin genes (4.9%) were analysed using genomic sequencing of a 904 bp amplified PCR product consisting of the promoter region, exon 1, intervening sequence (IVS) 1, exon 2 and the 5' IVS2 regions of the beta-globin gene. The rare beta-globin mutations detected in the Chinese patients were CD27/28 (+C) and CD43 (GAG-TAG), and -88 (C-T) in an Indian patient. Beta-globin mutations at CD16 (-C), IVS1-1 (G-A), IVS2-1 (G-A), -86 (C-G) and Haemoglobin South Florida (CD1, GTG-ATG) were confirmed in the Malay patients. The seven rare beta-globin mutations and a rare haemoglobin variant confirmed in this study have been described in other populations but have not been previously described in Malaysian beta-thalassemia patients.

  9. Hydroxyurea responses in clinically varied beta, HbE-beta thalassaemia and sickle cell anaemia patients of Eastern India.

    Science.gov (United States)

    Chatterjee, Tridip; Chakravarty, Amit; Chakravarty, Sudipa

    2018-02-17

    The haematological and clinical response to hydroxyurea was estimated in HbE-beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with variable clinical severity and transfusion requirement to determine whether hydroxyurea can help these patients to maintain their steady haemoglobin level without blood transfusions. Three hundred patients (189 HbE-beta thalassaemia, 95 beta thalassaemia and 16 other haemoglobinopathies including sickle cell anaemia) were selected for hydroxyurea therapy and were followed up for 48-60 months. Results suggest significant response to hydroxyurea therapy in 19 beta and 99 HbE-beta patients in the transfusion-dependent group (GR-I). All of them became transfusion-independent while on hydroxyurea therapy. The majority of responding patients were IVS1-5(G-C) in one of their alleles in HbE-beta cases (83 out of 119). Though IVS1-5(G-C) was found to be the commonest mutation in our selected patients, the mutational background of the patients does not found to have any significant correlation with the response category towards hydroxyurea as per the results observed in our study. But, the drug works pretty well in most of the transfusion-dependent patients, as these patients were withdrawn from regular blood transfusion. At the same time, partial or no response to the drug hydroxyurea was also recorded in our study.

  10. Consistent effects of a major QTL for thermal resistance in field-released Drosophila melanogaster

    DEFF Research Database (Denmark)

    Loeschcke, Volker; Kristensen, Torsten Nygård; Norry, Fabian M

    2011-01-01

    Molecular genetic markers can be used to identify quantitative trait loci (QTL) for thermal resistance and this has allowed characterization of a major QTL for knockdown resistance to high temperature in Drosophila melanogaster. The QTL showed trade-off associations with cold resistance under lab...

  11. α-Thalassaemia in Tunisia: some epidemiological and molecular data

    Indian Academy of Sciences (India)

    1981 Hemoglobin Bart's in Northern Algeria. Acta Haematol. 65, 240–246. Higgs D. R. 1993 α-thalassaemia. Baillere's Clin. Haematol. 6,. 117–150. Huisman T. H. J., Carver M. F. H. and Efremov G. D. 1996 A syl- labus of human hemoglobin variants. pp. 420 The sickle cell ane- mia foundation, Augusta. Kanavakis E.

  12. Prevalence and spectrum of thalassaemia in Changsha, Hunan ...

    Indian Academy of Sciences (India)

    2017-06-17

    Jun 17, 2017 ... Home; Journals; Journal of Genetics; Volume 96; Issue 2. Prevalence and spectrum of thalassaemia in Changsha, Hunan province, China: discussion of an innovative screening strategy. JUN HE HOULIN ZENG LIN ZHU HANMEI LI LIANGCHENG SHI LANPING HU. RESEARCH ARTICLE Volume 96 Issue ...

  13. Beta thalassaemia traits in Nigerian patients with sickle cell anaemia ...

    African Journals Online (AJOL)

    These three patients (1.2%) were found to have positive co-inheritance of thalassaemia trait and sickle cell anaemia. The erythrocyte indices were all reduced in these selected families except for one family whose mean cell haemoglobin concentration was within normal range. Peripheral blood film revealed the presence of ...

  14. Compound heterozygous sickle cell disease and β0- thalassaemia ...

    African Journals Online (AJOL)

    Haemoglobinopathies are a group of inherited disorders caused by structural variations of the haemoglobin molecule. We report the case of a 5-year-old girl suffering from chronic haemolytic anaemia. A diagnosis of compound heterozygous sickle cell disease (SCD) and β0-thalassaemia was established using ...

  15. Complementary and alternative medicine use in children with thalassaemia.

    Science.gov (United States)

    Efe, Emine; Işler, Ayşegül; Sarvan, Süreyya; Başer, Hayriye; Yeşilipek, Akif

    2013-03-01

    The aims of this study were to: (1) determine the types of complementary and alternative medicine use among children with thalassaemia as reported by parents and (2) describe sociodemographic and medical factors associated with the use of such treatments in families residing in southern Turkey. Thalassaemia is one of the most common human genetic diseases. Despite the therapeutic efforts, patients will encounter a variety of physical and psychological problems. Therefore, the use of complementary and alternative medicines among children thalassaemia is becoming increasingly popular. This is a descriptive study of complementary and alternative medicine. This study was conducted in the Hematology Outpatient Clinic at Akdeniz University Hospital and in the Thalassemia Centre at Ministry of Health Antalya Education and Research Hospital, Antalya, Turkey, between January 2010-December 2010. Parents of 97 paediatric patients, among 125 parents who applied to the haematology outpatient clinic and thalassaemia centre between these dates, agreed to take part in the study with whom contact could be made were included. Data were collected by using a questionnaire. The proportion of parents who reported using one or more of the complementary and alternative medicine methods was 82·5%. Of these parents, 61·8% were using prayer/spiritual practice, 47·4% were using nutritional supplements and 35·1% were using animal materials. It was determined that a significant portion of the parents using complementary and alternative medicine use it to treat their children's health problems, they were informed about complementary and alternative medicine by their paediatricians and family elders, and they have discussed the use of complementary and alternative medicine with healthcare professionals. To sustain medical treatment and prognosis of thalassaemia, it is important for nurses to consult with their patients and parents regarding the use and potential risks of some complementary

  16. CARDIAC FUNCTION AND IRON CHELATION IN THALASSEMIA MAJOR AND INTERMEDIA: A REVIEW OF THE UNDERLYING PATHOPHYSIOLOGY AND APPROACH TO CHELATION MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Athanasios Aessopos

    2009-07-01

    Full Text Available Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia.  The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload.  The high output state playing a major role in thalassaemia intermedia and the iron load being more significant in the major form. Arrhythmias, vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness and valvular abnormalities also contribute to the cardiac dysfunction in varying degrees according to the severity of the phenotype.  Endocrine abnormalities, infections, renal function and medications can also play a role in the overall cardiac function.  For thalassaemia major, regular and adequate blood transfusions and iron chelation therapy are the mainstays of management. The approach to thalassaemia intermedia, today, is aimed at monitoring for complications and initiating, timely, regular transfusions and/or iron chelation therapy.  Once the patients are on transfusions, then they should be managed in the same way as the thalassaemia major patients.  If cardiac manifestations of dysfunction are present in either form of thalassaemia, high pre transfusion Hb levels need to be maintained in order to reduce cardiac output and appropriate intensive chelation therapy needs to be instituted.  In general recommendations on chelation, today, are usually made according to the Cardiac Magnetic Resonance findings, if available.  With the advances in the latter technology and the ability to tailor chelation therapy according to the MRI findings as well as the availability of three iron chelators, together with

  17. Plasmodium falciparum Resistance to Artemisinin Derivatives and Piperaquine: A Major Challenge for Malaria Elimination in Cambodia

    Science.gov (United States)

    Duru, Valentine; Witkowski, Benoit; Ménard, Didier

    2016-01-01

    Artemisinin-based combination therapies (ACTs) are the cornerstone of current strategies for fighting malaria. Over the last decade, ACTs have played a major role in decreasing malaria burden. However, this progress is being jeopardized by the emergence of artemisinin-resistant Plasmodium falciparum parasites. Artemisinin resistance was first detected in western Cambodia in 2008 and has since been observed in neighboring countries in southeast Asia. The problem of antimalarial drug resistance has recently worsened in Cambodia, with reports of parasites resistant to piperaquine, the latest generation of partner drug used in combination with dihydroartemisinin, leading to worrying rates of clinical treatment failure. The monitoring and the comprehension of both types of resistance are crucial to prevent the spread of multidrug-resistant parasites outside southeast Asia, and particularly to Africa, where the public health consequences would be catastrophic. To this end, new tools are required for studying the biological and molecular mechanisms underlying resistance to antimalarial drugs and for monitoring the geographic distribution of the resistant parasites. In this review, we detail the major advances in our understanding of resistance to artemisinin and piperaquine and define the challenges that the malaria community will have to face in the coming years. PMID:27928074

  18. Expression of CD55, CD59, and CD35 on red blood cells of β-thalassaemia patients

    Science.gov (United States)

    Koçtekin, Belkls; Kurtoǧlu, Erdal; Yildiz, Mustafa; Bozkurt, Selen

    2017-01-01

    Aim of the study β-thalassaemia (β-Thal) is considered a severe, progressive haemolytic anaemia, which needs regular blood transfusions for life expectancy. Complement-mediated erythrocyte destruction can cause both intravascular and extravascular haemolysis. Complement regulatory proteins protect cells from such effects of the complement system. We aimed to perform quantitative analysis of membrane-bound complement regulators, CD55 (decay accelerating factor – DAF), CD35 (complement receptor type 1 – CR1), and CD59 (membrane attack complex inhibitory factor – MACIF) on peripheral red blood cells by flow cytometry. Material and methods The present study was carried out on 47 β-thalassemia major (β-TM) patients, 20 β-thalassaemia intermedia (β-TI) patients, and 17 healthy volunteers as control subjects. Results CD55 levels of β-TM patients (58.64 ±17.06%) were significantly decreased compared to β-TI patients (83.34 ±13.82%) and healthy controls (88.57 ±11.69%) (p < 0.01). CD59 levels of β-TM patients were not significantly different than β-TI patients and controls, but CD35 levels were significantly lower in the β-TM patients (3.56 ±4.87%) and β-TI patients (12.48 ±9.19%) than in the control group (39.98 ±15.01%) (p < 0.01). Conclusions Low levels of CD55 and CD35 in thalassaemia major patients indicates a role for them in the aetiopathogenesis of haemolysis in this disease, and also this defect in a complement system may be responsible for the chronic complications seen in these patients. PMID:28680334

  19. Genetic mapping of a major dominant gene for resistance to Ralstonia solanacearum in eggplant.

    Science.gov (United States)

    Lebeau, A; Gouy, M; Daunay, M C; Wicker, E; Chiroleu, F; Prior, P; Frary, A; Dintinger, J

    2013-01-01

    Resistance of eggplant against Ralstonia solanacearum phylotype I strains was assessed in a F(6) population of recombinant inbred lines (RILs) derived from a intra-specific cross between S. melongena MM738 (susceptible) and AG91-25 (resistant). Resistance traits were determined as disease score, percentage of wilted plants, and stem-based bacterial colonization index, as assessed in greenhouse experiments conducted in Réunion Island, France. The AG91-25 resistance was highly efficient toward strains CMR134, PSS366 and GMI1000, but only partial toward the highly virulent strain PSS4. The partial resistance found against PSS4 was overcome under high inoculation pressure, with heritability estimates from 0.28 to 0.53, depending on the traits and season. A genetic map was built with 119 AFLP, SSR and SRAP markers positioned on 18 linkage groups (LG), for a total length of 884 cM, and used for quantitative trait loci (QTL) analysis. A major dominant gene, named ERs1, controlled the resistance to strains CMR134, PSS366, and GMI1000. Against strain PSS4, this gene was not detected, but a significant QTL involved in delay of disease progress was detected on another LG. The possible use of the major resistance gene ERs1 in marker-assisted selection and the prospects offered for academic studies of a possible gene for gene system controlling resistance to bacterial wilt in solanaceous plants are discussed.

  20. Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various Multi-Drug Resistant Bacteria

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    Miklos Fuzi

    2017-11-01

    Full Text Available The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA, extended-spectrum β-lactamase (ESBL-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE, emerged by a similar mechanism. The reason(s why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated.

  1. Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various Multi-Drug Resistant Bacteria

    Science.gov (United States)

    Fuzi, Miklos; Szabo, Dora; Csercsik, Rita

    2017-01-01

    The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE), emerged by a similar mechanism. The reason(s) why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated. PMID:29250038

  2. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

    Directory of Open Access Journals (Sweden)

    Catherine L Moyes

    2017-07-01

    Full Text Available Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus, making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids. Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

  3. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

    Science.gov (United States)

    Moyes, Catherine L; Vontas, John; Martins, Ademir J; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

    2017-07-01

    Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

  4. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

    Science.gov (United States)

    Vontas, John; Martins, Ademir J.; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

    2017-01-01

    Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance. PMID:28727779

  5. Deferasirox effect on renal haemodynamic parameters in patients with transfusion-dependent β thalassaemia.

    Science.gov (United States)

    Piga, Antonio; Fracchia, Silvia; Lai, Maria E; Cappellini, Maria Domenica; Hirschberg, Raimund; Habr, Dany; Wegener, Antje; Bouillaud, Emmanuel; Forni, Gian Luca

    2015-03-01

    Some patients with β thalassaemia experience non-progressive creatinine increases with deferasirox, mostly within normal limits; the mechanisms involved are not fully elucidated. The effects of deferasirox on renal haemodynamics, including glomerular filtration rate (GFR) and renal plasma flow (RPF), were investigated in a Phase I, open-label study in β thalassaemia major patients with iron overload. Patients received deferasirox 30 mg/kg/d up to Week 8, followed by a 2-week washout period, and extended treatment up to Week 104 with a 4-week washout period. In the short-term study (n = 11), mean GFR and RPF declined from baseline to Week 8 (mean [%] change:-9·2 [-9·5%] and -105·7 ml/min [-17·8%], respectively). A similar pattern was observed during the long-term study (n = 5); mean GFR and RPF decreased up to Week 52 (-19·1 [-17·7%] and -155·6 ml/min [-26·1%]), with similar change at Week 104 (-18·4 [-17·2%] and -115·9 ml/min [-19·6%]). Measures returned to baseline values after each washout. Serum creatinine and creatinine clearance followed a similar pattern. Effects of deferasirox on renal haemodynamics were mild and reversible for up to 2 years of treatment, with no progressive worsening of renal function over time. www.clinicaltrials.gov: NCT00560820. © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  6. Haematological and genetic features of delta beta-thalassaemia in Pakistan

    International Nuclear Information System (INIS)

    Ahmad, S.; Anwar, M.

    2006-01-01

    Objective: To describe the hematological and genetic features of delta beta-thalassaemia in Pakistani patients. Design: Descriptive case series. Place and Duration of Study: Department of Pathology, PNS Shifa, Karachi and Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi, from January 1994 to April 2004. Patients and Methods: Thirteen individuals from six unrelated Pakistani families with a hematological diagnosis of delta beta-thalassaemia were studied. A brief clinical history, and the results of blood counts, absolute values, Hb-F, Hb-A/sub 2/, and hemoglobin electrophoresis were recorded. The DNA from each subject was first screened for the delta beta-thalassaemia mutations found in the Pakistani population. The samples were then screened for the Invl Del sup G/gamma(sup A/gamma delta beta). Results: The subjects included six heterozygote, six homozygotes and one compound heterozygote of delta beta and delta beta-thalassaemia. All heterozygote and 4/6 homozygotes were asymptomatic. One homo zygote had thalassaemia intermedia while another had transfusion dependent anemia. The mean Hb, TRBC, MCV, MCH, Hb-F and Hb-A/sub 2/ in delta beta-thalassaemia heterozygote were 11.6 g/dl, 5.37 x 1012/L, 70.9 fl, and 21.7 pg, 14% and 2.6% respectively. The same values in the four un transfused homo zygote were 10.6 g/dl, 5.34x1012/L, 69.211, and 20.8pg, 100% and 0% respectively. The mutation analysis revealed that all 13 individuals had the same Invl Del sup G/gamma(sup A/gamma delta beta). Conclusion: delta beta-thalassaemia is a rare disorder in Pakistan. Although the clinical picture is very mild its combination with delta beta-thalassaemia trait can produce a sever transfusion dependent thalassaemia. The DNA based diagnosis is possible in the prenatal as well as the postnatal period. (author)

  7. Relative protection from ischaemic heart disease in beta-thalassaemia carriers

    International Nuclear Information System (INIS)

    Bozdar, M.; Ahmed, S.; Anwar, J.

    2010-01-01

    To compare the frequency of beta thalassaemia trait in individuals with Ischaemic Heart Disease (IHD) and a control population without IHD. Study Design: Case control study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from September 2007 to May 2009. Methodology: Using non-probability consecutive sampling, a total of 544 subjects were selected, including 272 IHD patients and an equal number of age and gender matched normal controls. The subjects were tested for the presence of b-thalassaemia trait by performing their blood counts, haemoglobin electrophoresis and Haemoglobin A2 (HbA2) estimation. Proportions were compared using chi-square test. Odds ratio was also calculated. Results: The frequency of b-thalassaemia trait was determined in IHD patients and was compared to the frequency in normal Pakistani population. Six out of the 272 control subjects (2.2%) had b-thalassaemia trait and one of the control subject had Haemoglobin D trait. In contrast, none of the 272 IHD patients had b-thalassaemia trait. The calculated odds ratio was less than 1, which shows a significant negative association of b-thalassaemia trait with IHD. The difference in the frequency of b-thalassaemia trait in the two groups was statistically significant (p=0.033). Conclusion: The results suggest that b-thalassaemia carriers have some protection against IHD, though it is not an absolute cardio protection due to the role of other risk factors in IHD. This beneficial information may be communicated to the concerned individuals in their counselling sessions and as part of general awareness on thalassaemia. (author)

  8. Major Gene for Field Stem Rust Resistance Co-Locates with Resistance Gene Sr12 in 'Thatcher' Wheat.

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    Colin W Hiebert

    Full Text Available Stem rust, caused by Puccinia graminis (Pgt, is a damaging disease of wheat that can be controlled by utilizing effective stem rust resistance genes. 'Thatcher' wheat carries complex resistance to stem rust that is enhanced in the presence of the resistance gene Lr34. The purpose of this study was to examine APR in 'Thatcher' and look for genetic interactions with Lr34. A RIL population was tested for stem rust resistance in field nurseries in Canada, USA, and Kenya. BSA was used to find SNP markers associated with reduced stem rust severity. A major QTL was identified on chromosome 3BL near the centromere in all environments. Seedling testing showed that Sr12 mapped to the same region as the QTL for APR. The SNP markers were physically mapped and the region carrying the resistance was searched for sequences with homology to members of the NB-LRR resistance gene family. SNP marker from one NB-LRR-like sequence, NB-LRR3 co-segregated with Sr12. Two additional populations, including one that lacked Lr34, were tested in field nurseries. NB-LRR3 mapped near the maximum LOD for reduction in stem rust severity in both populations. Lines from a population that segregated for Sr12 and Lr34 were tested for seedling Pgt biomass and infection type, as well as APR to field stem rust which showed an interaction between the genes. We concluded that Sr12, or a gene closely linked to Sr12, was responsible for 'Thatcher'-derived APR in several environments and this resistance was enhanced in the presence of Lr34.

  9. Major Gene for Field Stem Rust Resistance Co-Locates with Resistance Gene Sr12 in 'Thatcher' Wheat.

    Science.gov (United States)

    Hiebert, Colin W; Kolmer, James A; McCartney, Curt A; Briggs, Jordan; Fetch, Tom; Bariana, Harbans; Choulet, Frederic; Rouse, Matthew N; Spielmeyer, Wolfgang

    2016-01-01

    Stem rust, caused by Puccinia graminis (Pgt), is a damaging disease of wheat that can be controlled by utilizing effective stem rust resistance genes. 'Thatcher' wheat carries complex resistance to stem rust that is enhanced in the presence of the resistance gene Lr34. The purpose of this study was to examine APR in 'Thatcher' and look for genetic interactions with Lr34. A RIL population was tested for stem rust resistance in field nurseries in Canada, USA, and Kenya. BSA was used to find SNP markers associated with reduced stem rust severity. A major QTL was identified on chromosome 3BL near the centromere in all environments. Seedling testing showed that Sr12 mapped to the same region as the QTL for APR. The SNP markers were physically mapped and the region carrying the resistance was searched for sequences with homology to members of the NB-LRR resistance gene family. SNP marker from one NB-LRR-like sequence, NB-LRR3 co-segregated with Sr12. Two additional populations, including one that lacked Lr34, were tested in field nurseries. NB-LRR3 mapped near the maximum LOD for reduction in stem rust severity in both populations. Lines from a population that segregated for Sr12 and Lr34 were tested for seedling Pgt biomass and infection type, as well as APR to field stem rust which showed an interaction between the genes. We concluded that Sr12, or a gene closely linked to Sr12, was responsible for 'Thatcher'-derived APR in several environments and this resistance was enhanced in the presence of Lr34.

  10. Major Gene for Field Stem Rust Resistance Co-Locates with Resistance Gene Sr12 in ‘Thatcher’ Wheat

    Science.gov (United States)

    Hiebert, Colin W.; Kolmer, James A.; McCartney, Curt A.; Briggs, Jordan; Fetch, Tom; Bariana, Harbans; Choulet, Frederic; Rouse, Matthew N.; Spielmeyer, Wolfgang

    2016-01-01

    Stem rust, caused by Puccinia graminis (Pgt), is a damaging disease of wheat that can be controlled by utilizing effective stem rust resistance genes. ‘Thatcher’ wheat carries complex resistance to stem rust that is enhanced in the presence of the resistance gene Lr34. The purpose of this study was to examine APR in ‘Thatcher’ and look for genetic interactions with Lr34. A RIL population was tested for stem rust resistance in field nurseries in Canada, USA, and Kenya. BSA was used to find SNP markers associated with reduced stem rust severity. A major QTL was identified on chromosome 3BL near the centromere in all environments. Seedling testing showed that Sr12 mapped to the same region as the QTL for APR. The SNP markers were physically mapped and the region carrying the resistance was searched for sequences with homology to members of the NB-LRR resistance gene family. SNP marker from one NB-LRR-like sequence, NB-LRR3 co-segregated with Sr12. Two additional populations, including one that lacked Lr34, were tested in field nurseries. NB-LRR3 mapped near the maximum LOD for reduction in stem rust severity in both populations. Lines from a population that segregated for Sr12 and Lr34 were tested for seedling Pgt biomass and infection type, as well as APR to field stem rust which showed an interaction between the genes. We concluded that Sr12, or a gene closely linked to Sr12, was responsible for ‘Thatcher’-derived APR in several environments and this resistance was enhanced in the presence of Lr34. PMID:27309724

  11. Major histocompatibility complex variation and the evolution of resistance to amphibian chytridiomycosis.

    Science.gov (United States)

    Fu, Minjie; Waldman, Bruce

    2017-08-01

    Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), has been implicated in population declines and species extinctions of amphibians around the world. Susceptibility to the disease varies both within and among species, most likely attributable to heritable immunogenetic variation. Analyses of transcriptional expression in hosts following their infection by Bd reveal complex responses. Species resistant to Bd generally show evidence of stronger innate and adaptive immune system responses. Major histocompatibility complex (MHC) class I and class II genes of some susceptible species are up-regulated following host infection by Bd, but resistant species show no comparable changes in transcriptional expression. Bd-resistant species share similar pocket conformations within the MHC-II antigen-binding groove. Among susceptible species, survivors of epizootics bear alleles encoding these conformations. Individuals with homozygous resistance alleles appear to benefit by enhanced resistance, especially in environmental conditions that promote pathogen virulence. Subjects that are repeatedly infected and subsequently cleared of Bd can develop an acquired immune response to the pathogen. Strong directional selection for MHC alleles that encode resistance to Bd may deplete genetic variation necessary to respond to other pathogens. Resistance to chytridiomycosis incurs life-history costs that require further study.

  12. alpha-Thalassaemia and hyperbilirubinaemia in G-6-PD-deficient newborns.

    OpenAIRE

    Meloni, T; Corti, R; Costa, S; Mele, G; Franca, V

    1980-01-01

    53 newborn infants with both G-6-PD deficiency (29 male hemizygotes and 24 female heterozygotes) and alpha-thalassaemia, and 120 newborn infants with only the enzymatic defect (60 male hemizygotes and 60 female heterozygotes) were studied. 12 of those with both G-6-PD deficiency and alpha=thalassaemia, and 32 of those with only G-6-PD deficiency showed hyperbilirubinaemia. alpha-Thalassaemia does not seem to be implicated in the development of hyperbilirubinaemia in G-6-PD-deficient newborns.

  13. Major QTLs Control Resistance to Rice Hoja Blanca Virus and Its Vector Tagosodes orizicolus

    Science.gov (United States)

    Romero, Luz E.; Lozano, Ivan; Garavito, Andrea; Carabali, Silvio J.; Triana, Monica; Villareal, Natalia; Reyes, Luis; Duque, Myriam C.; Martinez, César P.; Calvert, Lee; Lorieux, Mathias

    2013-01-01

    Rice hoja blanca (white leaf) disease can cause severe yield losses in rice in the Americas. The disease is caused by the rice hoja blanca virus (RHBV), which is transmitted by the planthopper vector Tagosodes orizicolus. Because classical breeding schemes for this disease rely on expensive, time-consuming screenings, there is a need for alternatives such as marker-aided selection. The varieties Fedearroz 2000 and Fedearroz 50, which are resistant to RHBV and to the feeding damage caused by T. orizicolus, were crossed with the susceptible line WC366 to produce segregating F2:3 populations. The F3 families were scored for their resistance level to RHBV and T. orizicolus. The F2:3 lines of both crosses were genotyped using microsatellite markers. One major QTL on the short arm of chromosome 4 was identified for resistance to RHBV in the two populations. Two major QTL on chromosomes 5 and 7 were identified for resistance to T. orizicolus in the Fd2000 × WC366 and Fd50 × WC366 crosses, respectively. This comparative study using two distinct rice populations allowed for a better understanding of how the resistance to RHBV and its vector are controlled genetically. Simple marker-aided breeding schemes based on QTL information can be designed to improve rice germplasm to reduce losses caused by this important disease. PMID:24240781

  14. Paraquat resistance in a Lolium rigidum population is governed by one major nuclear gene.

    Science.gov (United States)

    Yu, Qin; Han, Heping; Nguyen, Linh; Forster, John W; Powles, Stephen B

    2009-05-01

    Paraquat resistance in an annual ryegrass (Lolium rigidum Gaud.) population (AFLR1) has been attributed to reduced paraquat translocation. Genetic inheritance of paraquat resistance in this population was investigated in the present study. The paraquat dose response of progeny from 8 F(1) families was more similar to that of the resistant than the susceptible parent, while the equivalent data for a further three families were intermediate compared to those of the parental populations. No significant differences in dose response were observed between reciprocal crosses of specific F(1) families. These results suggest that paraquat resistance in AFLR1 is inherited as a dominant or partially dominant nuclear-encoded trait. Pseudo-F(2) (psi-F(2)) generation seedlings were treated with multiple dose rates sufficient to control the susceptible parental population, and observed segregation ratios in all instances conformed to a 3:1 (resistant:susceptible) segregation ratio, and this ratio was further confirmed by individual phenotyping of cloned plant genotypes. A single major nuclear gene is hence apparently responsible for evolved paraquat resistance in AFLR1.

  15. Understanding Immune Resistance to Infectious Bronchitis Using Major Histocompatibility Complex Chicken Lines.

    Science.gov (United States)

    da Silva, A P; Hauck, R; Zhou, H; Gallardo, R A

    2017-09-01

    Genetic resistance or susceptibility to infectious diseases has been largely associated with the avian major histocompatibility complex (MHC) genes. Our goal was to determine resistance and susceptibility of MHC B haplotype in congenic and inbred chicken lines in order to establish a resistant-susceptible model. Eight congenic lines (253/B18, 254/B15, 330/B21, 312/B24, 331/B2, 335/B19, 336/B21, and 342/BO), two inbred lines (003/B17 and 077/B19), and three commercial lines (white leghorn, brown layers, and broilers) were used in two experiments. We analyzed and compared immunologic responses and the effect of challenge by measuring viral load, IgG and IgA humoral responses, histopathology and histomorphometry, clinical signs, and immune cell populations in the different MHC B haplotype lines. We found that respiratory signs, tracheal deciliation and inflammation, airsacculitis, viral shedding in tears, and local humoral responses were good parameters to determine resistance or susceptibility. Based on these results, we identified 331/B2 as the most resistant and 335/B19 as the most susceptible congenic chicken lines. These two lines will be used as an animal model in subsequent experiments to understand the mechanisms by which the immune system in chickens generates resistance to infectious bronchitis virus.

  16. IDENTIFICATION OF A MAJOR QUANTITATIVE TRAIT LOCUS CONFERRING RICE BLAST RESISTANCE USING RECOMBINANT INBRED LINES

    Directory of Open Access Journals (Sweden)

    Sobrizal Sobrizal

    2013-05-01

    Full Text Available Blast disease caused by Pyricularia oryzae is one of the limiting factors for rice production world wide. The use of resistant varieties for managing blast disease is considered as the most eco-friendly approaches. However, their resistances may be broken down within a few years due to the appearance of new virulent blast races in the field. The objective of the present study was to identify the quantitative trait locus (QTL conferring resistance to blast disease using 126 recombinant inbred (RI lines originated from a crossing of a durably resistant upland rice genotype (Laka and a highly susceptible rice accession cultivar (Kencana Bali. The RI population was developed through a single seed descent method from 1997 to 2004. Resistance of the RI lines was evaluated for blast in an endemic area of Sukabumi, West Java, in 2005. Disease intensity of the blast was examined following the standard evaluation system developed by the International Rice Research Institute (IRRI. At the same year the RI lines were analyzed with 134 DNA markers. Results of the study showed that one major QTL was found to be associated with blast resistance, and this QTL was located near RM2136 marker on the long arm of chromosome 11. This QTL explained 87% of the phenotypic variation with 37% additive effect. The map position of this QTL differed from that of a partial resistant gene, Pi34, identified previously on chromosome 11 in the Japanese durably resistant variety, Chubu 32. The QTL, however, was almost at the same position as that of the multiple allele-resistant gene, Pik. Therefore, an allelic test should be conducted to clarify the allelic relationship between QTL identified in this study and the Pik. The RI lines are the permanent segregating population that could be very useful for analysing phenotypic variations of important agronomic traits possibly owned by the RI lines. The major QTL identified in this study could be used as a genetic resource in

  17. Distribution of triclosan-resistant genes in major pathogenic microorganisms revealed by metagenome and genome-wide analysis.

    Directory of Open Access Journals (Sweden)

    Raees Khan

    Full Text Available The substantial use of triclosan (TCS has been aimed to kill pathogenic bacteria, but TCS resistance seems to be prevalent in microbial species and limited knowledge exists about TCS resistance determinants in a majority of pathogenic bacteria. We aimed to evaluate the distribution of TCS resistance determinants in major pathogenic bacteria (N = 231 and to assess the enrichment of potentially pathogenic genera in TCS contaminated environments. A TCS-resistant gene (TRG database was constructed and experimentally validated to predict TCS resistance in major pathogenic bacteria. Genome-wide in silico analysis was performed to define the distribution of TCS-resistant determinants in major pathogens. Microbiome analysis of TCS contaminated soil samples was also performed to investigate the abundance of TCS-resistant pathogens. We experimentally confirmed that TCS resistance could be accurately predicted using genome-wide in silico analysis against TRG database. Predicted TCS resistant phenotypes were observed in all of the tested bacterial strains (N = 17, and heterologous expression of selected TCS resistant genes from those strains conferred expected levels of TCS resistance in an alternative host Escherichia coli. Moreover, genome-wide analysis revealed that potential TCS resistance determinants were abundant among the majority of human-associated pathogens (79% and soil-borne plant pathogenic bacteria (98%. These included a variety of enoyl-acyl carrier protein reductase (ENRs homologues, AcrB efflux pumps, and ENR substitutions. FabI ENR, which is the only known effective target for TCS, was either co-localized with other TCS resistance determinants or had TCS resistance-associated substitutions. Furthermore, microbiome analysis revealed that pathogenic genera with intrinsic TCS-resistant determinants exist in TCS contaminated environments. We conclude that TCS may not be as effective against the majority of bacterial pathogens as previously

  18. Spinal cord compression due to epidural extramedullary haematopoiesis in thalassaemia: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Aydingoez, Ue.; Oto, A.; Cila, A. [Department of Radiology, Hacettepe University School of Medicine, Ankara (Turkey)

    1997-12-01

    Spinal epidural extramedullary haematopoiesis is very rare in thalassaemia. A 27-year-old man with thalassaemia intermedia presented with symptoms and signs of spinal cord compression. MRI showed a thoracic spinal epidural mass, representing extramedullary haematopoietic tissue, compressing the spinal cord. Following radiotherapy, serial MRI revealed regression of the epidural mass and gradual resolution of spinal cord oedema. (orig.) With 3 figs., 6 refs.

  19. The improvement of rice varieties for major pest and diseases resistance

    International Nuclear Information System (INIS)

    Sahi, I.; Silitonga, T.S.

    1988-01-01

    Since 1971, the rice breeding program in Indonesia has developed on intensive program to improve varieties for yield potential, resistancy to major pests and diseases, early maturity good grain and eating quality. In recent years, the attacks of insects and diseases are very severe in rice cultivation in Asia. Much of the losses were due to acontinuous planting or certain varieties. Between 1966 and 1973 tungro occured in epidemic proportions on separate occasions in Indonesia, Thailand, Nort East India, Bangladesh, and Philippine. Since 1973, investation of brown planthopper and green leafhopper several damaged rice crop in most parts of Indonesia. Presently, rice improvement are directed to develop high yielding rice varieties that are resistant to brown planthopper, ragged stunt virus, blast, green leafhopper, and gallmidge. Screening for pests and diseases are conducted in the laboratory as well as in the field. The adoption of those improved varieties by farmers has contributed greatly in our efforts to attain self sufficiency in rice production in Indonesia. GH 147 -M-40 krad-Pn-89 (irradiated Barito) showed resistant to brown planthopper biotype 1 and 2 and moderately resistant to biotype 3. Napa 40 krad-St-12 has resistant reaction to blast. (authors). 4 refs, 8 tabs

  20. Major histocompatibility complex and host background genes in chickens influence resistance to high pathogenicity avian influenza virus

    Science.gov (United States)

    The chicken’s major histocompatibility complex (MHC) haplotype has a profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both li...

  1. Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin Resistance in Leishmania major.

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    Juliana Ide Aoki

    2016-09-01

    Full Text Available Tubercidin (TUB is a toxic adenosine analog with potential antiparasitic activity against Leishmania, with mechanism of action and resistance that are not completely understood. For understanding the mechanisms of action and identifying the potential metabolic pathways affected by this drug, we employed in this study an overexpression/selection approach using TUB for the identification of potential targets, as well as, drug resistance genes in L. major. Although, TUB is toxic to the mammalian host, these findings can provide evidences for a rational drug design based on purine pathway against leishmaniasis.After transfection of a cosmid genomic library into L. major Friedlin (LmjF parasites and application of the overexpression/selection method, we identified two cosmids (cosTUB1 and cosTU2 containing two different loci capable of conferring significant levels of TUB resistance. In the cosTUB1 contained a gene encoding NUPM1-like protein, which has been previously described as associated with TUB resistance in L. amazonensis. In the cosTUB2 we identified and characterized a gene encoding a 63 kDa protein that we denoted as tubercidin-resistance protein (TRP. Functional analysis revealed that the transfectants were less susceptible to TUB than LmjF parasites or those transfected with the control vector. In addition, the trp mRNA and protein levels in cosTUB2 transfectants were higher than LmjF. TRP immunolocalization revealed that it was co-localized to the endoplasmic reticulum (ER, a cellular compartment with many functions. In silico predictions indicated that TRP contains only a hypothetical transmembrane domain. Thus, it is likely that TRP is a lumen protein involved in multidrug efflux transport that may be involved in the purine metabolic pathway.This study demonstrated for the first time that TRP is associated with TUB resistance in Leishmania. The next challenge is to determine how TRP mediates TUB resistance and whether purine

  2. [Clinical management of beta-thalassaemia].

    Science.gov (United States)

    Thuret, Isabelle

    2014-10-01

    Beta-thalassemia syndromes are autosomal recessive disorders related to the inability to produce beta-globin chains. Thalassemia major is by definition a transfusion dependent anemia and iron overload is the leading cause of death and morbidity. Beta-thalassemia is rarely encountered in France where patients mainly originated from Mediterranean countries and South East Asia. Recently, two major advances have substantially improved the disease management: oral iron chelation therapy and the introduction of cardiac MRI for monitoring cardiac iron. Hematopoietic stem cell transplantation remains, in clinical practice, the only curative approach and is proposed to children having an HLA-identical sibling. Diagnosis of thalassemia trait is important in order to propose genetic counseling to couples at risk. Thalassemia intermedia is a clinical entity where anemia is mild or moderate, requiring no or occasional transfusion. Clinical severity increases with age with a more severe anemia, thrombotic complications and extra-medullary hematopoiesis. Iron overload, optimally monitored with liver MRI, occurs in adult patients and is related to increased iron hyper-absorption.

  3. Distribution of alpha thalassaemia gene variants in diverse ethnic populations in malaysia: data from the institute for medical research.

    Science.gov (United States)

    Ahmad, Rahimah; Saleem, Mohamed; Aloysious, Nisha Sabrina; Yelumalai, Punithawathy; Mohamed, Nurul; Hassan, Syahzuwan

    2013-09-10

    Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this retrospective analysis were to describe the distribution of various alpha thalassaemia alleles in different ethnic groups, along with their genotypic interactions, and to illustrate the haematological changes associated with each phenotype. Amongst the patients, 51.2% (n = 2567) were diagnosed with α thalassaemia. Of the 13 α thalassaemia determinants screened, eight different deletions and mutations were demonstrated: three double gene deletions, --(SEA), --(THAI), --(FIL); two single-gene deletions, α-³·⁷ and -α⁴·²; and three non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana), Cd125T > C (Hb Quong Sze) and Cd142 (Hb Constant Spring). A high incidence of α-³·⁷ deletion was observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people. However, the --SEA deletion was the most common cause of alpha thalassaemia in Chinese, followed by the α-³·⁷ deletion. As many as 27 genotypic interactions showed 1023 α thalassaemia silent carriers, 196 homozygous α⁺ thalassaemia traits, 973 heterozygous α⁰ thalassaemia carriers and 375 patients with Hb H disease. Statistical analysis showed a significant difference in the distribution of α thalassaemia determinants amongst the various ethnic groups. Hence, the heterogeneous distribution of common determinants indicated that the introduction of an ethnicity-targeted hierarchical α thalassaemia screening approach in this multi-ethnic Malaysian population would be effective.

  4. Distribution of Alpha Thalassaemia Gene Variants in Diverse Ethnic Populations in Malaysia: Data from the Institute for Medical Research

    Directory of Open Access Journals (Sweden)

    Syahzuwan Hassan

    2013-09-01

    Full Text Available Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this retrospective analysis were to describe the distribution of various alpha thalassaemia alleles in different ethnic groups, along with their genotypic interactions, and to illustrate the haematological changes associated with each phenotype. Amongst the patients, 51.2% (n = 2567 were diagnosed with α thalassaemia. Of the 13 α thalassaemia determinants screened, eight different deletions and mutations were demonstrated: three double gene deletions, ––SEA, ––THAI, ––FIL; two single-gene deletions, α–3.7 and –α4.2; and three non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana, Cd125T > C (Hb Quong Sze and Cd142 (Hb Constant Spring. A high incidence of α–3.7 deletion was observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people. However, the ––SEA deletion was the most common cause of alpha thalassaemia in Chinese, followed by the α–3.7 deletion. As many as 27 genotypic interactions showed 1023 α thalassaemia silent carriers, 196 homozygous α+ thalassaemia traits, 973 heterozygous α0 thalassaemia carriers and 375 patients with Hb H disease. Statistical analysis showed a significant difference in the distribution of α thalassaemia determinants amongst the various ethnic groups. Hence, the heterogeneous distribution of common determinants indicated that the introduction of an ethnicity-targeted hierarchical α thalassaemia screening approach in this multi-ethnic Malaysian population would be effective.

  5. Increased microerythrocyte count in homozygous alpha(+-thalassaemia contributes to protection against severe malarial anaemia.

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    Freya J I Fowkes

    2008-03-01

    Full Text Available The heritable haemoglobinopathy alpha(+-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb. Individuals homozygous for alpha(+-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA (Hb concentration 1.1 x 10(12/l as a result of the reduced mean cell Hb in homozygous alpha(+-thalassaemia. In addition, children homozygous for alpha(+-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02 for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09.The increased erythrocyte count and microcytosis in children homozygous for alpha(+-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.

  6. Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy

    Science.gov (United States)

    Zorumski, Charles F.; Nagele, Peter; Mennerick, Steven; Conway, Charles R.

    2015-01-01

    Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15–30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant. PMID:26696909

  7. Prevention of Cardiomyopathy in Transfusion-Dependent Homozygous Thalassaemia Today and the Role of Cardiac Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Athanassios Aessopos

    2009-01-01

    Full Text Available Transfusion and iron chelation therapy revolutionised survival and reduced morbidity in patients with transfusion-dependent beta thalassaemia major. Despite these improvements, cardiac disease remained the most common cause of death in those patients. Recently the ability to determine the degree of cardiac iron overload, through cardiac magnetic resonance imaging (CMR has allowed more logical approaches to iron removal, particularly from the heart. The availability of two oral chelators, deferiprone and deferasirox has reduced the need for the injectable chelator deferrioxamine and an additional benefit has been that deferiprone has been shown to be more cardioprotective than deferrioxamine. This review on the prevention of cardiac disease makes recommendations on the chelation regime that would be desirable for patients according to their cardiac iron status as determined by CMR determined by CMR. It also discusses approaches to chelation management should CMR not be available.

  8. Sickle cell disease in Madhya Pradesh, Central India: A comparison of clinical profile of sickle cell homozygote vs. sickle-beta thalassaemia individuals.

    Science.gov (United States)

    Yadav, Rajiv; Lazarus, Monica; Ghanghoria, Pawan; Singh, Mpss; Gupta, Rasik Behari; Kumar, Surendra; Sharma, Ravendra K; Shanmugam, Rajasubramaniam

    2016-10-01

    The clinical manifestation in sickle cell disease (SCD) patients varies from one individual to another due to factors like the presence of alpha-thalassaemia mutation, foetal haemoglobin, and β-globin gene haplotype. The present study enumerates the clinical profile of sickle cell anaemia patients from Central India. Seven hundred seventy-six SCD patients from Jabalpur and surrounding districts (Madhya Pradesh) in central India were registered with the sickle cell clinic of NIRTH, Jabalpur. The present study reveals recorded signs and symptoms of genetically confirmed sickle cell anaemia (404) and sickle beta thalassaemia (92) patients. Majority of the patients were from scheduled caste communities (47.9%) and Gond tribal community (13.8%). Splenomegaly was the most common clinical manifestation observed (71.4%). Overall, 63.5% patients had a history of blood transfusion. The most frequent signs and symptoms observed were Pallor, Icterus, Joint pain, Fever, and Fatigue. Majority of the patients revealed onset of disease prior to attaining the age of 3 years (sickle cell anaemia 44.3% and sickle beta thalassaemia 35.9%). Mean haemoglobin levels among SCA individuals were marginally higher than SBT patients. On the other hand, mean foetal haemoglobin levels among SBT individuals showed the reverse trend. Notably, the present study reports the first incidence of priapism recorded in Central India. The study revealed a high prevalence of SCD among scheduled caste, backward caste, and tribal communities. Dissemination of study findings, screening, pre-marriage counselling, and pre-natal diagnosis are fundamental to preventing or lowering of birth of sickle cell anaemia children in the affected populations.

  9. Diagnostic significance of red cell indices in beta-thalassaemia trait

    International Nuclear Information System (INIS)

    Hussain, Z.; Malik, N.; Chughtai, A.S.

    2005-01-01

    The purpose of this study was to evaluate the formulae for the diagnosis of beta-thalassemia trait cases in settings where electrophoreses is not available. The study included 50 cases of beta-thalassaemia trait already diagnosed by Hb electrophoresis. CBC samples were analyzed on Sysmex K4500 and red cell indices were used to evaluate formulae for differentiating beta thalassaemia trait from iron deficiency anemia. The formula MCV/RBC and MCH/RBC identified 56% of the cases. Formula MCV - (5 x Hb)- RBC - 8.4 identified 54% of beta thalassemia trait cases. The formula MCV x MCH identified 92% of cases. RBC indices given by 100 electronic counters can be used to differentiate iron deficiency anemia from beta-thalassaemia trait at least provisionally in areas where Hb electrophoresis is not available. (author)

  10. Acute liver failure in a patient with sickle cell/β+ thalassaemia

    International Nuclear Information System (INIS)

    Wigg, A.J.; Mounkley, A.D.; Cochlan, D.; Somers, S.

    2001-01-01

    We describe a rare, severe, vaso-occlusive presentation of sickle cell disease, named sickle cell intrahepatic cholestasis (SCIC). Patients with sickle cell/β + thalassaemia frequently have mild vaso-occlusive symptoms and only one case of SCIC developing in a patient with sickle cell/β + thalassaemia has been previously described in the world literature. The present report represents only the second described case of SCIC in a patient with sickle cell/β + thalassaemia. An abdominal computed tomography scan and Doppler ultrasound studies demonstrated massive hepatomegaly (25 cm span). Liver biopsy was performed and demonstrated dilatation and congestion of erythrocytes, severe cholestasis and fibrosis. The case demonstrates the importance of early recognition and institution of adequate therapy. Initial and correct diagnosis does not require biopsy or surgery which carry substantial risks of bleeding and mortality

  11. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    Directory of Open Access Journals (Sweden)

    Sulaiman S Ibrahim

    2015-10-01

    Full Text Available Scale up of Long Lasting Insecticide Nets (LLINs has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies.

  12. Pharmacoeconomic considerations in treating iron overload in patients with β-thalassaemia, sickle cell disease and myelodysplastic syndromes in the US: a literature review.

    Science.gov (United States)

    Zhang, Bin; Donga, Prina Z; Corral, Mitra; Sasane, Medha; Miller, Jeffrey D; Pashos, Chris L

    2011-06-01

    Patients with β-thalassaemia, sickle cell disease (SCD) and myelodysplastic syndromes (MDS) require chronic blood transfusions, which can lead to iron overload and substantial morbidity and mortality. To reduce the excess iron and its deleterious effects, available iron chelation therapy (ICT) in the US includes oral deferasirox or infusional deferoxamine (DFO). The aim of this study was to review and synthesize the available pharmacoeconomic evidence on ICT in patients with β-thalassaemia, SCD and MDS in the US. We systematically identified and reviewed pharmacoeconomic studies of ICT in patients with β-thalassaemia, SCD and MDS that either were published in MEDLINE-indexed, English-language journals from 1999 to 2009, or appeared in medical society websites and scientific meeting abstracts. We assessed available cost-of-illness, cost-of-treatment, cost-consequence, cost-effectiveness, utility and patient-satisfaction studies. The majority of the 20 identified studies assessed cost of treatment, mainly focusing on acquisition and administration costs of ICTs. Gaps in the published literature include current data on direct medical costs for patients with MDS, direct medical costs associated with complications of iron overload, direct non-medical costs, indirect costs and patient utilities. Different underlying model assumptions, methodologies and comparators were found in the cost-effectiveness studies, which yielded a broad range of incremental cost-effectiveness ratios for different ICTs. Comprehensive cost-of-illness studies are needed to address data gaps in the published literature regarding the economic burden of iron overload. Comparative-effectiveness studies that evaluate clinical, economic and patient-reported outcomes would help the medical community to better understand the value of different ICTs.

  13. Overexpression of BSR1 confers broad-spectrum resistance against two bacterial diseases and two major fungal diseases in rice.

    Science.gov (United States)

    Maeda, Satoru; Hayashi, Nagao; Sasaya, Takahide; Mori, Masaki

    2016-06-01

    Broad-spectrum disease resistance against two or more types of pathogen species is desirable for crop improvement. In rice, Xanthomonas oryzae pv. oryzae (Xoo), the causal bacteria of rice leaf blight, and Magnaporthe oryzae, the fungal pathogen causing rice blast, are two of the most devastating pathogens. We identified the rice BROAD-SPECTRUM RESISTANCE 1 (BSR1) gene for a BIK1-like receptor-like cytoplasmic kinase using the FOX hunting system, and demonstrated that BSR1-overexpressing (OX) rice showed strong resistance to the bacterial pathogen, Xoo and the fungal pathogen, M. oryzae. Here, we report that BSR1-OX rice showed extended resistance against two other different races of Xoo, and to at least one other race of M. oryzae. In addition, the rice showed resistance to another bacterial species, Burkholderia glumae, which causes bacterial seedling rot and bacterial grain rot, and to Cochliobolus miyabeanus, another fungal species causing brown spot. Furthermore, BSR1-OX rice showed slight resistance to rice stripe disease, a major viral disease caused by rice stripe virus. Thus, we demonstrated that BSR1-OX rice shows remarkable broad-spectrum resistance to at least two major bacterial species and two major fungal species, and slight resistance to one viral pathogen.

  14. Disappearing large calcified thoracic disc herniation in a patient with thalassaemia

    Science.gov (United States)

    Ahmad, Faiz U; Schallert, Erica; Bregy, Amade; Post, Judith D; Vanni, Steven

    2016-01-01

    Regression of herniated disc fragments with subsequent improvement in clinical symptoms has been reported in the lumbar and cervical spine. Such regressions in the thoracic spine are extremely rare. We report a case of a 38-year-old patient with thalassaemia who had regression of a large calcified herniated thoracic disc causing cord compression, with subsequent herniation of a second calcified disc at a different level and discuss the possible aetiopathogenesis. This is the first such case reported in the thalassaemia population. PMID:26823353

  15. Deferasirox pharmacokinetic evaluation in β-thalassaemia paediatric patients.

    Science.gov (United States)

    Allegra, Sarah; Cusato, Jessica; De Francia, Silvia; Pirro, Elisa; Massano, Davide; Piga, Antonio; D'Avolio, Antonio

    2017-05-01

    Iron chelation in the transfusion-dependent anaemias management is essential to prevent end-organ damage and to improve survival. Deferasirox is a once-daily orally active tridentate selective iron chelator which pharmacokinetic disposition could influence treatment efficacy and toxicity. Therapeutic drug monitoring is an important tool for optimizing drug utilization and doses. A fully validated chromatographic method was used to quantify deferasirox concentration in plasma collected from paediatric patients with β-thalassaemia. Samples obtained after 5 days of washout or in naïve patients before and after 2, 4, 6 and 24 h drug administration were evaluated. Associations between variables were tested using the Pearson test. Twenty paediatric patients were enrolled; they were mainly men (13.65%), with median age of 6.35 years and body mass index of 15.45 kg/m 2 . Concerning pharmacokinetic parameters, a higher interindividual variability was shown. A positive, but not significant, correlation (r = 0.363; P = 0.115) was found between deferasirox area under the concentration curve over 24 h (AUC) and drug dose. Monitoring plasma deferasirox concentrations appears beneficial for guiding appropriate patient treatment, enhancing effectiveness and minimizing toxicity. © 2016 Royal Pharmaceutical Society.

  16. Increasing temperature reduces wheat resistance mediated by major resistance genes to the gall midge Mayetiola destructor (Diptera: Cecidomyiidae)

    Science.gov (United States)

    Mayetiola destructor (Say) (Diptera: Cecidomyiidae) is a destructive pest of wheat and is mainly controlled by deploying resistant cultivars. Unfortunately, wheat resistance to Hessian fly is often lost when temperatures rise to a certain level. This study analyzed temperature sensitivity of 20 whea...

  17. Efflux Pumps Might Not Be the Major Drivers of QAC Resistance in Methicillin-Resistant Staphylococcus aureus.

    Science.gov (United States)

    Jennings, Megan C; Forman, Megan E; Duggan, Stephanie M; Minbiole, Kevin P C; Wuest, William M

    2017-08-17

    Quaternary ammonium compounds (QACs) are commonly used antiseptics that are now known to be subject to bacterial resistance. The prevalence and mechanisms of such resistance, however, remain underexplored. We investigated a variety of QACs, including those with multicationic structures (multiQACs), and the resistance displayed by a variety of Staphylococcus aureus strains with and without genes encoding efflux pumps, the purported main driver of bacterial resistance in MRSA. Through minimum inhibitory concentration (MIC)-, kinetic-, and efflux-based assays, we found that neither the qacR/qacA system present in S. aureus nor another efflux pump system is the main reason for bacterial resistance to QACs. Our findings suggest that membrane composition could be the predominant driver that allows CA-MRSA to withstand the assault of conventional QAC antiseptics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Selected highlights of the VIII International Symposium of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) on Growth, Puberty and Endocrine Complications in Thalassaemia. Auditorium of the Sultan Qaboos University (SQU) Muscat (Sultanate of Oman), 20th of December 2014.

    Science.gov (United States)

    De Sanctis, Vincenzo; Soliman, Ashraf T; Wali, Yasser; Elsedfy, Heba; Daar, Shahina; Al-Yaarubi, Saif A H; Mevada, Surekha Tony; Tony, Surekha; Elshinawy, Mohamed; Fawzy, Hanan; Al-Subhi, Taimoora; Al-Rawas, Abulhakim; Al-Muslehi, Muhanna; El Kholy, Mohamed

    2015-03-01

    The VIII ICET-A International Symposium was held in Muscat (Sultanate of Oman) on the 20th of December, 2014. The symposium included four sessions on a wide range of topics covering growth disorders and endocrine complications in thalassaemia. Despite the fact that endocrine complications are very common in multi-transfused thalassaemia patients a recent survey conducted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) in 2014 in Acitrezza (Catania, Italy) showed that the major difficulties reported by hematologists or pediatricians experienced in thalassaemias or thalassaemia syndromes in following endocrine complications included: Lack of familiarity with medical treatment of endocrine complications, interpretation of endocrine tests, lack of collaboration and on-time consultation between thalassaemic centres supervised by haematologists and endocrinologists. Endocrine monitoring of growth, pubertal development, reproductive ability and endocrine function in general are essential to achieve a good quality of life as well as controlling the pain which results from the defects of bone structure, all of which increase with the age of patients. Such comprehensive care is best provided by coordinated, multidisciplinary teams working in expert centres. The multidisciplinary team must include an endocrinologist, preferably someone experienced in the management of hormonal deficiencies caused early in life by transfusion-induced iron overload.

  19. Resistance to rust ( Puccinia psidii Winter) in eucalyptus: mode of inheritance and mapping of a major gene with RAPD markers.

    Science.gov (United States)

    Junghans, D T; Alfenas, A C; Brommonschenkel, S H; Oda, S; Mello, E J; Grattapaglia, D

    2003-12-01

    Rust is one of the most-damaging eucalypt diseases in Brazil and is considered a potential threat to eucalypt plantations worldwide. To determine the mode of inheritance of resistance in the Eucalyptus grandis- Puccinia psidii pathosystem, ten full-sib families, generated from crosses between susceptible and resistant trees, were inoculated with a single-pustule isolate of the pathogen and rust severity was scored. The observed segregation ratios in segregating families suggested major gene control of rust resistance, although clearly incomplete penetrance, variable expressivity and minor genes are also involved in the global rust-resistance response. To identify markers linked to the resistance locus, screening of RAPD polymorphisms was conducted using bulked segregant analysis in a large full-sib family. A linkage group was built around the Ppr1 gene ( P. psidii resistance gene 1) encompassing six RAPD markers, with a genetic window spanning 5 cM with the two most-closely linked flanking markers. Besides these two flanking markers, RAPD marker AT9/917 co-segregated with Ppr1 without a single recombinant in 994 meioses. This tightly linked marker should prove useful for marker-assisted introgression and will provide an initial lead for a positional cloning effort of this resistance allele. This is the first report of a disease resistance gene identified in Eucalyptus, and one of the few examples of the involvement of a major gene in a non-coevolved pathosystem.

  20. Genetic mapping of a major dominant gene for resistance to Ralstonia solanacearum in eggplant

    OpenAIRE

    Lebeau, A.; Gouy, M.; Daunay, Marie Christine; Wicker, E.; Chiroleu, F.; Prior, P.; Frary, Anne; Dintinger, J.

    2013-01-01

    Resistance of eggplant against Ralstonia solanacearum phylotype I strains was assessed in a F6 population of recombinant inbred lines (RILs) derived from a intra-specific cross between S. melongena MM738 (susceptible) and AG91-25 (resistant). Resistance traits were determined as disease score, percentage of wilted plants, and stem-based bacterial colonization index, as assessed in greenhouse experiments conducted in Réunion Island, France. The AG91-25 resistance was highly efficient toward st...

  1. Fasting: a major limitation for resistance exercise training effects in rodents

    Directory of Open Access Journals (Sweden)

    W. das Neves

    2017-11-01

    Full Text Available Protocols that mimic resistance exercise training (RET in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1 untrained control rats, 2 untrained rats submitted to fasting periods, and 3 rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks, the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks. After the short-term protocol, cumulative fasting periods promoted loss of weight (P0.05 for all. Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01. Altogether, these data indicate that fasting is a major limitation for RET in rats.

  2. Fasting: a major limitation for resistance exercise training effects in rodents.

    Science.gov (United States)

    das Neves, W; de Oliveira, L F; da Silva, R P; Alves, C R R; Lancha, A H

    2017-11-17

    Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (Pfasting is a major limitation for RET in rats.

  3. Calcium metabolism in children suffering from homozygous β-thalassaemia after oral administration of 47Ca

    International Nuclear Information System (INIS)

    Liakakos, D.; Vlachos, P.; Anoussakis, C.; Constantinides, C.; Tsakalosos, I.; Alexandra Hospital, Athens

    1976-01-01

    The study of calcium metabolism in ten thalassaemic children comperatively with controls after oral administration of 47 Ca has shown diminished intestinal absorption. It is suggested that this finding is propably related in part with the pathogenesis of the osteoporosis in thalassaemia. (orig.) [de

  4. Protector effect of α-thalassaemia on cholecystitis and cholecystectomy in sickle cell disease.

    Science.gov (United States)

    Pontes, Robéria M; Costa, Elaine S; Siqueira, Patrícia F R; Medeiros, Jussara F F; Soares, Andréa; de Mello, Fabiana V; Maioli, Maria C; Filho, Isaac L S; Alves, Liliane R; Land, Marcelo G P; Fleury, Marcos K

    2017-08-01

    Cholecystitis is one of the complications of symptomatic cholelithiasis responsible for high levels of morbidity of sickle cell disease (SCD) patients. Here, we investigated the possible protective role of single gene deletions of α-thalassaemia in the occurrence of cholelithiasis and cholecystitis in SCD patients, as well as the cholecystectomy requirements. The α-globin genotype was determined in 83 SCD patients using the multiplex-polymerase chain reaction and compared with clinical events. Overall, in 23% of patients, -α 3.7 deletion was found. α-Thalassaemia concomitant to SCD was an independent protective factor to cholecystitis (OR = 0.07; 95% CI: 0.01-0.66; p = 0.020) and cholecystectomy requirement (OR = 0.14; 95% CI: 0.03-0.60; p = 0.008). The risk of cholelithiasis was not affected by the α-thalassaemia concomitance. To the best our knowledge, our study is the first to show the protective effect of α-thalassaemia on cholecystitis and cholecystectomy requirements in SCD, which may be due to an improved splenic function.

  5. Ocular changes in multi-transfused children with β-thalassaemia ...

    African Journals Online (AJOL)

    Objectives. This study was planned to determine the prevalence of ocular abnormalities in multi-transfused children with β-thalassaemia receiving desferrioxamine and to determine the association of abnormalities with the patients' age, serum ferritin level, haemoglobin concentration, and dosage and duration of treatment ...

  6. Effectiveness of electroconvulsive therapy in a patient with a treatment-resistant major depressive episode and comorbid body dysmorphic disorder.

    Science.gov (United States)

    Rapinesi, Chiara; Serata, Daniele; Del Casale, Antonio; Carbonetti, Paolo; Fensore, Claudio; Scatena, Paola; Caccia, Federica; Di Pietro, Simone; Angeletti, Gloria; Tatarelli, Roberto; Kotzalidis, Georgios D; Giradi, Paolo

    2013-06-01

    A 24-year-old man experiencing comorbid body dysmorphic disorder since age 16 years, complicated in recent months by a major depressive episode with psychotic features, showed resistance to various drug and psychotherapy combinations. We suggested electroconvulsive therapy (ECT) to overcome treatment resistance. After 1 ECT cycle, mood and anxiety symptoms improved significantly, delusional interpretations and ideas of reference subsided, and dysmorphophobic symptoms improved as well. Six months later, the patient was doing well with a mood stabilizer/antipsychotic combination. Electroconvulsive therapy may improve symptoms of comorbid body dysmorphic disorder along with mood improvement in treatment-resistant depressive disorder.

  7. Emotional assistance in thalassaemia: pilot implementation of a standard protocol

    Directory of Open Access Journals (Sweden)

    M.T. Veit

    2011-12-01

    Full Text Available This study aims to describe the creation process of standard procedures to make possible multicentre studies related to emotional aspects of thalassaemic patients, their families and caregivers; and the pilot phase of the routine implementation. The objectives defined to perform this goal are: i develop routines to assess and manage/treat emotional issues; ii adjust the ABRASTA - Brazilian Association of Thalassaemia computer system to the input of collected data and its compilation; iii conduct a pilot implementation of the routines; iv discuss the whole process and propose next steps. Forty patients were assisted following the above mentioned routines of psychological evaluation, follow-up assistance and management of specific emotional issues. Conclusions are that the routines are adequate to enable multicenter research to compare findings and develop specific interventions to Thalassaemia patients, their families and caregivers; information gathered through them is an important means of supporting medical doctors and other members of the professional team, both in the therapeutic planning and in the communication process with patients and families; finally, considering the nature of the information, psychologists and psychiatrists are the most indicated professionals to perform the assessment and the interventions related to emotional issues, due to their professional background, training and specific skills that allow a free and candid communication with the patients and their families. 本研究旨在描述标准程序的创造过程,来进行关于地中海贫血患者、其家属和照顾者情感方面可能的多中心研究;以及例程实施的试点阶段。 为实现此目的而定下的目标有: 1)制定例程评估和管理/处理情感问题;2)调整巴西地中海贫血病协会(ABRASTA)计算机系统, 输入收集到的数据并对其进行编辑;3)对例程进行试点实施;4)讨论整个过

  8. Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management

    OpenAIRE

    Finley, Phillip J.; Norton, Rhy; Austin, Cindy; Mitchell, Amber; Zank, Sara; Durham, Paul

    2015-01-01

    Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. Here, we identified the first strains of clinical bacteria expressing silver resistance at a level that could significantly impact wound care and the use ...

  9. Antimicrobial resistance: the major contribution of poor governance and corruption to this growing problem.

    Directory of Open Access Journals (Sweden)

    Peter Collignon

    Full Text Available To determine how important governmental, social, and economic factors are in driving antibiotic resistance compared to the factors usually considered the main driving factors-antibiotic usage and levels of economic development.A retrospective multivariate analysis of the variation of antibiotic resistance in Europe in terms of human antibiotic usage, private health care expenditure, tertiary education, the level of economic advancement (per capita GDP, and quality of governance (corruption. The model was estimated using a panel data set involving 7 common human bloodstream isolates and covering 28 European countries for the period 1998-2010.Only 28% of the total variation in antibiotic resistance among countries is attributable to variation in antibiotic usage. If time effects are included the explanatory power increases to 33%. However when the control of corruption indicator is included as an additional variable, 63% of the total variation in antibiotic resistance is now explained by the regression. The complete multivariate regression only accomplishes an additional 7% in terms of goodness of fit, indicating that corruption is the main socioeconomic factor that explains antibiotic resistance. The income level of a country appeared to have no effect on resistance rates in the multivariate analysis. The estimated impact of corruption was statistically significant (p< 0.01. The coefficient indicates that an improvement of one unit in the corruption indicator is associated with a reduction in antibiotic resistance by approximately 0.7 units. The estimated coefficient of private health expenditure showed that one unit reduction is associated with a 0.2 unit decrease in antibiotic resistance.These findings support the hypothesis that poor governance and corruption contributes to levels of antibiotic resistance and correlate better than antibiotic usage volumes with resistance rates. We conclude that addressing corruption and improving governance

  10. Antimicrobial resistance: the major contribution of poor governance and corruption to this growing problem.

    Science.gov (United States)

    Collignon, Peter; Athukorala, Prema-Chandra; Senanayake, Sanjaya; Khan, Fahad

    2015-01-01

    To determine how important governmental, social, and economic factors are in driving antibiotic resistance compared to the factors usually considered the main driving factors-antibiotic usage and levels of economic development. A retrospective multivariate analysis of the variation of antibiotic resistance in Europe in terms of human antibiotic usage, private health care expenditure, tertiary education, the level of economic advancement (per capita GDP), and quality of governance (corruption). The model was estimated using a panel data set involving 7 common human bloodstream isolates and covering 28 European countries for the period 1998-2010. Only 28% of the total variation in antibiotic resistance among countries is attributable to variation in antibiotic usage. If time effects are included the explanatory power increases to 33%. However when the control of corruption indicator is included as an additional variable, 63% of the total variation in antibiotic resistance is now explained by the regression. The complete multivariate regression only accomplishes an additional 7% in terms of goodness of fit, indicating that corruption is the main socioeconomic factor that explains antibiotic resistance. The income level of a country appeared to have no effect on resistance rates in the multivariate analysis. The estimated impact of corruption was statistically significant (pcorruption indicator is associated with a reduction in antibiotic resistance by approximately 0.7 units. The estimated coefficient of private health expenditure showed that one unit reduction is associated with a 0.2 unit decrease in antibiotic resistance. These findings support the hypothesis that poor governance and corruption contributes to levels of antibiotic resistance and correlate better than antibiotic usage volumes with resistance rates. We conclude that addressing corruption and improving governance will lead to a reduction in antibiotic resistance.

  11. Role of peripheral vascular resistance for the association between major depression and cardiovascular disease

    DEFF Research Database (Denmark)

    Bouzinova, Elena V.; Wiborg, Ove; Aalkjaer, Christian

    2015-01-01

    , little attention was given to structural and functional changes in resistance arteries responsible for blood pressure control and tissue perfusion. This review discusses recent achievements in studies of depression-associated abnormalities in resistance arteries in humans and animal experimental models...

  12. Cuticle thickening associated with pyrethroid resistance in the major malaria vector Anopheles funestus

    Directory of Open Access Journals (Sweden)

    Coetzee M

    2010-08-01

    Full Text Available Abstract Background Malaria in South Africa is primarily transmitted by Anopheles funestus Giles. Resistance to pyrethroid insecticides in An. funestus in northern Kwazulu/Natal, South Africa, and in neighbouring areas of southern Mozambique enabled populations of this species to increase their ranges into areas where pyrethroids were being exclusively used for malaria control. Pyrethroid resistance in southern African An. funestus is primarily conferred by monooxygenase enzyme metabolism. However, selection for this resistance mechanism is likely to have occurred in conjunction with other factors that improve production of the resistance phenotype. A strong candidate is cuticle thickening. This is because thicker cuticles lead to slower rates of insecticide absorption, which is likely to increase the efficiency of metabolic detoxification. Results Measures of mean cuticle thickness in laboratory samples of female An. funestus were obtained using scanning electron microscopy (SEM. These females were drawn from a laboratory colony carrying the pyrethroid resistance phenotype at a stable rate, but not fixed. Prior to cuticle thickness measurements, these samples were characterised as either more or less tolerant to permethrin exposure in one experiment, and either permethrin resistant or susceptible in another experiment. There was a significant and positive correlation between mean cuticle thickness and time to knock down during exposure to permethrin. Mean cuticle thickness was significantly greater in those samples characterised either as more tolerant or resistant to permethrin exposure compared to those characterised as either less tolerant or permethrin susceptible. Further, insecticide susceptible female An. funestus have thicker cuticles than their male counterparts. Conclusion Pyrethroid tolerant or resistant An. funestus females are likely to have thicker cuticles than less tolerant or susceptible females, and females generally have

  13. A radioattenuated Leishmania major vaccine markedly increases the resistance of CBA mice to subsequent infection with Leishmania mexicana mexicana

    International Nuclear Information System (INIS)

    Alexander, J.

    1982-01-01

    Vaccinating CBA mice with radioattenuated Leishmania major amastigotes but not with radioattenuated L. mexicana amastigotes rendered them highly resistant to subsequent infection with L. m. mexicana. Unvaccinated CBA mice were highly susceptible to infection with L. m. mexicana producing rapidly growing non-ulcerating cutaneous lesions. Two manifestations of resistance were induced in vaccinated animals depending on the timing of the challenge infection: no lesions appeared at the site of subcutaneous challenge in animals vaccinated four or more weeks previously, while lesions grew rapidly but ulcerated and healed in animals vaccinated less than 3 weeks beforehand. L. major amastigotes were found to be markedly more resistant to γ irradiation than L. m.mexicana amastigotes both as measured by their ability to infect susceptible strains of mice and to transform and multiply as promastigotes in NNN medium. (author)

  14. Major histocompatibility (MH) class II ß gene polymorphism influences disease resistance of common carp (Cyprinus carpio L.)

    NARCIS (Netherlands)

    Rakus, K.L.; Wiegertjes, G.F.; Jurecka, P.M.; Walker, P.D.; Pilarczyk, A.; Irnazarow, I.

    2009-01-01

    Genes of the major histocompatibility complex (MHC) are crucial elements of adaptive immunity. High polymorphism renders the MHC genes highly suitable for studies on association with disease resistance. In common carp (Cyprinus carpio L.), there are two paralogous groups of MH class II B genes,

  15. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

  16. Review of a major epidemic of methicillin-resistant Staphylococcus aureus: The costs of screening and consequences of outbreak management

    NARCIS (Netherlands)

    A. van der Zee (Anneke); W. Hendriks; L.D. Roorda (Lieuwe); J.M. Ossewaarde (Jacobus); J. Buitenwerf (Johannes)

    2013-01-01

    textabstractBackground: A major outbreak of methicillin-resistant Staphylococcus aureus (MRSA) occurred in locations C and Z of our hospital and lasted for several years. It affected 1,230 patients and 153 personnel. Methods: Outbreak management was installed according to the Dutch "search and

  17. Distribution and frequency of Bru1, a major brown rust resistance gene, in the sugarcane world collection

    Science.gov (United States)

    Brown rust, caused by Puccinia melanocephala, is an important disease of sugarcane worldwide. Molecular markers for a major brown rust resistance gene, Bru1, were used to screen a total of 1,282 clones in the World Collection of Sugarcane and Related Grasses (WCSRG) to determine the distribution and...

  18. Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management.

    Science.gov (United States)

    Finley, Phillip J; Norton, Rhy; Austin, Cindy; Mitchell, Amber; Zank, Sara; Durham, Paul

    2015-08-01

    Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. Here, we identified the first strains of clinical bacteria expressing silver resistance at a level that could significantly impact wound care and the use of silver-based dressings. Screening of 859 clinical isolates confirmed 31 harbored at least 1 silver resistance gene. Despite the presence of these genes, MIC testing revealed most of the bacteria displayed little or no increase in resistance to ionic silver (200 to 300 μM Ag(+)). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of robust growth at exceedingly high silver concentrations, with MIC values reaching 5,500 μM Ag(+). DNA sequencing of these two strains revealed the presence of genes homologous to known genetic determinants of heavy metal resistance. Darkening of the bacteria's pigment was observed after exposure to high silver concentrations. Scanning electron microscopy images showed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested that the isolates may neutralize ionic silver via reduction to elemental silver. Antimicrobial testing revealed both organisms to be completely resistant to many commercially available silver-impregnated burn and wound dressings. Taken together, these findings provide the first evidence of clinical bacteria capable of expressing silver resistance at levels that could significantly impact wound management. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management

    Science.gov (United States)

    Norton, Rhy; Austin, Cindy; Mitchell, Amber; Zank, Sara; Durham, Paul

    2015-01-01

    Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. Here, we identified the first strains of clinical bacteria expressing silver resistance at a level that could significantly impact wound care and the use of silver-based dressings. Screening of 859 clinical isolates confirmed 31 harbored at least 1 silver resistance gene. Despite the presence of these genes, MIC testing revealed most of the bacteria displayed little or no increase in resistance to ionic silver (200 to 300 μM Ag+). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of robust growth at exceedingly high silver concentrations, with MIC values reaching 5,500 μM Ag+. DNA sequencing of these two strains revealed the presence of genes homologous to known genetic determinants of heavy metal resistance. Darkening of the bacteria's pigment was observed after exposure to high silver concentrations. Scanning electron microscopy images showed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested that the isolates may neutralize ionic silver via reduction to elemental silver. Antimicrobial testing revealed both organisms to be completely resistant to many commercially available silver-impregnated burn and wound dressings. Taken together, these findings provide the first evidence of clinical bacteria capable of expressing silver resistance at levels that could significantly impact wound management. PMID:26014954

  20. Development of pyramidal lines with two major QTLs conferring resistance to sheath blight in rice (Oryza sativa L.)

    Science.gov (United States)

    Hossain, Md Kamal; Jena, Kshirod; Bhuiyan, Md Atiqur Rahman; Ratnam, Wickneswari

    2014-09-01

    Sheath blight is an emerging threat in rice cultivation. It is animportant disease caused by the soil-borne necrotrophic pathogenic fungus, Rhizoctonia solani Kühn. However, to date neither known major genes for quantitative resistance, nor any rice lines immune to this disease has been identified. The disease resistance is quantitative in nature. Numerous genes are involved in this resistance process. There are few quantitative trait loci (QTLs) detected conferring improved resistance against the disease. Teqing and Tetepshowimproved resistance having QTLs, qSB-9 and qSBR11-1, respectively. Since, these QTLs demonstrates additive effects, pyramiding of these QTLs might be an option to increase the sheath blight resistance in rice. Nine rice cultivars were screened at greenhouse conditions. Results showed that Tetep and Teqing had the lowest disease ratings. UKMRC2a new high yielding cultivar was as recipient parent. Crosses between UKMRC2 and Teqing, and UKMRC2 and Tetep were made and confirmed. Subsequently 4-way crosses between the two F1s were performed to develop pyramidal lines.

  1. Improving transfusion practice in transfusion dependent thalassaemia patients

    Directory of Open Access Journals (Sweden)

    Chathupa Wickremaarachchi

    2017-10-01

    Full Text Available The aim of this study was to improve current transfusion practice in transfusiondependent thalassaemia patients by determining whether safe transition from triplewashed red cells (TWRC to leucodepleted red cells (LDRC, increasing transfusion rates, reducing the use of frusemide and creating uniform practice across patients is possible. In patients receiving regular transfusions (50, triple-washed red blood cells were changed to LDRC, transfusion rates were increased to 5 mL/kg/h (in line with the Cooley’s Foundation guidelines to a maximum of 300 mL/h and frusemide was ceased. Medical review occurred at completion of the transfusion. Of the 20 patients on TWRC, 18 were transitioned to leucodepleted red cells (90%. Recurrent allergic reactions in 2 patients required re-institution of TWRC. 7 of the 8 patients on regular frusemide ceased this practice with no documented transfusion-related fluid overload. One patient refused. Of the eligible 50 patients, 20 patients (40% were increased to the maximum transfusion rate of 300 mLs/h; 6 (12% increased rate but refused to go to the maximum; 9 (18% refused a change in practice and 15 (30% were already at the maximum rate. There was only one documented transfusion reaction (palpitations however this patient was able to tolerate a higher transfusion rate on subsequent transfusions. Thalassemia patients on TWRC were safely transitioned to LDRC. Transfusion rates were safely increased, with a calculated reduction in day-stay bed time of 17.45 h per month. This confirms a guideline of 5 mL/kg/h for transfusion-dependant thalassaemia patients with preserved cardiac function is well tolerated and may be translated to other centres worldwide.   本研究的目的是通过确定是否有可能进行从三洗红细胞(TWRC)到去白细胞红细胞(LDRC)的安全过渡,提高输血速率,减少速尿的使用,并在患者中实施统一规则,从而改进输血依赖型地中海贫血患者中

  2. Characterization of putative multidrug resistance transporters of the major facilitator-superfamily expressed in Salmonella Typhi

    DEFF Research Database (Denmark)

    Shaheen, Aqsa; Ismat, Fouzia; Iqbal, Mazhar

    2015-01-01

    -hypersensitive Escherichia coli strain KAM42, and tested for transport of 25 antibacterial compounds, including representative antibiotics of various classes, antiseptics, dyes and detergents. Of the 15 tested putative transporters, STY0901, STY2458 and STY4874 exhibited a drug-resistance phenotype. Among these, STY4874...

  3. Short communication. Inheritance of yield, yield components and resistance to major diseases in Sesamum indicum L

    Energy Technology Data Exchange (ETDEWEB)

    El-Bramaway, M. A. S.; Shaban, W. I.

    2008-07-01

    Field experiments were conducted over 2005 and 2006 to study the gene action associated with yield and ten yield components, as well as resistance Fusarium wilt, charcoal rot and Alternaria leaf spot, in 6x6 half-diallel sesame progenies (F1). Highly significant differences among the 15 F1s and their six parents were detected with respect to all the investigated traits. A preponderance of non-additive genetic variance was seen for all the studied traits, except for days to maturity and resistance to Alternaria leaf spot. Ten traits showed over dominance. Recessive alleles were predominantly involved in fruiting branches plant-1, capsules plant-1 and single plant yield. The distribution of genes with positive and negative effects were symmetrical or nearly symmetrical with respect to 1000-seed weight, charcoal rot disease resistance, fruiting branches plant-1, capsules plant-1, single plant yield, and oil content. The parents possessed mostly negative genes in dominant form with respect to capsules plant-1, 1000-seed weight, oil content, and resistance to charcoal rot and Alternaria leaf spot; positive genes in recessive form were observed for the rest of the studied traits. Given the gene action observed, bi parental mating or diallel selective mating and heterosis breeding is suggested for the improvement of sesame. (Author) 24 refs.

  4. Selection for immunoresponsiveness in chickens : effects of the major histocompatibility complex and resistance to Marek's disease

    NARCIS (Netherlands)

    Pinard, M.H.

    1992-01-01

    Improving genetic disease resistance may be an attractive preventive measure in the control of infectious diseases in livestock production. Chickens were selected for high and low antibody response to sheep red blood cells for ten generations. Divergent selection was successfully achieved

  5. White pine blister rust resistance in limber pine: Evidence for a major gene

    Science.gov (United States)

    A. W. Schoettle; R. A. Sniezko; A. Kegley; K. S. Burns

    2014-01-01

    Limber pine (Pinus flexilis) is being threatened by the lethal disease white pine blister rust caused by the non-native pathogen Cronartium ribicola. The types and frequencies of genetic resistance to the rust will likely determine the potential success of restoration or proactive measures. These first extensive inoculation trials using individual tree seed collections...

  6. Cultivar-Based Introgression Mapping Reveals Wild Species-Derived Pm-0, the Major Powdery Mildew Resistance Locus in Squash

    Science.gov (United States)

    Holdsworth, William L.; LaPlant, Kyle E.; Bell, Duane C.; Jahn, Molly M.; Mazourek, Michael

    2016-01-01

    Powdery mildew is a major fungal disease on squash and pumpkin (Cucurbita spp.) in the US and throughout the world. Genetic resistance to the disease is not known to occur naturally within Cucurbita pepo and only infrequently in Cucurbita moschata, but has been achieved in both species through the introgression of a major resistance gene from the wild species Cucurbita okeechobeensis subsp. martinezii. At present, this gene, Pm-0, is used extensively in breeding, and is found in nearly all powdery mildew-resistant C. pepo and C. moschata commercial cultivars. In this study, we mapped C. okeechobeensis subsp. martinezii-derived single nucleotide polymorphism (SNP) alleles in a set of taxonomically and morphologically diverse and resistant C. pepo and C. moschata cultivars bred at Cornell University that, by common possession of Pm-0, form a shared-trait introgression panel. High marker density was achieved using genotyping-by-sequencing, which yielded over 50,000 de novo SNP markers in each of the three Cucurbita species genotyped. A single 516.4 kb wild-derived introgression was present in all of the resistant cultivars and absent in a diverse set of heirlooms that predated the Pm-0 introgression. The contribution of this interval to powdery mildew resistance was confirmed by association mapping in a C. pepo cultivar panel that included the Cornell lines, heirlooms, and 68 additional C. pepo cultivars and with an independent F2 population derived from C. okeechobeensis subsp. martinezii x C. moschata. The interval was refined to a final candidate interval of 76.4 kb and CAPS markers were developed inside this interval to facilitate marker-assisted selection. PMID:27936008

  7. Extramedullary haematopoiesis in Thalassaemia: results of radiotherapy: a report of three patients

    Energy Technology Data Exchange (ETDEWEB)

    Pistevou-Gompaki, K.; Paraskevopoulos, P.; Kotsa, K. [Theagenion Cancer Center, Thessaloniki (Greece); Skaragas, G.; Repanta, E. [Saint Paul`s Hospital, Thessaloniki (Greece)

    1996-10-01

    Extramedullary haematopoiesis is sometimes encountered in serve anaemia. Rarely, it may cause neurological symptoms, leading to spinal cord or cauda equina compression. Three patients with thalassaemia intermedia, who developed neurological complications, are described. The diagnoses were based on the clinical findings, computed tomography and magnetic resonance imaging. Small doses of radiotherapy (10-20 Gy in 5-10 fractions) relieved symptoms in all of these patients. Our experience supports the role of radiation therapy as a treatment for this complication. (Author).

  8. Investigation of Rifampicin Resistance Outcome among Tuberculosis Patients Visiting Two Major Health Facilities in Port Harcourt in Niger Delta

    Directory of Open Access Journals (Sweden)

    Wokem Gloria Ngozika

    2018-03-01

    Full Text Available Background: Tuberculosis is caused by Mycobacterium tuberculosis and is spread mainly through contact with air droplets and respiratory fluid from an infected person. Drug of choice for its treatment are rifampicin and isoniazid respectively. However, in recent times, resistance to these drugs as with other antibiotics has been observed across the globe. This study was thus aimed at determining the prevalence of rifampicin resistance strain among TB patients attending two major hospitals (Braithwaite Memorial Hospital and University of Port Harcourt Teaching Hospital in Port Harcourt. Method: Sputum of patients was collected, tested for the presence of TB and rifampicin resistance of the isolates were determined using GeneXpert assay approach. Result: A total of 158 isolates from patients who were TB positive were tested for rifampicin resistance. 13.3% of these were resistant to rifampicin drug. 8.9% was from UPTH while 4.4% was from BMSH. 9.5% were less than age 45 while 3.8% were greater than or equal to age 45 (≥45. Males made up 8.2% of the total prevalence while females made up 5.1% of the total prevalence. Alternative drugs to rifampicin and isoniazid drug should however, be prescribed in confirmed cases of resistance outcome in our health facilities especially in the rural communities. Conclusion: Nonetheless, the use of antibiotics indiscriminately without the effective laboratory assay and physician’s prescription should be discouraged at all levels and patients receiving treatment should be monitored to adhere strictly to the desired dosage as non-adhering to the gold standard option may lead to drug resistance outcome among vulnerable patients who are literally exposed to lack of health education and functional health facilities in the remote communities which are also hard to reach area due to the environmental terrine

  9. White pine blister rust resistance in limber pine: evidence for a major gene.

    Science.gov (United States)

    Schoettle, A W; Sniezko, R A; Kegley, A; Burns, K S

    2014-02-01

    Limber pine (Pinus flexilis) is being threatened by the lethal disease white pine blister rust caused by the non-native pathogen Cronartium ribicola. The types and frequencies of genetic resistance to the rust will likely determine the potential success of restoration or proactive measures. These first extensive inoculation trials using individual tree seed collections from >100 limber pine trees confirm that genetic segregation of a stem symptom-free trait to blister rust is consistent with inheritance by a single dominant resistance (R) gene, and the resistance allele appears to be distinct from the R allele in western white pine. Following previous conventions, we are naming the R gene for limber pine "Cr4." The frequency of the Cr4 allele across healthy and recently invaded populations in the Southern Rocky Mountains was unexpectedly high (5.0%, ranging from 0 to 13.9%). Cr4 is in equilibrium, suggesting that it is not a product of a recent mutation and may have other adaptive significance within the species, possibly related to other abiotic or biotic stress factors. The identification of Cr4 in native populations of limber pine early in the invasion progress in this region provides useful information for predicting near-term impacts and structuring long-term management strategies.

  10. Role of genetic counselling in prenatal diagnosis of beta-thalassaemia in pakistan

    International Nuclear Information System (INIS)

    Bozdar, M.; Hanif, T.B.

    2013-01-01

    To compare the response towards prenatal diagnosis (PND) of b-thalassaemia, in individuals who had not received genetic counselling and a genetically counselled population. Study Design: Cross-sectional survey. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from March 2009 to December 2010. Methodology: Using non-probability consecutive sampling, a total of 176 individuals having thalassaemic children, were interviewed regarding PND of thalassaemia, by using a structured questionnaire. Forty two individuals were taken as controls as they had received genetic counselling for PND, whereas the remaining 134 were taken as cases. Responses towards PND were compared using chi-square test. Odds ratio was also calculated for subsequent PND utilization. Results: Seventy (52.2%) cases and 42 (100%) controls were aware of the availability of PND in Pakistan. This difference in awareness was statistically significant (p < 0.001). In the controls, 40 (95.3%) individuals were aware of the appropriate timing of the test, in contrast to 52 (39%) cases (p < 0.001). PND was used in subsequent pregnancies by 50 (37.3%) cases and 32 (80%) controls (p < 0.001). The calculated odds ratio for subsequent PND utilization was 5.37. Conclusion: The study reflects a very positive attitude of genetically counselled thalassaemia affected families towards PND. For better utilization of PND, genetic counselling services should be available at all health strata. (author)

  11. Development of transgenic cotton lines expressing Allium sativum agglutinin (ASAL for enhanced resistance against major sap-sucking pests.

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    Chakravarthy S K Vajhala

    Full Text Available Mannose-specific Allium sativum leaf agglutinin encoding gene (ASAL and herbicide tolerance gene (BAR were introduced into an elite cotton inbred line (NC-601 employing Agrobacterium-mediated genetic transformation. Cotton transformants were produced from the phosphinothricin (PPT-resistant shoots obtained after co-cultivation of mature embryos with the Agrobacterium strain EHA105 harbouring recombinant binary vector pCAMBIA3300-ASAL-BAR. PCR and Southern blot analysis confirmed the presence and stable integration of ASAL and BAR genes in various transformants of cotton. Basta leaf-dip assay, northern blot, western blot and ELISA analyses disclosed variable expression of BAR and ASAL transgenes in different transformants. Transgenes, ASAL and BAR, were stably inherited and showed co-segregation in T1 generation in a Mendelian fashion for both PPT tolerance and insect resistance. In planta insect bioassays on T2 and T3 homozygous ASAL-transgenic lines revealed potent entomotoxic effects of ASAL on jassid and whitefly insects, as evidenced by significant decreases in the survival, development and fecundity of the insects when compared to the untransformed controls. Furthermore, the transgenic cotton lines conferred higher levels of resistance (1-2 score with minimal plant damage against these major sucking pests when bioassays were carried out employing standard screening techniques. The developed transgenics could serve as a potential genetic resource in recombination breeding aimed at improving the pest resistance of cotton. This study represents the first report of its kind dealing with the development of transgenic cotton resistant to two major sap-sucking insects.

  12. ACQUIRED HYPOGONADOTROPIC HYPOGONADISM (AHH IN THALASSAEMIA MAJOR PATIENTS: AN UNDERDIAGNOSED CONDITION?

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    Vincenzo De Sanctis

    2016-01-01

    Fasting venous blood samples were collected two weeks after  transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4, thyrotropin (TSH, cortisol,  luteinizing hormone (LH, follicle stimulating hormone (FSH, total testosterone (TT, prolactin and estradiol (E2, glucose, urea, creatinine and electrolytes (including calcium and phosphat

  13. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia: the ESCALATOR study

    Science.gov (United States)

    Taher, Ali; El-Beshlawy, Amal; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Habr, Dany; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Al Jefri, Abdullah

    2009-01-01

    Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20–30 mg/kg/d reduces iron burden, depending on transfusional iron intake. Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients ≥2 yr with β-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of ≥3 mg Fe/g dry weight (dw) if baseline LIC was ≥10 mg Fe/g dw, or final LIC of 1–7 mg Fe/g dw for patients with baseline LIC of 2 to deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment. Conclusions: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with β-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden. PMID:19187278

  14. Non-specific activities of the major herbicide-resistance gene BAR.

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    Christ, Bastien; Hochstrasser, Ramon; Guyer, Luzia; Francisco, Rita; Aubry, Sylvain; Hörtensteiner, Stefan; Weng, Jing-Ke

    2017-12-01

    Bialaphos resistance (BAR) and phosphinothricin acetyltransferase (PAT) genes, which convey resistance to the broad-spectrum herbicide phosphinothricin (also known as glufosinate) via N-acetylation, have been globally used in basic plant research and genetically engineered crops 1-4 . Although early in vitro enzyme assays showed that recombinant BAR and PAT exhibit substrate preference toward phosphinothricin over the 20 proteinogenic amino acids 1 , indirect effects of BAR-containing transgenes in planta, including modified amino acid levels, have been seen but without the identification of their direct causes 5,6 . Combining metabolomics, plant genetics and biochemical approaches, we show that transgenic BAR indeed converts two plant endogenous amino acids, aminoadipate and tryptophan, to their respective N-acetylated products in several plant species. We report the crystal structures of BAR, and further delineate structural basis for its substrate selectivity and catalytic mechanism. Through structure-guided protein engineering, we generated several BAR variants that display significantly reduced non-specific activities compared with its wild-type counterpart in vivo. The transgenic expression of enzymes can result in unintended off-target metabolism arising from enzyme promiscuity. Understanding such phenomena at the mechanistic level can facilitate the design of maximally insulated systems featuring heterologously expressed enzymes.

  15. Nucleotide diversity analysis of three major bacterial blight resistance genes in rice.

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    Waikhom Bimolata

    Full Text Available Nucleotide sequence polymorphisms among R gene alleles influence the process of co-evolutionary interaction between host and pathogen by shaping the response of host plants towards invading pathogens. Here, we present the DNA sequence polymorphisms and diversities present among natural alleles of three rice bacterial blight resistance genes, Xa21, Xa26 and xa5. The diversity was examined across different wild relatives and cultivars of Oryza species. Functional significance of selected alleles was evaluated through semi-quantitative reverse transcription polymerase chain reaction and real time PCR. The greatest nucleotide diversity and singleton variable sites (SVS were present in Xa26 (π = 0.01958; SVS = 182 followed by xa5 and Xa21 alleles. The highest frequency of single nucleotide polymorphisms were observed in Xa21 alleles and least in xa5. Transition bias was observed in all the genes and 'G' to 'A' transitions were more favored than other form of transitions. Neutrality tests failed to show the presence of selection at these loci, though negative Tajima's D values indicate the presence of a rare form of polymorphisms. At the interspecies level, O. nivara exhibited more diversity than O. sativa. We have also identified two nearly identical resistant alleles of xa5 and two sequentially identical alleles of Xa21. The alleles of xa5 showed basal levels of expression while Xa21 alleles were functionally not expressed.

  16. Mapping of a Leishmania major gene/locus that confers pentamidine resistance by deletion and insertion of transposable element

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    Coelho Adriano C.

    2004-01-01

    Full Text Available Pentamidine (PEN is an alternative compound to treat antimony-resistant leishmaniasis patients, which cellular target remains unclear. One approach to the identification of prospective targets is to identify genes able to mediate PEN resistance following overexpression. Starting from a genomic library of transfected parasites bearing a multicopy episomal cosmid vector containing wild-type Leishmania major DNA, we isolated one locus capable to render PEN resistance to wild type cells after DNA transfection. In order to map this Leishmania locus, cosmid insert was deleted by two successive sets of partial digestion with restriction enzymes, followed by transfection into wild type cells, overexpression, induction and functional tests in the presence of PEN. To determine the Leishmania gene related to PEN resistance, nucleotide sequencing experiments were done through insertion of the transposon Mariner element of Drosophila melanogaster (mosK into the deleted insert to work as primer island. Using general molecular techniques, we described here this method that permits a quickly identification of a functional gene facilitating nucleotide sequence experiments from large DNA fragments. Followed experiments revealed the presence of a P-Glycoprotein gene in this locus which role in Leishmania metabolism has now been analyzed.

  17. Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese.

    Science.gov (United States)

    Fujii, Chikako; Kawai, Toshihide; Azuma, Koichiro; Oguma, Yuko; Katsukawa, Fuminori; Hirose, Hiroshi; Tanaka, Kumiko; Meguro, Shu; Matsumoto, Hideo; Itoh, Hiroshi

    2017-01-01

    Objective . The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese. Methods . The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally. Results . The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area ( r = -0.411, p acid percentage was also significantly negatively correlated with HOMA-IR ( r = -0.416, p acid in diabetic subjects was significantly lower than that in normal subjects. Conclusion . We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.

  18. MAJOR RISK FACTORS OF THE DISEASE IN THE FOCI OF DRUG-RESISTANT TUBERCULOSIS

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    T. Sh. Abildaev

    2014-01-01

    Full Text Available The paper analyzes contamination factors in children and adolescents from the foci of multidrug-resistant tuberculosis. The analysis of a study of these disease sources, the people who discontinued treatment and contacted with the children and adolescents in the foci demonstrated that these were mainly male alcoholics, as well as unemployed, intensive-phase therapy non-compliant inpatients, patients who went home without permission; 16% of them had convictions. The contacted children and adolescents from a group of patients who discontinued treatment were significantly more frequently stated to have a hyperergic response to tuberculin (10.8% than those who continued treatment (3.4% (p ≤ 0.05. Two children and 3 adolescents (15% fell ill in the treatment discontinuation group. One (3.0% adolescent did in the treatment continuation group (p ≤ 0.05.

  19. Deep brain stimulation of the subcallosal cingulate gyrus: further evidence in treatment-resistant major depression.

    Science.gov (United States)

    Puigdemont, Dolors; Pérez-Egea, Rosario; Portella, Maria J; Molet, Joan; de Diego-Adeliño, Javier; Gironell, Alexandre; Radua, Joaquim; Gómez-Anson, Beatriz; Rodríguez, Rodrigo; Serra, Maria; de Quintana, Cristian; Artigas, Francesc; Álvarez, Enric; Pérez, Víctor

    2012-02-01

    Deep brain stimulation (DBS) is currently tested as an experimental therapy for patients with treatment-resistant depression (TRD). Here we report on the short- and long-term (1 yr) clinical outcomes and tolerance of DBS in eight TRD patients. Electrodes were implanted bilaterally in the subgenual cingulate gyrus (SCG; Broadman areas 24-25), and stimulated at 135 Hz (90-μs pulsewidth). Voltage and active electrode contacts were adjusted to maximize short-term responses. Clinical assessments included the 17-item Hamilton Depression Rating Scale (HAMD17; primary measure), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) Scale. In the first week after surgery, response and remission (HAMD ⩽7) rates were, respectively 87.5% and 50%. These early responses were followed by an overall worsening, with a response and remission rates of 37.5% (3/8) at 1 month. From then onwards, patients showed a progressive improvement, with response and remission rates of 87.5% and 37.5%, respectively, at 6 months. The corresponding figures at 1 yr were 62.5% and 50%, respectively. Clinical effects were seen in all HAMD subscales without a significant incidence of side-effects. Surgical procedure and post-operative period were well-tolerated for all patients. This is the second independent study on the use of DBS of the SCG to treat chronic depression resistant to current therapeutic strategies. DBS fully remitted 50% of the patients at 1 yr, supporting its validity as a new therapeutic strategy for TRD.

  20. Default mode network coherence in treatment-resistant major depressive disorder during electroconvulsive therapy.

    Science.gov (United States)

    Mulders, Peter C R; van Eijndhoven, Philip F P; Pluijmen, Joris; Schene, Aart H; Tendolkar, Indira; Beckmann, Christian F

    2016-11-15

    Functional connectivity in the "default mode network" (DMN) is changed in depression, and evidence suggests depression also affects the DMN's spatial topography and might cause a dissociation between its anterior and posterior regions. As antidepressive treatment affects anterior and posterior regions of the network differently, how depression and treatment change DMN-organization is crucial for understanding their mechanisms. We present a novel way of assessing the coherence of a network's regions to the network as a whole, and apply this to investigate treatment-resistant depression and the effects of electroconvulsive therapy (ECT). Resting-state functional MRI was collected from 16 patients with treatment-resistant depression before and after ECT and 16 healthy controls matched for age and sex. For each subject, the mean time series of the DMN was used as a regressor for each voxel within the DMN, creating a map of "network coherence" (NC). The obtained maps were compared across groups using permutation testing. NC was significantly decreased in depressed subjects in the precuneus and the angular gyrus. With ECT the NC normalized in responders (n=8), but not in non-responders (n=8). We present a novel method of investigating within-network coherence and apply this to show that in depression, a large area of the DMN shows a decrease in coherence to the network as a whole. Although tentative due to the small sample size, we find that this effect is not present after ECT in those improving clinically, but persists in patients not responding to ECT. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Diversity of multi-drug resistant Acinetobacter baumannii population in a major hospital in Kuwait

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    Leila eVali

    2015-07-01

    Full Text Available Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious health care associated complications in critically ill patients. In the current study we report on the diversity of the clinical multi-drug resistant A. baumannii in Kuwait by molecular characterization. One hundred A. baumannii were isolated from one of the largest governmental hospitals in Kuwait. Following the identification of the isolates by molecular methods, the amplified blaOXA-51-like gene product of one isolate (KO-12 recovered from blood showed the insertion of the ISAba19 at position 379 in blaOXA-78. Of the 33 multi-drug resistant isolates, 28 (85% contained blaOXA-23, 2 (6% blaOXA-24 and 6 (18% blaPER-1 gene. We did not detect blaOXA-58, blaVIM, blaIMP, blaGES, blaVEB and blaNDM genes in any of the tested isolates. In 3 blaPER-1 positive isolates the genetic environment of blaPER-1 consisted of two copies of ISPa12 (tnpiA1 surrounding the blaPER-1 gene on a highly stable plasmid of ca. 140-kb. MLST analysis of the 33 A. baumannii isolates identified 20 different STs, of which 6 (ST-607, ST-608, ST-609, ST-610, ST-611 and ST-612 were novel. Emerging STs such as ST15 (identified for the first time in the Middle East, ST78 and ST25 were also detected. The predominant clonal complex was CC2. PFGE and MLST defined the MDR isolates as multi-clonal with diverse lineages. Our results lead us to believe that A. baumannii is diverse in clonal origins and / or is undergoing clonal expansion continuously while multiple lineages of MDR A. baumannii circulate in hospital wards simultaneously.

  2. Insecticidal and repellent activities of pyrethroids to the three major pyrethroid-resistant malaria vectors in western Kenya.

    Science.gov (United States)

    Kawada, Hitoshi; Ohashi, Kazunori; Dida, Gabriel O; Sonye, George; Njenga, Sammy M; Mwandawiro, Charles; Minakawa, Noboru

    2014-05-02

    The dramatic success of insecticide treated nets (ITNs) and long-lasting insecticidal nets (LLINs) in African countries has been countered by the rapid development of pyrethroid resistance in vector mosquitoes over the past decade. One advantage of the use of pyrethroids in ITNs is their excito-repellency. Use of the excito-repellency of pyrethroids might be biorational, since such repellency will not induce or delay the development of any physiological resistance. However, little is known about the relationship between the mode of insecticide resistance and excito-repellency in pyrethroid-resistant mosquitoes. Differences in the reactions of 3 major malaria vectors in western Kenya to pyrethroids were compared in laboratory tests. Adult susceptibility tests were performed using World Health Organization (WHO) test tube kits for F1 progenies of field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s., and laboratory colonies of An. gambiae s.s. and An. arabiensis. The contact repellency to pyrethroids or permethrin-impregnated LLINs (Olyset® Nets) was evaluated with a simple choice test modified by WHO test tubes and with the test modified by the WHO cone bioassay test. Field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s. showed high resistance to both permethrin and deltamethrin. The allelic frequency of the point mutation in the voltage-gated sodium channel (L1014S) in An. gambiae s.s. was 99.3-100%, while no point mutations were detected in the other 2 species. The frequency of takeoffs from the pyrethroid-treated surface and the flying times without contacting the surface increased significantly in pyrethroid-susceptible An. gambiae s.s. and An. arabiensis colonies and wild An. arabiensis and An. funestus s.s. colonies, while there was no significant increase in the frequency of takeoffs or flying time in the An. gambiae s.s. wild colony. A different repellent reaction was observed in the field-collected An. gambiae s.s. than

  3. 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.

  4. Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial.

    Science.gov (United States)

    Nagele, Peter; Duma, Andreas; Kopec, Michael; Gebara, Marie Anne; Parsoei, Alireza; Walker, Marie; Janski, Alvin; Panagopoulos, Vassilis N; Cristancho, Pilar; Miller, J Philip; Zorumski, Charles F; Conway, Charles R

    2015-07-01

    N-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 points, p nitrous oxide and placebo, p nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI, .31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Comparison of biofilm formation between major clonal lineages of methicillin resistant Staphylococcus aureus.

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    Evelyn Vanhommerig

    Full Text Available Epidemic methicillin-resistant S. aureus (MRSA clones cause infections in both hospital and community settings. As a biofilm phenotype further facilitates evasion of the host immune system and antibiotics, we compared the biofilm-forming capacities of various MRSA clones.Seventy-six MRSA classified into 13 clones (USA300, EMRSA-15, Hungarian/Brazilian etc., and isolated from infections or from carriers were studied for biofilm formation under static and dynamic conditions. Static biofilms in microtitre plates were quantified colorimetrically. Dynamic biofilms (Bioflux 200, Fluxion, USA were studied by confocal laser-scanning and time-lapse microscopy, and the total volume occupied by live/dead bacteria quantified by Volocity 5.4.1 (Improvision, UK.MRSA harbouring SCCmec IV produced significantly more biomass under static conditions than SCCmec I-III (P = 0.003, and those harbouring SCCmec II significantly less than those harbouring SCCmec I or III (P<0.001. In the dynamic model, SCCmec I-III harbouring MRSA were significantly better biofilm formers than SCCmec IV (P = 0.036. Only 16 strains successfully formed biofilms under both conditions, of which 13 harboured SCCmec IV and included all tested USA300 strains (n = 3. However, USA300 demonstrated remarkably lower percentages of cell-occupied space (6.6% compared to the other clones (EMRSA-15 = 19.0% under dynamic conditions. Time-lapse microscopy of dynamic biofilms demonstrated that USA300 formed long viscoelastic tethers that stretched far from the point of attachment, while EMRSA-15 consisted of micro-colonies attached densely to the surface.MRSA harbouring SCCmec types IV and I-III demonstrate distinct biofilm forming capacities, possibly owing to their adaptation to the community and hospital settings, respectively. USA300 demonstrated abundant biofilm formation under both conditions, which probably confers a competitive advantage, contributing to its remarkable success as a pathogen.

  6. Differing epidemiology of two major healthcare-associated meticillin-resistant Staphylococcus aureus clones.

    Science.gov (United States)

    Jeremiah, C J; Kandiah, J P; Spelman, D W; Giffard, P M; Coombs, G W; Jenney, A W; Tong, S Y

    2016-02-01

    Two meticillin-resistant Staphylococcus aureus (MRSA) clones, sequence type (ST) 22 and ST239, have successfully spread globally. Across Australia, ST22 has supplanted ST239 as the main healthcare-associated MRSA. To understand the reasons underlying this shift, the epidemiology and clinical features of infections due to ST22 and ST239 MRSA isolates from a tertiary hospital in Melbourne, Australia were compared. Over six months, consecutive MRSA isolates with clinical data were collected from specimens referred to Alfred Health Pathology (AHP). Isolates were genotyped by a multi-locus-sequence-typing-based high-resolution melting method. Three hundred and twenty-eight of 1079 (30%) S. aureus isolated by AHP were MRSA. Of these, 313 were genotyped; 78 (25%) were clonal complex (CC) 22 (representing ST22) and 142 (45%) were CC239 (representing ST239). Common clinical syndromes included skin or soft tissue, respiratory tract and osteo-articular infections. On multi-variate logistic regression, compared with CC239, CC22 was associated with older patients [adjusted odds ratio (aOR) 1.04 for each year increase, 95% confidence interval (CI) 1.02-1.07)], and patients from subacute hospitals (aOR 2.7, 95% CI 1.2-5.8) or long-term care facilities (LTCFs; aOR 5.5, 95% CI 2.0-14.5). Median time from patient admission to MRSA isolation was nine days for CC239 and one day for CC22 (P < 0.01). MRSA strain epidemiology varied according to hospital unit. CC22 and CC239 MRSA have differing ecological niches. CC22 is associated with elderly patients in LTCFs, and CC239 is associated with nosocomial acquisition. Infection control strategies involving LTCFs and their residents will likely be required to achieve continued MRSA control. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  7. Treatment-Resistant Major Depression:Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy

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    Charles eZorumski

    2015-12-01

    Full Text Available Major depressive disorder (MDD remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD, which afflicts 15-30% of MDD patients. There has been recent interest in N-methyl-D-aspartate (receptors (NMDARs as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant.

  8. The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications.

    Science.gov (United States)

    Moylan, S; Maes, M; Wray, N R; Berk, M

    2013-05-01

    In some patients with major depressive disorder (MDD), individual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems, inflammatory, oxidative and nitrosative stress pathways, neurotrophins and regulation of neurogenesis, cortisol and the hypothalamic-pituitary-adrenal axis modulation, mitochondrial dysfunction and epigenetic and dietary influences. Evidence-based novel treatments informed by this knowledge are discussed.

  9. The role of radiation therapy in the management of spinal cord compression due to extramedullary haematopoiesis in thalassaemia

    International Nuclear Information System (INIS)

    Singhal, S.; Sharma, S.; Dixit, S.; De, S.; Chander, S.; Rath, G.K.; Mehta, V.S.

    1992-01-01

    Extramedullary haematopoiesis associated with thalassaemia leading to spinal cord compression is an extremely rare event in the course of the disease. The efficacy of radiation therapy is advocated in the management of such a complication. Two patients with thalassaemia, who had presented with spinal cord compression, were successfully treated by a modest dose of local radiotherapy. In one of the patients, however, radiotherapy was resorted to after an initial decompressive laminectomy and partial removal of the intraspinal haematopoietic mass proved unsuccessful. The other patient was managed solely by radiation therapy. (Author)

  10. High prevalence of multidrug resistance and random distribution of mobile genetic elements among uropathogenic Escherichia coli (UPEC) of the four major phylogenetic groups.

    Science.gov (United States)

    Rijavec, Matija; Starcic Erjavec, Marjanca; Ambrozic Avgustin, Jerneja; Reissbrodt, Rolf; Fruth, Angelika; Krizan-Hergouth, Veronika; Zgur-Bertok, Darja

    2006-08-01

    One hundred and ten UTI Escherichia coli strains, from Ljubljana, Slovenia, were analyzed for antibiotic resistances, mobile DNA elements, serotype, and phylogenetic origin. A high prevalence of drug resistance and multidrug resistance was found. Twenty-six percent of the isolates harbored a class 1 integron, while a majority of the strains (56%) harbored rep sequences characteristic of F-like plasmids. int as well as rep sequences were found to be distributed in a random manner among strains of the four major phylogenetic groups indicating that all groups have a similar tendency to acquire and maintain mobile genetic elements frequently associated with resistance determinants.

  11. Association mapping of insecticide resistance in wild Anopheles gambiae populations: major variants identified in a low-linkage disequilbrium genome.

    Directory of Open Access Journals (Sweden)

    David Weetman

    2010-10-01

    Full Text Available Association studies are a promising way to uncover the genetic basis of complex traits in wild populations. Data on population stratification, linkage disequilibrium and distribution of variant effect-sizes for different trait-types are required to predict study success but are lacking for most taxa. We quantified and investigated the impacts of these key variables in a large-scale association study of a strongly selected trait of medical importance: pyrethroid resistance in the African malaria vector Anopheles gambiae.We genotyped ≈1500 resistance-phenotyped wild mosquitoes from Ghana and Cameroon using a 1536-SNP array enriched for candidate insecticide resistance gene SNPs. Three factors greatly impacted study power. (1 Population stratification, which was attributable to co-occurrence of molecular forms (M and S, and cryptic within-form stratification necessitating both a partitioned analysis and genomic control. (2 All SNPs of substantial effect (odds ratio, OR>2 were rare (minor allele frequency, MAF<0.05. (3 Linkage disequilibrium (LD was very low throughout most of the genome. Nevertheless, locally high LD, consistent with a recent selective sweep, and uniformly high ORs in each subsample facilitated significant direct and indirect detection of the known insecticide target site mutation kdr L1014F (OR≈6; P<10(-6, but with resistance level modified by local haplotypic background.Primarily as a result of very low LD in wild A. Gambiae, LD-based association mapping is challenging, but is feasible at least for major effect variants, especially where LD is enhanced by selective sweeps. Such variants will be of greatest importance for predictive diagnostic screening.

  12. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    Science.gov (United States)

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2018-03-14

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle

  13. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Magdalena Radwanska

    2007-05-01

    Full Text Available Effector responses induced by polarized CD4+ T helper 2 (Th2 cells drive nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha. IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(creIL-4Ralpha(-/lox deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox BALB/c mice, which developed ulcerating lesions following infection with L. major, Lck(creIL-4Ralpha(-/lox mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(creIL-4Ralpha(-/lox mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate that abrogation of IL-4 signaling in CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL-4Ralpha signaling in L

  14. Delay between pregnancy confirmation and sickle cell and thalassaemia screening: a population-based cohort study

    Science.gov (United States)

    Dormandy, Elizabeth; Gulliford, Martin C; Reid, Erin P; Brown, Katrina; Marteau, Theresa M

    2008-01-01

    Background Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. Aim To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. Design of study Cohort study of reported pregnancies. Setting Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. Method Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. Results There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0–10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6–18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7–9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. Conclusion About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated. PMID:18318968

  15. Chronic liver disease in transfusion-dependent thalassaemia: hepatitis B virus marker studies.

    OpenAIRE

    De Virgiliis, S; Fiorelli, G; Fargion, S; Cornacchia, G; Sanna, G; Cossu, P; Murgia, V; Cao, A

    1980-01-01

    The systematic screening of 253 children with transfusion-dependent homozygous beta-thalassaemia revealed a high incidence of hepatitis B virus markers. The highest frequencies of hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) were found in the group of patients with the smallest number of transfusions, while the highest frequency of antibody to hepatitis B surface antigen (anti-HBs) was detected in the patients who had had the largest number of transf...

  16. Development and evaluation of near-isogenic lines for major blast resistance gene(s) in Basmati rice.

    Science.gov (United States)

    Khanna, Apurva; Sharma, Vinay; Ellur, Ranjith K; Shikari, Asif B; Gopala Krishnan, S; Singh, U D; Prakash, G; Sharma, T R; Rathour, Rajeev; Variar, Mukund; Prashanthi, S K; Nagarajan, M; Vinod, K K; Bhowmick, Prolay K; Singh, N K; Prabhu, K V; Singh, B D; Singh, Ashok K

    2015-07-01

    A set of NILs carrying major blast resistance genes in a Basmati rice variety has been developed. Also, the efficacy of pyramids over monogenic NILs against rice blast pathogen Magnaporthe oryzae has been demonstrated. Productivity and quality of Basmati rice is severely affected by rice blast disease. Major genes and QTLs conferring resistance to blast have been reported only in non-Basmati rice germplasm. Here, we report incorporation of seven blast resistance genes from the donor lines DHMASQ164-2a (Pi54, Pi1, Pita), IRBLz5-CA (Pi2), IRBLb-B (Pib), IRBL5-M (Pi5) and IRBL9-W (Pi9) into the genetic background of an elite Basmati rice variety Pusa Basmati 1 (PB1). A total of 36 near-isogenic lines (NILs) comprising of 14 monogenic, 16 two-gene pyramids and six three-gene pyramids were developed through marker-assisted backcross breeding (MABB). Foreground, recombinant and background selection was used to identify the plants with target gene(s), minimize the linkage drag and increase the recurrent parent genome (RPG) recovery (93.5-98.6 %), respectively, in the NILs. Comparative analysis performed using 50,051 SNPs and 500 SSR markers revealed that the SNPs provided better insight into the RPG recovery. Most of the monogenic NILs showed comparable performance in yield and quality, concomitantly, Pusa1637-18-7-6-20 (Pi9), was significantly superior in yield and stable across four different environments as compared to recurrent parent (RP) PB1. Further, among the pyramids, Pusa1930-12-6 (Pi2+Pi5) showed significantly higher yield and Pusa1633-7-8-53-6-8 (Pi54+Pi1+Pita) was superior in cooking quality as compared to RP PB1. The NILs carrying gene Pi9 were found to be the most effective against the concoction of virulent races predominant in the hotspot locations for blast disease. Conversely, when analyzed under artificial inoculation, three-gene pyramids expressed enhanced resistance as compared to the two-gene and monogenic NILs.

  17. Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese.

    Science.gov (United States)

    Kabadi, Udaya M

    2017-06-01

    Lowering of body mass index (BMI) to ≥25 kg/m 2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI DM2. Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. All indices of IS and IR were lower ( P DM2 ( P < 0.05) in both groups. However, the declines in IS were greater ( P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher ( P < 0.05) than declines in IS in ObPreDM and ObDM2. In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.

  18. Bcr-Abl Amplification Plays a Major Role in Resistance to Tyrosine Kinase Inhibitors in K-562 Cell Line

    OpenAIRE

    Czyżewski, Krzysztof; Skonieczka, Katarzyna; Różycki, Patryk; Kołodziej, Beata; Kuryło-Rafińska, Beata; Kubicka, Małgorzata; Matiakowska, Karolina; Mucha, Barbara; Haus, Olga; Wysocki, Mariusz; Styczyński, Jan

    2012-01-01

    An emerging problem in patients with chronic myeloid leukemia (CML) is increasing resistance to tyrosine kinase inhibitors (TKIs). To determine genetic and cellular mechanisms involved in the development of resistance to TKIs, nine imatinib-resistant cell lines were derived from K- 562 cell line followed by testing of drug sensitivity, multidrug resistance proteins and cytogenetic studies. In imatinib-resistant cell lines cross-resistance to daunorubicin, etoposide and cytarabine were observe...

  19. Role of major histocompatibility complex class II in resistance of mice to naturally acquired infection with Syphacia obvelata

    Science.gov (United States)

    Stewart, Patricia W.; Chapes, Stephen K.

    2003-01-01

    Genetics plays a substantial role in host resistance in many host-parasite interactions. We examined the prevalence of naturally acquired infection with Syphacia obvelata in a number of mouse strains housed in a non-barrier facility. These mice, which included cross-bred and congenic, inbred strains on various genetic backgrounds, differ in the loci for the immune function genes--major histocompatibility complex class II (MHCII), toll-like receptor 4 (Tlr4), and solute carrier family 11, member 1 (Slc11a1)--which allowed comparisons of the impact of these genes on resistance to pinworm infection. Male and female mice of various ages were sampled over an 18-month period; infection was determined by use of the cellophane tape test. Results indicated that mice that were MHCII+/+ had a significantly lower prevalence of infection than did mice that were MHCII-/-. Differences were not seen between male and female mice. Although MHCII+/+ mice had an age-associated decrease in infection prevalence, such decrease was not seen in MHCII-/- mice. In contrast, infection prevalence in mice with the normal Tlr4 gene (Tlr4(LPS-n/LPS-n)) gene did not differ significantly compared with that in mice that were homozygous for either the point mutation (Tlr4(LPS-d/LPS-d)) or deletion (Tlr4(LPS-del/LPS-del)) of that gene. Likewise, the presence (Sle11a1r/r) or absence (Slc11a1s/s) of functional alleles for Slc11a1 had no effect on the prevalence of infection with S. obvelata. In conclusion, presence of MHCII, but not Tlr4 or Slc11a1 significantly influences prevalence of naturally acquired infection with S. obvelata. These data justify further comprehensive analyses of the immune components that are involved in pinworm resistance.

  20. Effect of a+ -thalassaemia on episodes of fever due to malaria and other causes: a communitybased cohort study in Tanzania

    NARCIS (Netherlands)

    Veenemans, J.; Jansen, E.J.S.; Baidjoe, A.Y.; Mbugi, E.V.; Demir, A.Y.; Kraaijenhagen, R.J.; Savelkoul, H.F.J.; Verhoef, H.

    2011-01-01

    Background It is controversial to what degree a+-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium. Methods In Tanzania, in children aged 6-60 months and height-for-age z-score <-1.5 SD (n = 612), rates of fevers due to

  1. Effects of iron salts and haemosiderin from a thalassaemia patient on oxygen radical damage as measured in the comet assay

    NARCIS (Netherlands)

    Anderson, D.; Yardley-Jones, A.; Hambly, R.J.; Vives-Bauza, C.; Smykatz-Kloss, V.; Chua-anusorn, W.; Webb, J.

    2000-01-01

    Thalassaemia is a group of genetic diseases where haemoglobin synthesis is impaired. This chronic anaemia leads to increased dietary iron absorption, which develops into iron overload pathology. Treatment through regular transfusions increases oxygen capacity but also provides iron through the red

  2. Electroconvulsive therapy and age: Age-related clinical features and effectiveness in treatment resistant major depressive episode.

    Science.gov (United States)

    Socci, Chiara; Medda, Pierpaolo; Toni, Cristina; Lattanzi, Lorenzo; Tripodi, Beniamino; Vannucchi, Giulia; Perugi, Giulio

    2018-02-01

    This study was aimed to compare clinical features, treatments outcomes and tolerability between young (18-45 years), middle age (46-64 years) and old (≥ 65 years) patients treated with bilateral ECT for treatment resistant major depressive episode. 402 patients were evaluated 1 day prior to ECT and a week after the treatment termination using the Clinical Global Impression Scale (CGI), the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS) and the Mini Mental State Examination (MMSE). Response was defined as a reduction of at least 50% from baseline on the HAM-D-17 score. Remission was defined as a score ≤ 7 on the HAM-D-17 at the final evaluation. Rates of response were not statistically different in the three groups (69.6% in old versus 63.5% in young and 55.5% in middle age groups). No significant differences were also observed in the proportions of remitters between the age groups (31.4% in young group, 27.7% in middle age group and 29.3% in old group). One week after the end of the ECT course the middle and old age groups showed a statistically significant increase in the MMSE score compared to baseline. We did not find significant differences between the three age groups in rates of premature drops-out due to ECT-related side effects. Our data support the use of ECT in elderly patients with treatment-resistant major depressive episode, with rates of response around 70% and effectiveness being independent from age. In the old age group the baseline cognitive impairment improved after ECT and no life-threatening adverse event was detected. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Relationship between major depression and insulin resistance: does it vary by gender or race/ethnicity among young adults aged 20-39 years?

    Science.gov (United States)

    Shen, Qiuhua; Bergquist-Beringer, Sandra

    2013-12-01

    To examine the relationship between major depression and insulin resistance by gender and race/ethnicity among young adults without diabetes mellitus. Secondary analyses of cross-sectional data from the National Health and Nutrition Examination Survey 1999-2008 were performed (n = 2265). Major depression was measured by the Composite International Diagnostic Interview and the Patient Health Questionnaire 9. Insulin resistance was measured by the homeostasis model assessment of insulin resistance. Multivariate logistic regression analyses adjusted for risk factors of insulin resistance were conducted. There was a significant negative association between major depression and insulin resistance among men. For women, no significant association was found. There was no significant interaction between race/ethnicity and major depression on insulin resistance (Wald χ(2) = 4.2927, P = 0.2315). Body mass index (BMI) and waist circumference (WC) were significantly associated with insulin resistance among both men (odds ratio [OR] 1.255, 95% confidence interval [CI] 1.195-1.318 for BMI; OR 1.095, 95% CI 1.076-1.115 for WC) and women (OR 1.220, 95% CI 1.182-1.260 for BMI; OR 1.084, 95% CI 1.064-1.105 for WC). There are gender differences in the relationship between major depression and insulin resistance among adults aged 20-39 years. No evidence was found to support the role of race/ethnicity in this relationship. Health care professionals should be aware of risk factors for insulin resistance and develop interventions to help prevent the progression of insulin resistance to type 2 diabetes mellitus. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  4. VITAMIN D STATUS IN CHILDREN WITH THALASSAEMIA IN NORTH EAST INDIA

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    Dipangkar Hazarika

    2016-11-01

    Full Text Available BACKGROUND The aim of the study was to determine the frequency of vitamin D deficiency and insufficiency in children with thalassaemia who were on regular blood transfusion. MATERIALS AND METHODS Total 25 children were included in this retrospective study in the age group of 2-14 years with confirmed diagnosis of thalassaemia syndrome. They were on regular blood transfusion every 3-4 weeks and they had serum ferritin >1000 µg/L irrespective of chelation therapy. Serum level of calcium, phosphorous, alkaline phosphatase, serum ferritin and 25OH vitamin D were estimated. RESULTS Out of 25 patients, 6 (24% showed sufficient amount of vitamin D, 6 (24% showed insufficiency, 10 (40% showed deficiency and 3 (12% showed severe deficiency. Children with vitamin D deficiency showed high level of serum ferritin level. Severe vitamin D deficiency was seen when number of transfusions were >20.14 children showed abnormal vitamin D level when their serum ferritin level was between 1000-2000 ng/dL. There was no association between use of iron-chelating agent, duration of their use and nutritional status with vitamin D level. CONCLUSION In regularly transfused thalassaemic children, vitamin D insufficiency and deficiency were common and they need frequent monitoring for early detection and management.

  5. Methicillin-resistant coagulase-negative staphylococci in the community: high homology of SCCmec IVa between Staphylococcus epidermidis and major clones of methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Barbier, François; Ruppé, Etienne; Hernandez, David; Lebeaux, David; Francois, Patrice; Felix, Benjamin; Desprez, Adeline; Maiga, Aminata; Woerther, Paul-Louis; Gaillard, Kevin; Jeanrot, Cécile; Wolff, Michel; Schrenzel, Jacques; Andremont, Antoine; Ruimy, Raymond

    2010-07-15

    Data on community spread of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) are scarce. We assessed their potential role as a reservoir of staphylococcal cassette chromosome mec (SCCmec) IVa, the leading SCCmec subtype in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Nasal carriage of MR-CoNS was prospectively investigated in 291 adults at hospital admission. MR-CoNS were characterized by SCCmec typing, long-range polymerase chain reaction (PCR) for SCCmec IV, and multiple-locus variable-number tandem repeat analysis (MLVA) for Staphylococcus epidermidis (MRSE) strains. Three SCCmec IVa elements were fully sequenced. The carriage rate of MR-CoNS was 19.2% (25.9% and 16.5% in patients with and patients without previous exposure to the health care system, respectively; P = .09). MR-CoNS strains (n = 83, including 58 MRSE strains with highly heterogeneous MLVA patterns) carried SCCmec type IVa (n = 9, all MRSE), other SCCmec IV subtypes (n = 9, including 7 MRSE), other SCCmec types (n = 15), and nontypeable SCCmec (n = 50). Long-range PCR indicated structural homology between SCCmec IV in MRSE and that in MRSA. Complete sequences of SCCmec IVa from 3 MRSE strains were highly homologous to those available for CA-MRSA, including major clones USA300 and USA400. MR-CoNS are probably disseminated in the community, notably in subjects without previous exposure to the health care system. MRSE, the most prevalent species, may act as a reservoir of SCCmec IVa for CA-MRSA.

  6. Rise of multiple insecticide resistance in Anopheles funestus in Malawi: a major concern for malaria vector control.

    Science.gov (United States)

    Riveron, Jacob M; Chiumia, Martin; Menze, Benjamin D; Barnes, Kayla G; Irving, Helen; Ibrahim, Sulaiman S; Weedall, Gareth D; Mzilahowa, Themba; Wondji, Charles S

    2015-09-15

    Deciphering the dynamics and evolution of insecticide resistance in malaria vectors is crucial for successful vector control. This study reports an increase of resistance intensity and a rise of multiple insecticide resistance in Anopheles funestus in Malawi leading to reduced bed net efficacy. Anopheles funestus group mosquitoes were collected in southern Malawi and the species composition, Plasmodium infection rate, susceptibility to insecticides and molecular bases of the resistance were analysed. Mosquito collection revealed a predominance of An. funestus group mosquitoes with a high hybrid rate (12.2 %) suggesting extensive species hybridization. An. funestus sensu stricto was the main Plasmodium vector (4.8 % infection). Consistently high levels of resistance to pyrethroid and carbamate insecticides were recorded and had increased between 2009 and 2014. Furthermore, the 2014 collection exhibited multiple insecticide resistance, notably to DDT, contrary to 2009. Increased pyrethroid resistance correlates with reduced efficacy of bed nets (change in resistance dynamics is mirrored by prevalent resistance mechanisms, firstly with increased over-expression of key pyrethroid resistance genes (CYP6Pa/b and CYP6M7) in 2014 and secondly, detection of the A296S-RDL dieldrin resistance mutation for the first time. However, the L119F-GSTe2 and kdr mutations were absent. Such increased resistance levels and rise of multiple resistance highlight the need to rapidly implement resistance management strategies to preserve the effectiveness of existing insecticide-based control interventions.

  7. May Renal Resistive Index Be an Early Predictive Tool of Postoperative Complications in Major Surgery? Preliminary Results

    Directory of Open Access Journals (Sweden)

    Enrico Giustiniano

    2014-01-01

    Full Text Available Background. Patients who undergo high-risk surgery represent a large amount of post-operative ICU-admissions. These patients are at high risk of experiencing postoperative complications. Renal Resistive Index was found to be related with renal dysfunction, hypertension, and posttraumatic hemorrhagic shock, probably due to vasoconstriction. We explored whether Renal Resistive Index (RRI, measured after awakening from general anesthesia, could have any relationship with postoperative complications. Methods. In our observational, stratified dual-center trial, we enrolled patients who underwent general anesthesia for high-risk major surgery. After awakening in recovery room (or during awakening period in subjects submitted to cardiac surgery we measured RRI by echo-color-Doppler method. Primary endpoint was the association of altered RRI (>0.70 and outcome during the first postoperative week. Results. 205 patients were enrolled: 60 (29.3% showed RRI > 0.70. The total rate of adverse event was 27 (18.6% in RRI ≤ 0.7 group and 19 (31.7% in RRI > 0.7 group (P=0.042. Significant correlation between RRI > 0.70 and complications resulted in pneumonia (P=0.016, septic shock (P=0.003, and acute renal failure (P=0.001 subgroups. Patients with RRI > 0.7 showed longer ICU stay (P=0.001 and lasting of mechanical ventilation (P=0.004. These results were confirmed in cardiothoracic surgery subgroup. RRI > 0.7 duplicates triplicates the risk of complications, both in general (OR 2.03 93 95% CI 1.02–4.02, P=0.044 and in cardiothoracic (OR 2.62 95% CI 1.11–6.16, P=0.027 population. Furthermore, we found RRI > 0.70 was associated with a triplicate risk of postoperative septic shock (OR 3.04, CI 95% 1.5–7.01; P=0.002.

  8. A Randomized Double-Blind Sham-Controlled Study of Transcranial Direct Current Stimulation for Treatment-Resistant Major Depression

    Directory of Open Access Journals (Sweden)

    Daniel eBlumberger

    2012-08-01

    Full Text Available Objectives: Transcranial direct current stimulation (tDCS has demonstrated some efficacy in treatment-resistant major depression (TRD. The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC and a control location such as the supraorbital region on for the cathode. Several open label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS. Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups.Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated. Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD.

  9. A single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector.

    Science.gov (United States)

    Riveron, Jacob M; Yunta, Cristina; Ibrahim, Sulaiman S; Djouaka, Rousseau; Irving, Helen; Menze, Benjamin D; Ismail, Hanafy M; Hemingway, Janet; Ranson, Hilary; Albert, Armando; Wondji, Charles S

    2014-02-25

    Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. Here, we demonstrate that the single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2, confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus. Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin-resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further supports the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and to design suitable resistance management strategies.

  10. A single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector

    Science.gov (United States)

    2014-01-01

    Background Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. Results Here, we demonstrate that the single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2, confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus. Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin-resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further supports the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. Conclusions This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and to design suitable resistance management strategies. PMID:24565444

  11. A major QTL corresponding to the Rk locus for resistance to root-knot nematodes in cowpea (Vigna unguiculata L. Walp.).

    Science.gov (United States)

    Huynh, Bao-Lam; Matthews, William C; Ehlers, Jeffrey D; Lucas, Mitchell R; Santos, Jansen R P; Ndeve, Arsenio; Close, Timothy J; Roberts, Philip A

    2016-01-01

    Genome resolution of a major QTL associated with the Rk locus in cowpea for resistance to root-knot nematodes has significance for plant breeding programs and R gene characterization. Cowpea (Vigna unguiculata L. Walp.) is a susceptible host of root-knot nematodes (Meloidogyne spp.) (RKN), major plant-parasitic pests in global agriculture. To date, breeding for host resistance in cowpea has relied on phenotypic selection which requires time-consuming and expensive controlled infection assays. To facilitate marker-based selection, we aimed to identify and map quantitative trait loci (QTL) conferring the resistance trait. One recombinant inbred line (RIL) and two F2:3 populations, each derived from a cross between a susceptible and a resistant parent, were genotyped with genome-wide single nucleotide polymorphism (SNP) markers. The populations were screened in the field for root-galling symptoms and/or under growth-chamber conditions for nematode reproduction levels using M. incognita and M. javanica biotypes. One major QTL was mapped consistently on linkage group VuLG11 of each population. By genotyping additional cowpea lines and near-isogenic lines derived from conventional backcrossing, we confirmed that the detected QTL co-localized with the genome region associated with the Rk locus for RKN resistance that has been used in conventional breeding for many decades. This chromosomal location defined with flanking markers will be a valuable target in marker-assisted breeding and for positional cloning of genes controlling RKN resistance.

  12. Deferasirox pharmacokinetics evaluation in a woman with hereditary haemochromatosis and heterozygous β-thalassaemia.

    Science.gov (United States)

    Allegra, Sarah; De Francia, Silvia; Longo, Filomena; Massano, Davide; Cusato, Jessica; Arduino, Arianna; Pirro, Elisa; Piga, Antonio; D'Avolio, Antonio

    2016-12-01

    We present the deferasirox pharmacokinetics evaluation of a female patient on iron chelation, for the interesting findings from her genetic background (hereditary haemochromatosis and heterozygous β-thalassaemia) and clinical history (ileostomy; iron overload from transfusions). Drug plasma concentrations were measured by an HPLC-UV validated method, before and after ileum resection. Area under deferasirox concentration curve over 24h (AUC) values were determined by the mixed log-linear rule, using Kinetica software. AUC was low also with high deferasirox dose as well as tolerability. Non invasive tissue iron quantification by magnetic resonance imaging or superconducting quantum interference device were prevented by a metal hip replacement. Good efficacy and normalisation of iron markers was obtained on long term. Therapeutic drug monitoring in patient in critical conditions may help to understand reasons for non response and set individualised treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Pharmacokinetics of Deferiprone in Patients with β-Thalassaemia : Impact of Splenectomy and Iron Status.

    Science.gov (United States)

    Limenta, Lie Michael George; Jirasomprasert, Totsapol; Jittangprasert, Piyada; Wilairat, Prapin; Yamanont, Praveena; Chantharaksri, Udom; Fucharoen, Suthat; Morales, Noppawan Phumala

    2011-01-01

    Iron-rich transfusions and/or a compensatory increase in iron absorption ultimately result in iron loading in patients with β-thalassaemia. Hence, without iron chelation, iron accumulates relentlessly. Deferiprone has been shown to be capable of reducing the iron burden in patients with b-thalassaemia. However, there is wide interpatient variation in deferiprone-induced urinary iron excretion (UIE). We hypothesized that splenectomy and iron status might influence the pharmacokinetic profiles of deferiprone in patients with β-thalassaemia/haemoglobin E, and the present study was aimed at examining this hypothesis. Thirty-one patients with β-thalassaemia/haemoglobin E (20 splenecto-mized and 11 non-splenectomized patients) were enrolled in the study. After an overnight fast, the subjects received a single oral dose of deferiprone 25 mg/kg of body weight. Blood samples were collected pre-dosing and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 and 480 minutes after dosing. Urine output was pooled and collected at 0-2, 2-4, 4-8, 8-12 and 12-24 hour intervals. Serum and urine concentrations of deferiprone and its metabolite deferiprone glucuronide were determined using a validated high-performance liquid chromatography method. Serum deferiprone-chelated iron and UIE were determined using a validated colourimetric method. No significant difference in the pharmacokinetic parameters of non-conjugated deferiprone was observed between splenectomized and non-splenectomized patients. However, the maximum serum concentration (C max ) and the area under the serum concentration-time curve (AUC) from time zero to infinity (AUC∞) values of deferiprone glucuronide were significantly lower (both p values of serum deferiprone-chelated iron, as well as UIE, were significantly higher (p values 7.1 µmol/L, 1645 mmol · min/L and 77.1 mmol, respectively) than in non-splenectomized patients (median values 3.1 µmol/L, 545 mmol · min/L and 12.5 µmol, respectively). Urinary

  14. The genetics of resistance to powdery mildew in cultivated oats (Avena sativa L.): current status of major genes.

    Science.gov (United States)

    Hsam, Sai L K; Mohler, Volker; Zeller, Friedrich J

    2014-05-01

    The genetics of resistance to powdery mildew caused by Blumeria graminis f. sp. avenae of four cultivated oats was studied using monosomic analysis. Cultivar 'Bruno' carries a gene (Pm6) that shows a recessive mode of inheritance and is located on chromosome 10D. Cultivar 'Jumbo' possesses a dominant resistance gene (Pm1) on chromosome 1C. In cultivar 'Rollo', in addition to the gene Pm3 on chromosome 17A, a second dominant resistance gene (Pm8) was identified and assigned to chromosome 4C. In breeding line APR 122, resistance was conditioned by a dominant resistance gene (Pm7) that was allocated to chromosome 13A. Genetic maps established for resistance genes Pm1, Pm6 and Pm7 employing amplified fragment length polymorphism (AFLP) markers indicated that these genes are independent of each other, supporting the results from monosomic analysis.

  15. QUANTITATIVE ULTRASOUND BONE DENSITOMETRY IN CHILDREN WITH THALASSAEMIA IN NORTH EAST INDIA

    Directory of Open Access Journals (Sweden)

    Chao Rochek Buragohain

    2016-11-01

    Full Text Available BACKGROUND Thalassaemic children who are on regular blood transfusion are at increased risk of hypothyroidism, growth hormone deficiency, hypoparathyroidism, diabetes mellitus and osteoporosis because of deposition of iron in various endocrine glands with age. Low bone mineral density is a significant problem in these children, which may lead to increased risk for fractures and suboptimal peak bone mass. The aim of the study is to determine the bone health status of children with thalassaemia using quantitative ultrasound densitometry. MATERIALS AND METHODS A case control study was done at Department of Paediatrics, Jorhat Medical College and Hospital, which included 32 regularly transfused thalassaemic children. Age and sex matched healthy controls were included. Quantitative ultrasound bone densitometry was done in both the groups and compared with each other. RESULTS Broadband Ultrasound Attenuation (BUA and Speed of Sound (SOS measurements were found to be independent of sex. BUA values in boys showed increasing trend with age, which was not observed in girls. SOS values did not show any increasing trend with age in both sexes. In both the groups, the BUA and SOS increased continuously with increasing age. The values of BUA were more in control group compared to case group while opposite was noticed with SOS values. BUA values were more when ferritin level was >2000 ng/dL and increased number of blood transfusion, whereas SOS values decreased with increase in serum ferritin level and number of transfusion, which was statistically significant (P=0.0125. Both BUA and SOS values decreased with increased severity of malnutrition, which was statistically significant for SOS (P=0.0266. CONCLUSION Quantitative ultrasound bone densitometry can be used as a screening method to assess the bone health status in children, particularly those with thalassaemia, but requires further studies in large groups.

  16. Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258.

    Science.gov (United States)

    Breurec, S; Guessennd, N; Timinouni, M; Le, T A H; Cao, V; Ngandjio, A; Randrianirina, F; Thiberge, J M; Kinana, A; Dufougeray, A; Perrier-Gros-Claude, J D; Boisier, P; Garin, B; Brisse, S

    2013-04-01

    The molecular epidemiology of third-generation cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in developing countries is poorly documented. From February 2007 to March 2008, we collected 135 3GC-R K. pneumoniae isolates from seven major towns in Maghreb (Morocco), West Africa (Senegal, Côte d'Ivoire), Central Africa (Cameroon), East Africa (Madagascar) and Southeast Asia (Vietnam). Their genetic diversity, assessed by multilocus sequence typing, was high (60 sequence types), reflecting multiclonality. However, two major clonal groups, CG15 (n = 23, 17% of isolates) and CG258 (n = 18, 13%), were detected in almost all participating centres. The two major clonal groups have previously been described in other parts of the world, indicating their global spread. The high diversity of enterobacterial repetitive intergenic consensus sequence-PCR banding patterns at the local level indicates that most isolates were epidemiologically unrelated. The isolates were characterized by the presence of multiple resistance determinants, most notably the concomitant presence of the aac(6')-Ib-cr, qnr and blaCTX-M-15 genes in 61 isolates (45%) belonging to 31 sequence types. These isolates were detected across a large geographical area including Cameroon (n = 1), Vietnam (n = 4), Madagascar (n = 10), Côte d'Ivoire (n = 12), Morocco (n = 13) and Senegal (n = 21). These results have major implications for patient management and highlight a potential reservoir for resistance determinants. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  17. Neurocognitive Effects of Repetitive Transcranial Magnetic Stimulation with a 2-Coil Device in Treatment-Resistant Major Depressive Disorder.

    Science.gov (United States)

    Kavanaugh, Brian C; Aaronson, Scott T; Clarke, Gregory N; Holtzheimer, Paul E; Johnson, Clark W; McDonald, William M; Schneider, M Bret; Carpenter, Linda L

    2018-04-02

    Neurocognitive dysfunction is an understudied and undertreated aspect of psychiatric research and treatment. There is emerging evidence to suggest that repetitive transcranial magnetic stimulation (rTMS) may possess neurocognition-enhancing capabilities. This study examined the neurocognitive data from a randomized, double-blind, sham-controlled trial of an investigational 2-coil rTMS device in antidepressant treatment or treatment-intolerant major depressive disorder patients. This device has the potential to stimulate deeper areas of the brain than the Food and Drug Administration-approved TMS devices, which primarily stimulate cortical brain areas and may therefore have different neurocognitive adverse effects. Patients received 20 daily rTMS treatments (10-Hz stimulation; either active or sham) with coil centers positioned over the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex. Neurocognitive safety was evaluated at baseline and within 72 hours of final treatment session with a computerized battery assessing aspects of attention and memory in 84 participants. There were no observed negative neurocognitive effects of the 2-coil rTMS device. A significant effect of active rTMS was observed on the quality of episodic memory. There were no observed effects for attention or working memory. Baseline quality of episodic memory predicted depression treatment response and remission, in that lower baseline episodic memory was associated with greater likelihood of depression response/remission. This was observed in logistic regression analyses controlling for treatment and baseline depressive symptoms. The 2-coil rTMS device is a cognitively safe treatment for treatment-resistant depression that may possess episodic memory-enhancing capabilities. Furthermore, baseline episodic memory may reflect an important predictor of subsequent depression treatment response/remission to rTMS.

  18. Nonconvulsive Electrotherapy for Treatment Resistant Unipolar and Bipolar Major Depressive Disorder: A Proof-of-concept Trial.

    Science.gov (United States)

    Regenold, William T; Noorani, Robert J; Piez, Deborah; Patel, Palak

    2015-01-01

    Electroconvulsive therapy (ECT) is the most effective therapy for treatment resistant major depressive disorder (TRD); however, some individuals with TRD refuse ECT over concern about adverse cognitive effects. Clinical observation of two patients with TRD who had a therapeutic response to intended ECT despite having only one or no seizure suggested that nonconvulsive electrical stimulation may be effective in some patients. This study tested the hypothesis that electrical brain stimulation applied like standard ECT, but below seizure threshold, can have therapeutic effects on TRD with fewer adverse cognitive effects. Thirteen outpatients with TRD (6 unipolar, 7 bipolar) who refused ECT participated in this open label adjunctive treatment study of nonconvulsive electrotherapy (NET) at the University of Maryland Medical Center. Brief pulse bifrontal electrical stimulation was given thrice weekly with a Thymatron System IV Integrated ECT Instrument. Seizure-free data were obtained from 11 of 13 subjects. Group mean Hamilton Depression Rating Scale 17-item version scores declined significantly (P = 0.001) from 20.3 to 8.6. Response and remission rates were 73% (8) and 55% (6), respectively. Cognitive testing using the Mini-Mental State Exam and the Autobiographical Memory Inventory-Short Form did not show declines typically observed with ECT. The therapeutic effect of NET on TRD was similar to that of ECT. Serious adverse effects and adverse cognitive effects were not observed. These results challenge the widespread belief that a seizure is necessary for the antidepressant effect of ECT and merit further investigation to determine whether NET is a viable alternative to ECT in some patients with TRD. Clinical trial posted on www.clinicaltrials.gov, identifier: NCT01065597. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Molecular Characterisation of α- and β-Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia.

    Science.gov (United States)

    Koh, Danny Xuan Rong; Raja Sabudin, Raja Zahratul Azma; Mohd Yusoff, Malisa; Hussin, Noor Hamidah; Ahmad, Rahimah; Othman, Ainoon; Ismail, Endom

    2017-09-01

    Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of α- and β-thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for α- and β-globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of α- and β-globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for α-thalassaemia were termination codon (T>C) Hb CS (α CS α), Cd59 (G>A) haemoglobin Adana (Hb Adana) (α Cd59 α), initiation codon (ATG>A-G) (α IniCd α), two-gene deletion (- SEA ), and single-gene 3.7-kb deletion (-α 3.7 ). For β-thalassaemia, there were Cd26 (G>A) Hb E (β E ), Cd19 (A>G) Haemoglobin Malay (Hb Malay) (β Cd19 ), and IVS 1-5 (G>C) (β IVS 1-5 ). © 2017 John Wiley & Sons Ltd/University College London.

  20. CLINICAL APPLICATION OF RECOMBINANT ERYTHROPOIETIN IN BETA-THALASSAEMIA INTERMEDIA.

    Science.gov (United States)

    Asadov, Ch; Alimirzoyeva, Z; Hasanova, M; Mammadova, T; Shirinova, A

    2016-06-01

    Research objective is to study the efficacy of recombinant erythropoietin (epoetin alfa) as alternative method of treatment beta-thalassemia intermedia. Study involved 58 patients with beta-thalassemia intermedia (23 women and 35 men). In all observed patients was defined levels of hemoglobin (Hb), red blood cells (RBC), erythrocyte indexes (MCV, MCH, MCHC), hemoglobin fractions (HbA, HbA2, HbF), serum ferritin, serum erythropoietin before and after administrated rEPO. All patients received rEPO during 6 month at the dose - 10000 IU subcutaneously. The majority of patients - 39 (67%) had a good response to rEPO (increase in hemoglobin level more than 20 g/l); 16 patients (28%) had a mean response (increase in Hb 10 - 20 g/l); in 3 (5%) patients occurred poor response to rEPO therapy (increase in Hb beta-thalassemia intermedia patients there was a statistically significant change in the number of RBC, levels of HbF and sEPO. The evaluation of interdependence between the indices of the baseline sEPO and increased Hb values in patients after rEPO treatment revealed the presence of the reverse direct relationship (r=-0.67). Based on the results, it can be concluded that the use of rEPO in complex therapy of beta-thalassemia intermedia leads to increased levels of Hb and consequently reducing the need for blood transfusions, and accordingly expected to prevent severe complications of blood transfusion (alloimmunization, hypersplenism, iron overload, contamination transmissible infections) facilitating normal growth and development, and a better quality of life.

  1. Identification of a major QTL together with several minor additive or epistatic QTLs for resistance to fire blight in apple in two related progenies

    NARCIS (Netherlands)

    Calenge, F.; Drouet, D.; Denance, C.; Weg, van de W.E.; Brisset, M.N.; Paulin, J.P.; Durel, C.E.

    2005-01-01

    Although fire blight, caused by the bacterium Erwinia amylovora, is one of the most destructive diseases of apple (Malus x domestica) worldwide, no major, qualitative gene for resistance to this disease has been identified to date in apple. We conducted a quantitative trait locus (QTL) analysis in

  2. Multiple resistances and complex mechanisms of Anopheles sinensis mosquito: a major obstacle to mosquito-borne diseases control and elimination in China.

    Directory of Open Access Journals (Sweden)

    Xuelian Chang

    2014-05-01

    Full Text Available Malaria, dengue fever, and filariasis are three of the most common mosquito-borne diseases worldwide. Malaria and lymphatic filariasis can occur as concomitant human infections while also sharing common mosquito vectors. The overall prevalence and health significance of malaria and filariasis have made them top priorities for global elimination and control programmes. Pyrethroid resistance in anopheline mosquito vectors represents a highly significant problem to malaria control worldwide. Several methods have been proposed to mitigate insecticide resistance, including rotational use of insecticides with different modes of action. Anopheles sinensis, an important malaria and filariasis vector in Southeast Asia, represents an interesting mosquito species for examining the consequences of long-term insecticide rotation use on resistance. We examined insecticide resistance in two An. Sinensis populations from central and southern China against pyrethroids, organochlorines, organophosphates, and carbamates, which are the major classes of insecticides recommended for indoor residual spray. We found that the mosquito populations were highly resistant to the four classes of insecticides. High frequency of kdr mutation was revealed in the central population, whereas no kdr mutation was detected in the southern population. The frequency of G119S mutation in the ace-1 gene was moderate in both populations. The classification and regression trees (CART statistical analysis found that metabolic detoxification was the most important resistance mechanism, whereas target site insensitivity of L1014 kdr mutation played a less important role. Our results indicate that metabolic detoxification was the dominant mechanism of resistance compared to target site insensitivity, and suggests that long-term rotational use of various insecticides has led An. sinensis to evolve a high insecticide resistance. This study highlights the complex network of mechanisms conferring

  3. Mapping and validation of a major QTL affecting resistance to pancreas disease (salmonid alphavirus) in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Gonen, S; Baranski, M; Thorland, I; Norris, A; Grove, H; Arnesen, P; Bakke, H; Lien, S; Bishop, S C; Houston, R D

    2015-11-01

    Pancreas disease (PD), caused by a salmonid alphavirus (SAV), has a large negative economic and animal welfare impact on Atlantic salmon aquaculture. Evidence for genetic variation in host resistance to this disease has been reported, suggesting that selective breeding may potentially form an important component of disease control. The aim of this study was to explore the genetic architecture of resistance to PD, using survival data collected from two unrelated populations of Atlantic salmon; one challenged with SAV as fry in freshwater (POP 1) and one challenged with SAV as post-smolts in sea water (POP 2). Analyses of the binary survival data revealed a moderate-to-high heritability for host resistance to PD in both populations (fry POP 1 h(2)~0.5; post-smolt POP 2 h(2)~0.4). Subsets of both populations were genotyped for single nucleotide polymorphism markers, and six putative resistance quantitative trait loci (QTL) were identified. One of these QTL was mapped to the same location on chromosome 3 in both populations, reaching chromosome-wide significance in both the sire- and dam-based analyses in POP 1, and genome-wide significance in a combined analysis in POP 2. This independently verified QTL explains a significant proportion of host genetic variation in resistance to PD in both populations, suggesting a common underlying mechanism for genetic resistance across lifecycle stages. Markers associated with this QTL are being incorporated into selective breeding programs to improve PD resistance.

  4. QTLs for Resistance to Major Rice Diseases Exacerbated by Global Warming: Brown Spot, Bacterial Seedling Rot, and Bacterial Grain Rot.

    Science.gov (United States)

    Mizobuchi, Ritsuko; Fukuoka, Shuichi; Tsushima, Seiya; Yano, Masahiro; Sato, Hiroyuki

    2016-12-01

    In rice (Oryza sativa L.), damage from diseases such as brown spot, caused by Bipolaris oryzae, and bacterial seedling rot and bacterial grain rot, caused by Burkholderia glumae, has increased under global warming because the optimal temperature ranges for growth of these pathogens are relatively high (around 30 °C). Therefore, the need for cultivars carrying genes for resistance to these diseases is increasing to ensure sustainable rice production. In contrast to the situation for other important rice diseases such as blast and bacterial blight, no genes for complete resistance to brown spot, bacterial seedling rot or bacterial grain rot have yet been discovered. Thus, rice breeders have to use partial resistance, which is largely influenced by environmental conditions. Recent progress in molecular genetics and improvement of evaluation methods for disease resistance have facilitated detection of quantitative trait loci (QTLs) associated with resistance. In this review, we summarize the results of worldwide screening for cultivars with resistance to brown spot, bacterial seedling rot and bacterial grain rot and we discuss the identification of QTLs conferring resistance to these diseases in order to provide useful information for rice breeding programs.

  5. Positive selection pressure introduces secondary mutations at Gag cleavage sites in human immunodeficiency virus type 1 harboring major protease resistance mutations

    DEFF Research Database (Denmark)

    Banke, S.; Lillemark, M.R.; Gerstoft, J.

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) specifically target the HIV-1 protease enzyme. Mutations in the enzyme can result in PI resistance (termed PI mutations); however, mutations in the HIV-1 gag region, the substrate for the protease enzyme, might also lead to PI...... resistance. We analyzed gag and pol sequence data from the following 313 HIV-1-infected patients: 160 treatment-naive patients, 93 patients failing antiretroviral treatment that included a PI (with no major PI mutations), and 60 patients failing antiretroviral treatment that included a PI (with major PI...... that positive selection pressure was the driving evolutionary force for the gag region in all three patient groups. An increase in positive selection was observed in gag cleavage site regions p7/p1/p6 only after the acquisition of major PI mutations, suggesting that amino acids in gag cleavage sites under...

  6. Major diseases, extensive misuse, and high antimicrobial resistance of Escherichia coli in large- and small-scale dairy cattle farms in Jordan.

    Science.gov (United States)

    Obaidat, Mohammad M; Bani Salman, Alaa E; Davis, Margaret A; Roess, Amira A

    2018-03-01

    This study aimed to determine the major diseases, antimicrobial use, and resistance in commensal Escherichia coli in dairy cattle in Jordan. Forty-three (large, n = 21; small, n = 22) farms were surveyed. A validated questionnaire was administered to the herdsmen to elicit information about disease prevalence, antimicrobial knowledge, and antimicrobial use. In addition, fecal samples were collected from 5 lactating animals on each farm. A total of 520 E. coli isolates were tested for resistance to 12 antimicrobials. From the herdsmen's perspective, the diseases that require use of veterinary services in large and small production systems were mastitis (51.2%), metritis (51.2%), and enteritis (39.5%), and the most commonly used antimicrobials were oxytetracycline and streptomycin. Dairy herdsmen (83.7%) reported that it is easy to purchase antimicrobials without a veterinary prescription and 97.7% of them more frequently changed the antimicrobial drug rather than increasing the dose when presented with nonresponse to treatment. Escherichia coli isolates exhibited high resistance to streptomycin (47.5%), tetracycline (45.4%), and ampicillin (34.2%). Less than 10% of isolates were resistant to chloramphenicol, kanamycin, gentamicin, ciprofloxacin, and ceftriaxone. Overall, 64.6 and 37.1% of the E. coli isolates exhibited resistance to ≥1 antimicrobial and multidrug resistance (resistance to ≥3 antimicrobial classes), respectively. The isolates exhibited 107 antimicrobial resistance profiles. This study indicates that antimicrobials are frequently misused in dairies in Jordan and that resistance among commensal E. coli toward antimicrobials of human and veterinary importance is high. Therefore, educational programs for herdsmen and enacting regulations and guidelines are necessary to promote the judicious use of antimicrobials in dairy animals in Jordan. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. The effect of multiple blood-feeding on the longevity and insecticide resistant phenotype in the major malaria vector Anopheles arabiensis (Diptera: Culicidae).

    Science.gov (United States)

    Oliver, Shüné V; Brooke, Basil D

    2014-08-23

    Anopheles arabiensis is a major malaria vector in Africa. Adult females are likely to imbibe multiple blood meals during their lifetime. This results in regular exposure to potential toxins and blood-meal induced oxidative stress. Defence responses to these stressors may affect other factors of epidemiological significance, such as insecticide resistance and longevity. The aims of this study were to examine the effect of multiple blood-feeding on insecticide tolerance/resistance with increasing age, to assess the underlying biochemical mechanisms for the responses recorded, and to assess the effect of multiple blood-feeding on the life histories of adult females drawn from insecticide resistant and susceptible laboratory reared An. arabiensis. Laboratory reared An. arabiensis females from an insecticide resistant and an insecticide susceptible colony were offered either a single blood meal or multiple blood meals at 3-day intervals. Their tolerance or resistance to insecticide was then monitored by WHO bioassay four hours post blood-feeding. The biochemical basis of the phenotypic response was assessed by examining the effect of blood on detoxification enzyme activity and the effect of blood-meals on detoxification enzyme activity in ageing mosquitoes. Control cohorts that were not offered any blood meals showed steadily decreasing levels of insecticide tolerance/resistance with age, whereas a single blood meal significantly increased tolerance/resistance primarily at the age of three days. The expression of resistance/tolerance in those cohorts fed multiple blood meals generally showed the least variation with age. These results were consistent following exposure to DDT and pyrethroids but not to malathion. Multiple blood-meals also maintained the DDT and permethrin resistant phenotype, even after treatment females had stopped taking blood-meals. Biochemical analysis suggests that this phenotypic effect in resistant females may be mediated by the maintenance of

  8. Molecular Characterization of Methicillin Resistant Staphylococcus aureus Strains Isolated from Intensive Care Units in Iran: ST22-SCCmec IV/t790 Emerges as the Major Clone.

    Science.gov (United States)

    Goudarzi, Mehdi; Goudarzi, Hossein; Sá Figueiredo, Agnes Marie; Udo, Edet E; Fazeli, Maryam; Asadzadeh, Mohammad; Seyedjavadi, Sima Sadat

    2016-01-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different patient populations is a major public health concern. This study determined the prevalence and distribution of circulating molecular types of MRSA in hospitalized patients in ICU of hospitals in Tehran. A total of 70 MRSA isolates were collected from patients in eight hospitals. Antimicrobial resistance patterns were determined using the disk diffusion method. The presence of toxin encoding genes and the vancomycin resistance gene were determined by PCR. The MRSA isolates were further analyzed using multi-locus sequence, spa, SCCmec, and agr typing. The MRSA prevalence was 93.3%. Antimicrobial susceptibility testing revealed a high resistance rate (97.1%) to ampicillin and penicillin. The rate of resistance to the majority of antibiotics tested was 30% to 71.4%. Two isolates belonging to the ST22-SCCmec IV/t790 clone (MIC ≥ 8 μg/ml) had intermediate resistance to vancomycin. The majority of MRSA isolates (24.3%) were associated with the ST22-SCCmec IV/t790 clone; the other MRSA clones were ST859-SCCmec IV/t969 (18.6%), ST239-SCCmec III/t037 (17.1%), and ST291-SCCmec IV/t030 (8.6%). The circulating MRSA strains in Iranian hospitals were genetically diverse with a relatively high prevalence of the ST22-SCCmec IV/t790 clone. These findings support the need for future surveillance studies on MRSA to better elucidate the distribution of existing MRSA clones and detect emergence of new MRSA clones.

  9. High-resolution mapping and characterization of qRgls2, a major quantitative trait locus involved in maize resistance to gray leaf spot.

    Science.gov (United States)

    Xu, Ling; Zhang, Yan; Shao, Siquan; Chen, Wei; Tan, Jing; Zhu, Mang; Zhong, Tao; Fan, Xingming; Xu, Mingliang

    2014-08-31

    Gray leaf spot (GLS) caused by Cercospora zeae-maydis (Czm) or Cercospora zeina (Cz) is a devastating maize disease and results in substantial yield reductions worldwide. GLS resistance is a quantitatively inherited trait. The development and cultivation of GLS-resistant maize hybrids are the most cost-effective and efficient ways to control this disease. We previously detected a major GLS resistance QTL, qRgls2, in bin 5.03-04, which spans the whole centromere of chromosome 5 encompassing a physical distance of ~110-Mb. With advanced backcross populations derived from the cross between the resistant Y32 and susceptible Q11 inbred lines, a sequential recombinant-derived progeny testing strategy was adapted to fine map qRgls2. We narrowed the region of qRgls2 from an initial ~110-Mb to an interval of ~1-Mb, flanked by the markers G346 and DD11. qRgls2 showed predominantly additive genetic effects and significantly increased the resistance percentage by 20.6 to 24.6% across multiple generations. A total of 15 genes were predicted in the mapped region according to the 5b.60 annotation of the maize B73 genome v2. Two pieces of the mapped qRgls2 region shared collinearity with two distant segments on maize chromosome 4. qRgls2, a major QTL involved in GLS resistance, was mapped to a ~1-Mb region close to the centromere of chromosome 5. There are 15 predicted genes in the mapped region. It is assumed that qRgls2 could be widely used to improve maize resistance to GLS.

  10. Pyrethroid resistance discovered in a major agricultural pest in southern Australia: the redlegged earth mite Halotydeus destructor (Acari: Penthaleidae).

    Science.gov (United States)

    Umina, Paul A

    2007-12-01

    The redlegged earth mite (Halotydeus destructor Tucker) is an important pest of field crops and pastures. Control of this pest relies heavily on chemicals, with few genuine alternatives presently available. Pesticide responses of H. destructor from the field with reported chemical control failures were compared with mites from susceptible 'control' populations. Toxicology bioassays were conducted on adult mites across multiple generations. Very high levels of resistance to two synthetic pyrethroids, bifenthrin and alpha-cypermethrin, were detected in this species for the first time. For bifenthrin, LC(50) estimates showed a difference in resistance of greater than 240 000-fold. Resistance to alpha-cypermethrin was almost 60 000-fold. This resistance was shown to be heritable, persisting after several generations of culturing. There was no evidence that resistance to organophosphorus chemicals had evolved, which is likely to be a direct consequence of the history of chemical applications these mites have experienced. These results highlight the need for more judicious management decisions in order to control pest species in a sustainable manner. The implications of these findings in regard to the management and future research of the redlegged earth mite are discussed. Copyright (c) 2007 Society of Chemical Industry.

  11. Antibiotic pollution in the Katari subcatchment of the Titicaca Lake: Major transformation products and occurrence of resistance genes.

    Science.gov (United States)

    Archundia, D; Duwig, C; Lehembre, F; Chiron, S; Morel, M-C; Prado, B; Bourdat-Deschamps, M; Vince, E; Aviles, G Flores; Martins, J M F

    2017-01-15

    An increasing number of studies pointed out the ubiquitous presence of medical residues in surface and ground water as well as in soil compartments. Not only antibiotics can be found in the environment but also their transformation products about which little information is generally available. The development of bacterial resistance to antibiotics is particularly worrying as it can lead to sanitary and health problems. Studies about the dissemination of antibiotics and associated resistances in the Bolivian Altiplano are scarce. We provide baseline information on the occurrence of Sulfamethoxazole (SMX) and Trimethoprim (TMP) antibiotics as well as on the most common human SMX transformation products (TP) and on the occurrence of sulfonamide resistance genes. The studied water and soil compartments presented high levels of antibiotic pollution. This situation was shown to be mainly linked with uncontrolled discharges of treated and untreated wastewaters, resulting on the presence of antibiotics in the Titicaca Lake. SMX TPs were detected in surface waters and on soil sampled next to the wastewater treatment plant (WWTP). SMX resistance genes sulI and sulII were widely detected in the basin hydrological network, even in areas unpolluted with antibiotics. Mechanisms of co-selection of antibiotic- and metal- resistance may be involved in the prevalence of ARG's in pristine areas with no anthropogenic activity and free of antibiotic pollution. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Thioridazine Induces Major Changes in Global Gene Expression and Cell Wall Composition in Methicillin-Resistant Staphylococcus aureus USA300

    DEFF Research Database (Denmark)

    Thorsing, Mette; Klitgaard, Janne Kudsk; Atilano, Magda L.

    2013-01-01

    Subinhibitory concentrations of the neuroleptic drug thioridazine (TDZ) are well-known to enhance the killing of methicillin-resistant Staphylococcus aureus (MRSA) by β-lactam antibiotics, however, the mechanism underlying the synergy between TDZ and β-lactams is not fully understood. In the pres......Subinhibitory concentrations of the neuroleptic drug thioridazine (TDZ) are well-known to enhance the killing of methicillin-resistant Staphylococcus aureus (MRSA) by β-lactam antibiotics, however, the mechanism underlying the synergy between TDZ and β-lactams is not fully understood....... In the present study, we have examined the effect of a subinhibitory concentration of TDZ on antimicrobial resistance, the global transcriptome, and the cell wall composition of MRSA USA300. We show that TDZ is able to sensitize the bacteria to several classes of antimicrobials targeting the late stages...

  13. Major depressive disorder and insulin resistance in nondiabetic young adults in the United States: the National Health and Nutrition Examination Survey, 1999-2002.

    Science.gov (United States)

    Qiuhua Shen; Bergquist-Beringer, Sandra; Sousa, Valmi D

    2011-04-01

    The association between depression and insulin resistance has been evaluated in previous studies with conflicting results. This study aimed to explore the relationship between major depressive disorder (MDD) and insulin resistance among nondiabetic young adult men and women in the United States. Analyses of cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 1999-2002, were conducted. The nationally representative sample consisted of 279 men and 358 women aged 20-39 years. MDD was determined by the WHO Composite International Diagnostic Interview (CIDI). Insulin resistance was measured by the homeostasis model assessment for insulin resistance. Of 637 subjects, 16 men and 18 women had MDD (weighted percentage = 6.6%, SE = 1.2). Using logistic regression, no significant association was found between MDD and insulin resistance among the nondiabetic young adults in bivariate analysis (β = -0.01, OR = 0.99, 95% CI = [0.38, 2.57], p = .98). A significant interaction effect between gender and MDD was observed. For men, MDD was negatively associated with insulin resistance after adjusting for age, race/ethnicity, waist circumference, smoking status, systolic blood pressure and triglyceride level (β = -2.12, OR = 0.12, 95% CI = [0.02, 0.62], p = .01). No significant association between MDD and insulin resistance among women was found (β = 0.61, OR = 1.84, 95% CI = [0.47, 7.14], p = .38). Overall findings suggest there is no significant association between MDD and insulin resistance among nondiabetic young adults aged 20-39 years. However, gender differences in this relationship were noted.

  14. A prospective study of the influence of a thalassaemia on morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in Gambian children

    DEFF Research Database (Denmark)

    Allen, S J; Rowe, P; Allsopp, C E

    1993-01-01

    The protective effect of alpha thalassaemia (-alpha/alpha alpha) against morbidity from falciparum malaria was assessed in a prospective study of rural Gambian children. The gene frequency for single alpha-globin gene deletions was 0.12. Malariometric indices measured during cross-sectional surveys...... and morbidity from malaria determined by weekly surveillance were similar in children with alpha thalassaemia and in those with a normal alpha-globin genotype. However, the small number of children who carried both alpha thalassaemia and the sickle cell trait had fewer clinical episodes of malaria than children...... with the sickle cell trait alone. Specific antibody responses and cell-mediated immune responses in vitro to defined Plasmodium falciparum antigens were measured in children participating in the study. In general, there was no evidence of an increased prevalence or intensity of humoral or cell-mediated immune...

  15. Identification of QTLs for resistance to sclerotinia stem rot and BnaC.IGMT5.a as a candidate gene of the major resistant QTL SRC6 in Brassica napus.

    Directory of Open Access Journals (Sweden)

    Jian Wu

    Full Text Available Stem rot caused by Sclerotinia sclerotiorum in many important dicotyledonous crops, including oilseed rape (Brassica napus, is one of the most devastating fungal diseases and imposes huge yield loss each year worldwide. Currently, breeding for Sclerotinia resistance in B. napus, as in other crops, can only rely on germplasms with quantitative resistance genes. Thus, the identification of quantitative trait locus (QTL for S. sclerotiorum resistance/tolerance in this crop holds immediate promise for the genetic improvement of the disease resistance. In this study, ten QTLs for stem resistance (SR at the mature plant stage and three QTLs for leaf resistance (LR at the seedling stage in multiple environments were mapped on nine linkage groups (LGs of a whole genome map for B. napus constructed with SSR markers. Two major QTLs, LRA9 on LG A9 and SRC6 on LG C6, were repeatedly detected across all environments and explained 8.54-15.86% and 29.01%-32.61% of the phenotypic variations, respectively. Genotypes containing resistant SRC6 or LRA9 allele showed a significant reduction in disease lesion after pathogen infection. Comparative mapping with Arabidopsis and data mining from previous gene profiling experiments identified that the Arabidopsis homologous gene of IGMT5 (At1g76790 was related to the SRC6 locus. Four copies of the IGMT5 gene in B. napus were isolated through homologous cloning, among which, only BnaC.IGMT5.a showed a polymorphism between parental lines and can be associated with the SRC6. Furthermore, two parental lines exhibited a differential expression pattern of the BnaC.IGMT5.a gene in responding to pathogen inoculation. Thus, our data suggested that BnaC.IGMT5.a was very likely a candidate gene of this major resistance QTL.

  16. Common variation in oxidative phosphorylation genes is not a major cause of insulin resistance or type 2 diabetes

    DEFF Research Database (Denmark)

    Snogdal, Lena Sønder; Wod, Mette; Grarup, Niels

    2012-01-01

    There is substantial evidence that mitochondrial dysfunction is linked to insulin resistance and is present in several tissues relevant to the pathogenesis of type 2 diabetes. Here, we examined whether common variation in genes involved in oxidative phosphorylation (OxPhos) contributes to type 2...

  17. Effect of α(+)-thalassaemia on episodes of fever due to malaria and other causes: a community-based cohort study in Tanzania.

    Science.gov (United States)

    Veenemans, Jacobien; Jansen, Esther J S; Baidjoe, Amrish Y; Mbugi, Erasto V; Demir, Ayşe Y; Kraaijenhagen, Rob J; Savelkoul, Huub F J; Verhoef, Hans

    2011-09-22

    It is controversial to what degree α(+)-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium. In Tanzania, in children aged 6-60 months and height-for-age z-score malaria and other causes were compared between those with heterozygous or homozygotes α(+)-thalassaemia and those with a normal genotype, using Cox regression models that accounted for multiple events per child. The overall incidence of malaria was 3.0/child-year (1, 572/526 child-years); no differences were found in malaria rates between genotypes (hazard ratios, 95% CI: 0.93, 0.82-1.06 and 0.91, 0.73-1.14 for heterozygotes and homozygotes respectively, adjusted for baseline factors that were predictive for outcome). However, this association strongly depended on age: among children aged 6-17 months, those with α(+)-thalassaemia experienced episodes more frequently than those with a normal genotype (1.30, 1.02-1.65 and 1.15, 0.80-1.65 for heterozygotes and homozygotes respectively), whereas among their peers aged 18-60 months, α(+)-thalassaemia protected against malaria (0.80, 0.68-0.95 and 0.78, 0.60-1.03; p-value for interaction 0.001 and 0.10 for hetero- and homozygotes respectively). No effect was observed on non-malarial febrile episodes. In this population, the association between α(+)-thalassaemia and malaria depends on age. Our data suggest that protection by α(+)-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity.

  18. Positive selection pressure introduces secondary mutations at Gag cleavage sites in human immunodeficiency virus type 1 harboring major protease resistance mutations

    DEFF Research Database (Denmark)

    Banke, S.; Lillemark, M.R.; Gerstoft, J.

    2009-01-01

    mutations). Additional sequences from 13 patients were included for longitudinal analysis. We assessed positive selection pressure on the gag/protease region using a test for the overall influence of positive selection and a total of five tests to identify positively selected single codons. We found...... that positive selection pressure was the driving evolutionary force for the gag region in all three patient groups. An increase in positive selection was observed in gag cleavage site regions p7/p1/p6 only after the acquisition of major PI mutations, suggesting that amino acids in gag cleavage sites under...... positive selection pressure could function as compensatory mutations for major PI mutations in the protease region. Isolated gag mutations did not appear to confer PI resistance, but mutations in the gag cleavage sites could substitute for minor PI resistance mutations in the protease region Udgivelsesdato...

  19. Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes.

    OpenAIRE

    Warren, A P; Ducroq, D H; Lehner, P J; Borysiewicz, L K

    1994-01-01

    Viruses which cause persistence in the naturally infected host are predicted to have evolved immune evasion mechanisms. Human cytomegalovirus (HCMV) causes significant morbidity and mortality in immunocompromised patients yet persists without clinical manifestations in seropositive individuals who have normal immune function. We report that HCMV infection in vitro impairs major histocompatibility complex class I (MHC-I) assembly accompanied by resistance to killing by cytotoxic CD8+ T lymphoc...

  20. A prospective study of the influence of a thalassaemia on morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in Gambian children

    DEFF Research Database (Denmark)

    Allen, S J; Rowe, P; Allsopp, C E

    1993-01-01

    and morbidity from malaria determined by weekly surveillance were similar in children with alpha thalassaemia and in those with a normal alpha-globin genotype. However, the small number of children who carried both alpha thalassaemia and the sickle cell trait had fewer clinical episodes of malaria than children...... with the sickle cell trait alone. Specific antibody responses and cell-mediated immune responses in vitro to defined Plasmodium falciparum antigens were measured in children participating in the study. In general, there was no evidence of an increased prevalence or intensity of humoral or cell-mediated immune...

  1. A Multiple Decrement Life Table Reveals That Host Plant Resistance and Parasitism Are Major Causes of Mortality for the Wheat Stem Sawfly.

    Science.gov (United States)

    Buteler, Micaela; Peterson, Robert K D; Hofland, Megan L; Weaver, David K

    2015-12-01

    This study investigated the dynamics of parasitism, host plant resistance, pathogens, and predation on the demography of wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), developing in susceptible (hollow stem) and resistant (solid stem) wheat hosts. This study is also the first to investigate the prevalence and impact of cannibalism on wheat stem sawfly mortality. Wheat stem sawflies were sampled in two commercial wheat fields over 4 yr from the egg stage through adult emergence, and multiple decrement life tables were constructed and analyzed. Cannibalism, host plant resistance, or unknown factors were the most prevalent factors causing egg mortality. Summer mortality of prediapause larvae ranged from 28 to 84%, mainly due to parasitism by Bracon cephi (Gahan) and Bracon lissogaster Muesebeck, cannibalism, and host plant resistance. Winter mortality ranged from 6 to 54% of the overwintering larvae, mainly due to unknown factors or pathogens. Cannibalism is a major cause of irreplaceable mortality because it is absolute, with only a single survivor in every multiple infested stem. Subsequent to obligate cannibalism, mortality of feeding larvae due to host plant resistance was lower in hollow stem wheat than in solid stem wheat. Mortality from host plant resistance was largely irreplaceable. Irreplaceable mortality due to parasitoids was greater in hollow stem wheat than in solid stem wheat. Host plant resistance due to stem solidness and parasitism in hollow stems cause substantial mortality in populations of actively feeding larvae responsible for all crop losses. Therefore, enhancing these mortality factors is vital to effective integrated pest management of wheat stem sawfly. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. QTLs for Resistance to Major Rice Diseases Exacerbated by Global Warming: Brown Spot, Bacterial Seedling Rot, and Bacterial Grain Rot

    OpenAIRE

    Mizobuchi, Ritsuko; Fukuoka, Shuichi; Tsushima, Seiya; Yano, Masahiro; Sato, Hiroyuki

    2016-01-01

    In rice (Oryza sativa L.), damage from diseases such as brown spot, caused by Bipolaris oryzae, and bacterial seedling rot and bacterial grain rot, caused by Burkholderia glumae, has increased under global warming because the optimal temperature ranges for growth of these pathogens are relatively high (around 30??C). Therefore, the need for cultivars carrying genes for resistance to these diseases is increasing to ensure sustainable rice production. In contrast to the situation for other impo...

  3. The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar typhimurium phage type DT204.

    Science.gov (United States)

    Baucheron, Sylvie; Imberechts, Hein; Chaslus-Dancla, Elisabeth; Cloeckaert, Axel

    2002-01-01

    Salmonella enterica serovar Typhimurium phage type DT204 strains isolated from cattle and animal feed in Belgium were characterized for high-level fluoroquinolone resistance mechanisms [MICs to enrofloxacin (Enr) and ciprofloxacin (Cip), 64 and 32 microg/ml, respectively]. These strains isolated during the periods 1991-1994, and in 2000 were clonally related as shown by pulsed-field gel electrophoresis (PFGE). Selected strains studied carried several mutations in the quinolone target genes, i.e., a double mutation in the quinolone resistance-determining region (QRDR) of gyrA leading to amino acid changes Ser83Ala and Asp87Asn, a single mutation in the QRDR of gyrB leading to amino acid change Ser464Phe, and a single mutation in the QRDR of parC leading to amino acid change Ser80Ile. Moreover, Western blot analysis showed overproduction of the AcrA periplasmic protein belonging to the AcrAB-ToIC efflux system. This suggested active efflux as additional resistance mechanism resulting in a multiple antibiotic resistance (MAR) phenotype, which was measurable by an increased level of resistance to the structurally unrelated antibiotic florfenicol in the absence of the specific floR resistance gene. The importance of the AcrAB-TolC efflux system in high-level fluoroquinolone resistance was further confirmed by inactivating the acrB gene coding for the multidrug transporter. This resulted in a 32-fold reduction of resistance level to Enr (MIC = 2 microg/ml) and actually in a susceptible phenotype according to clinical breakpoints. Thus, AcrB plays a major role in high-level fluoroquinolone resistance, even when multiple target gene mutations are present. The same effect was obtained using the recently identified efflux pump inhibitor (EPI) Phe-Arg-naphthylamide also termed MC207,110. Among several fluoroquinolones tested in combination with EPI, the MIC of Enr was reduced most significantly. Thus, using EPI together with fluoroquinolones such as Enr may be promising in

  4. Narrative as re-fusion: Making sense and value from sickle cell and thalassaemia trait.

    Science.gov (United States)

    Dyson, Simon M; Ahmad, Waqar Iu; Atkin, Karl

    2016-08-03

    The moral turn within sociology suggests that we need to be attentive to values and have a rapprochement with philosophy. The study of illness narratives is one area of sociology that has consistently addressed itself to moral domains but has tended to focus on stories of living with genetic or chronic illness per se rather than liminal states such as genetic traits. This article takes the case of genetic carriers within racialized minority groups, namely, those with sickle cell or thalassaemia trait, and takes seriously the notion that their narratives are ethical practices In line with the work of Paul Ricoeur, such storied practices are found to link embodiment, social relationships with significant others and wider socio-cultural and socio-political relations. At the same time, such practices are about embodying values. These narratives may be considered as practices that re-fuse what genetic counselling has de-fused, in order to make sense of a life in its entirety and to strive ethically and collectively towards preferred social realities. © The Author(s) 2016.

  5. Environmental monitoring of bacterial contamination and antibiotic resistance patterns of the fecal coliforms isolated from Cauvery River, a major drinking water source in Karnataka, India.

    Science.gov (United States)

    Skariyachan, Sinosh; Mahajanakatti, Arpitha Badarinath; Grandhi, Nisha Jayaprakash; Prasanna, Akshatha; Sen, Ballari; Sharma, Narasimha; Vasist, Kiran S; Narayanappa, Rajeswari

    2015-05-01

    The present study focuses prudent elucidation of microbial pollution and antibiotic sensitivity profiling of the fecal coliforms isolated from River Cauvery, a major drinking water source in Karnataka, India. Water samples were collected from ten hotspots during the year 2011-2012. The physiochemical characteristics and microbial count of water samples collected from most of the hotspots exhibited greater biological oxygen demand and bacterial count especially coliforms in comparison with control samples (p ≤ 0.01). The antibiotic sensitivity testing was performed using 48 antibiotics against the bacterial isolates by disk-diffusion assay. The current study showed that out of 848 bacterial isolates, 93.51% (n = 793) of the isolates were found to be multidrug-resistant to most of the current generation antibiotics. Among the major isolates, 96.46% (n = 273) of the isolates were found to be multidrug-resistant to 30 antibiotics and they were identified to be Escherichia coli by 16S rDNA gene sequencing. Similarly, 93.85% (n = 107), 94.49% (n = 103), and 90.22% (n = 157) of the isolates exhibited multiple drug resistance to 32, 40, and 37 antibiotics, and they were identified to be Enterobacter cloacae, Pseudomonas trivialis, and Shigella sonnei, respectively. The molecular studies suggested the prevalence of bla TEM genes in all the four isolates and dhfr gene in Escherichia coli and Sh. sonnei. Analogously, most of the other Gram-negative bacteria were found to be multidrug-resistant and the Gram-positive bacteria, Staphylococcus spp. isolated from the water samples were found to be methicillin and vancomycin-resistant Staphylococcus aureus. This is probably the first study elucidating the bacterial pollution and antibiotic sensitivity profiling of fecal coliforms isolated from River Cauvery, Karnataka, India.

  6. A review of three major fungal diseases of Coffea arabica L. in the rainforests of Ethiopia and progress in breeding for resistance in Kenya

    Directory of Open Access Journals (Sweden)

    Holger Hindorf

    2011-04-01

    Full Text Available In a review of their own research the authors summarize incidences and distributions of the most important fungal diseases in Ethiopia and progress in breeding for resistance. Ethiopia, as the centre of origin for Coffea arabica, hosts a large diversity of germplasm. The incidences of diseases are based on observations in the montane rainforests of the southeast (Harenna and southwest (Bonga, Berhane-Kontir, Yayu of Ethiopia. Major diseases are Coffee Leaf Rust (CLR, Hemileia vastatrix; Coffee Berry Disease (CBD, Colletotrichum kahawae and Coffee Wilt Disease (CWD, Gibberella xylarioides (Fusarium xylarioides. CLR incidences in Ethiopia were present in all regions with highs between January and March and lows between June and October. CBD was present mostly in Bonga (40.0% and Yayu (26.3%, but less frequent in Harenna (18.6% and Berhane-Kontir (6.0%. CWD as a recently developed disease in Arabica coffee could be detected ranging from 2.4% in Berhane-Kontir to 16.9% in Yayu. CLR has been a serious constraint in all production countries since it became prominent in Ceylon in the late 19th century after leaf infection defoliation affects plants. CBD was first observed in Kenya in 1922. The disease is currently confined to the African continent in all countries that grow Arabica coffee. In the mid-1990s in the Democratic Republic of Congo, Uganda and Tanzania a resurgence of CWD in Robusta coffee and in Ethiopia in Arabica coffee occurred. Over the last 40 years breeding activities have been carried out to combat CLR, CBD and CWD. Breeding for resistance against CLR in Arabica coffee has successfully utilized single or combinations of major genes designated as SH genes. Major gene resistance has also been deployed in breeding for resistance against CBD, whereas in the case of CWD, selections of tolerant Arabica accessions are being pursued from local landraces in Ethiopia.

  7. Genetic diversity of oxytetracycline-resistant bacteria and tet(M) genes in two major coastal areas of South Korea.

    Science.gov (United States)

    Germond, Arno; Kim, Soo-Jin

    2015-09-01

    This study aimed to analyse the prevalence and genetic diversity of the tet(M) resistance gene as well as the species composition of oxytetracycline-resistant bacteria in coastal areas of South Korea. Both culturable and non-culturable bacterial communities were sampled in 2010 and 2011 within two coastal areas (Wando and Geoje). tet(M) and 16S rRNA gene sequences were obtained by PCR and sequencing and were used for phylogenetic analyses. Quantitative PCR (qPCR) was performed to determine the prevalence of tet(M) in sampled areas. Phylogenetic analyses revealed high heterogeneity of tet(M) sequences between Wando and Geoje areas. Sequences found in Wando were highly similar to each other and were similar to sequences found in Japanese aquaculture sites. A larger diversity of tet(M) sequences was obtained from natural assemblage in Geoje. qPCR showed a high prevalence of tet(M) in Wando's aquaculture sites (up to 10 -2 gene copies per 16S rRNA copy) and for industrial sites in Geoje (up to 10 -3 gene copies per 16S rRNA copy). 16 rRNA-based identification showed that Vibrio sp. and Photobacterium sp. were the most representative species in Wando, whereas in Geoje a broader range of species was found, with several isolates identified as pathogenic Acinetobacter, Aeromonas and Klebsiella. Altogether, these results showed a high prevalence of tet(M) in both sites, and different origins of contamination were identified. Because several pathogenic strains of oxytetracycline-resistant bacteria were reported for the first time, these results strongly warrant further analyses and actions to prevent contamination events by antibiotics in South Korea. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  8. The effect of a single blood meal on the phenotypic expression of insecticide resistance in the major malaria vector Anopheles funestus

    Directory of Open Access Journals (Sweden)

    Coetzee Maureen

    2008-10-01

    Full Text Available Abstract Background Anopheles funestus is a major malaria vector in southern Africa. Vector control relies on the use of insecticide chemicals to significantly reduce the number of malaria vectors by targeting that portion of the female population that takes blood meals and subsequently rests indoors. It has been suggested that the intake of a blood meal may assist female mosquitoes to tolerate higher doses of insecticide through vigour tolerance. It is hypothesized that during the process of blood digestion, detoxification mechanisms required for the neutralizing of harmful components in the blood meal may also confer an increased ability to tolerate insecticide intoxication through increased enzyme regulation. Methods Bottle bioassays using a range of concentrations of the pyrethroid insecticide permethrin were performed on pyrethroid susceptible and resistant laboratory strains of An. funestus in order to detect differences in insecticide susceptibility following a single blood meal. Based on these results, a discriminating dosage was identified (double the lowest dosage that resulted in 100% mortality of the susceptible strain. Blood-fed and unfed females drawn from the resistant strain of An. funestus were then assayed against this discriminating dose, and the percentage mortality for each sample was scored and compared. Results In the insecticide dose response assays neither the fully susceptible nor the resistant strain of An. funestus showed any significant difference in insecticide susceptibility following a blood meal, regardless of the stage of blood meal digestion. A significant increase in the level of resistance was however detected in the resistant An. funestus strain following a single blood meal, based on exposure to a discriminating dose of permethrin. Conclusion The fully susceptible An. funestus strain did not show any significant alteration in susceptibility to insecticide following a blood meal suggesting that vigour

  9. The effect of a single blood meal on the phenotypic expression of insecticide resistance in the major malaria vector Anopheles funestus

    Science.gov (United States)

    Spillings, Belinda L; Coetzee, Maureen; Koekemoer, Lizette L; Brooke, Basil D

    2008-01-01

    Background Anopheles funestus is a major malaria vector in southern Africa. Vector control relies on the use of insecticide chemicals to significantly reduce the number of malaria vectors by targeting that portion of the female population that takes blood meals and subsequently rests indoors. It has been suggested that the intake of a blood meal may assist female mosquitoes to tolerate higher doses of insecticide through vigour tolerance. It is hypothesized that during the process of blood digestion, detoxification mechanisms required for the neutralizing of harmful components in the blood meal may also confer an increased ability to tolerate insecticide intoxication through increased enzyme regulation. Methods Bottle bioassays using a range of concentrations of the pyrethroid insecticide permethrin were performed on pyrethroid susceptible and resistant laboratory strains of An. funestus in order to detect differences in insecticide susceptibility following a single blood meal. Based on these results, a discriminating dosage was identified (double the lowest dosage that resulted in 100% mortality of the susceptible strain). Blood-fed and unfed females drawn from the resistant strain of An. funestus were then assayed against this discriminating dose, and the percentage mortality for each sample was scored and compared. Results In the insecticide dose response assays neither the fully susceptible nor the resistant strain of An. funestus showed any significant difference in insecticide susceptibility following a blood meal, regardless of the stage of blood meal digestion. A significant increase in the level of resistance was however detected in the resistant An. funestus strain following a single blood meal, based on exposure to a discriminating dose of permethrin. Conclusion The fully susceptible An. funestus strain did not show any significant alteration in susceptibility to insecticide following a blood meal suggesting that vigour tolerance through increased body

  10. The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

    Directory of Open Access Journals (Sweden)

    Shüné V Oliver

    Full Text Available Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and

  11. Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H30R and O1-ST648.

    Science.gov (United States)

    Sato, Toyotaka; Suzuki, Yuuki; Shiraishi, Tsukasa; Honda, Hiroyuki; Shinagawa, Masaaki; Yamamoto, Soh; Ogasawara, Noriko; Takahashi, Hiroki; Takahashi, Satoshi; Tamura, Yutaka; Yokota, Shin-Ichi

    2017-02-01

    Tigecycline (TGC) is a last-line drug for multidrug-resistant Enterobacteriaceae We investigated the mechanism(s) underlying TGC nonsusceptibility (TGC resistant/intermediate) in Escherichia coli clinical isolates. The MIC of TGC was determined for 277 fluoroquinolone-susceptible isolates (ciprofloxacin [CIP] MIC, fluoroquinolone-resistant isolates (CIP MIC, >2 mg/liter). The MIC 50 and MIC 90 for TGC in fluoroquinolone-resistant isolates were 2-fold higher than those in fluoroquinolone-susceptible isolates (MIC 50 , 0.5 mg/liter versus 0.25 mg/liter; MIC 90 , 1 mg/liter versus 0.5 mg/liter, respectively). Two fluoroquinolone-resistant isolates (O25b:H4-ST131-H30R and O125:H37-ST48) were TGC resistant (MICs of 4 and 16 mg/liter, respectively), and four other isolates of O25b:H4-ST131-H30R and an isolate of O1-ST648 showed an intermediate interpretation (MIC, 2 mg/liter). No TGC-resistant/intermediate strains were found among the fluoroquinolone-susceptible isolates. The TGC-resistant/intermediate isolates expressed higher levels of acrA and acrB and had lower intracellular TGC concentrations than susceptible isolates, and they possessed mutations in acrR and/or marR The MICs of acrAB-deficient mutants were markedly lower (0.25 mg/liter) than those of the parental strain. After continuous stepwise exposure to CIP in vitro, six of eight TGC-susceptible isolates had reduced TGC susceptibility. Two of them acquired TGC resistance (TGC MIC, 4 mg/liter) and exhibited expression of acrA and acrB and mutations in acrR and/or marR In conclusion, a population of fluoroquinolone-resistant E. coli isolates, including major extraintestinal pathogenic lineages O25b:H4-ST131-H30R and O1-ST648, showed reduced susceptibility to TGC due to overexpression of the efflux pump AcrAB-TolC, leading to decreased intracellular concentrations of the antibiotics that may be associated with the development of fluoroquinolone resistance. Copyright © 2017 American Society for Microbiology.

  12. Association of a specific major histocompatibility complex class IIβ single nucleotide polymorphism with resistance to lactococcosis in rainbow trout, Oncorhynchus mykiss (Walbaum).

    Science.gov (United States)

    Colussi, S; Prearo, M; Bertuzzi, S A; Scanzio, T; Peletto, S; Favaro, L; Modesto, P; Maniaci, M G; Ru, G; Desiato, R; Acutis, P L

    2015-01-01

    Major histocompatibility complex (MHC) loci encode glycoproteins that bind to foreign peptides and initiate immune responses through their interaction with T cells. MHC class II molecules are heterodimers consisting of α and β chains encoded by extremely variable genes; variation in exon 2 is responsible for the majority of observed polymorphisms, mostly concentrated in the codons specifying the peptide-binding region. Lactococcus garvieae is the causative agent of lactococcosis, a warm-water bacterial infection pathogenic for cultured freshwater and marine fish. It causes considerable economic losses, limiting the profitability and development of fish industries in general and the intensive production of rainbow trout, Oncorhynchus mykiss (Walbaum), in particular. The disease is currently controlled with vaccines and antibiotics; however, vaccines have short-term efficacy, and increasing concerns regarding antibiotic residues have called for alternative strategies. To explore the involvement of the MHC class II β-1 domain as a candidate gene for resistance to lactococcosis, we exposed 400 rainbow trout to naturally contaminated water. One single nucleotide polymorphism (SNP) and one haplotype were associated with resistance (P trout resistant to lactococcosis. © 2014 John Wiley & Sons Ltd.

  13. Single Breath-Hold Physiotherapy Technique; Effective tool for T2* magnetic resonance imaging in young patients with thalassaemia major

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    Surekha T. Mevada

    2016-02-01

    Full Text Available Magnetic resonance imaging using T2* (MRI T2* is a highly sensitive and non-invasive technique for the detection of tissue iron load. Although the single breath-hold multi-echo T2* technique has been available at the Sultan Qaboos University Hospital (SQUH, Muscat, Oman, since 2006, it could not be performed on younger patients due to their inability to hold their breath after expiration. This study was carried out between May 2007 and May 2015 and assessed 50 SQUH thalassaemic patients aged 7‒17 years old. Seven of these patients underwent baseline and one-year follow-up MRI T2* scans before receiving physiotherapy training. Subsequently, all patients were trained by a physiotherapist to hold their breath for approximately 15‒20 seconds at the end of expiration before undergoing baseline and one-year follow-up MRI T2* scans. Failure rates for the pre- and post-training groups were 6.0% and 42.8%, respectively. These results indicate that the training of thalassaemic patients in breathhold techniques is beneficial and increases rates of compliance for MRI T2* scans.

  14. Predominance of carbapenem-resistant Pseudomonas aeruginosa isolates carrying blaIMP and blaVIM metallo-β-lactamases in a major hospital in Costa Rica.

    Science.gov (United States)

    Toval, Francisco; Guzmán-Marte, Anel; Madriz, Vivian; Somogyi, Teresita; Rodríguez, César; García, Fernando

    2015-01-01

    This study aimed to assess the molecular basis of the resistance to carbapenems in clinical isolates of Pseudomonas aeruginosa recovered from a tertiary-level health facility in San José, Costa Rica. A total of 198 non-duplicated isolates were evaluated for their susceptibility to β-lactams, aminoglycosides and fluoroquinolones. The production of metallo-β-lactamases (MBLs), the presence of MBL encoding genes (blaIMP, blaVIM and blaGIM-1) and the occurrence of these genes within class 1 integrons were investigated. In addition, an ERIC2 PCR fingerprinting method was used to elucidate the distribution of the detected MBL genes within the strain collection. Of the 198 isolates tested, 125 (63.1 %) were categorized as carbapenem-resistant. The majority (88.8 %) of the carbapemen-resistant isolates also showed resistance to ceftazidime, cefepime, aztreonam, ticarcillin/clavulanic acid, amikacin, gentamicin, tobramycin, ciprofloxacin and gatifloxacin. Among the carbapenem-resistant isolates, 102 (81.6 %) showed MBL activity. Strikingly, both blaIMP and blaVIM genes were simultaneously detected in most (94.1 %) of the 102 MBL producers. Five carbapenem-resistant MBL producers were positive only for blaIMP genes. Almost 70 % of the isolates examined harboured the intI1 gene, accompanied by the sul1 and qacEΔ1 genes in 136 (99 %) and 122 (89 %) isolates, respectively. The majority (94.4 %) of the carbapenem-resistant isolates carried the intI1 gene, in contrast to 26 % of the carbapenem-susceptible isolates. Ninety-three out of 96 (96.9 %) isolates carrying both blaIMP and blaVIM genes also harboured the intI1, sul1 and qacEΔ1 genes. Gene cassettes from carbapenem-susceptible and MBL-negative carbapenem-resistant isolates encoded aminoglycoside-resistance enzymes (aadA2, aadA4 and aadA6) as well as orfD and qacF genes. RAPD analysis distributed 126 of the isolates in 29 clusters. Eighty of the 90 blaIMP (+) blaVIM (+) isolates were sorted into 16

  15. γδβ-thalassaemias 1 and 2 are the result of a 100 kpb deletion in the human β-globin cluster.

    NARCIS (Netherlands)

    R. Taramelli; D. Kioussis; E. Vanin; K. Bartram; J. Groffen; J. Hurst; F.G. Grosveld (Frank)

    1986-01-01

    textabstractThe DNA spanning two large deletions in the human beta-globin gene cluster (gamma beta-thalassaemia 1 and 2) has been cloned by cosmid cloning and chromosomal walking. The entire region was mapped and analyzed for the presence of repetitive sequences. The results show that the affected

  16. Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox.

    Science.gov (United States)

    Viprakasit, Vip; Ibrahim, Hishamshah; Ha, Shau-Yin; Ho, Phoebe Joy; Li, Chi-Kong; Chan, Lee-Lee; Chiu, Chang-Fang; Sutcharitchan, Pranee; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Xue, Hong-Ling; Bowden, Donald K; Lin, Kai-Hsin

    2011-03-01

    Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.

  17. Fine mapping of Msv1, a major QTL for resistance to Maize Streak Virus leads to development of production markers for breeding pipelines.

    Science.gov (United States)

    Nair, Sudha K; Babu, Raman; Magorokosho, Cosmos; Mahuku, George; Semagn, Kassa; Beyene, Yoseph; Das, Biswanath; Makumbi, Dan; Lava Kumar, P; Olsen, Michael; Boddupalli, Prasanna M

    2015-09-01

    Msv1 , the major QTL for MSV resistance was delimited to an interval of 0.87 cM on chromosome 1 at 87 Mb and production markers with high prediction accuracy were developed. Maize streak virus (MSV) disease is a devastating disease in the Sub-Saharan Africa (SSA), which causes significant yield loss in maize. Resistance to MSV has previously been mapped to a major QTL (Msv1) on chromosome 1 that is germplasm and environment independent and to several minor loci elsewhere in the genome. In this study, Msv1 was fine-mapped through QTL isogenic recombinant strategy using a large F 2 population of CML206 × CML312 to an interval of 0.87 cM on chromosome 1. Genome-wide association study was conducted in the DTMA (Drought Tolerant Maize for Africa)-Association mapping panel with 278 tropical/sub-tropical breeding lines from CIMMYT using the high-density genotyping-by-sequencing (GBS) markers. This study identified 19 SNPs in the region between 82 and 93 Mb on chromosome 1(B73 RefGen_V2) at a P < 1.00E-04, which coincided with the fine-mapped region of Msv1. Haplotype trend regression identified a haplotype block significantly associated with response to MSV. Three SNPs in this haplotype block at 87 Mb on chromosome 1 had an accuracy of 0.94 in predicting the disease reaction in a collection of breeding lines with known responses to MSV infection. In two biparental populations, selection for resistant Msv1 haplotype demonstrated a reduction of 1.03-1.39 units on a rating scale of 1-5, compared to the susceptible haplotype. High-throughput KASP assays have been developed for these three SNPs to enable routine marker screening in the breeding pipeline for MSV resistance.

  18. Genetic diversity of methicillin resistant Staphylococcus aureus strains isolated from burn patients in Iran: ST239-SCCmec III/t037 emerges as the major clone.

    Science.gov (United States)

    Goudarzi, Mehdi; Bahramian, Mahnaz; Satarzadeh Tabrizi, Mahboobeh; Udo, Edet E; Figueiredo, Agnes Marie Sá; Fazeli, Maryam; Goudarzi, Hossein

    2017-04-01

    Methicillin-resistant Staphylococcus aureus (MRSA) as a major cause of infection in health care, hospital and community settings is a global health concern. The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of circulating molecular types of MRSA in a burn hospital in Tehran, the capital of Iran. During a 10-month study period, 106 Staphylococcus aureus isolates were assessed. Isolates were subjected to susceptibility testing using the disk diffusion method and Polymerase Chain Reaction (PCR) for detection of mecA, fem and nuc genes. The presence of PVL and tst encoding genes were determined by PCR method. All the MRSA isolates were genotyped by multilocus sequence typing (MLST), spa typing, SCCmec typing and agr typing. The presence of mecA gene was confirmed in all the Staphylococcus aureus isolates. Antimicrobial susceptibility testing revealed a high resistance rate (90.6%) to ampicillin, tetracycline, and erythromycin. The rates of resistance to remaining antibiotics tested varied between 18.9% and 84.9%. The high- level of resistance to mupirocin was confirmed in 19.8% of MRSA strains isolated from burn patients. Multi-drug resistance was observed in 90.6% of isolates. Sixteen of the 106 MRSA isolates (15.1%) harbored PVL-encoding genes. The majority of our MRSA strains carried SCCmec III (71.7%). ST239-SCCmec III/t037 (34%) was the most common genotype followed by ST239-SCCmec III/t030 (24.5%), ST15-SCCmec IV/t084 (15.1%), ST22-SCCmec IV/t790 (13.2%), and ST239-SCCmec III/t631 (13.2%). Mupirocin resistant MRSA isolates belonged to ST15-SCCmec IV/t084 (40%), ST22-SCCmec IV/t790 (23.3%), ST239-SCCmec III/t631 (20%), and ST239-SCCmec III/t030 (16.7%) clones. The results showed that genetically diverse strains of MRSA are circulating in our burn hospitals with relatively high prevalence of ST239-SCCmec III/t037 clone. The findings support the need for regular surveillance of MRSA to determine the distribution of

  19. Temporal distribution and insecticide resistance profile of two major arbovirus vectors Aedes aegypti and Aedes albopictus in Yaoundé, the capital city of Cameroon.

    Science.gov (United States)

    Kamgang, Basile; Yougang, Aurelie P; Tchoupo, Micareme; Riveron, Jacob M; Wondji, Charles

    2017-10-10

    Aedes aegypti and Ae. albopictus are the major epidemic vectors of several arbovirus diseases such as yellow fever, dengue, Zika and chikungunya worldwide. Both Aedes vectors are presents in Cameroon; however, knowledge on the dynamic of the distribution of these species across cities and their resistance profile to insecticide are limited. Here, we assessed the current distribution of Ae. aegypti and Ae. albopictus in Yaoundé, the Capital City, established the resistance profile to insecticides and explored the resistance mechanisms involved. Immature stages of Aedes were sampled in several breeding sites in December 2015 (dry season) and June 2016 (rainy season) in three central neighborhoods and four peripheral neighborhoods and reared to adult stage. The G0 adults were used for molecular identification and genotyping of F1534C mutation in Ae. aegypti. Bioassays and piperonyl butoxide (PBO) assays were carried out according to WHO guidelines. Analysis revealed that both species Ae. aegypti and Ae. albopictus are present in all prospected sites in Yaounde. However, in the dry season Ae. aegypti is most abundant in neighborhoods located in downtown. In contrast, Ae. albopictus was found most prevalent in suburbs whatever the season and in downtown during the rainy season. Bioassay analysis showed that both Ae. aegypti and Ae. albopictus, are resistant to 0.05% deltamethrin, 0.1% bendiocarb and 4% dichlorodiphenyltrichloroethane (DDT). A decreased of susceptibility to 0.75% permethrin and a full susceptibility to malathion 5% was observed. The mortality rate was increased after pre-exposure to synergist PBO. None of Ae. aegypti assayed revealed the presence of F1534C mutation. These findings are useful to planning vector control programme against arbovirus vectors in Cameroon and can be used as baseline in Africa where data on Aedes resistance is very scarce to plan further works.

  20. THE IMPACT OF FERTILIZATION AND FOLIAR STIMULATION PRODUCTS BOTH ON INCREASING THE RESISTANCE TO MAJOR PHYTOPATHOGENS ATTACKS, AND ON INCREASING THE QUANTITY AND QUALITY OF WINE GRAPES HARVEST

    Directory of Open Access Journals (Sweden)

    Cristina BUNESCU

    2014-12-01

    Full Text Available The paper aimed to demonstrate the impact of fertilization and foliar stimulation products both on increasing the resistance to major phytopathogens attacks, and on increasing the quantity and quality of wine grapes harvest. Applying the foliar fertilizer products Plonvit Kali (c1, Tytanit (c2 and Optysil (c3 to vines, for a period of three years (2011/2013, in phenophases of intensive growth of shoots and grapes at approved dosages, simultaneously with pesticide treatment, not only a reduction of pathogenic fungi attack was obtained, but also and an increase of harvest without diminishing the quality of the grapes.

  1. Confirmation and fine-mapping of a major QTL for resistance to infectious pancreatic necrosis in Atlantic salmon (Salmo salar: population-level associations between markers and trait

    Directory of Open Access Journals (Sweden)

    Moen Thomas

    2009-08-01

    Full Text Available Abstract Background Infectious pancreatic necrosis (IPN is one of the most prevalent and economically devastating diseases in Atlantic salmon (Salmo salar farming worldwide. The disease causes large mortalities at both the fry- and post-smolt stages. Family selection for increased IPN resistance is performed through the use of controlled challenge tests, where survival rates of sib-groups are recorded. However, since challenge-tested animals cannot be used as breeding candidates, within-family selection is not performed and only half of the genetic variation for IPN resistance is being exploited. DNA markers linked to quantitative trait loci (QTL affecting IPN resistance would therefore be a powerful selection tool. The aim of this study was to identify and fine-map QTL for IPN-resistance in Atlantic salmon, for use in marker-assisted selection to increase the rate of genetic improvement for this trait. Results A genome scan was carried out using 10 large full-sib families of challenge-tested Atlantic salmon post-smolts and microsatellite markers distributed across the genome. One major QTL for IPN-resistance was detected, explaining 29% and 83% of the phenotypic and genetic variances, respectively. This QTL mapped to the same location as a QTL recently detected in a Scottish Atlantic salmon population. The QTL was found to be segregating in 10 out of 20 mapping parents, and subsequent fine-mapping with additional markers narrowed the QTL peak to a 4 cM region on linkage group 21. Challenge-tested fry were used to show that the QTL had the same effect on fry as on post-smolt, with the confidence interval for QTL position in fry overlapping the confidence interval found in post-smolts. A total of 178 parents were tested for segregation of the QTL, identifying 72 QTL-heterozygous parents. Genotypes at QTL-heterozygous parents were used to determine linkage phases between alleles at the underlying DNA polymorphism and alleles at single markers or

  2. Transfusion-related acute lung injury (TRALI in two thalassaemia patients caused by the same multiparous blood donor

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    George J Kontoghiorghes

    2017-10-01

    Full Text Available Two separate episodes of transfusion-related acute lung injury (TRALI in thalassaemia patients caused by red blood cell transfusions from the same multiparous blood donor are reported. Both cases had the same symptomatology and occurred 10-60 minutes of transfusion. The patients presented dyspnea, sweating, fatigue, dizziness, fever, and sense of losing consciousness. The chest x-ray showed a pulmonary oedema-like picture with both lungs filled with fluid. The patients were treated in the intensive therapy unit. They were weaned off the ventilator and discharged following hospitalization 7 and 9 days respectively. The TRALI syndrome was diagnosed to be associated with HLA-specific donor antibodies against mismatched HLA-antigens of the transfused patients. Haemovigilance improvements are essential for reducing the morbidity and mortality in transfused patients. Blood from multiparous donors should be tested for the presence of IgG HLA-Class I and –Class II antibodies before being transfused in thalassaemia and other chronically transfused patients.

  3. Amino acid substitutions at the major insertion loop of Candida albicans sterol 14alpha-demethylase are involved in fluconazole resistance.

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    Nidia Alvarez-Rueda

    Full Text Available BACKGROUND: In the fungal pathogen Candida albicans, amino acid substitutions of 14alpha-demethylase (CaErg11p, CaCYP51 are associated with azole antifungals resistance. This is an area of research which is very dynamic, since the stakes concern the screening of new antifungals which circumvent resistance. The impact of amino acid substitutions on azole interaction has been postulated by homology modeling in comparison to the crystal structure of Mycobacterium tuberculosis (MT-CYP51. Modeling of amino acid residues situated between positions 428 to 459 remains difficult to explain to date, because they are in a major insertion loop specifically present in fungal species. METHODOLOGY/PRINCIPAL FINDING: Fluconazole resistance of clinical isolates displaying Y447H and V456I novel CaErg11p substitutions confirmed in vivo in a murine model of disseminated candidiasis. Y447H and V456I implication into fluconazole resistance was then studied by site-directed mutagenesis of wild-type CaErg11p and by heterogeneously expression into the Pichia pastoris model. CLSI modified tests showed that V447H and V456I are responsible for an 8-fold increase in fluconazole MICs of P. pastoris mutants compared to the wild-type controls. Moreover, mutants showed a sustained capacity for producing ergosterol, even in the presence of fluconazole. Based on these biological results, we are the first to propose a hybrid homology structure-function model of Ca-CYP51 using 3 different homology modeling programs. The variable position of the protein insertion loop, using different liganded or non-liganded templates of recently solved CYP51 structures, suggests its inherent flexibility. Mapping of recognized azole-resistant substitutions indicated that the flexibility of this region is probably enhanced by the relatively high glycine content of the consensus. CONCLUSIONS/SIGNIFICANCE: The results highlight the potential role of the insertion loop in azole resistance in the human

  4. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    Directory of Open Access Journals (Sweden)

    Rima eMoghnieh

    2015-02-01

    Full Text Available Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO-associated bacteremia.This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012.It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP, and 57.3% were gram-negative (GN. GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias. Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms and Klebsiellapneumoniae(13.3% of total, 23.3% of GN organisms were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/ tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p value<0.05.

  5. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.

    Science.gov (United States)

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Our findings have major

  6. Prevalence and Antimicrobial Resistance of Salmonella Isolates Recovered from Retail Pork in Major Village Markets in Tai'an Region, China.

    Science.gov (United States)

    Miao, Zengmin; Li, Song; Qin, Kun; Zhou, Yufa

    2017-10-01

    The current study was undertaken to evaluate Salmonella contamination in retail pork at major village markets of the Tai'an region, China. In total, 200 retail pork samples were collected from four village markets between June 2015 and February 2016, of which 69 samples (34.5%) were determined to be positive for Salmonella. Eleven serotypes were identified from the 69 Salmonella isolates, and Salmonella Derby was the most common (18 of 69, 26.1%), followed by Typhimurium (17 of 69, 24.6%) and Meleagridis (11 of 69, 15.9%). Antimicrobial susceptibility testing showed that antimicrobial resistance against tetracycline was the most prevalent (42 of 69, 60.9%), but antimicrobial resistance against both ceftriaxone and cefotaxime was 1.4% (1 of 69) and 2.9% (2 of 69), respectively. Multilocus sequence typing revealed that the 69 Salmonella isolates were divided into 11 sequence types (STs), among which ST40 (18 of 69, 26.1%) was the most common, followed by ST34 (15 of 69, 21.7%) and ST64 (13 of 69, 18.8%). Collectively, retail pork at village markets in the Tai'an region has a high Salmonella contamination rate, and these isolates exhibit broad-spectrum antimicrobial resistance. However, the absence of a dominant ST demonstrates that the Salmonella isolates from retail pork may be of diverse origins.

  7. Dietary supplementation with Cynodon dactylon (L.) enhances innate immunity and disease resistance of Indian major carp, Catla catla (Ham.).

    Science.gov (United States)

    Kaleeswaran, B; Ilavenil, S; Ravikumar, S

    2011-12-01

    Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P feeding. Administration of C. dactylon mixed diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the experimental diet groups than the control. All these experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Etiology of Infectious Complications and Antibiotic-Resistance of Major Causative Agents in Victims with Severe Injury

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    T. A. Vasina

    2007-01-01

    Full Text Available Objective: to analyze the spectrum of major pathogens of infectious complications in patients with concomitant injury.Materials and methods. 560 biological samples taken from 331 patients were bacteriologically studied. A significant reduction in the isolation frequency of Pseudomonas aeruginosa and an increase in etiological role of Staphylococcus aureus were ascertained in victims with severe injury and concomitant infectious complications during long-term 1982—1984 and 2002—2004 follow-ups.Results. The significant pathogens of infectious complications in concomitant injuries are Staphylococcus aureus, Klebsiella and Escherichia coli. Vancomycin, imipenem/cilastatin, and amikacin are shown to be the most effective drugs for early antibiotic therapy. Thus, the findings reflect structural changes in the leading causative agents of infectious complications in victims with severe injury. If their principal pathogen was Pseudomonas aeruginosa in the 1990s, Staphylococcus aureus and representatives in the colibacillus group prevail today. This supports and generates a need for continuous microbiological monitoring of the causative agents of pyoin-flammatory complications in intensive care units wherein patients with immunosuppression are also present. Pathogen monitoring makes it possible to apply of a well-grounded and rational package of preventive and therapeutic measures and to perform early target antibiotic therapy. 

  9. The effect of metal pollution on the life history and insecticide resistance phenotype of the major malaria vector Anopheles arabiensis (Diptera: Culicidae.

    Directory of Open Access Journals (Sweden)

    Shüné V Oliver

    Full Text Available Metal exposure is one of the commonest anthropogenic pollutants mosquito larvae are exposed to, both in agricultural and urban settings. As members of the Anopheles gambiae complex, which contains several major malaria vector species including An. arabiensis, are increasingly adapting to polluted environments, this study examined the effects of larval metal exposure on various life history traits of epidemiological importance. Two laboratory strains of An. arabiensis, SENN (insecticide susceptible and SENN DDT (insecticide resistant, were reared in maximum acceptable toxicity concentrations, (MATC-the highest legally accepted concentration of cadmium chloride, lead nitrate and copper nitrate. Following these exposures, time to pupation, adult size and longevity were determined. Larvae reared in double the MATC were assessed for changes in malathion and deltamethrin tolerance, measured by lethal time bottle bioassay, as well as changes in detoxification enzyme activity. As defence against oxidative stress has previously been demonstrated to affect the expression of insecticide resistance, catalase, glutathione peroxidase and superoxide dismutase activity was assessed. The relative metal toxicity to metal naïve larvae was also assessed. SENN DDT larvae were more tolerant of metal pollution than SENN larvae. Pupation in SENN larvae was significantly reduced by metal exposure, while adult longevity was not affected. SENN DDT showed decreased adult size after larval metal exposure. Adult insecticide tolerance was increased after larval metal exposure, and this effect appeared to be mediated by increased β-esterase, cytochrome P450 and superoxide dismutase activity. These data suggest an enzyme-mediated positive link between tolerance to metal pollutants and insecticide resistance in adult mosquitoes. Furthermore, exposure of larvae to metal pollutants may have operational consequences under an insecticide-based vector control scenario by increasing

  10. Heterogeneity of chromosome damage in [beta]-thalassaemia traits. An evaluation of spontaneous and [gamma]-ray-induced micronuclei and chromosome aberrations in lymphocytes in vitro after G[sub 0] and G[sub 2] phase irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaja, A.P.; Sharma, N.K. (Bhabha Atomic Research Centre, Bombay (India). Molecular Biology and Agriculture Div.)

    1994-07-01

    This study is an attempt to evaluate the chromosomal radiosensitivity of [beta]-thalassaemia traits compared with healthy individuals from the general population, necessitated by the fact that [beta]-thalassaemia trait is present in 1-17% of different population groups in India and the chances of encountering them in radiation and chemical related industries do exist. Spontaneous chromosome aberration frequencies in peripheral blood lymphocytes from [beta]-thalassaemia traits were found to be in the normal range, whereas significantly higher frequencies of micronuclei (MN) were observed in thalassaemia traits. Based on MN frequency at 2 Gy, [beta]-thalassaemia traits fall into two distinct categories. A hypersensitive group with significant increase in radiation-induced MN over the control group, and a second group with MN frequency slightly above normal individuals. Even when compared with the fitted data at 2 Gy obtained from the pooled results of extensive dose-response investigations from 0.5-5 Gy [gamma]-rays with normal donors for MN, dicentrics and total aberrations, the difference between the means of MN frequencies in [beta]-thalassaemia traits and normals is significant. (author).

  11. SLI1 (YGR212W) is a major gene conferring resistance to the sphingolipid biosynthesis inhibitor ISP-1, and encodes an ISP-1 N-acetyltransferase in yeast.

    Science.gov (United States)

    Momoi, Michiko; Tanoue, Daisuke; Sun, Yidi; Takematsu, Hiromu; Suzuki, Yusuke; Suzuki, Minoru; Suzuki, Akemi; Fujita, Tetsuro; Kozutsumi, Yasunori

    2004-07-01

    ISP-1 (myriocin) is a potent inhibitor of serine palmitoyltransferase, the primary enzyme of sphingolipid biosynthesis, and is a useful tool for studying the biological functions of sphingolipids in both mammals and yeast (Saccharomyces cerevisiae). In a previous study, we cloned yeast multicopy suppressor genes for ISP-1, and one of these, YPK1/SLI2, was shown to encode a serine/threonine kinase which is a yeast homologue of mammalian SGK1 (serum/glucocorticoid-regulated kinase 1). In the present study, another gene, termed SLI1 (YGR212W; GenBank accession number CAA97239.1), was characterized. Sli1p has weak similarity to Atf1p and Atf2p, which are alcohol acetyltransferases. Although a sli1-null strain grew normally, the IC50 of ISP-1 for the growth of this strain was markedly decreased compared with that for the parental strain, indicating that Sli1p is a major contributor to ISP-1 resistance in yeast. On a sli1-null background, the increase in resistance to ISP-1 induced by YPK1 gene transfection was almost abolished. These data indicate that Sli1p co-operates with Ypk1p in mediating resistance to ISP-1 in yeast. Sli1p was found to convert ISP-1 into N-acetyl-ISP-1 in vitro. Furthermore, N-acetyl-ISP-1 did not share the ability of ISP-1 to inhibit the growth of yeast cells, and the serine palmitoyltransferase inhibitory activity of N-acetyl-ISP-1 was much lower than that of ISP-1. These data suggest that Sli1p inactivates ISP-1 due to its N-acetyltransferase activity towards ISP-1.

  12. A Major Facilitator Superfamily Transporter-Mediated Resistance to Oxidative Stress and Fungicides Requires Yap1, Skn7, and MAP Kinases in the Citrus Fungal Pathogen Alternaria alternata.

    Directory of Open Access Journals (Sweden)

    Li-Hung Chen

    Full Text Available Major Facilitator Superfamily (MFS transporters play an important role in multidrug resistance in fungi. We report an AaMFS19 gene encoding a MFS transporter required for cellular resistance to oxidative stress and fungicides in the phytopathogenic fungus Alternaria alternata. AaMFS19, containing 12 transmembrane domains, displays activity toward a broad range of substrates. Fungal mutants lacking AaMFS19 display profound hypersensitivities to cumyl hydroperoxide, potassium superoxide, many singlet oxygen-generating compounds (eosin Y, rose Bengal, hematoporphyrin, methylene blue, and cercosporin, and the cell wall biosynthesis inhibitor, Congo red. AaMFS19 mutants also increase sensitivity to copper ions, clotrimazole, fludioxonil, and kocide fungicides, 2-chloro-5-hydroxypyridine (CHP, and 2,3,5-triiodobenzoic acid (TIBA. AaMFS19 mutants induce smaller necrotic lesions on leaves of a susceptible citrus cultivar. All observed phenotypes in the mutant are restored by introducing and expressing a wild-type copy of AaMFS19. The wild-type strain of A. alternata treated with either CHP or TIBA reduces radial growth and formation and germination of conidia, increases hyphal branching, and results in decreased expression of the AaMFS19 gene. The expression of AaMFS19 is regulated by the Yap1 transcription activator, the Hog1 and Fus3 mitogen-activated protein (MAP kinases, the 'two component' histidine kinase, and the Skn7 response regulator. Our results demonstrate that A. alternata confers resistance to different chemicals via a membrane-bound MFS transporter.

  13. Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial

    Directory of Open Access Journals (Sweden)

    B Salehi

    2015-01-01

    Full Text Available Background: Electroconvulsive therapy (ECT is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD. Materials and Methods: In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2 nd , 4 th , 6 th , and 8 th ECT. Depression was assessed by Hamilton depression scale. Results: The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P 0.05. But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05. The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05. Conclusion: Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD.

  14. Increased cortical excitability with prefrontal high-frequency repetitive transcranial magnetic stimulation in adolescents with treatment-resistant major depressive disorder.

    Science.gov (United States)

    Croarkin, Paul E; Wall, Christopher A; Nakonezny, Paul A; Buyukdura, Jeylan S; Husain, Mustafa M; Sampson, Shirlene M; Emslie, Graham J; Kozel, F Andrew

    2012-02-01

    To examine changes in motor cortical excitability in adolescent subjects receiving 30 sessions of high-frequency prefrontal repetitive transcranial magnetic stimulation (rTMS). Eight adolescents with treatment-resistant major depressive disorder (MDD) enrolled in an open augmentation trial of 10 Hz rTMS. Resting motor thresholds were obtained by the visualization of movement method with a maximum likelihood threshold hunting computer algorithm at baseline and after every five sessions of rTMS. Motor threshold was recorded as the percentage of total machine output at each measurement. Motor threshold data from baseline, weeks 2, 4, and 5 were included in a mixed model repeated measure analysis to examine a change in least square mean effect over time. The omnibus effect did not reach statistical significance (F=1.25, p=0.32). However, multiple comparisons from the overall model demonstrated a decrease in the least square mean motor threshold. The mean contrast from baseline to week 5 approached significance (p=0.07). Moreover, a post-hoc analysis with a Wilcoxon signed ranks test demonstrated a significant decrease at week 5 (p=0.03). This suggests that high-frequency rTMS may increase cortical excitability in adolescents with treatment-resistant MDD.

  15. LIGHT Is critical for IL-12 production by dendritic cells, optimal CD4+ Th1 cell response, and resistance to Leishmania major.

    Science.gov (United States)

    Xu, Guilian; Liu, Dong; Okwor, Ifeoma; Wang, Yang; Korner, Heinrich; Kung, Sam K P; Fu, Yang-Xin; Uzonna, Jude E

    2007-11-15

    Although studies indicate LIGHT (lymphotoxin (LT)-like, exhibits inducible expression and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) enhances inflammation and T cell-mediated immunity, the mechanisms involved in this process remain obscure. In this study, we assessed the role of LIGHT in IL-12 production and development of CD4(+) Th cells type one (Th1) in vivo. Bone marrow-derived dendritic cells from LIGHT(-/-) mice were severely impaired in IL-12p40 production following IFN-gamma and LPS stimulation in vitro. Furthermore, blockade of LIGHT in vitro and in vivo with HVEM-Ig and LT beta receptor (LTbetaR)-Ig leads to impaired IL-12 production and defective polyclonal and Ag-specific IFN-gamma production in vivo. In an infection model, injection of HVEM-Ig or LTbetaR-Ig into the usually resistant C57BL/6 mice results in defective IL-12 and IFN-gamma production and severe susceptibility to Leishmania major that was reversed by rIL-12 treatment. This striking susceptibility to L. major in mice injected with HVEM-Ig or LTbetaR-Ig was also reproduced in LIGHT(-/-) --> RAG1(-/-) chimeric mice. In contrast, L. major-infected LTbeta(-/-) mice do not develop acute disease, suggesting that the effect of LTbetaR-Ig is not due to blockade of membrane LT (LTalpha1beta2) signaling. Collectively, our data show that LIGHT plays a critical role for optimal IL-12 production by DC and the development of IFN-gamma-producing CD4(+) Th1 cells and its blockade results in severe susceptibility to Leishmania major.

  16. Endocrine investigation and follow up in thalassaemia. Time for specific guidelines

    Directory of Open Access Journals (Sweden)

    N. Skordis

    2011-12-01

    Full Text Available Iron overload due to multiple transfusions affects the endocrine glands especially the anterior pituitary, the pancreas, the thyroid and the parathyroids. This leads to a variety of endocrinopathies and growth failure. Delayed puberty, hypogonadism, growth hormone deficiency in adults, hypothyroidism, hypoparathyroidism and diabetes are common and around 20% of patients have more than one endocrinopathy. In this paper suggestions for guidelines concerning diagnosis, investigation and treatment are proposed for the following clinical entities encountered in thalassaemia patients: i Growth failure: after the age of 9-10 rears there is a slowing of growth velocity, the pathogenesis of which is multifactorial and anaemia, folate deficiency and hypersplenism are implicated. Desferrioxamine toxicity has been reported as cause of the abnormal upper to lower segment ratio. Growth hormone is given in selected cases. ii Delayed puberty and hypogonadism: are the most obvious clinical consequences of iron overload in both sexes. Primary and secondary amenorrhoea are very common in women. Sex steroid replacement therapy is the optimal therapeutic regime which has a great impact on the quality of life of adult thalassaemia patients. iii Fertility: Women with TM, who are regularly transfused and are well chelated can now become pregnant either spontaneously or by inducing ovulation. Pregnancy must carefully monitored. iv Growth hormone deficiency in adult thalassaemics: This occurs in a high prevalence and since GH in adults is involved in numerous biological functions, especially of the heart, proper assessment of this hormone is needed and consideration of the need for replacement. v Hypothyroidism and hypoparathyroidism: these deficiencies are also discussed. 由于多次输血引起的铁过载影响内分泌腺,尤其是垂体前叶、胰腺、甲状腺以及甲状旁腺 这导致各种内分泌病和成长失败。 青春期延迟、性腺机能减

  17. Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Niggemann, P.; Krings, T.; Thron, A. [Dept. of Neuroradiology, RWTH-Aachen Hosital (Germany); Hans, F. [Dept. of Neurosurgery, RWTH Aachen Hospital (Germany); 1

    2005-04-01

    A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained.

  18. Estimation of folate binding capacity (unsaturated and total) in normal human serum and in β-thalassaemia

    International Nuclear Information System (INIS)

    Moulopoulos, S.; Mantzos, J.; Gyftaki, E.; Kesse-Elias, M.; Alevizou-Terzaki, V.; Souli-Tsimili, E.

    1978-01-01

    A method is described for measuring the total serum folate binding capacity (TBC) after treating the serum with urea at pH5.5, the unsaturated serum folate binding capacity (UBC) being determined without treatment with urea. The method was applied to 50 normal controls and 20 patients with homozygous β-thalassaemia. The results show an increase in folate binding capacity after treating the serum with urea in all cases studied. There is no correlation between serum folic acid level and total or unsaturated folate binding capacity or per cent saturation. The method described is a simple and rapid one for screening the different groups studied for saturated and unsaturated specific folate-binding proteins. (author)

  19. Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

    International Nuclear Information System (INIS)

    Niggemann, P.; Krings, T.; Thron, A.; Hans, F.

    2005-01-01

    A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained

  20. Saturation Mapping of a Major Effect QTL for Stripe Rust Resistance on Wheat Chromosome 2B in Cultivar Napo 63 Using SNP Genotyping Arrays

    Directory of Open Access Journals (Sweden)

    Dejun Han

    2017-04-01

    Full Text Available Stripe rust or yellow rust (YR, caused by Puccinia striiformis f. sp. tritici (Pst, is one of the most important diseases of wheat (Triticum aestivum L.. Widespread deployment of resistant cultivars is the best means of achieving durable disease control. The red grain, spring wheat cultivar Napo 63 produced by CIMMYT in the 1960s shows a high level of adult-plant resistance to stripe rust in the field. To elucidate the genetic basis of resistance in this cultivar we evaluated 224 F2:3 lines and 175 F2:6 recombinant inbred lines (RILs derived from a cross between Napo 63 and the Pst-susceptible line Avocet S. The maximum disease severity (MDS data of F2:3 lines and the relative area under the disease progress curve (rAUDPC data of RILs were collected during the 2014–2015 and 2015–2016 wheat growing seasons, respectively. Combined bulked segregant analysis and 90K single nucleotide polymorphism (SNP arrays placed 275 of 511 polymorphic SNPs on chromosome 2B. Sixty four KASP markers selected from the 275 SNPs and 76 SSR markers on 2B were used to identify a chromosome region associated with rust response. A major effect QTL, named Qyrnap.nwafu-2BS, was identified by inclusive composite interval mapping and was preliminarily mapped to a 5.46 cM interval flanked by KASP markers 90K-AN34 and 90K-AN36 in chromosome 2BS. Fourteen KASP markers more closely linked to the locus were developed following a 660K SNP array analysis. The QTL region was finally narrowed to a 0.9 cM interval flanked by KASP markers 660K-AN21 and 660K-AN57 in bin region 2BS-1-0.53. The resistance of Napo 63 was stable across all environments, and as a QTL, explained an average 66.1% of the phenotypic variance in MDS of F2:3 lines and 55.7% of the phenotypic variance in rAUDPC of F5:6 RILs. The short genetic interval and flanking KASP markers developed in the study will facilitate marker-assisted selection, gene pyramiding, and eventual positional cloning of Qyrnap.nwafu-2BS.

  1. Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing.

    Directory of Open Access Journals (Sweden)

    Max Lataillade

    Full Text Available It is unknown whether HIV-positive patients experiencing virologic failure (VF on boosted-PI (PI/r regimens without drug resistant mutations (DRM by standard genotyping harbor low-level PI resistant variants. CASTLE compared the efficacy of atazanavir/ritonavir (ATV/r with lopinavir/ritonavir (LPV/r, each in combination with TVD in ARV-naïve subjects.To determine if VF on an initial PI/r-based regimen possess low-level resistant variants that may affect a subsequent PI-containing regimen.Patients experiencing VF on a Tenofovir/Emtricitabine+PI/r regimen were evaluated by ultra deep sequencing (UDS for mutations classified/weighted by Stanford HIVdb. Samples were evaluated for variants to 0.4% levels. 36 VF subjects were evaluated by UDS; 24 had UDS for PI and RT DRMs. Of these 24, 19 (79.2% had any DRM by UDS. The most common UDS-detected DRM were NRTI in 18 subjects: M184V/I (11, TAMs(7 & K65R(4; PI DRMs were detected in 9 subjects: M46I/V(5, F53L(2, I50V(1, D30N(1, and N88S(1. The remaining 12 subjects, all with VLs12 for ATV or LPV: N88S (at 0.43% level-mutational load 1,828 in 1 subject on ATV; I50V (0.44%-mutational load 110 and L76V (0.52%-mutational load 20 in 1 subject each, both on LPV. All VF samples remained phenotypically susceptible to the treatment PI/r.Among persons experiencing VF without PI DRMs with standard genotyping on an initial PI/r regimen, low-level variants possessing major PI DRMs were present in a minority of cases, occurred in isolation, and did not result in phenotypic resistance. NRTI DRMs were detected in a high proportion of subjects. These data suggest that PIs may remain effective in subjects experiencing VF on a PI/r-based regimen when PI DRMs are not detected by standard or UDS genotyping.

  2. Frequency of Gγ-globin promoter -158 (C>T) XmnI polymorphism in patients with homozygous/compound heterozygous beta thalassaemia.

    Science.gov (United States)

    Ali, Nadir; Ayyub, Muhammad; Khan, Saleem Ahmed; Ahmed, Suhaib; Abbas, Kazim; Malik, Hamid Saeed; Tashfeen, Sunila

    2015-03-01

    Response to hydroxyurea therapy in homozygous or compound heterozygous beta thalassaemia (BT) has been reported as more favourable in the presence of XmnI polymorphism. The prevalence of XmnI polymorphism may vary with BT phenotypes and genotypes, and differs geographically in distribution. Prevalence of XmnI polymorphism is not known in northern Pakistan. To determine the frequency of Gγ-globin promoter -158 (C>T) XmnI polymorphism (XmnI polymorphism) in patients with homozygous or compound heterozygous beta thalassaemia. Polymerase chain reaction (PCR) for common beta thalassaemia mutations and Gγ-globin promoter -158 (C>T) XmnI polymorphism was performed on 107 blood samples of transfusion dependent beta thalassaemia (BT) patients in Pakistan. One hundred samples of unrelated BT traits and 94 samples of healthy subjects as controls were also analysed for BT mutations and XmnI polymorphism. Out of 301 DNA samples, XmnI polymorphism was detected in 71(24%); in normal controls, XmnI polymorphism was detected in 34/94 (36%) subjects; while in homozygous/compound heterozygous BT, it was detected in 14/107(13%) patients (Fisher's exact test, p=.0002). In heterozygous BT group, XmnI polymorphism was detected in 23/100 subjects (Fisher's exact test, p=.03 with normal controls, and p=.049 with homozygous/compound heterozygous BT). The most common BT genotype was Frame Shift (Fr) 8-9/Fr 8-9, and none of the patients with this genotype had XmnI polymorphism. The second most common genotype was IVSI-5/IVSI-5; 4/26 (15%). Cases with this genotype had XmnI polymorphism. XmnI polymorphism in homozygous/compound heterozygous BT group is 13%. The most common genotype associated with XmnI polymorphism was IVSI-5/IVSI-5. Copyright © 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  3. Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

    Science.gov (United States)

    Pornprasert, Sakorn; Wanachantararak, Phenphichar; Kantawong, Fahsai; Chamnanprai, Supoj; Kongpan, Chatpat; Pienthai, Nattasit; Yanola, Jintana; Duangmano, Suwit; Prasannarong, Mujalin

    2017-08-01

    Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

  4. Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study.

    Science.gov (United States)

    Kondo, Douglas G; Sung, Young-Hoon; Hellem, Tracy L; Fiedler, Kristen K; Shi, Xianfeng; Jeong, Eun-Kee; Renshaw, Perry F

    2011-12-01

    Adolescent major depressive disorder (MDD) is a life-threatening brain disease with limited interventions. Treatment resistance is common, and the illness burden is disproportionately borne by females. 31-Phosphorus magnetic resonance spectroscopy ((31)P MRS) is a translational method for in vivo measurement of brain energy metabolites. We recruited 5 female adolescents who had been on fluoxetine (Prozac®) for ≥ 8 weeks, but continued meet diagnostic criteria for MDD with a Children's Depression Rating Scale-Revised (CDRS-R) raw score ≥ 40. Treatment response was measured with the CDRS-R. (31)P MRS brain scans were performed at baseline, and repeated following adjunctive creatine 4 g daily for 8 weeks. For comparison, 10 healthy female adolescents underwent identical brain scans performed 8 weeks apart. The mean CDRS-R score declined from 69 to 30.6, a decrease of 56%. Participants experienced no Serious Adverse Events, suicide attempts, hospitalizations or intentional self-harm. There were no unresolved treatment-emergent adverse effects or laboratory abnormalities. MDD participants' baseline CDRS-R score was correlated with baseline pH (p=0.04), and was negatively correlated with beta-nucleoside triphosphate (β-NTP) concentration (p=0.03). Compared to healthy controls, creatine-treated adolescents demonstrated a significant increase in brain Phosphocreatine (PCr) concentration (p=0.02) on follow-up (31)P MRS brain scans. Lack of placebo control; and small sample size. Further study of creatine as an adjunctive treatment for adolescents with SSRI-resistant MDD is warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Dietary substitution of fishmeal by alternative protein with guanosine monophosphate supplementation influences growth, digestibility, blood chemistry profile, immunity, and stress resistance of red sea bream, Pagrus major.

    Science.gov (United States)

    Hossain, Md Sakhawat; Koshio, Shunsuke

    2017-12-01

    We determined the effects of complete fishmeal (FM) replacement by alternative protein (soy protein concentrate, SPC) with guanosine monophosphate (GMP) supplementation on growth, digestibility, immunity, blood chemistry profile, and stress resistance of juvenile red sea bream, Pagrus major. FM protein of a FM-based control diet (FM0) was replaced with 33.3 (FM33.3), 66.6 (FM66.7), and 100% (FM100) by SPC protein, and each replacement group was supplemented with 0.4% GMP to formulate four experimental diets. Each diet was randomly allocated to triplicate groups of fish (4.8 g) for 56 days. Results demonstrated that fish fed diet group FM33.3 had the significantly highest final weight, weight gain-specific growth rate, and feed intake. Meanwhile, in comparison to control, growth performance and feed utilization did not significantly differ with 66.7% FM replacement by SPC with GMP supplementation. Apparent digestibility coefficient of protein and lipid also followed a similar trend. All growth, feed utilization, and digestibility parameters were significantly lower in FM100 diet group. Blood urea nitrogen (BUN) and triglycerides (TG) increased (P supplementation. Fish fed FM0 diet group showed the best condition of both oxidative and freshwater stress resistance. Meanwhile, FM33.3 and FM66.7 diet groups showed acceptable conditions. Innate immune responses enhanced with the increasing FM replacement level by SPC with GMP supplementation. In conclusion, FM could be replaced ≤66.7% by SPC with GMP supplementation in diets for red sea bream without any adverse effects on fish performances.

  6. Indices of insulin resistance and glucotoxicity are not associated with bipolar disorder or major depressive disorder, but are differently associated with inflammatory, oxidative and nitrosative biomarkers.

    Science.gov (United States)

    Landucci Bonifácio, Kamila; Sabbatini Barbosa, Décio; Gastaldello Moreira, Estefânia; de Farias, Carine Coneglian; Higachi, Luciana; Camargo, Alissana Ester Iakmiu; Favaro Soares, Janaina; Odebrecht Vargas, Heber; Nunes, Sandra Odebrecht Vargas; Berk, Michael; Dodd, Seetal; Maes, Michael

    2017-11-01

    Insulin resistance (IR) is a key factor in diabetes mellitus, metabolic syndrome (MetS) and obesity and may occur in mood disorders and tobacco use disorder (TUD), where disturbances of immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways are important shared pathophysiological pathways. This study aimed to a) examine IR and β-cell function as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity and β cell function (HOMA-B) and glucotoxicity (conceptualized as increased glucose levels versus lowered HOMA-B values) in 74 participants with major depressive disorder (MDD) and bipolar disorder, with and or without MetS and TUD, versus 46 healthy controls, and b) whether IR is associated with IO&NS biomarkers, including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), plasma advanced oxidation protein products (AOPP), C-reactive protein (CRP), haptoglobin (Hp) and uric acid. Mood disorders are not associated with changes in IR or glucotoxicity, although the number of mood episodes may increase IR. 47.8% of the variance in HOMA-IR is explained by AOPP and body mass index (BMI, both positively) and NOx, Hp and TUD (all inversely). 43.2% of the variance in HOMA-B is explained by NOx, Hp and age (all inversely associated) and higher BMI and sex. The glucotoxic index is strongly associated with NOx, Hp and BMI (positively), male gender and lower education. This is a cross-sectional study and therefore we cannot draw firm conclusions on causal associations. Activated IO&NS pathways (especially increased Hp and NOx) increase glucotoxicity and exert very complex effects modulating IR. Mood disorders are not associated with increased IR. Copyright © 2017. Published by Elsevier B.V.

  7. Interspecies Recombination in Type II Topoisomerase Genes Is Not a Major Cause of Fluoroquinolone Resistance in Invasive Streptococcus pneumoniae Isolates in the United States

    OpenAIRE

    Pletz, Mathias W. R.; McGee, Lesley; Beall, Bernard; Whitney, Cynthia G.; Klugman, Keith P.

    2005-01-01

    Mutations in the topoisomerase type II enzymes account for fluoroquinolone resistance in Streptococcus pneumoniae. These mutations can arise spontaneously or be transferred by intraspecies or interspecies recombination, primarily with viridans streptococci. We analyzed the nucleotide sequences of the quinolone resistance-determining regions of 49 invasive levofloxacin-resistant pneumococcal isolates and did not find any evidence for interspecies recombination.

  8. Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein demonstrate major conformational changes in the transmembrane domains upon nucleotide binding.

    Science.gov (United States)

    Rosenberg, Mark F; Kamis, Alhaji Bukar; Callaghan, Richard; Higgins, Christopher F; Ford, Robert C

    2003-03-07

    P-glycoprotein is an ATP-binding cassette transporter that is associated with multidrug resistance and the failure of chemotherapy in human patients. We have previously shown, based on two-dimensional projection maps, that P-glycoprotein undergoes conformational changes upon binding of nucleotide to the intracellular nucleotide binding domains. Here we present the three-dimensional structures of P-glycoprotein in the presence and absence of nucleotide, at a resolution limit of approximately 2 nm, determined by electron crystallography of negatively stained crystals. The data reveal a major reorganization of the transmembrane domains throughout the entire depth of the membrane upon binding of nucleotide. In the absence of nucleotide, the two transmembrane domains form a single barrel 5-6 nm in diameter and about 5 nm deep with a central pore that is open to the extracellular surface and spans much of the membrane depth. Upon binding nucleotide, the transmembrane domains reorganize into three compact domains that are each 2-3 nm in diameter and 5-6 nm deep. This reorganization opens the central pore along its length in a manner that could allow access of hydrophobic drugs (transport substrates) directly from the lipid bilayer to the central pore of the transporter.

  9. Assembly of the Lactuca sativa, L. cv. Tizian draft genome sequence reveals differences within major resistance complex 1 as compared to the cv. Salinas reference genome.

    Science.gov (United States)

    Verwaaijen, Bart; Wibberg, Daniel; Nelkner, Johanna; Gordin, Miriam; Rupp, Oliver; Winkler, Anika; Bremges, Andreas; Blom, Jochen; Grosch, Rita; Pühler, Alfred; Schlüter, Andreas

    2018-02-10

    Lettuce (Lactuca sativa, L.) is an important annual plant of the family Asteraceae (Compositae). The commercial lettuce cultivar Tizian has been used in various scientific studies investigating the interaction of the plant with phytopathogens or biological control agents. Here, we present the de novo draft genome sequencing and gene prediction for this specific cultivar derived from transcriptome sequence data. The assembled scaffolds amount to a size of 2.22 Gb. Based on RNAseq data, 31,112 transcript isoforms were identified. Functional predictions for these transcripts were determined within the GenDBE annotation platform. Comparison with the cv. Salinas reference genome revealed a high degree of sequence similarity on genome and transcriptome levels, with an average amino acid identity of 99%. Furthermore, it was observed that two large regions are either missing or are highly divergent within the cv. Tizian genome compared to cv. Salinas. One of these regions covers the major resistance complex 1 region of cv. Salinas. The cv. Tizian draft genome sequence provides a valuable resource for future functional and transcriptome analyses focused on this lettuce cultivar. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Efficacy and safety of olanzapine/fluoxetine combination vs fluoxetine monotherapy following successful combination therapy of treatment-resistant major depressive disorder.

    Science.gov (United States)

    Brunner, Elizabeth; Tohen, Mauricio; Osuntokun, Olawale; Landry, John; Thase, Michael E

    2014-10-01

    This study assessed prevention of relapse in patients with treatment-resistant depression (TRD) taking olanzapine/fluoxetine combination (OFC). Patients with major depressive disorder (MDD) who failed to satisfactorily respond to ≥ 2 different antidepressants for ≥ 6 weeks within the current MDD episode were acutely treated for 6-8 weeks, followed by stabilization (12 weeks) on OFC. Those who remained stable were randomized to OFC or fluoxetine for up to 27 weeks. Time-to-relapse was the primary efficacy outcome defined as 50% increase in Montgomery-Åsberg Depression Rating Scale score with Clinical Global Impressions-Severity of Depression score of ≥ 4; hospitalization for depression or suicidality; or discontinuation for lack of efficacy or worsening of depression or suicidality. A total of 444 patients were randomized 1:1 to OFC (N=221) or fluoxetine (N=223). Time-to-relapse was significantly longer in OFC-treated patients compared with fluoxetine-treated patients (pserious adverse events. We believe this is the first controlled relapse-prevention study in subjects with TRD that supports continued use of a second-generation antipsychotic beyond stabilization. A thorough assessment of benefits and risks (in particular metabolic changes) associated with continuing treatment with OFC or fluoxetine must be done based on individual patient needs.

  11. Titanium surfaces immobilized with the major antimicrobial fragment FK-16 of human cathelicidin LL-37 are potent against multiple antibiotic-resistant bacteria.

    Science.gov (United States)

    Mishra, Biswajit; Wang, Guangshun

    2017-08-01

    Infections on implanted medical devices are a challenging problem, especially when bacteria form difficult-to-treat biofilms. Antimicrobial peptides are considered to be a solution due to their potency against antibiotic-resistant superbugs. Previously, the authors' laboratory demonstrated the prevention of staphylococcal biofilm formation in an animal catheter model by injecting merecidin (formerly known as 17BIPHE2), a peptide engineered based on the only human cathelicidin. This study documents an alternative solution via covalent immobilization of FK-16, amino acid sequence FKRIVQRIKDFLRNLV-amide, which corresponds to the major antimicrobial region (residues 17-32) of LL-37. FK-16 is superior to the longer peptide LL-37 in terms of synthesis cost and the shorter peptide KR-12 in terms of activity spectrum. Indeed, the FK16-coated titanium surface showed a broad-spectrum activity against the ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. It also demonstrated anti-adhesion and biofilm inhibition capabilities against both S. aureus and E. coli.

  12. S-Adenosyl-L-Methionine Augmentation in Patients with Stage II Treatment-Resistant Major Depressive Disorder: An Open Label, Fixed Dose, Single-Blind Study

    Directory of Open Access Journals (Sweden)

    Domenico De Berardis

    2013-01-01

    Full Text Available We investigated the efficacy of S-Adenosyl-L-Methionine (SAMe augmentation in patients with treatment-resistant depressive disorder (TRD. Thirty-three outpatients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe (800 mg for 8 weeks, added to existing medication. The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression (HAM-D. The Clinical Global Impression of Improvement (CGI-I was rated at the endpoint. Patients with a reduction of 50% or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders; remission was defined as a HAM-D score ≤7. Secondary outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS and the Sheehan Disability Scale (SDS. At 8 weeks, a significant decrease in HAM-D score was observed with response achieved by 60% of the patients and remission by 36%. Also a statistically significant reduction in SHAPS and SDS was observed. Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD. However, limitations of the present study must be considered and further placebo-controlled trials are needed.

  13. Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes.

    Science.gov (United States)

    Warren, A P; Ducroq, D H; Lehner, P J; Borysiewicz, L K

    1994-05-01

    Viruses which cause persistence in the naturally infected host are predicted to have evolved immune evasion mechanisms. Human cytomegalovirus (HCMV) causes significant morbidity and mortality in immunocompromised patients yet persists without clinical manifestations in seropositive individuals who have normal immune function. We report that HCMV infection in vitro impairs major histocompatibility complex class I (MHC-I) assembly accompanied by resistance to killing by cytotoxic CD8+ T lymphocytes. Pulse-chase metabolic labelling experiments show that MHC-I complexes continue to be assembled by both uninfected and HCMV-infected cells. However, MHC-I molecules are unstable in HCMV-infected cells and are rapidly broken down. Endoglycosidase H treatment of immunoprecipitates indicates that the breakdown of MHC-I complexes in HCMV-infected cells occurs primarily in a pre-Golgi compartment. Interference with normal MHC-I assembly and expression, if relevant in vivo, may have implications for the restriction of the diversity of the CD8+ cytotoxic T lymphocyte repertoire directed against HCMV antigens and may be an important mechanism of viral persistence.

  14. High resolution mapping of trypanosomosis resistance loci Tir2 and Tir3 using F12 advanced intercross lines with major locus Tir1 fixed for the susceptible allele

    Directory of Open Access Journals (Sweden)

    Soller Morris

    2010-06-01

    Full Text Available Abstract Background Trypanosomosis is the most economically important disease constraint to livestock productivity in Africa. A number of trypanotolerant cattle breeds are found in West Africa, and identification of the genes conferring trypanotolerance could lead to effective means of genetic selection for trypanotolerance. In this context, high resolution mapping in mouse models are a promising approach to identifying the genes associated with trypanotolerance. In previous studies, using F2 C57BL/6J × A/J and C57BL/6J × BALB/cJ mouse resource populations, trypanotolerance QTL were mapped within a large genomic intervals of 20-40 cM to chromosomes MMU17, 5 and 1, and denoted Tir1, Tir2 and Tir3 respectively. Subsequently, using F6 C57BL/6J × A/J and C57BL/6J × BALB/cJ F6 advanced intercross lines (AIL, Tir1 was fine mapped to a confidence interval (CI of less than 1 cM, while Tir2 and Tir3, were mapped within 5-12 cM. Tir1 represents the major trypanotolerance QTL. Results In order to improve map resolutions of Tir2 and Tir3, an F12 C57BL/6J × A/J AIL population fixed for the susceptible alleles at Tir1 QTL was generated. An F12 C57BL/6J × A/J AIL population, fixed for the resistant alleles at Tir1 QTL was also generated to provide an additional estimate of the gene effect of Tir1. The AIL populations homozygous for the resistant and susceptible Tir1 alleles and the parental controls were challenged with T. congolense and followed for survival times over 180 days. Mice from the two survival extremes of the F12 AIL population fixed for the susceptible alleles at Tir1 were genotyped with a dense panel of microsatellite markers spanning the Tir2 and Tir3 genomic regions and QTL mapping was performed. Tir2 was fine mapped to less than 1 cM CI while Tir3 was mapped to three intervals named Tir3a, Tir3b and Tir3c with 95% confidence intervals (CI of 6, 7.2 and 2.2 cM, respectively. Conclusions The mapped QTL regions encompass genes that are

  15. Renal resistive index by transesophageal and transparietal echo-doppler imaging for the prediction of acute kidney injury in patients undergoing major heart surgery.

    Science.gov (United States)

    Regolisti, Giuseppe; Maggiore, Umberto; Cademartiri, Carola; Belli, Loredana; Gherli, Tiziano; Cabassi, Aderville; Morabito, Santo; Castellano, Giuseppe; Gesualdo, Loreto; Fiaccadori, Enrico

    2017-04-01

    Acute kidney injury (AKI) following major heart surgery (MHS) is associated with early decrease in renal blood flow and worsened prognosis. Doppler-derived renal resistive index (RRI), which reflects renal vascular resistance, may predict the development of AKI in patients undergoing MHS. We studied 60 consecutive patients (mean age 69.5 years, range 30-88, 41 males) undergoing MHS. We measured RRI, both at the renal sinus and intraparenchymally, by transesophageal echo-Doppler ultrasound (TE-ED us ) at anesthesia induction and at the end of surgery in all patients. Additionally, we measured RRI by external transparietal echo-Doppler ultrasound (TP-ED us ) at the following time points: anesthesia induction, end of surgery, 4 and 24 h from cardiopulmonary bypass (CPB) start. We also measured serum neutrophil gelatinase associated lipocalin (NGAL) at the same time points. AKI [serum creatinine (sCr) increase ≥0.3 mg/dl vs. baseline within 72 h] developed in 23/60 (38.3 %) patients, with two requiring dialysis. Systemic hemodynamic parameters were similar in the patients who developed AKI (AKI+) and in those who did not (AKI-). Intraparenchymal RRI at end-surgery was significantly higher in AKI+ compared to AKI- patients, both at TE-ED us and TP-ED us (TE-ED us mean difference, p = 0.004; TP-ED us mean difference, p = 0.013; difference between TE-ED us and TP-ED us results, p = 0.066), although the predictive performance was limited with both methods (area under the curve [AUC] of the receiver-operator characteristics: 0.71 and 0.70 for TE-ED us and TP-ED us , respectively). Serum NGAL values were higher in AKI + than in AKI- patients (anesthesia induction, p = 0.037; end-surgery, p = 0.007; 4 h from CPB start, p = 0.093; 24 h from CPB start, p = 0.024. However, combining RRI with serum NGAL at end-surgery did not provide a clear-cut advantage in predicting AKI. In patients undergoing MHS, increased echo-Doppler ultrasound-derived RRI at end

  16. Effectiveness of earlier antenatal screening for sickle cell disease and thalassaemia in primary care: cluster randomised trial

    Science.gov (United States)

    Dormandy, Elizabeth; Gulliford, Martin; Bryan, Stirling; Roberts, Tracy E; Calnan, Michael; Atkin, Karl; Karnon, Jonathan; Logan, Jane; Kavalier, Fred; Harris, Hilary J; Johnston, Tracey A; Anionwu, Elizabeth N; Tsianakas, Vicki; Jones, Patricia

    2010-01-01

    Objective To evaluate the effectiveness of offering antenatal screening for sickle cell disease and thalassaemia in primary care as a way of facilitating earlier uptake of screening. Design Partial factorial cluster randomised controlled trial. Setting 25 UK general practices from deprived inner city areas. Participants Anonymised data on all pregnant women attending participating practices during a six month period before randomisation and a seven month period after randomisation. This included 1708 eligible women. Intervention Practices were randomised to three groups for seven months: parallel testing in general practice (tests for sickle cell disease and thalassaemia offered to both parents when pregnancy was first reported); sequential testing in general practice (tests offered to mothers when pregnancy was first reported, and subsequently to the partners of women who were found to be carriers); and midwife care (tests offered to mothers at first consultation with a midwife). Main outcome measures The primary outcome (available for all women) was the proportion of eligible women screened before 10 weeks’ (70 days’) gestation. Secondary outcomes were an offer of screening to women before 10 weeks’ gestation, gestational age at testing, mean interval from first visit to the general practice visit to screening, and women’s knowledge of the carrier status of their baby’s father before 77 days’ (11 weeks’) gestation. The study was designed to detect a 20% absolute increase in screening uptake. Cluster level analyses were adjusted for age group, parity, ethnic group, primary care organisation, and number of general practitioners per practice. Results Data were analysed for 1708 eligible women. In the midwife care arm, 2% (9/441) of women were screened before 10 weeks’ gestation compared with 24% (161/677) in the GP parallel testing arm and 28% (167/590) in the GP sequential testing arm. The estimated adjusted difference between the midwife care and

  17. Lifetime cost-utility analyses of deferasirox in beta-thalassaemia patients with chronic iron overload: a UK perspective.

    Science.gov (United States)

    Karnon, Jonathan; Tolley, Keith; Vieira, Joao; Chandiwana, David

    2012-12-01

    Regular blood transfusions for beta-thalassaemia patients lead to the accumulation of iron deposits in the body. In order to remove such deposits, iron chelation therapy is required. Subcutaneously administered deferoxamine has been the gold standard chelation therapy for over 40 years. Deferasirox is a newer chelation therapy that is taken orally once daily. The objective of this study was to estimate the long-term costs and quality-adjusted life-years (QALYs) associated with deferoxamine and deferasirox in a cohort of transfusion-dependent beta-thalassaemia patients from a UK health service perspective. A 50-year annual cycle state transition model comprised three core health states: alive without cardiac complications, alive with cardiac complications, and dead, as well as representing other chronic complications of iron overload: diabetes, hypogonadism, hypoparathyroidism and hypothyroidism. The model was calibrated to identify sets of convergent input parameter values that predicted observed overall survival by mean lifetime compliance with chelation therapy. A pivotal non-inferiority trial informed the main estimates of the effectiveness of deferasirox, which were applied to the calibrated model. Using cost values for the year 2011, costs and utilities were summed over patients' lifetimes to estimate lifetime costs and QALY gains. Mean lifetime treatment costs for patients receiving deferoxamine were £70,000 higher than deferasirox. Drug acquisition costs were £100,000 higher for deferasirox, but administration costs associated with deferoxamine were £170,000 higher. Higher compliance associated with oral deferasirox administration led to fewer complications. Combined with the quality-of-life effects of an oral mode of administration, an average gain of 4.85 QALYs for deferasirox was estimated. In the base case, deferasirox dominates deferoxamine, i.e., costs less and patients gain more QALYs. The key parameter is the proportion of deferoxamine patients

  18. ST2249-MRSA-III: a second major recombinant methicillin-resistant Staphylococcus aureus clone causing healthcare infection in the 1970s.

    Science.gov (United States)

    Nimmo, G R; Steen, J A; Monecke, S; Ehricht, R; Slickers, P; Thomas, J C; Appleton, S; Goering, R V; Robinson, D A; Coombs, G W

    2015-05-01

    Typing of healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) from Australia in the 1970s revealed a novel clone, ST2249-MRSA-III (CC45), present from 1973 to 1979. This clone was present before the Australian epidemic caused by the recombinant clone, ST239-MRSA-III. This study aimed to characterize the genome of ST2249-MRSA-III to establish its relationship to other MRSA clones. DNA microarray analysis was conducted and a draft genome sequence of ST2249 was obtained. The recombinant structure of the ST2249 genome was revealed by comparisons to publicly available ST239 and ST45 genomes. Microarray analysis of genomic DNA of 13 ST2249 isolates showed gross similarities with the ST239 chromosome in a segment around the origin of replication and with ST45 for the remainder of the chromosome. Recombination breakpoints were precisely determined by the changing pattern of nucleotide polymorphisms in the genome sequence of ST2249 isolate SK1585 compared with ST239 and ST45. One breakpoint was identified to the right of oriC, between sites 1014 and 1065 of the gene D484_00045. Another was identified to the left of oriC, between sites 1185 and 1248 of D484_01632. These results indicate that ST2249 inherited approximately 35.3% of its chromosome from an ST239-like parent and 64.7% from an ST45-like parent. ST2249-MRSA-III resulted from a major recombination between parents that resemble ST239 and ST45. Although only limited Australian archival material is available, the oldest extant isolate of ST2249 predates the oldest Australian isolate of ST239 by 3 years. It is therefore plausible that these two recombinant clones were introduced into Australia separately. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Simultaneous detection of major drug resistance mutations in the protease and reverse transcriptase genes for HIV-1 subtype C by use of a multiplex allele-specific assay.

    Science.gov (United States)

    Zhang, Guoqing; Cai, Fangping; Zhou, Zhiyong; DeVos, Joshua; Wagar, Nick; Diallo, Karidia; Zulu, Isaac; Wadonda-Kabondo, Nellie; Stringer, Jeffrey S A; Weidle, Paul J; Ndongmo, Clement B; Sikazwe, Izukanji; Sarr, Abdoulaye; Kagoli, Matthew; Nkengasong, John; Gao, Feng; Yang, Chunfu

    2013-11-01

    High-throughput, sensitive, and cost-effective HIV drug resistance (HIVDR) detection assays are needed for large-scale monitoring of the emergence and transmission of HIVDR in resource-limited settings. Using suspension array technology, we have developed a multiplex allele-specific (MAS) assay that can simultaneously detect major HIVDR mutations at 20 loci. Forty-five allele-specific primers tagged with unique 24-base oligonucleotides at the 5' end were designed to detect wild-type and mutant alleles at the 20 loci of HIV-1 subtype C. The MAS assay was first established and optimized with three plasmid templates (C-wt, C-mut1, and C-mut2) and then evaluated using 148 plasma specimens from HIV-1 subtype C-infected individuals. All the wild-type and mutant alleles were unequivocally distinguished with plasmid templates, and the limits of detection were 1.56% for K219Q and K219E, 3.13% for L76V, 6.25% for K65R, K70R, L74V, L100I, K103N, K103R, Q151M, Y181C, and I47V, and 12.5% for M41L, K101P, K101E, V106A, V106M, Y115F, M184V, Y188L, G190A, V32I, I47A, I84V, and L90M. Analyses of 148 plasma specimens revealed that the MAS assay gave 100% concordance with conventional sequencing at eight loci and >95% (range, 95.21% to 99.32%) concordance at the remaining 12 loci. The differences observed were caused mainly by 24 additional low-abundance alleles detected by the MAS assay. Ultradeep sequencing analysis confirmed 15 of the 16 low-abundance alleles. This multiplex, sensitive, and straightforward result-reporting assay represents a new efficient genotyping tool for HIVDR surveillance and monitoring.

  20. Electroconvulsive therapy and aerobic exercise training increased BDNF and ameliorated depressive symptoms in patients suffering from treatment-resistant major depressive disorder.

    Science.gov (United States)

    Salehi, Iraj; Hosseini, Seyed Mohammad; Haghighi, Mohammad; Jahangard, Leila; Bajoghli, Hafez; Gerber, Markus; Pühse, Uwe; Kirov, Roumen; Holsboer-Trachsler, Edith; Brand, Serge

    2014-10-01

    To treat patients suffering from treatment-resistant major depressive disorder (TR-MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. 60 patients with TR-MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 30 min, three times a week. Both depression severity and BDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. BDNF levels increased over time in all three study conditions. After completion of the intervention program, the ECT group showed significantly higher BDNF levels compared to the ECT + AET and the AET conditions. Depressive symptoms decreased in all three conditions over time. The combination of ECT + AET led to a significantly greater decrease than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. The pattern of results suggests that ECT, AET and particularly their combination are promising directions for treatment patients suffering from TR-MDD, and that it remains unclear to what extent BDNF is key and a reliable biomarker for TR-MDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Brief review of the chicken Major Histocompatibility Complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance

    Science.gov (United States)

    Miller, Marcia M.; Taylor, Robert L.

    2016-01-01

    Nearly all genes presently mapped to chicken chromosome 16 (GGA 16) have either a demonstrated role in immune responses or are considered to serve in immunity by reason of sequence homology with immune system genes defined in other species. The genes are best described in regional units. Among these, the best known is the polymorphic major histocompatibility complex-B (MHC-B) region containing genes for classical peptide antigen presentation. Nearby MHC-B is a small region containing two CD1 genes, which encode molecules known to bind lipid antigens and which will likely be found in chickens to present lipids to specialized T cells, as occurs with CD1 molecules in other species. Another region is the MHC-Y region, separated from MHC-B by an intervening region of tandem repeats. Like MHC-B, MHC-Y is polymorphic. It contains specialized class I and class II genes and c-type lectin-like genes. Yet another region, separated from MHC-Y by the single nucleolar organizing region (NOR) in the chicken genome, contains olfactory receptor genes and scavenger receptor genes, which are also thought to contribute to immunity. The structure, distribution, linkages and patterns of polymorphism in these regions, suggest GGA 16 evolves as a microchromosome devoted to immune defense. Many GGA 16 genes are polymorphic and polygenic. At the moment most disease associations are at the haplotype level. Roles of individual MHC genes in disease resistance are documented in only a very few instances. Provided suitable experimental stocks persist, the availability of increasingly detailed maps of GGA 16 genes combined with new means for detecting genetic variability will lead to investigations defining the contributions of individual loci and more applications for immunogenetics in breeding healthy poultry. PMID:26740135

  2. Characterization of major lithologic units underlying the lower American River using water-borne continuous resistivity profiling, Sacramento, California, June 2008

    Science.gov (United States)

    Ball, Lyndsay B.; Teeple, Andrew

    2013-01-01

    The levee system of the lower American River in Sacramento, California, is situated above a mixed lithology of alluvial deposits that range from clay to gravel. In addition, sand deposits related to hydraulic mining activities underlie the floodplain and are preferentially prone to scour during high-flow events. In contrast, sections of the American River channel have been observed to be scour resistant. In this study, the U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, explores the resistivity structure of the American River channel to characterize the extent and thickness of lithologic units that may impact the scour potential of the area. Likely lithologic structures are interpreted, but these interpretations are non-unique and cannot be directly related to scour potential. Additional geotechnical data would provide insightful data on the scour potential of certain lithologic units. Additional interpretation of the resistivity data with respect to these results may improve interpretations of lithology and scour potential throughout the American River channel and floodplain. Resistivity data were collected in three profiles along the American River using a water-borne continuous resistivity profiling technique. After processing and modeling these data, inverted resistivity profiles were used to make interpretations about the extent and thickness of possible lithologic units. In general, an intermittent high-resistivity layer likely indicative of sand or gravel deposits extends to a depth of around 30 feet (9 meters) and is underlain by a consistent low-resistivity layer that likely indicates a high-clay content unit that extends below the depth of investigation (60 feet or 18 meters). Immediately upstream of the Watt Avenue Bridge, the high-resistivity layer is absent, and the low-resistivity layer extends to the surface where a scour-resistant layer has been previously observed in the river bed.

  3. Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa.

    Science.gov (United States)

    Riveron, Jacob M; Ibrahim, Sulaiman S; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J; Ishak, Intan H; Wondji, Charles S

    2017-06-07

    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes ( CYP6P9a and CYP6P9b ) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. Copyright © 2017 Riveron et al.

  4. Sociodemographic profile and oral health status of thalassemic patients attending the National Thalassaemia Centre, Kurunegala, Sri Lanka.

    Science.gov (United States)

    Kularatne, Wickramasooriyage Nandana; Jayasinghe, Rasika M; Diyunugala, Mahinda Chandika; Bandara, Dayananda; Abeysundara, Sachith; Perera, Irosha

    2017-09-01

    The aim of the present study was to investigate the sociodemographic profile and oral health status (Decayed, Missing, Filled Teeth [DMFT] and periodontal health) of thalassemic patients compared to healthy individuals. The data were collected by means of an interviewer-administered, pretested, and validated questionnaire, followed by oral examination. Patients attending the outpatient department, who were age and sex matched, but without any diagnosed or suspected long-term illnesses, were considered for the control group. Both groups were compared in terms of facial profile, skeletal pattern, facial angles, DMFT, and periodontal health (plaque index, bleeding on probing, and probing pocket depth). The association of convex facial profile and class II skeletal pattern with Thalassemic status was statistically significant when compared to healthy individuals. Decayed, missing, and filled teeth in the permanent and deciduous dentition, plaque index, and probing pocket depths of the control group were significantly higher compared with the thalassemic group. Surprisingly, 67.8% of thalassemic patients did not show bleeding on probing. Families of the thalassemic patients attending the National Thalassaemia Centre are from a low socioeconomic background. Their DMFT and periodontal health are significantly better than those of healthy individuals. © 2017 John Wiley & Sons Australia, Ltd.

  5. Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study.

    Science.gov (United States)

    Taher, Ali T; Cappellini, M Domenica; Aydinok, Yesim; Porter, John B; Karakas, Zeynep; Viprakasit, Vip; Siritanaratkul, Noppadol; Kattamis, Antonis; Wang, Candace; Zhu, Zewen; Joaquin, Victor; Uwamahoro, Marie José; Lai, Yong-Rong

    2016-03-01

    Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose±SD over 1year was 14.70±5.48mg/kg/day. At week 52, mean LIC±SD decreased significantly from 15.13±10.72mg Fe/g dw at baseline to 8.46±6.25mg Fe/g dw (absolute change from baseline, -6.68±7.02mg Fe/g dw [95% CI: -7.91, -5.45]; Pdeferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Deferasirox: a review of its use for chronic iron overload in patients with non-transfusion-dependent thalassaemia.

    Science.gov (United States)

    Shirley, Matt; Plosker, Greg L

    2014-06-01

    Deferasirox (Exjade(®)) is a once-daily orally administered iron chelator which has been approved for use in the treatment of transfusional-dependent chronic iron overload since 2005. Based primarily on the findings of the THALASSA (Assessment of Exjade(®) in Non-Transfusion-Dependent THALASSemiA) trial, the approval for deferasirox has recently been expanded to include the management of chronic iron overload in patients with non-transfusion-dependent thalassaemia (NTDT) syndromes. Despite the lack of regular blood transfusions, NTDT patients can still develop clinically relevant iron overload, primarily due to increased gastrointestinal absorption secondary to ineffective erythropoiesis, and may require chelation therapy. The THALASSA trial, the first placebo-controlled clinical trial of an iron chelator in NTDT patients, demonstrated that deferasirox was effective in reducing liver iron and serum ferritin levels in this population. Deferasirox has an acceptable tolerability profile, with the most common adverse events reported in the THALASSA trial being related to mild to moderate gastrointestinal disorders. Although further long-term studies will be required to clearly demonstrate the clinical benefit of chelation therapy in NTDT patients, deferasirox presents a useful tool in the management of iron overload in this population.

  7. A FACS Based Case Study on Two HbE-β Thalassaemia Members of a Family, Having Similar Mutational Background

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    Tridip Chatterjee

    2016-01-01

    Full Text Available In this report we have tried to explain the reasons behind the difference in the pattern of transfusion requirement between two members of a family with similar β-globin mutation. The father and younger son both are HbE-β, but the father never had transfusion, whereas the younger son takes transfusion monthly. Mother and the elder son are HbEE without any history of transfusion. β-globin mutations of all family members were determined by ARMS-PCR. These were reconfirmed by direct sequencing of β-globin gene. Father and younger son were found to be Cod 26 (G-A/IVS 1-5 (G-C, whereas mother and elder son were found to be Cod 26 (G-A/Cod 26 (G-A. XmnI sequencing also revealed that all members of the family were CC. Then, flow cytometry study of red blood cells (RBCs was performed to measure the oxidative stress of the RBCs. This study was also done on the light and dense fractions of the RBC population of the father and younger son. It was seen that the younger son suffers severe oxidative stress, which can be explained by his higher transfusion requirement. From our work, we have established the importance of taking oxidative stress of RBCs into consideration to explain the clinical manifestation and progression of haemoglobin related diseases like thalassaemia.

  8. Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial.

    Science.gov (United States)

    Sepehrmanesh, Zahra; Kolahdooz, Fariba; Abedi, Fatemeh; Mazroii, Navid; Assarian, Amin; Asemi, Zatollah; Esmaillzadeh, Ahmad

    2016-02-01

    Vitamin D may decrease depression symptoms through its beneficial effects on neurotransmitters, metabolic profiles, biomarkers of inflammation, and oxidative stress. This study was designed to assess whether vitamin D supplementation can reduce symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). This randomized, double-blind, placebo-controlled clinical trial was performed in 40 patients between 18 and 65 y of age with a diagnosis of MDD based on criteria from the Diagnostic and Statistical Manual of Mental Disorders. Patients were randomly assigned to receive either a single capsule of 50 kIU vitamin D/wk (n = 20) or placebo (n = 20) for 8 wk. Fasting blood samples were taken at baseline and postintervention to quantify relevant variables. The primary [Beck Depression Inventory (BDI), which examines depressive symptoms] and secondary (glucose homeostasis variables, lipid profiles, hs-CRP, and biomarkers of oxidative stress) outcomes were assessed. Baseline concentrations of mean serum 25-hydroxyvitamin D were significantly different between the 2 groups (9.2 ± 6.0 and 13.6 ± 7.9 μg/L in the placebo and control groups, respectively, P = 0.02). After 8 wk of intervention, changes in serum 25-hydroxyvitamin D concentrations were significantly greater in the vitamin D group (+20.4 μg/L) than in the placebo group (-0.9 μg/L, P < 0.001). A trend toward a greater decrease in the BDI was observed in the vitamin D group than in the placebo group (-8.0 and -3.3, respectively, P = 0.06). Changes in serum insulin (-3.6 compared with +2.9 μIU/mL, P = 0.02), estimated homeostasis model assessment of insulin resistance (-1.0 compared with +0.6, P = 0.01), estimated homeostasis model assessment of β cell function (-13.9 compared with +10.3, P = 0.03), plasma total antioxidant capacity (+63.1 compared with -23.4 mmol/L, P = 0.04), and glutathione

  9. Predictors of poor retention on antiretroviral therapy as a major HIV drug resistance early warning indicator in Cameroon: results from a nationwide systematic random sampling

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    Serge Clotaire Billong

    2016-11-01

    Full Text Available Abstract Background Retention on lifelong antiretroviral therapy (ART is essential in sustaining treatment success while preventing HIV drug resistance (HIVDR, especially in resource-limited settings (RLS. In an era of rising numbers of patients on ART, mastering patients in care is becoming more strategic for programmatic interventions. Due to lapses and uncertainty with the current WHO sampling approach in Cameroon, we thus aimed to ascertain the national performance of, and determinants in, retention on ART at 12 months. Methods Using a systematic random sampling, a survey was conducted in the ten regions (56 sites of Cameroon, within the “reporting period” of October 2013–November 2014, enrolling 5005 eligible adults and children. Performance in retention on ART at 12 months was interpreted following the definition of HIVDR early warning indicator: excellent (>85%, fair (85–75%, poor (<75; and factors with p-value < 0.01 were considered statistically significant. Results Majority (74.4% of patients were in urban settings, and 50.9% were managed in reference treatment centres. Nationwide, retention on ART at 12 months was 60.4% (2023/3349; only six sites and one region achieved acceptable performances. Retention performance varied in reference treatment centres (54.2% vs. management units (66.8%, p < 0.0001; male (57.1% vs. women (62.0%, p = 0.007; and with WHO clinical stage I (63.3% vs. other stages (55.6%, p = 0.007; but neither for age (adults [60.3%] vs. children [58.8%], p = 0.730 nor for immune status (CD4351–500 [65.9%] vs. other CD4-staging [59.86%], p = 0.077. Conclusions Poor retention in care, within 12 months of ART initiation, urges active search for lost-to-follow-up targeting preferentially male and symptomatic patients, especially within reference ART clinics. Such sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.

  10. 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.

  11. Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014.

    Science.gov (United States)

    Gandra, Sumanth; Mojica, Nestor; Klein, Eili Y; Ashok, Ashvin; Nerurkar, Vidya; Kumari, Mamta; Ramesh, Uma; Dey, Sunanda; Vadwai, Viral; Das, Bibhu R; Laxminarayan, Ramanan

    2016-09-01

    There have been no long-term studies on trends in antibiotic resistance (ABR) on a national scale in India. Using a private laboratory network, the ABR patterns of organisms most commonly associated with bacteremia, obtained from patients across India between 2008 and 2014, were examined. A retrospective study of patient blood cultures collected over a 7-year period (January 1, 2008-December 31, 2014) was conducted. Data on the microorganism(s) identified and their antimicrobial susceptibility were obtained from SRL Diagnostics (Mumbai, India). Of 135268 blood cultures, 18695 (14%) had at least one identified pathogen. In addition to continual high rates of methicillin-resistant Staphylococcus aureus (MRSA; approximately 44.2%), high resistance to nalidixic acid among Salmonella Typhi (98%) was observed, and carbapenem resistance increased in both Escherichia coli (7.8% to 11.5%; p=0.332) and Klebsiella pneumoniae (41.5% to 56.6%; presistance was also stable and high for both Acinetobacter species (approximately 69.6%) and Pseudomonas aeruginosa (approximately 49%). Resistance was also detected to colistin in the Gram-negatives and to vancomycin and linezolid in S. aureus. Increasing resistance to antibiotics of last-resort, particularly among Gram-negatives, suggests an urgent need for new antibiotics and improved antimicrobial stewardship programs in India. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Combined linkage and association mapping reveals candidates for Scmv1, a major locus involved in resistance to sugarcane mosaic virus (SCMV) in maize.

    Science.gov (United States)

    Tao, Yongfu; Jiang, Lu; Liu, Qingqing; Zhang, Yan; Zhang, Rui; Ingvardsen, Christina Roenn; Frei, Ursula Karoline; Wang, Baobao; Lai, Jinsheng; Lübberstedt, Thomas; Xu, Mingliang

    2013-10-18

    Sugarcane mosaic virus (SCMV) disease causes substantial losses of grain yield and forage biomass in susceptible maize cultivars. Maize resistance to SCMV is associated with two dominant genes, Scmv1 and Scmv2, which are located on the short arm of chromosome 6 and near the centromere region of chromosome 3, respectively. We combined both linkage and association mapping to identify positional candidate genes for Scmv1. Scmv1 was fine-mapped in a segregating population derived from near-isogenic lines and further validated and fine-mapped using two recombinant inbred line populations. The combined results assigned the Scmv1 locus to a 59.21-kb interval, and candidate genes within this region were predicted based on the publicly available B73 sequence. None of three predicted genes that are possibly involved in the disease resistance response are similar to receptor-like resistance genes. Candidate gene-based association mapping was conducted using a panel of 94 inbred lines with variable resistance to SCMV. A presence/absence variation (PAV) in the Scmv1 region and two polymorphic sites around the Zmtrx-h gene were significantly associated with SCMV resistance. Combined linkage and association mapping pinpoints Zmtrx-h as the most likely positional candidate gene for Scmv1. These results pave the way towards cloning of Scmv1 and facilitate marker-assisted selection for potyvirus resistance in maize.

  13. The major aminoglycoside-modifying enzyme AAC(3)-II found in Escherichia coli determines a significant disparity in its resistance to gentamicin and amikacin in China.

    Science.gov (United States)

    Xiao, Yonghong; Hu, Yunjian

    2012-02-01

    The aim of this study was to investigate the prevalence of aminoglycoside-modifying enzymes in Escherichia coli in different areas of China and to explore the relationship between pandemic enzyme type and bacterial resistance to antimicrobial agents in China. Gentamicin- or etimicin-resistant clinical isolates of E. coli were collected from different areas of China, and the in vitro antibacterial activity of 11 aminoglycoside agents was determined using standard (Clinical and Laboratory Standards Institute) agar dilution methods. Twelve aminoglycoside-modifying enzyme genes were detected by PCR and confirmed by DNA sequencing. A total of 205 E. coli strains were collected from nine hospitals in seven cities. All strains were highly resistant to gentamicin or etimicin, whereas resistance to tobramycin, netilmicin, and kanamycin was slightly lower. However, less than 15% of isolates were resistant to amikacin and isepamicin. Of the gentamicin-resistant strains, 88.2% and 86.7% were sensitive to isepamicin and amikacin, respectively. Five aminoglycoside-modifying enzyme genes were detected in 191 strains, whereas the remaining 14 strains were negative. The most common gene type was aac(3)-II (162 strains), followed by aac(6')-I (50 strains), ant(3″)-I (28 strains), aph(3')-II (20 strains), and ant(2″)-I (20 strains). Ninety-five strains yielded aac(3)-II only, whereas the others contained two or three genes. The three main gene combinations were aac(6')-I/aac(3)-II (28 strains), aac(3)-II/ant(3″)-I (11 strains), and aac(3)-II/aac(6')-I (10 strains). Regional bacterial resistance and enzyme distribution were roughly similar, although minor differences were found in Guangzhou, Jinan, and Dalian, which were the sources of most of the amikacin- or isepamicin-resistant strains. Chinese clinical isolates of E. coli remain highly resistant to gentamicin and etimicin, but are susceptible to amikacin and isepamicin. The dominant type of aminoglycoside-modifying enzyme

  14. Transcriptomic characterization of two major Fusarium resistance quantitative trait loci (QTLs), Fhb1 and Qfhs.ifa-5A, identifies novel candidate genes

    Science.gov (United States)

    Schweiger, Wolfgang; Steiner, Barbara; Ametz, Christian; Siegwart, Gerald; Wiesenberger, Gerlinde; Berthiller, Franz; Lemmens, Marc; Jia, Haiyan; Adam, Gerhard; Muehlbauer, Gary J; Kreil, David P; Buerstmayr, Hermann

    2013-01-01

    Fusarium head blight, caused by Fusarium graminearum, is a devastating disease of wheat. We developed near-isogenic lines (NILs) differing in the two strongest known F. graminearum resistance quantitative trait loci (QTLs), Qfhs.ndsu-3BS (also known as resistance gene Fhb1) and Qfhs.ifa-5A, which are located on the short arm of chromosome 3B and on chromosome 5A, respectively. These NILs showing different levels of resistance were used to identify transcripts that are changed significantly in a QTL-specific manner in response to the pathogen and between mock-inoculated samples. After inoculation with F. graminearum spores, 16 transcripts showed a significantly different response for Fhb1 and 352 for Qfhs.ifa-5A. Notably, we identified a lipid transfer protein which is constitutively at least 50-fold more abundant in plants carrying the resistant allele of Qfhs.ifa-5A. In addition to this candidate gene associated with Qfhs.ifa-5A, we identified a uridine diphosphate (UDP)-glycosyltransferase gene, designated TaUGT12887, exhibiting a positive difference in response to the pathogen in lines harbouring both QTLs relative to lines carrying only the Qfhs.ifa-5A resistance allele, suggesting Fhb1 dependence of this transcript. Yet, this dependence was observed only in the NIL with already higher basal resistance. The complete cDNA of TaUGT12887 was reconstituted from available wheat genomic sequences, and a synthetic recoded gene was expressed in a toxin-sensitive strain of Saccharomyces cerevisiae. This gene conferred deoxynivalenol resistance, albeit much weaker than that observed with the previously characterized barley HvUGT13248. PMID:23738863

  15. Silencing of the major family of NBS-LRR-encoding genes in lettuce results in the loss of multiple resistance specificities.

    Science.gov (United States)

    Wroblewski, Tadeusz; Piskurewicz, Urszula; Tomczak, Anna; Ochoa, Oswaldo; Michelmore, Richard W

    2007-09-01

    The RGC2 gene cluster in lettuce (Lactuca sativa) is one of the largest known families of genes encoding nucleotide binding site-leucine-rich repeat (NBS-LRR) proteins. One of its members, RGC2B, encodes Dm3 which determines resistance to downy mildew caused by the oomycete Bremia lactucae carrying the cognate avirulence gene, Avr3. We developed an efficient strategy for analysis of this large family of low expressed genes using post-transcriptional gene silencing (PTGS). We transformed lettuce cv. Diana (carrying Dm3) using chimeric gene constructs designed to simultaneously silence RGC2B and the GUS reporter gene via the production of interfering hairpin RNA (ihpRNA). Transient assays of GUS expression in leaves accurately predicted silencing of both genes and were subsequently used to assay silencing in transgenic T(1) plants and their offspring. Levels of mRNA were reduced not only for RGC2B but also for all seven diverse RGC2 family members tested. We then used the same strategy to show that the resistance specificity encoded by the genetically defined Dm18 locus in lettuce cv. Mariska is the result of two resistance specificities, only one of which was silenced by ihpRNA derived from RGC2B. Analysis of progeny from crosses between transgenic, silenced tester stocks and lettuce accessions carrying other resistance genes previously mapped to the RGC2 locus indicated that two additional resistance specificities to B. lactucae, Dm14 and Dm16, as well as resistance to lettuce root aphid (Pemphigus bursarius L.), Ra, are encoded by RGC2 family members.

  16. Identification of a novel aminopeptidase P-like gene (OnAPP possibly involved in Bt toxicity and resistance in a major corn pest (Ostrinia nubilalis.

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    Chitvan Khajuria

    Full Text Available Studies to understand the Bacillus thuringiensis (Bt resistance mechanism in European corn borer (ECB, Ostrinia nubilalis suggest that resistance may be due to changes in the midgut-specific Bt toxin receptor. In this study, we identified 10 aminopeptidase-like genes, which have previously been identified as putative Bt toxin receptors in other insects and examined their expression in relation to Cry1Ab toxicity and resistance. Expression analysis for the 10 aminopeptidase-like genes revealed that most of these genes were expressed predominantly in the larval midgut, but there was no difference in the expression of these genes in Cry1Ab resistant and susceptible strains. This suggested that altered expression of these genes was unlikely to be responsible for resistance in these ECB strains. However, we found that there were changes in two amino acid residues of the aminopeptidase-P like gene (OnAPP involving Glu(305 to Lys(305 and Arg(307 to Leu(307 in the two Cry1Ab-resistant strains as compared with three Cry1Ab-susceptible strains. The mature OnAPP contains 682 amino acid residues and has a putative signal peptide at the N-terminus, a predicted glycosylphosphatidyl-inositol (GPI-anchor signal at the C-terminal, three predicted N-glycosylation sites at residues N178, N278 and N417, and an O-glycosylation site at residue T653. We used a feeding based-RNA interference assay to examine the role of the OnAPP gene in Cry1Ab toxicity and resistance. Bioassays of Cry1Ab in larvae fed diet containing OnAPP dsRNA resulted in a 38% reduction in the transcript level of OnAPP and a 25% reduction in the susceptibility to Cry1Ab as compared with larvae fed GFP dsRNA or water. These results strongly suggest that the OnAPP gene could be involved in binding the Cry1Ab toxin in the ECB larval midgut and that mutations in this gene may be associated with Bt resistance in these two ECB strains.

  17. Major haplotype divergence including multiple germin-like protein genes, at the wheat Sr2 adult plant stem rust resistance locus

    Czech Academy of Sciences Publication Activity Database

    Mago, R.; Tabe, L.; Vautrin, S.; Šimková, Hana; Kubaláková, Marie; Upadhyaya, N.; Berges, H.; Kong, X.Y.; Breen, J.; Doležel, Jaroslav; Appels, R.; Ellis, J.G.; Spielmeyer, W.

    2014-01-01

    Roč. 14, č. 379 (2014) ISSN 1471-2229 R&D Projects: GA ČR GBP501/12/G090; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Adult plant resistance (APR) * Map-based cloning * Sr2 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.813, year: 2014

  18. Fine mapping and introgressing qFIS1-2, a major QTL for kernel fissure resistance in rice (Oryza sativa L.)

    Science.gov (United States)

    Rice (Oryza sativa L.) kernel fissuring increases breakage during milling and decreases the value of processed rice. This study employed molecular gene tagging methods to fine-map a fissure resistance (FR) locus in ‘Cybonnet’, a semidwarf tropical japonica cultivar, as well as transfer this trait to...

  19. MHC polymorphism and disease resistance in Atlantic salmon (Salmo salar); facing pathogens with single expressed major histocompatibility class I and class II loci

    NARCIS (Netherlands)

    Grimholt, U.; Larsen, S.; Nordmo, R.; Midtlyng, P.; Kjoeglum, S.; Storset, A.; Saebo, S.; Stet, R.J.M.

    2003-01-01

    Few studies have yet addressed the functional aspects of MHC molecules in fish. To lay the foundation for this, we evaluated the association between disease resistance and MHC class I and class II polymorphism in Atlantic salmon. Standardized disease challenge trials were performed on a semi-wild

  20. Comparative sequence analysis of the potato cyst nematode resistance locus H1 reveals a major lack of co-linearity between three haplotypes in potato (Solanum tuberosum ssp.)

    NARCIS (Netherlands)

    Finkers-Tomczak, A.M.; Bakker, E.H.; Boer, de J.M.; Vossen, van der E.A.G.; Achenbach, U.; Golas, T.M.; Suryaningrat, S.; Smant, G.; Bakker, J.; Goverse, A.

    2011-01-01

    The H1 locus confers resistance to the potato cyst nematode Globodera rostochiensis pathotypes 1 and 4. It is positioned at the distal end of chromosome V of the diploid Solanum tuberosum genotype SH83-92-488 (SH) on an introgression segment derived from S. tuberosum ssp. andigena. Markers from a

  1. Impact on informed choice of offering antenatal sickle cell and thalassaemia screening in primary care: a randomized trial

    Science.gov (United States)

    Brown, Katrina; Dormandy, Elizabeth; Reid, Erin; Gulliford, Martin; Marteau, Theresa

    2011-01-01

    Objectives Offering antenatal sickle cell and thalassaemia (SCT) screening early in pregnancy can maximize the range of post-screening choices available, however these benefits should not be obtained at the expense of informed choice.  This study examined whether offering this screening in primary care at the time of pregnancy confirmation compromises women making informed choices. Design Partial factorial, cluster randomized controlled trial. Setting 25 general practices in two socially deprived UK areas. Participants 464 pregnant women offered antenatal SCT screening. Intervention Practices were randomly allocated to offer pregnant women screening:  i) in primary care at time of pregnancy confirmation, with parallel partner testing (n = 191), ii) in primary care at time of pregnancy confirmation, with sequential partner testing (n = 158), or iii) in secondary care by midwives, with sequential partner testing (standard care, n = 115). Main outcome Informed choice – a classification based on attitudes, knowledge and test uptake. Results 91% of woman underwent screening. About a third (30.6%) made an informed choice to accept or decline screening: 34% in primary care parallel group; 23.4% in primary care sequential and 34.8% in secondary care sequential. Allowing for adjustments, rates of informed choice did not vary by intervention group: secondary care versus primary care with parallel partner testing OR 1.07 (95% CI 0.56 to 2.02); secondary care versus primary care with sequential partner testing OR 0.67 (95% CI 0.36 to 1.25).  Uninformed choices were generally attributable to poor knowledge (65%). Conclusion Offering antenatal SCT screening in primary care did not reduce the likelihood that women made informed choices. Rates of informed choice were low and could be increased by improving knowledge. PMID:21852698

  2. Comparative studies on physical-chemical properties and major nutritional components of rice grain in dwarf mutant resistant to insect pests and its parent

    International Nuclear Information System (INIS)

    Cui Hairui; Wu Dianxing; Shen Shengquan; Shu Qingyao

    2004-01-01

    Starch characteristics and key nutritional compositions in the dwarf mutant from transgenic rice with crylAb gene were compared with its original parent, Xiushuill. It was found that peak viscosity, hot paste viscosity and cool paste viscosity of RVA profile between the dwarf mutant and its parent were significantly different at 1% level, but apparent amylose content, gel consistence existed and breakdown viscosity of RVA profile were similar, and no significant differences existed in contents of crude protein, crude fat, total ash, amino acids and mineral compositions. It was suggested that no notable changes occurred in grain quality traits in the dwarf mutant with insect resistance. (authors)

  3. The MRD1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes.

    Science.gov (United States)

    Martel, J; Payet, M D; Dupuis, G

    1997-08-01

    The response of T cells in relation to the cell cycle has not been extensively studied. We have attempted to address this question using Jurkat T cells treated with cytostatic drugs known to arrest cells at various transition points of their cycle. We tested various concentrations of drugs that act at G1/S (hydroxyurea, lovastatin, thymidine), early S [aphidicolin, cyclosporin A (CsA), rapamycin] or G2 + M (colchicine, nocodazole) in 24 h cultures. Cytofluorimetric analyses showed that cycling Jurkat cells were equally distributed between the G1 (44.9 +/- 6.5%) and S (42.3 +/- 8.0%) phases. Cell distribution in G2 + M was 12.7 +/- 2.8%. Hydroxyurea but not lovastatin increased the percentage of cells in S phase to ca 60-70% and both drugs decreased it to ca 30% in G1. Thymidine had no effects. Aphidicolin increased the distribution in S phase to ca 70% with a decrease in G1 to ca 30%. CsA and rapamycin increased the percentage of the cells in G1 to ca 70% and decreased it to ca 25% in S phase. Nocodazole increased cell distribution in G2 + M to ca 60% and induced a decrease in G1 to ca 10%. The effects of the drugs were not related to their toxicity and their limited efficiency raised the possibility that Jurkat cells possessed an intrinsic resistance to these xenobiotics. Time-course analysis showed (scanning electron microscopy) that the early morphological changes induced by colchicine were reversible. Drug efflux experiments (vinblastine) suggested that an ATP-dependent process could be involved. However, Northern blot analyses showed a weak signal for MDR1 (MDR, multiple drug resistance). In contrast, a probe for multidrug resistance-associated protein (P-190; MRP) showed a strong signal in Jurkat and peripheral lymphocytes. The presence of drugs (CsA, nocodazole, thymidine) (24 h) did not up-regulate its message and cell treatment with BSO only moderately affected the efficiency of the glutathione S-conjugate MRP transporter. Our data suggest that the

  4. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2016-09-01

    Full Text Available Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs, and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS of A. flavus resistance and a characterisation of the causal gene.

  5. Fine mapping of a dominantly inherited powdery mildew resistance major-effect QTL, Pm1.1, in cucumber identifies a 41.1 kb region containing two tandemly arrayed cysteine-rich receptor-like protein kinase genes.

    Science.gov (United States)

    Xu, Xuewen; Yu, Ting; Xu, Ruixue; Shi, Yang; Lin, Xiaojian; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao

    2016-03-01

    A dominantly inherited major-effect QTL for powdery mildew resistance in cucumber was fine mapped. Two tandemly arrayed cysteine-rich receptor-like protein kinase genes were identified as the most possible candidates. Powdery mildew (PM) is one of the most severe fungal diseases of cucumber (Cucumis sativus L.) and other cucurbit crops, but the molecular genetic mechanisms of powdery mildew resistance in cucurbits are still poorly understood. In this study, through marker-assisted backcrossing with an elite cucumber inbred line, D8 (PM susceptible), we developed a single-segment substitution line, SSSL0.7, carrying 95 kb fragment from PM resistance donor, Jin5-508, that was defined by two microsatellite markers, SSR16472 and SSR16881. A segregating population with 3600 F2 plants was developed from the SSSL0.7 × D8 mating; segregation analysis confirmed a dominantly inherited major-effect QTL, Pm1.1 in cucumber chromosome 1 underlying PM resistance in SSSL0.7. New molecular markers were developed through exploring the next generation resequenced genomes of Jin5-508 and D8. Linkage analysis and QTL mapping in a subset of the F2 plants delimited the Pm1.1 locus into a 41.1 kb region, in which eight genes were predicted. Comparative gene expression analysis revealed that two concatenated genes, Csa1M064780 and Csa1M064790 encoding the same function of a cysteine-rich receptor-like protein kinase, were the most likely candidate genes. GFP fusion protein-aided subcellular localization indicated that both candidate genes were located in the plasma membrane, but Csa1M064780 was also found in the nucleus. This is the first report of dominantly inherited PM resistance in cucumber. Results of this study will provide new insights into understanding the phenotypic and genetic mechanisms of PM resistance in cucumber. This work should also facilitate marker-assisted selection in cucumber breeding for PM resistance.

  6. Elevated Plasmodium infection rates and high pyrethroid resistance in major malaria vectors in a forested area of Cameroon highlight challenges of malaria control.

    Science.gov (United States)

    Ndo, Cyrille; Kopya, Edmond; Donbou, Marie Agathe; Njiokou, Flobert; Awono-Ambene, Parfait; Wondji, Charles

    2018-03-08

    High coverage of long-lasting insecticidal nets (LLINs) is the cornerstone of the malaria control strategy of the national malaria control program (NMCP) in Cameroon, with a target of reducing malaria transmission to less than 10% by 2035. To this end, more than 20 million LLINs have been distributed to populations countrywide since 2011. The present study evaluated entomological indices and Anopheles susceptibility to pyrethroids in a rural forested area of south Cameroon with high coverage of LLINs. The study was conducted between July 2014 and May 2016 in Obout, a village located in a rural forested area in south Cameroon. Resting mosquitoes were collected using electric aspirators and were identified to species using morphological criteria and PCR tools. Mosquito feeding preferences and infection status to Plasmodium falciparum were determined by ELISA and using TaqMan assays. The susceptibility of wild F1 adults to pyrethroids was monitored using WHO insecticide susceptibility bioassays. During the study period, 5,993 Anopheles mosquitoes were collected indoors both in rooms with and without nets. Two main vector species, namely An. funestus and An. gambiae, were identified in the locality, with An. funestus being by far the most abundant (89.68%). ELISA analysis revealed high percentage of blood meal taken exclusively on human (97.65-98.95%) supporting the high antropohilic behaviour of both species. Plasmodium falciparum infection rate detected by ELISA was high throughout the study period and varied between 3.28-14.04% (mean: 10.40%) in An. funestus, and between 5.55-22.22% (mean: 13.87%) in An. gambiae. This trend was confirmed by TaqMan assays, with P. falciparum infection prevalence of 23.33% in An. funestus. Significant decrease of mortality associated with high frequency of kdr mutation was observed in An. gambiae (deltamethrin: 36.6-56.45%; permethrin: 6-18.65%) indicating high level of resistance to pyrethroids. For An. funestus, resistance was

  7. Dark blood versus bright blood T2* acquisition in cardiovascular magnetic resonance (CMR) for thalassaemia major (TM) patients: Evaluation of feasibility, reproducibility and image quality

    International Nuclear Information System (INIS)

    Liguori, Carlo; Di Giampietro, Ilenia; Pitocco, Francesca; De Vivo, Aldo Eros; Schena, Emiliano; Mortato, Luca; Pirro, Federica; Cianciulli, Paolo; Zobel, Bruno Beomonte

    2014-01-01

    Objectives: To compare the effectiveness of dark blood (DB) versus bright blood (BB) sequences. To assess the intra and inter-observer variability and inter-study reproducibility between BB versus DB. To evaluate image quality level in the two sequences. Methods: In a setting of 138 patients we performed CMR using cardiac gated Gradient-multiecho single breath-hold BB and DB sequences in the middle ventricular septum. Each acquisition was repeated during the same exam. Truncation method was used to account for background noise. Image quality (IQ) was assessed using a 5 point grading scale and image analysis was conducted by 2 experienced observers. Results: Compared with the conventional BB acquisition, the coefficient of correlation and significance of the DB technique was superior for intra-observer reproducibility (p < 0.001), inter-observer reproducibility (p < 0.001) and inter-study reproducibility (p < 0.001). The variability is also lower for DB sequences for T2* values <14 ms. Assessment of artifacts showed a superior score for DB versus BB scans (4 versus 3, p < 0.001). Conclusions: Improvement in terms of inter observer and inter study variability using DB sequences was obtained. The greatest disparity between them was seen in inter-study reproducibility and higher IQ in DB was seen. Study demonstrates better performance of DB imaging compared to BB in presence of comparable effectiveness

  8. Intra-leukocytic hemosiderin inclusions detected as pseudoeosinophils by automated depolarization analysis in a patient with beta-thalassaemia major and immune hemolysis.

    Science.gov (United States)

    Roberts, George T; Perry, J Leonard; Al-Jefri, Abdullah; Scott, Colin Stephen

    2005-01-01

    This report describes a patient with intra-leukocytic hemosiderin inclusions associated with iron overload and acute infection. These inclusions resulted in a false identification of eosinophils rather than neutrophils using an automated analyzer. The analyzer interpreted the aberrant increased depolarization as a reflection of eosinophils. No eosinophils were found by examination of the blood smear. The implications for the hematology morphologist is that visual inspection of a blood smear is nearly always indicated whenever any departure from strict normality is noted in the output from an automated blood cell counter.

  9. Dark blood versus bright blood T2* acquisition in cardiovascular magnetic resonance (CMR) for thalassaemia major (TM) patients: Evaluation of feasibility, reproducibility and image quality

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Carlo, E-mail: c.liguori@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Di Giampietro, Ilenia; Pitocco, Francesca; De Vivo, Aldo Eros [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Schena, Emiliano [Unit of Measurements and Biomedical Instrumentation, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Mortato, Luca [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Pirro, Federica [Department of Biomaging and Radiological Sciences, Catholic University of Sacred Herart, Largo A. Gemelli 1, 00135 Rome (Italy); Cianciulli, Paolo [Thalassemia Unit, Ospedale Sant Eugenio, Piazzale dell’Umanesimo 10, 00143 Rome (Italy); Zobel, Bruno Beomonte [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy)

    2014-01-15

    Objectives: To compare the effectiveness of dark blood (DB) versus bright blood (BB) sequences. To assess the intra and inter-observer variability and inter-study reproducibility between BB versus DB. To evaluate image quality level in the two sequences. Methods: In a setting of 138 patients we performed CMR using cardiac gated Gradient-multiecho single breath-hold BB and DB sequences in the middle ventricular septum. Each acquisition was repeated during the same exam. Truncation method was used to account for background noise. Image quality (IQ) was assessed using a 5 point grading scale and image analysis was conducted by 2 experienced observers. Results: Compared with the conventional BB acquisition, the coefficient of correlation and significance of the DB technique was superior for intra-observer reproducibility (p < 0.001), inter-observer reproducibility (p < 0.001) and inter-study reproducibility (p < 0.001). The variability is also lower for DB sequences for T2* values <14 ms. Assessment of artifacts showed a superior score for DB versus BB scans (4 versus 3, p < 0.001). Conclusions: Improvement in terms of inter observer and inter study variability using DB sequences was obtained. The greatest disparity between them was seen in inter-study reproducibility and higher IQ in DB was seen. Study demonstrates better performance of DB imaging compared to BB in presence of comparable effectiveness.

  10. Major Links.

    Science.gov (United States)

    Henderson, Tona

    1995-01-01

    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  11. The Thal-index with the BTT prediction.exe to discriminate β-thalassaemia traits from other microcytic anaemias

    Directory of Open Access Journals (Sweden)

    Ahangama Arachchige Nilanga Nishad

    2012-06-01

    Full Text Available Several attempts have been made previously to differentiate β-thalassaemia trait (BTT from other microcytic anaemias using formulae with red cell (RC parameters. Presently available formulae have low sensitivity and specificity. We wanted to develop a more precise algorithm, which could be used in situations where the gold-standard test for thalassaemia diagnosis: the high performance liquid chromatography (HPLC is not available. The study was carried out prospectively from November 2008 to March 2010 from randomly collected blood samples with a mean cell volume (MCV of less than 80 fL. HbA2 measured by HPLC was used to diagnose BTT. We used Fishers stepwise linear discriminant function analysis to develop an algorithm with RC parameters. Calculated new index Thal-index was then subjected to receiver operating characteristic curve analysis to identify best cutoff to discriminate BTT from other microcytic blood films. Software was developed to predict the BTT status (BTT prediction.exe. New index, referred to as the Thal-index, was calculated using discriminant function analysis and is given as Thal-index=[(0.615xMCV +(0.518xmean corpuscular hemoglobin+ (0.446xred cell distribution width]. A value of 59 for Thal-index has 90% sensitivity and 85% specificity for differentiating BTT from other microcytic anaemias. This showed better sensitivity and specificity compared to other formulae presently used (i.e., Mentzer in Eshani, et al.. Our study gives a better answer to set-up where HPLC is not available. Although this cannot replace HPLC, BTT prediction.exe is useful to predict instantly and is the first ever computer program available for this function. 先前已利用含红细胞(RC)参数的公式做出若干尝试,以鉴别β-地中海贫血(BTT)和其他小红细胞性贫血。目前可用公式的敏感度和特异度均低。我们想要开发更精确的算法,在地中海贫血诊断的金标准测试法(即高效液相色

  12. Achieving treatment goals of reducing or maintaining body iron burden with deferasirox in patients with β-thalassaemia: results from the ESCALATOR study

    Science.gov (United States)

    Taher, Ali; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Al Jefri, Abdullah; Habr, Dany; Kriemler-Krahn, Ulrike; Roubert, Bernard; El-Beshlawy, Amal

    2011-01-01

    This analysis evaluated the effects of deferasirox on liver iron concentration in moderate and heavily iron-overloaded patients with β-thalassaemia from the ESCALATOR trial (n = 231). Mean liver iron concentrations (LIC) decreased significantly from 21.1 ± 8.2 to 14.2 ± 12.1 mg Fe/g dry weight (dw) at 2 yr (P deferasirox enabled therapeutic goals to be achieved, by maintaining LIC in patients with LIC <7 mg Fe/g dw at a mean dose of 22.4 ± 5.2 mg/kg/d and significantly reducing LIC in patients with LIC ≥7 mg Fe/g dw at a mean dose of 25.7 ± 4.2 mg/kg/d, along with a manageable safety profile. PMID:21668501

  13. In vitro selection of Phytomonas serpens cells resistant to the calpain inhibitor MDL28170: alterations in fitness and expression of the major peptidases and efflux pumps.

    Science.gov (United States)

    Oliveira, Simone S C; Gonçalves, Inês C; Ennes-Vidal, Vitor; Lopes, Angela H C S; Menna-Barreto, Rubem F S; D'Ávila-Levy, Claudia M; Santos, André L S; Branquinha, Marta H

    2018-03-01

    The species Phytomonas serpens is known to express some molecules displaying similarity to those described in trypanosomatids pathogenic to humans, such as peptidases from Trypanosoma cruzi (cruzipain) and Leishmania spp. (gp63). In this work, a population of P. serpens resistant to the calpain inhibitor MDL28170 at 70 µ m (MDLR population) was selected by culturing promastigotes in increasing concentrations of the drug. The only relevant ultrastructural difference between wild-type (WT) and MDLR promastigotes was the presence of microvesicles within the flagellar pocket of the latter. MDLR population also showed an increased reactivity to anti-cruzipain antibody as well as a higher papain-like proteolytic activity, while the expression of calpain-like molecules cross-reactive to anti-Dm-calpain (from Drosophila melanogaster) antibody and calcium-dependent cysteine peptidase activity were decreased. Gp63-like molecules also presented a diminished expression in MDLR population, which is probably correlated to the reduction in the parasite adhesion to the salivary glands of the insect vector Oncopeltus fasciatus. A lower accumulation of Rhodamine 123 was detected in MDLR cells when compared with the WT population, a phenotype that was reversed when MDLR cells were treated with cyclosporin A and verapamil. Collectively, our results may help in the understanding of the roles of calpain inhibitors in trypanosomatids.

  14. IFNγ producing CD8+T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas.

    Science.gov (United States)

    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie

    2015-02-01

    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8 + T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell surface expression of MHC-I, but MHC-I expression could be rescued by exposure of these cells to IFNγ. We show that CD8 + T cells specific for tumor antigen/MHC-I were efficient at inducing regression of the MHC-I-deficient melanoma, provided that the T cells were endowed with properties permitting their migration into the tumor and their efficient production of IFNγ. This was the case for CD8 + T cells transfected to express an active form of STAT5 (STAT5CA). The amount of IFNγ produced ex vivo from T cells present in tumors after adoptive transfer of the CD8 + T cells was correlated with an increase in surface expression of MHC-I molecules by the tumor cells. We also show that these CD8 + T cells expressed PD-1 and upregulated its ligand PDL-1 on melanoma cells within the tumor. Despite upregulation of this immunosuppressive pathway, efficient IFNγ production in the melanoma microenvironment was found associated with resistance of STAT5CA-expressing CD8 + T cells to inhibition both by PD-1/PDL-1 engagement and by TGFβ1, two main immune regulatory mechanisms hampering the efficiency of immunotherapy in patients.

  15. aac(6')-Ib-cr is the major plasmid-mediated quinolone resistance determinant in extended-spectrum β-lactamase-producing Escherichia coli in eastern France.

    Science.gov (United States)

    Guillard, Thomas; Bertrand, Xavier; de Champs, Christophe; Cholley, Pascal; Bajolet, Odile; Gbaguidi-Haore, Houssein

    2014-06-01

    The aim of this study was to describe the presence of plasmid-mediated quinolone resistance (PMQR) determinants in extended spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) in hospitals in eastern France. All ESBL-Ec isolated from May 2008 to April 2009 in nine hospitals in eastern France were collected and screened by PCR for the presence of PMQR genes. bla genes were identified by PCR and sequencing. Randomly chosen PMQR-positive ESBL-Ec isolates were characterised by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and phylogenetic group identification. Of the 447 ESBL-Ec tested, 122 (27.3%) had a PMQR determinant. aac(6')-Ib-cr was more prevalent (118/122; 96.7%) than qnr [4/122 (3.3%), comprising 2 qnrB2, 1 qnrB1 and 1 qnrA1]. Among 37 PMQR-positive ESBL-Ec isolates selected for typing, 26 (70%) carried bla CTX-M-15 of which 25/26 (96%) co-harboured aac(6')-Ib-cr. Of the 37 isolates, 14 belonged to the B2:ST131 clone, all of which produced AAC(6')-Ib-cr. On the other hand, most of the qnr genes (3/4) were observed in strains carrying bla genes other than bla CTX-M (qnrB2 and bla SHV-12 ; qnrA1 and bla TEM-52 ). These findings suggest that aac(6')-Ib-cr, rather than qnr, is the spreading PMQR determinant in ESBL-Ec isolates, and the qnr determinant is not specifically associated with bla CTX-M genes in France. aac(6')-Ib-cr was the predominant PMQR gene in ESBL-Ec isolated in eastern France hospitals, suggesting that the distribution may be due to clonal spread of ST131 CTX-M-15-producing E. coli isolates. Copyright © 2014 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  16. THE LRP GENE ENCODING A MAJOR VAULT PROTEIN ASSOCIATED WITH DRUG-RESISTANCE MAPS PROXIMAL TO MRP ON CHROMOSOME-16 - EVIDENCE THAT CHROMOSOME BREAKAGE PLAYS A KEY ROLE IN MRP OR LRP GENE AMPLIFICATION

    NARCIS (Netherlands)

    SLOVAK, ML; HO, JP; COLE, SPC; DEELEY, RG; GREENBERGER, L; DEVRIES, EGE; BROXTERMAN, HJ; SCHEFFER, GL; SCHEPER, RJ

    1995-01-01

    A cDNA encoding the novel drug resistance gene, LRP (originally termed lung resistance-related protein), was isolated from HT1080/DR4, a 220-fold doxorubicin-resistant human fibrosarcoma cell line which displays a multidrug resistance phenotype and overexpresses the multidrug resistance protein

  17. Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus).

    Science.gov (United States)

    Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

    2015-01-01

    An intraspecific genetic map for watermelon was constructed using an F2 population derived from 'Arka Manik' × 'TS34' and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits.

  18. Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus)

    Science.gov (United States)

    Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

    2015-01-01

    An intraspecific genetic map for watermelon was constructed using an F2 population derived from ‘Arka Manik’ × ‘TS34’ and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits. PMID:26700647

  19. Behavior of Leishmania major metacyclic promastigotes during the course of infection and immune response development in resistant versus susceptible hosts Comportamento de promastigoteas metacíclicos de Leishmania major durante o curso da infecção e da resposta imune em hospedeiros resistentes versus suscetíveis

    Directory of Open Access Journals (Sweden)

    Regina Coeli Cunha Dórea

    2003-11-01

    Full Text Available Little is known on the epitopes derived from metacyclic promastigotes of Leishmania that are important on the regulation or destruction of the parasite, as targets of immune attack in the vertebrate host. In this study we investigated an alternative method to obtain metacyclic promasigotes of Leishmania major, as evaluated by the course of infection and delayed-type hipersensitivity (DTH in resistant versus susceptible inbred mice. Non-infective (procyclic promastigotes of L. major recently transformed from tissue amastigotes were attached to a negatively charged glass-wool column, whereas metacyclic promastigotes were not bound to columns and could be easily recovered. Optimal chromatography conditions were validated through statistical analyses. Parasite average yield from glass wool columns and promastigote viability were estimated by light microscopy. Metacyclic promastigotes yielded 43.5% to 57.5%. Different patterns of cutaneous lesions were obtained in BALB/c (susceptible and C57BL/6 (resistant mice, the former with highly infective lesions induced by metacyclic promastigotes. DTH responses proved to be higher in groups of C57BL/6 mice which were infected with metacyclic promastigotes. These results indicate that the new method could be integrated with the investigation of metacyclogenesis of Leishmania in vivo.Pouco se conhece sobre os epítopos derivados de promastigotas metacíclicos de Leishmania que são importantes para a regulação ou destruição do parasita, como alvos de ação imunológica no hospedeiro vertebrado. Neste estudo, nós investigamos um método alternativo para obter promastigotas metacíclicos de Leishmania major, pela avaliação do curso da infecção e reação de hipersensibilidade do tipo retardado (HTR em hospedeiros resistentes e susceptíveis. Promastigotas não-infectantes (procíclicos de L. major, recentemente isolados de amastigotas, foram selecionados pela adesão a colunas de lã de vidro

  20. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  1. Antibiotic resistance reservoirs

    NARCIS (Netherlands)

    Versluis, Dennis

    2016-01-01

    One of the major threats to human health in the 21st century is the emergence of pathogenic bacteria that are resistant to multiple antibiotics, thereby limiting treatment options. An important route through which pathogens become resistant is via acquisition of resistance genes from environmental

  2. Antibiotic resistance reservoirs

    NARCIS (Netherlands)

    Versluis, Dennis

    2016-01-01

    One of the major threats to human health in the 21st century is the emergence of pathogenic bacteria that are resistant to multiple antibiotics, thereby limiting treatment options. An important route through which pathogens become resistant is via acquisition of resistance genes from

  3. 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.

  4. A new tool for the assessment of satisfaction with iron chelation therapy (ICT-Sat) for patients with β-thalassemia major.

    Science.gov (United States)

    Elalfy, Mohsen S; Massoud, Walid; Elsherif, Nayera H; Labib, Jonair H; Elalfy, Omar M; Elaasar, Safaa; von Mackensen, Sylvia

    2012-06-01

    High satisfaction with iron chelation is a major determinant for adherence to ICT in beta-thalassaemia major (β-TM) patients. In this study, a new tool to assess different domains of satisfaction for available forms of ICT was developed and validated. The impact of patients' satisfaction with ICT has been tested. Items were generated via focus groups and a preliminary version with 24 items (ICT-Sat) with an additional item for treatment preference and a knowledge questionnaire (KQ) was developed. 170 β-TM patients from three Thalassaemia centers in Egypt, aged 2-32 years received three questionnaires to fill in; the new ICT-Sat, a KQ, and a previously validated tool for satisfaction with ICT (SICT) and retested 4-6 weeks later to ensure re-test reliability. Type of chelation, drug related adverse events, compliance with ICT, and serum ferritin level (SF) during the year prior to the study as well as available cardiac T2*data were recorded. One hundred and fifty two β-TM patients completed all questionnaires; median age was 12 years. The final 15 remaining ICT-Sat items, yielding to four domain scores, explained 70.6% of the total variance. The "perceived effectiveness" and "fear and worries" domains of the ICT-Sat correlated significantly with the domains "perceived effectiveness" and "acceptance" of the SICT. Patients treated with oral ICT were more satisfied with perceived effectiveness, and their side effects. A new clinically based ICT-Sat tool was developed and revealed good psychometric characteristics. Adherence to ICT was better correlated with "perceived effectiveness" and SF level. Copyright © 2012 Wiley Periodicals, Inc.

  5. Resistance to Powdery Mildews

    DEFF Research Database (Denmark)

    Siwoszek, Agnieszka Izabela

    in majority of them. Resistance to barley powdery mildew in the field is controlled by use of resistant varieties in a combination with fungicides. Early disease management is crucial for effective control. Yet, the pathogen commonly develops fungicide resistance due to simple point mutations. Several studies...... investigated reduced fitness of plants as a cost of resistance to pathogens. In case of barley powdery mildew, most common resistance (mlo) is linked to a higher susceptibility to other pathogens and spontaneous necrosis that leads to yield reduction. Thus, there is a clear need for alternative methods of crop...... protection. In the present study, I provide an overview of the current knowledge about plant pathogens and plant disease resistance. I use Arabidopsis as a model to investigate the mechanism of non-host resistance, presumed to be the most durable and broad-spectrum form of resistance. I attempt to determine...

  6. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Hansen, Malene Plejdrup; Hoffmann, Tammy C; McCullough, Amanda R

    2015-01-01

    Numerous opportunities are available in primary care for alleviating the crisis of increasing antibiotic resistance. Preventing patients from developing an acute respiratory infection (ARI) will obviate any need for antibiotic use downstream. Hygiene measures such as physical barriers and hand...... will greatly improve the use of antibiotics for ARIs. However, used in concert, combinations are likely to enable clinicians and health care systems to implement the strategies that will reduce antimicrobial resistance in the future....... antibiotic prescribing are a major factor in the prescribing for ARIs. Professional interventions with educational components are effective, although they have modest effects, and are expensive. GPs' perceptions - that mistakenly assume as a default that patients want antibiotics for their ARIs - are often...

  7. Major Depression Among Adults

    Science.gov (United States)

    ... Depressive Episode Among Adolescents Data Sources Share Major Depression Definitions Major depression is one of the most common mental disorders in the United States. For some individuals, major depression can result in severe impairments that interfere with ...

  8. P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients

    International Nuclear Information System (INIS)

    Tang, Ruoping; Legrand, Ollivier; Marie, Jean-Pierre; Cohen, Simy; Perrot, Jean-Yves; Faussat, Anne-Marie; Zuany-Amorim, Claudia; Marjanovic, Zora; Morjani, Hamid; Fava, Fanny; Corre, Elise

    2009-01-01

    AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML). This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays. P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC 50 > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells. P-gp activity is not a crucial mechanism of chemoresistance to AVE9633. For patients whose resistance to conventional anthracycline AML regimens is related to ABC protein expression, a combination with AVE9633 could be beneficial. Other mechanisms such as microtubule alteration could play an important role in chemoresistance to AVE9633

  9. DNA microarray profiling of a diverse collection of nosocomial methicillin-resistant staphylococcus aureus isolates assigns the majority to the correct sequence type and staphylococcal cassette chromosome mec (SCCmec) type and results in the subsequent identification and characterization of novel SCCmec-SCCM1 composite islands.

    LENUS (Irish Health Repository)

    Shore, Anna C

    2012-10-01

    One hundred seventy-five isolates representative of methicillin-resistant Staphylococcus aureus (MRSA) clones that predominated in Irish hospitals between 1971 and 2004 and that previously underwent multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing were characterized by spa typing (175 isolates) and DNA microarray profiling (107 isolates). The isolates belonged to 26 sequence type (ST)-SCCmec types and subtypes and 35 spa types. The array assigned all isolates to the correct MLST clonal complex (CC), and 94% (100\\/107) were assigned an ST, with 98% (98\\/100) correlating with MLST. The array assigned all isolates to the correct SCCmec type, but subtyping of only some SCCmec elements was possible. Additional SCCmec\\/SCC genes or DNA sequence variation not detected by SCCmec typing was detected by array profiling, including the SCC-fusidic acid resistance determinant Q6GD50\\/fusC. Novel SCCmec\\/SCC composite islands (CIs) were detected among CC8 isolates and comprised SCCmec IIA-IIE, IVE, IVF, or IVg and a ccrAB4-SCC element with 99% DNA sequence identity to SCC(M1) from ST8\\/t024-MRSA, SCCmec VIII, and SCC-CI in Staphylococcus epidermidis. The array showed that the majority of isolates harbored one or more superantigen (94%; 100\\/107) and immune evasion cluster (91%; 97\\/107) genes. Apart from fusidic acid and trimethoprim resistance, the correlation between isolate antimicrobial resistance phenotype and the presence of specific resistance genes was ≥97%. Array profiling allowed high-throughput, accurate assignment of MRSA to CCs\\/STs and SCCmec types and provided further evidence of the diversity of SCCmec\\/SCC. In most cases, array profiling can accurately predict the resistance phenotype of an isolate.

  10. Resistant plasmid profile analysis of multidrug resistant Escherichia ...

    African Journals Online (AJOL)

    Background: Multi-drug resistant Escherichia coli has become a major threat and cause of many urinary tract infections (UTIs) in Abeokuta, Nigeria. Objectives: This study was carried out to determine the resistant plasmids of multidrug resistant Escherichia coli isolated from (Urinary tract infections)UTIs in Abeokuta.

  11. Resistance-resistant antibiotics.

    Science.gov (United States)

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Major Sport Venues

    Data.gov (United States)

    Department of Homeland Security — The Major Public Venues dataset is composed of facilities that host events for the National Association for Stock Car Auto Racing, Indy Racing League, Major League...

  13. Bestemmelse af T2*-relaksationstiden i myokardiet, med magnetisk resonans, kan indikere patologisk jernophobning hos børn med β-thalassaemia major

    DEFF Research Database (Denmark)

    Brix, Lau; Lundorf, Erik; Clausen, Niels

    på 1.6x3.6x10.0mm3 og en matrix-størrelse på 256x128. Der blev optaget 8 faser (2.0-18.0ms) i et enkelt, slutdiastolisk, midt-ventrikulært, kortakse snit under breath-hold. Akkvisitionstiden var 16 sekunder (Figur 1). Dataanalyser blev efterfølgende udført i MatLab® ved at plotte signalintensiteter...

  14. A pilot study of the efficacy and safety of paroxetine augmented with risperidone, valproate, buspirone, trazodone, or thyroid hormone in adult Chinese patients with treatment-resistant major depression.

    Science.gov (United States)

    Fang, Yiru; Yuan, Chengmei; Xu, Yifeng; Chen, Jun; Wu, Zhiguo; Cao, Lan; Yi, Zhenghui; Hong, Wu; Wang, Yong; Jiang, Kaida; Cui, Xingjia; Calabrese, Joseph R; Gao, Keming

    2011-10-01

    To compare the efficacy and safety of augmenting paroxetine with risperidone, buspirone, valproate, trazodone, or thyroid hormone in patients with treatment-resistant depression (TRD), 225 patients with retrospectively and/or prospectively identified stage II TRD were randomly assigned to receive an 8-week treatment of paroxetine 20 mg/d augmented with risperidone 2 mg/d (n = 45), sodium valproate 600 mg/d (n = 39), buspirone 30 mg/d (n = 46), trazodone 100 mg/d (n = 47), or thyroid hormone 80 mg/d (n = 48). The primary outcome was the remission rate defined as the 17-item Hamilton Rating Scale for Depression score of 7 or less at the end of study. Secondary outcomes included remission rate based on the Self-rating Depression Scale score of 50 or less at the end of study, response rate based on 17-item Hamilton Rating Scale for Depression total score of 50% improvement or greater from baseline, and the change in scores of Clinical Global Impression-Improvement scale, the Short Form 36 Health Survey, and the Life Satisfaction Rating Scale. The remission rates were 26.7% for risperidone, 48.7% for valproate, 32.6% for buspirone, 42.6% for trazodone, and 37.5% for thyroid hormone. There was no statistical significance among treatment arms in remission rates, secondary outcome measures, and adverse events. Risperidone, valproate, buspirone, trazodone, or thyroid hormone augmentation to paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD. Large-sample studies are warranted to support or refute these findings.

  15. Mechanisms of Antibiotic Resistance

    Science.gov (United States)

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  16. Prospects after Major Trauma

    NARCIS (Netherlands)

    Holtslag, H.R.

    2007-01-01

    Introduction. After patients survived major trauma, their prospects, in terms of the consequences for functioning, are uncertain, which may impact severely on patient, family and society. The studies in this thesis describes the long-term outcomes of severe injured patients after major trauma. In

  17. Resistance of Major Histocompatibility Complex Class B (MHC-B) to Nef-Mediated Downregulation Relative to that of MHC-A Is Conserved among Primate Lentiviruses and Influences Antiviral T Cell Responses in HIV-1-Infected Individuals.

    Science.gov (United States)

    Mwimanzi, Francis; Toyoda, Mako; Mahiti, Macdonald; Mann, Jaclyn K; Martin, Jeffrey N; Bangsberg, David; Brockman, Mark A; Goulder, Philip; Kirchhoff, Frank; Brumme, Zabrina L; Ndung'u, Thumbi; Ueno, Takamasa

    2018-01-01

    Patient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently than HLA-B. However, it remains unknown whether this property is common to Nef proteins across primate lentiviruses and how antiviral immune responses may be affected. We examined 263 Nef clones from diverse primate lentiviruses including different pandemic HIV-1 group M subtypes for their ability to downregulate major histocompatibility complex class A (MHC-A) and MHC-B from the cell surface. Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC-B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A, on average, 11 to 32% more efficiently than MHC-B. Nef genotype/phenotype analyses in a cohort of HIV-1 subtype C-infected patients ( n = 168), together with site-directed mutagenesis, revealed Nef position 9 as a subtype-specific determinant of differential HLA-A versus HLA-B downregulation activity. Nef clones harboring nonconsensus variants at codon 9 downregulated HLA-B (though not HLA-A) significantly better than those harboring the consensus sequence at this site, resulting in reduced recognition of infected target cells by HIV-1-specific CD8 + effector cells in vitro Among persons expressing protective HLA class I alleles, carriage of Nef codon 9 variants was also associated with reduced ex vivo HIV-specific T cell responses. Our results demonstrate that Nef's inferior ability to downregulate MHC-B compared to that of MHC-A is conserved across primate lentiviruses and suggest that this property influences antiviral cellular immune responses. IMPORTANCE Primate lentiviruses encode the Nef protein that plays an essential role in establishing persistent infection in their respective host species. Nef interacts with the cytoplasmic region of MHC-A and MHC-B molecules and downregulates them from the infected cell surface to escape recognition by host cellular immunity. Using a panel of Nef alleles isolated from diverse primate lentiviruses

  18. Candidemia in major burns patients.

    Science.gov (United States)

    Renau Escrig, Ana I; Salavert, Miguel; Vivó, Carmen; Cantón, Emilia; Pérez Del Caz, M Dolores; Pemán, Javier

    2016-06-01

    Major burn patients have characteristics that make them especially susceptible to candidemia, but few studies focused on this have been published. The objectives were to evaluate the epidemiological, microbiological and clinical aspects of candidemia in major burn patients, determining factors associated with a poorer prognosis and mortality. We conducted a retrospective observational study of candidemia between 1996 and 2012 in major burn patients admitted to the La Fe University Hospital, Valencia, Spain. The study included 36 episodes of candidemia in the same number of patients, 55.6% men, mean age 37.33 years and low associated comorbidity. The incidence of candidemia varied between 0.26 and 6.09 episodes/1000 days stay in the different years studied. Candida albicans was the most common species (61.1%) followed by Candida parapsilosis (27.8%). Candidemia by C. krusei, C. glabrata or C. tropicalis were all identified after 2004. Central vascular catheter (CVC) was established as a potential source of candidemia in 36.1%, followed by skin and soft tissues of thermal injury (22.2%) and urinary tract (8.3%). Fluconazole was used in 19 patients (52.7%) and its in vitro resistance rate was 13.9%. The overall mortality was 47.2%, and mortality related to candidemia was 30.6%. Factors associated with increased mortality were those related to severe infection and shock. CVC was the most usual focus of candidemia. Fluconazole was the most common antifungal drug administered. The management of candidemia in major burn patients is still a challenge. © 2016 Blackwell Verlag GmbH.

  19. A major safety overhaul

    CERN Multimedia

    2003-01-01

    A redefined policy, a revamped safety course, an environmental project... the TIS (Technical Inspection and Safety) Division has begun a major safety overhaul. Its new head, Wolfgang Weingarten, explains to the Bulletin why and how this is happening.

  20. Allegheny County Major Rivers

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This dataset contains locations of major rivers that flow through Allegheny County. These shapes have been taken from the Hydrology dataset. The Ohio River,...

  1. Retinal detachment associated with thalassemia major and Marfan′s syndrome-A case report

    Directory of Open Access Journals (Sweden)

    Chatterjee Pranab

    1987-01-01

    Full Text Available The thalassaemias, unlike a few other disorders of the haemopoietic system, are very rarely accompanied by ophthalmological changed. Marfan′s Syndrome, on the other hand, exhibits a number of ocular manifestations 2. This article describes a case of uniocular retinal detachment associated with both these conditions

  2. Metabolic Resistance in Bed Bugs

    Directory of Open Access Journals (Sweden)

    Omprakash Mittapalli

    2011-03-01

    Full Text Available Blood-feeding insects have evolved resistance to various insecticides (organochlorines, pyrethroids, carbamates, etc. through gene mutations and increased metabolism. Bed bugs (Cimex lectularius are hematophagous ectoparasites that are poised to become one of the major pests in households throughout the United States. Currently, C. lectularius has attained a high global impact status due to its sudden and rampant resurgence. Resistance to pesticides is one factor implicated in this phenomenon. Although much emphasis has been placed on target sensitivity, little to no knowledge is available on the role of key metabolic players (e.g., cytochrome P450s and glutathione S-transferases towards pesticide resistance in C. lectularius. In this review, we discuss different modes of resistance (target sensitivity, penetration resistance, behavioral resistance, and metabolic resistance with more emphasis on metabolic resistance.

  3. Strategies to combat antimicrobial resistance.

    Science.gov (United States)

    Uchil, Rajesh R; Kohli, Gurdeep Singh; Katekhaye, Vijay M; Swami, Onkar C

    2014-07-01

    The global burden of antimicrobial resistance is rising and is associated with increased morbidity and mortality in clinical and community setting. Spread of antibiotic resistance to different environmental niches and development of superbugs have further complicated the effective control strategies. International, national and local approaches have been advised for control and prevention of antimicrobial resistance. Rational use of antimicrobials, regulation on over-the-counter availability of antibiotics, improving hand hygiene and improving infection prevention and control are the major recommended approaches. Thorough understanding of resistance mechanism and innovation in new drugs and vaccines is the need. A multidisciplinary, collaborative, regulatory approach is demanded for combating antimicrobial resistance.

  4. Drug resistance in malaria

    Directory of Open Access Journals (Sweden)

    S C Parija

    2011-01-01

    Full Text Available Antimalarial chemotherapy is an important component of all malaria control programmes throughout the world. This is especially so in light of the fact that there are no antimalarial vaccines which are available for clinical use at present. Emergence and spread of malaria parasites which are resistant to many of the available antimalarials today is, therefore, a major cause for concern. Till date, resistance to all groups of antimalarials excluding artemisinin has been reported. In recent years, in vitro resistance to even artemisinin has been described. While resistance to antibacterial agents has come to prominence as a clinical problem in recent years, antiparasitic resistance in general and antimalarial resistance in particular has not received much attention, especially in the Indian scenario. The present review deals with commonly used antimalarial drugs and the mechanisms of resistance to them. Various methods of detecting antimalarial resistance and avoiding the same have also been dealt with. Newer parasite targets which can be used in developing newer antimalarial agents and antimalarials obtained from plants have also been mentioned.

  5. Metal Resistance and Its Association With Antibiotic Resistance.

    Science.gov (United States)

    Pal, Chandan; Asiani, Karishma; Arya, Sankalp; Rensing, Christopher; Stekel, Dov J; Larsson, D G Joakim; Hobman, Jon L

    2017-01-01

    Antibiotic resistance is recognised as a major global threat to public health by the World Health Organization. Currently, several hundred thousand deaths yearly can be attributed to infections with antibiotic-resistant bacteria. The major driver for the development of antibiotic resistance is considered to be the use, misuse and overuse of antibiotics in humans and animals. Nonantibiotic compounds, such as antibacterial biocides and metals, may also contribute to the promotion of antibiotic resistance through co-selection. This may occur when resistance genes to both antibiotics and metals/biocides are co-located together in the same cell (co-resistance), or a single resistance mechanism (e.g. an efflux pump) confers resistance to both antibiotics and biocides/metals (cross-resistance), leading to co-selection of bacterial strains, or mobile genetic elements that they carry. Here, we review antimicrobial metal resistance in the context of the antibiotic resistance problem, discuss co-selection, and highlight critical knowledge gaps in our understanding. © 2017 Elsevier Ltd. All rights reserved.

  6. [Major's and Schirmer's Gaustad].

    Science.gov (United States)

    Hvattum, Mari

    2016-07-01

    The psychiatrist Herman Wedel Major planned Gaustad asylum in collaboration with his brother-in-law, the architect Heinrich Ernst Schirmer. The planning of Gaustad took place in parallel with the preparation of the first Norwegian Mental Health Act, adopted by the Storting on 30 July 1848, and Gaustad's architecture provides a good illustration of the ideals behind the mental health reform of the 19th century. In particular, Major's and Schirmer's Gaustad represents a break with Frederik Holst's ideal of the panoptic institution. Whereas Holst and his architect Christian Heinrich Grosch promoted a radial plan institution based on the type used for penitentiaries, Schirmer and Major designed a modern, pavilion-style hospital with wards placed independently in the landscape.

  7. Major international sport profiles.

    Science.gov (United States)

    Patel, Dilip R; Stier, Bernhard; Luckstead, Eugene F

    2002-08-01

    Sports are part of the sociocultural fabric of all countries. Although different sports have their origins in different countries, many sports are now played worldwide. International sporting events bring athletes of many cultures together and provide the opportunity not only for athletic competition but also for sociocultural exchange and understanding among people. This article reviews five major sports with international appeal and participation: cricket, martial arts, field hockey, soccer, and tennis. For each sport, the major aspects of physiological and biomechanical demands, injuries, and prevention strategies are reviewed.

  8. Antimicrobial Resistance

    Science.gov (United States)

    ... least 10 countries (Australia, Austria, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom ... plan Global report on surveillance Country situation analysis Policy to combat antimicrobial resistance More on antimicrobial resistance ...

  9. Prehabilitation Before Major Surgery

    OpenAIRE

    Johnson Francis

    2018-01-01

    Prehabilitation is a new term for preoperative rehabilitation before major surgery. Some authors use the short form 'Prehab', though it is not so widely used. Prehabilitation involves measures to improve the physical, physiological, metabolic and psychosocial reserves in preparation for an elective surgery. This involves exercise, nutrition, education and psychosocial interventions.

  10. Major New Initiatives

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Major New Initiatives. Multi-party multi-rate video conferencing OOPS. Live Lecture OOPS. Rural ATM Machine Vortex. Finger print detection HP-IITM. Medical Diagnostic kit NeuroSynaptic. LCD projection system TeNeT. Web Terminal MeTeL Midas. Entertainment ...

  11. Drug Resistance

    Science.gov (United States)

    ... infected with a drug-resistant strain of HIV. Drug-resistance testing results are used to decide which HIV medicines to include in a person’s first HIV regimen. After treatment is started, drug-resistance testing is repeated if ...

  12. Resistance governance in IT projects

    OpenAIRE

    Vrhovec, Simon

    2010-01-01

    The failure rate of projects introducing major changes is worrying. Resistance to change is recognized as an important factor in project failure. Resistance is a natural part of the change process and is therefore present in all changes. IS changes are mostly evolutionary. Organizations infrequently implement more important strategic changes with a broader scope. Resistance often remains overlooked and usually does not constitute a serious threat to the change as it is proportional to the cha...

  13. Profiling Prostate Cancer Therapeutic Resistance

    OpenAIRE

    Cameron A. Wade; Natasha Kyprianou

    2018-01-01

    The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival ...

  14. Awareness among Parents of β-Thalassemia Major Patients Regarding Prenatal Diagnosis and Premarital Screening in Day Care Centre of Transfusion Medicine Department.

    Science.gov (United States)

    Rudra, S; Chakrabarty, P; Hossain, M A; Ripon, M J; Rudra, M; Mirza, T T

    2016-01-01

    Thalassemia is one of the most common genetic diseases in the world. It is a major health problem, brings much morbidity, early mortality and a great deal of misery for a family both financially and emotionally. The patients suffering from beta thalassemia major do not survive for more than 5 years without blood transfusion. Blood transfusion is usually administered every two to five weeks to maintain the pre-transfusion hemoglobin level of 9-10 gm/dL. This study carried out in the department of Transfusion Medicine of Mymensingh Medical College Hospital from January 2014 to June 2014. A total of 200 parents were interviewed. There was a slight preponderance of females which accounted for 57.5% of the parents. Ninety seven (45.5%) had an income less than Rs. 5000 per month. Nearly 50% were illiterate with only 24.5% with a higher education. Consanguinity was positive in 72.5% of the parents with extended family history of thalassemia positive in 40.8%. Only 29.5% were immunized against Hepatitis B. Around 27.5% did not know whether they should be immunized. Fifty five percent of parents knew children should receive Dysferol. Twelve percent were aware of consanguinity to be a risk factor for thalassaemia with only 5% having undergone antenatal diagnosis. Parental knowledge about thalassemia and its preventive measures is inadequate; this requires intervention in the form of public health education programs concentrating on high risk/targeted population.

  15. Overcoming Resistance to Change

    Science.gov (United States)

    Hull, Ted H.; Balka, Don S.; Miles, Ruth Harbin

    2010-01-01

    Resistance to change is a major obstacle in developing and implementing effective instructional programs, yet it is rarely considered, discussed, or addressed. The school leaders who are responsible for improvement frequently feel that their efforts are being blocked or thwarted. For the most part, they are correct, but they may not realize that…

  16. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... emerges and proliferates among bacteria. Over time, the use of antimicrobial drugs will result in the development of resistant strains ... human medicine to preserve the effectiveness of these drugs. One of the major obstacles to understanding the ... Page Last Updated: 02/23/2018 ...

  17. Multidrug resistance in Lactococcus lactis

    NARCIS (Netherlands)

    Bolhuis, Hendrik

    1996-01-01

    Multidrug resistance (MDR) was initially recongnized as the major cause of the failure of the drug-based treatment of human cancers. It has become increasingly clear that MDR occurs in mammalian cells but also in lower eukaryotes and bacteria. The appearance of multiple antibiotic resistant

  18. Importance of optimal dosing ≥30 mg/kg/d during deferasirox treatment: 2.7-yr follow-up from the ESCALATOR study in patients with β-thalassaemia

    Science.gov (United States)

    Taher, Ali; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Al Jefri, Abdullah; Habr, Dany; Kriemler-Krahn, Ulrike; El-Ali, Ali; Roubert, Bernard; El-Beshlawy, Amal

    2011-01-01

    Following 1-yr deferasirox therapy in the ESCALATOR study, 57% of previously chelated patients with β-thalassaemia achieved treatment success (maintenance of or reduction in liver iron concentration (LIC) vs. baseline LIC). Seventy-eight per cent had dose increases at median of 26 wk, suggesting that 1-yr results may not have reflected full deferasirox efficacy. Extension data are presented here. Deferasirox starting dose was 20 mg/kg/d (increases to 30/40 mg/kg/d permitted in the core/extension, respectively). Efficacy was primarily assessed by absolute change in LIC and serum ferritin. Overall, 231 patients received deferasirox in the extension; 67.4% (P < 0.0001) achieved treatment success. By the end of the extension, 66.2% of patients were receiving doses ≥30 mg/kg/d. By the end of the 1-yr extension, mean LIC had decreased by 6.6 ± 9.4 mg Fe/g dw (baseline 19.6 ± 9.2; P < 0.001) and median serum ferritin by 929 ng/mL (baseline 3356; P < 0.0001). There was a concomitant improvement in liver function markers (P < 0.0001). Fewer drug-related adverse events were reported in extension than core study (23.8% vs. 44.3%). Doses ≥30 mg/kg/d were generally required because of high transfusional iron intake and high baseline serum ferritin levels, highlighting the importance of administering an adequate dose to achieve net negative iron balance. PMID:21668502

  19. Insulin resistance in obesity can be reliably identified from fasting plasma insulin

    NARCIS (Netherlands)

    ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

    2015-01-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

  20. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    of antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I......Bacteria can avoid extinction during antimicrobial exposure by becoming resistant. They achieve this either via adaptive mutations or horizontally acquired resistance genes. If resistance emerges in clinical relevant species, it can lead to treatment failure and ultimately result in increasing...... morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources...

  1. Major SSC tunneling begins

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    In Texas, work has been completed on the first on the Superconducting Supercollider's major shafts. Now a boring machine has started driving the fifty-four mile elliptical accelerator tunnel. To date, contracts let for the tunnel have come in far below preliminary estimates. Five of the main fourteen foot diameter tunnel contracts have been awarded for a total of 107.4 million dollars, about forty million dollars below estimates. These contracts represent %60 percent of the total tunneling project

  2. Ramadan major dietary patterns.

    Science.gov (United States)

    Shadman, Zhaleh; Poorsoltan, Nooshin; Akhoundan, Mahdieh; Larijani, Bagher; Soleymanzadeh, Mozhdeh; Akhgar Zhand, Camelia; Seyed Rohani, Zahra Alsadat; Khoshniat Nikoo, Mohsen

    2014-09-01

    There has been no data on population based dietary patterns during the Ramadan fasting month. The purpose of this study was to detect Ramadan major dietary patterns among those who fast in Tehran. This cross-sectional study included 600 subjects, aged 18-65 with body mass index (BMI) of 18.5-40, who had decided to fast during Ramadan. Anthropometric measurements, usual physical activity level and educational status were collected two weeks before Ramadan. Information on Ramadan dietary intakes was obtained using a food frequency questionnaire and factor analysis was used to identify major dietary patterns. We identified four major dietary patterns: 1) Western-like pattern; high in fast foods, salty snacks, nuts, potato, fish, poultry, chocolates, juices; 2) high cholesterol and high sweet junk food pattern; high in pickles, sweets and condiments, butter and cream, canned fish, visceral meats and eggs; 3) Mediterranean-like pattern; high in vegetables, olive oil, dates, dairy, dried fruits, fruits, red meats, tea and coffee and 4) Ramadan-style pattern; large consumption of Halim, soups, porridges, legumes and whole grains, soft drinks, Zoolbia and Bamieh. Age was positively and inversely associated with Mediterranean-like (P = 0.003; r = 0.17) and Ramadan style (P = 0.1; r = -0.13) dietary pattern, respectively. Pre-Ramadan physical activity level was associated with a Mediterranean-like dietary pattern (P characteristics, which has not yet been identified as a model of dietary pattern. Also, among identified dietary patterns, Mediterranean-like was the healthiest.

  3. The Ursa Major supercluster

    International Nuclear Information System (INIS)

    Schuch, N.J.

    1983-01-01

    An optical and a radio survey have been carried out. The optical observations consist of a spectroscopic survey in which redshift data for cluster galaxies and optical identifications of radio sources were obtained with the 98-inch Isaac Newton telescope at the Royal Greenwich Observatory, and the 200-inch Hale telescope; the photographic survey in B, V and R colors was made with the 48-inch Schmidt telescope at Palomar. Some results on the galaxy distribution in the Ursa Major supercluster are briefly discussed. (Auth.)

  4. Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinolone resistance

    OpenAIRE

    Alame-Emane , Amel Kevin; Xu , Peng; Pierre-Audigier , C; Cadet-Daniel , Véronique; Shen , X; Sraouia , M; Djoba Siawaya , J F; Takiff , H; Gao , Q; Gicquel , B

    2015-01-01

    International audience; Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) constitute a major public health concern. The objective was to determine the timing of pncA mutations that confer pyrazinamide (PZA) resistance in relation to mutations conferring resistance to isoniazid (INH) and rifampicin (RMP). For this goal, isolates from two major urban centres—Paris (101 strains) and Shanghai (171 strains)—were investigated for t...

  5. Securing Major Events

    International Nuclear Information System (INIS)

    Loeoef, Susanna

    2013-01-01

    When asked why the IAEA should provide nuclear security support to countries that organize large public events, Nuclear Security Officer Sophia Miaw answers quickly and without hesitation. ''Imagine any major public event such as the Olympics, a football championship, or an Expo. If a dirty bomb were to be exploded at a site where tens of thousands of people congregate, the radioactive contamination would worsen the effects of the bomb, increase the number of casualties, impede a rapid emergency response, and cause long term disruption in the vicinity,'' she said. Avoiding such nightmarish scenarios is the driving purpose behind the assistance the IAEA offers States that host major sporting or other public events. The support can range from a single training course to a comprehensive programme that includes threat assessment, training, loaned equipment and exercises. The type and scope of assistance depends on the host country's needs. ''We incorporate nuclear security measures into their security plan. We don't create anything new,'' Miaw said

  6. Camptothecin resistance

    DEFF Research Database (Denmark)

    Brangi, M; Litman, Thomas; Ciotti, M

    1999-01-01

    The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells...... and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines...... demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment...

  7. Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    G Grobler

    2013-08-01

    Full Text Available The treatment guideline draws on several international guidelines: (iPractice Guidelines of the American Psychiatric Association (APAfor the Treatment of Patients with Major Depressive Disorder, SecondEdition;[1](ii Clinical Guidelines for the Treatment of DepressiveDisorders by the Canadian Psychiatric Association and the CanadianNetwork for Mood and Anxiety Treatments (CANMAT;[2](iiiNational Institute for Clinical Excellence (NICE guidelines;[3](iv RoyalAustralian and New Zealand College of Psychiatrists Clinical PracticeGuidelines Team for Depression (RANZCAP;[4](v Texas MedicationAlgorithm Project (TMAP Guidelines;[5](vi World Federation ofSocieties of Biological Psychiatry (WFSBP Treatment Guideline forUnipolar Depressive Disorder;[6]and (vii British Association forPsychopharmacology Guidelines.[7

  8. Multidrug resistant to extensively drug resistant tuberculosis: What is ...

    Indian Academy of Sciences (India)

    Prakash

    major anti tuberculosis drugs; Isoniazid and Rifampicin with or without resistance to other anti-TB drugs has been termed. MDR-TB. MDR-TB is more difficult to treat than drug- susceptible TB, requiring the use of less effective second line anti tubercular drugs (SLDs) which are often associated with major side effects. 2.

  9. Multidrug-resistant tuberculosis

    Directory of Open Access Journals (Sweden)

    McNerney Ruth

    2008-01-01

    Full Text Available Abstract Background With almost 9 million new cases each year, tuberculosis remains one of the most feared diseases on the planet. Led by the STOP-TB Partnership and WHO, recent efforts to combat the disease have made considerable progress in a number of countries. However, the emergence of mutated strains of Mycobacterium tuberculosis that are resistant to the major anti-tuberculosis drugs poses a deadly threat to control efforts. Multidrug-resistant tuberculosis (MDR-TB has been reported in all regions of the world. More recently, extensively drug resistant-tuberculosis (XDR-TB that is also resistant to second line drugs has emerged in a number of countries. To ensure that adequate resources are allocated to prevent the emergence and spread of drug resistance it is important to understand the scale of the problem. In this article we propose that current methods of describing the epidemiology of drug resistant tuberculosis are not adequate for this purpose and argue for the inclusion of population based statistics in global surveillance data. Discussion Whereas the prevalence of tuberculosis is presented as the proportion of individuals within a defined population having disease, the prevalence of drug resistant tuberculosis is usually presented as the proportion of tuberculosis cases exhibiting resistance to anti-tuberculosis drugs. Global surveillance activities have identified countries in Eastern Europe, the former Soviet Union and regions of China as having a high proportion of MDR-TB cases and international commentary has focused primarily on the urgent need to improve control in these settings. Other regions, such as sub-Saharan Africa have been observed as having a low proportion of drug resistant cases. However, if one considers the incidence of new tuberculosis cases with drug resistant disease in terms of the population then countries of sub-Saharan Africa have amongst the highest rates of transmitted MDR-TB in the world. We propose

  10. Resistant Hypertension.

    Science.gov (United States)

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  11. Managing Resistance.

    Science.gov (United States)

    Maag, John W.

    2000-01-01

    This article presents some considerations and ideas for managing students' resistance. They are organized around four topics: the impact of context on behavior, the importance of being comprehensive and nonrestrictive in behavior, the adaptive function of resistant behavior, and the benefit of joining children in their frame of reference.…

  12. The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder.

    Science.gov (United States)

    Höfer, Peter; Schosser, Alexandra; Calati, Raffaella; Serretti, Alessandro; Massat, Isabelle; Kocabas, Neslihan Aygun; Konstantinidis, Anastasios; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Juven-Wetzler, Alzbeta; Montgomery, Stuart; Kasper, Siegfried

    2013-08-01

    Recently published data have reported associations between cytochrome P450 metabolizer status and suicidality. The aim of our study was to investigate the role of genetic polymorphisms of the cytochrome P450 genes on suicide risk and/or a personal history of suicide attempts. Two hundred forty-three major depressive disorder patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for all relevant variations of the CYP1A2 gene (*1A, *1F, *1C, *1 J, *1 K), the CYP2C9 gene (*2, *3), the CYP2C19 gene (*2, *17) and the CYP2D6 gene (*3, *4, *5, *6, *9, *19, *XN). No association between both suicide risk and personal history of suicide attempts, and the above mentioned metabolic profiles were found after multiple testing corrections. In conclusion, the investigated cytochrome gene polymorphisms do not seem to be associated with suicide risk and/or a personal history of suicide attempts, though methodological and sample size limitations do not allow definitive conclusions.

  13. Obesity and Insulin Resistance: Management in Diabetes

    OpenAIRE

    Suhel Ashraff; Muhammad A. Siddiqui; Thomas E. Carline

    2013-01-01

    Obesity today, is a major public health problem across the world. The rapid increase in the incidence of obesity and associated co-morbidities presents a major challenge to health care globally. Insulin resistance is commonly associated with obesity and other life style diseases. However, much uncertainty remains about the mechanism regarding the association between insulin resistance and human disease mainly because of the difficulties of defining insulin resistance in clinical terms and of ...

  14. User resistance in IT: a literature review

    OpenAIRE

    Ali, Mahmood; Zhou, Li; Miller, Lloyd; Ieromonachou, Petros

    2016-01-01

    User resistance is a complex phenomenon long viewed as a major constraint in successful information technology implementation. User resistance, which can vary between passive and active, could be a source of guidance towards reducing problems associated with organisational change. However, rather than embracing user resistance and seeing it as a learning opportunity and a tool for managing current and future difficulties around user resistance, organisations fear it. There exist a wide litera...

  15. Antimicrobial Resistance

    Science.gov (United States)

    ... life-threatening infections – to a last resort treatment (carbapenem antibiotics) has spread to all regions of the ... unit patients. In some countries, because of resistance, carbapenem antibiotics do not work in more than half ...

  16. The role of Schmidt 'Antonovka' in apple scab resistance breeding

    NARCIS (Netherlands)

    Bus, V.G.M.; Weg, van de W.E.; Peil, A.; Dunemann, F.; Zini, E.; Laurens, F.N.D.; Blazek, J.; Hanke, V.; Forsline, P.L.

    2012-01-01

    'Antonovka' has long been recognised as a major source of scab (Venturia inaequalis) resistance useful for apple breeding worldwide. Both major gene resistances in the form of the Rvi10 and Rvi17 and quantitative resistance, collectively identified as VA, have been identified in different accessions

  17. Outwitting the series resistance in scanning spreading resistance microscopy

    International Nuclear Information System (INIS)

    Schulze, A.; Cao, R.; Eyben, P.; Hantschel, T.; Vandervorst, W.

    2016-01-01

    The performance of nanoelectronics devices critically depends on the distribution of active dopants inside these structures. For this reason, dopant profiling has been defined as one of the major metrology challenges by the international technology roadmap of semiconductors. Scanning spreading resistance microscopy (SSRM) has evolved as one of the most viable approaches over the last decade due to its excellent spatial resolution, sensitivity and quantification accuracy. However, in case of advanced device architectures like fins and nanowires a proper measurement of the spreading resistance is often hampered by the increasing impact of parasitic series resistances (e.g. bulk series resistance) arising from the confined nature of the aforementioned structures. In order to overcome this limitation we report in this paper the development and implementation of a novel SSRM mode (fast Fourier transform-SSRM: FFT-SSRM) which essentially decouples the spreading resistance from parasitic series resistance components. We show that this can be achieved by a force modulation (leading to a modulated spreading resistance signal) in combination with a lock-in deconvolution concept. In this paper we first introduce the principle of operation of the technique. We discuss in detail the underlying physical mechanisms as well as the technical implementation on a state-of-the-art atomic force microscope (AFM). We demonstrate the performance of FFT-SSRM and its ability to remove substantial series resistance components in practice. Eventually, the possibility of decoupling the spreading resistance from the intrinsic probe resistance will be demonstrated and discussed. - Highlights: • A novel electrical AFM mode for carrier profiling in confined volumes is presented. • Thereby the force and hence the contact area between AFM probe and sample is modulated. • Information on the spreading resistance is derived using a lock-in approach. • Bulk series resistance components are

  18. Mapping of stripe rust resistance gene in an Aegilops caudata ...

    Indian Academy of Sciences (India)

    ... rust resistance depicted a single major gene conditioning adult plant resistance (APR) with stripe rust reaction varying from TR-20MS in resistant RILs signifying the presence of some minor genes as well. Genetic association with leaf rust resistance revealed that two genes are located at a recombination distance of 13%.

  19. Drug-resistant post-neurosurgical nosocomial Acinetobacter ...

    African Journals Online (AJOL)

    The majority of carbapenem-resistant isolates were resistant to at least three other antibiotic classes. The emergence of postsurgical multi-drug resistant Acinetobacter meningitis highlights the importance of implementing preventative strategies towards nosocomial infections. Key words: Acinetobacter baumannii, resistance ...

  20. Major Histocompatibility Complex and Background Genes in Chickens Influence Susceptibility to High Pathogenicity Avian Influenza Virus

    Science.gov (United States)

    The chicken’s major histocompatibility complex (MHC) haplotype has profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both line...

  1. Overview of glyphosate-resistant weeds worldwide.

    Science.gov (United States)

    Heap, Ian; Duke, Stephen O

    2018-05-01

    Glyphosate is the most widely used and successful herbicide discovered to date, but its utility is now threatened by the occurrence of several glyphosate-resistant weed species. Glyphosate resistance first appeared in Lolium rigidum in an apple orchard in Australia in 1996, ironically the year that the first glyphosate-resistant crop (soybean) was introduced in the USA. Thirty-eight weed species have now evolved resistance to glyphosate, distributed across 37 countries and in 34 different crops and six non-crop situations. Although glyphosate-resistant weeds have been identified in orchards, vineyards, plantations, cereals, fallow and non-crop situations, it is the glyphosate-resistant weeds in glyphosate-resistant crop systems that dominate the area infested and growing economic impact. Glyphosate-resistant weeds present the greatest threat to sustained weed control in major agronomic crops because this herbicide is used to control weeds with resistance to herbicides with other sites of action, and no new herbicide sites of action have been introduced for over 30 years. Industry has responded by developing herbicide resistance traits in major crops that allow existing herbicides to be used in a new way. However, over reliance on these traits will result in multiple-resistance in weeds. Weed control in major crops is at a precarious point, where we must maintain the utility of the herbicides we have until we can transition to new weed management technologies. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  2. Resident resistance.

    Science.gov (United States)

    Price, J L; Cleary, B

    1999-01-01

    Clearly, faculty must work hard with residents to explore the nature of their resistance to a program's learning and growth opportunities. Initial steps to a deeper, more effective, and longer-lasting change process must be pursued. If resident resistance is mishandled or misunderstood, then learning and professional growth may be sidetracked and the purposes of residency training defeated. Listening to the whole person of the resident and avoiding the trap of getting caught up in merely responding to select resident behaviors that irritate us is critical. Every faculty member in the family practice residency program must recognize resistance as a form of defense that cannot immediately be torn down or taken away. Resident defenses have important purposes to play in stress reduction even if they are not always healthy. Residents, especially interns, use resistance to avoid a deeper and more truthful look at themselves as physicians. A family practice residency program that sees whole persons in their residents and that respects resident defenses will effectively manage the stress and disharmony inherent to the resistant resident.

  3. Red cell indices and discriminant functions in the detection of beta-thalassaemia trait in a population with high prevalence of iron deficiency anaemia.

    Science.gov (United States)

    Madan, N; Sikka, M; Sharma, S; Rusia, U; Kela, K

    1999-01-01

    Red cell indices and discriminant functions were studied in 463 heterozygous beta-thalassaemics (337 without iron deficiency, 126 with iron deficiency) and 195 patients of iron deficiency anaemia (IDA) to ascertain their utility in the detection of betathalassaemia trait (BTT). Majority of traits in both groups had an elevated RBC count (> or = 5.0 x 10(12)/L). The counts were significantly higher than of patients with IDA, only 4.6% of whom had this degree of erythrocytosis. Mean Hb concentration was significantly higher in traits as compared to iron deficient subjects (p < 0.0001). Mean MCV and MCH were significantly (p < 0.0001) lower in traits more so in those with ID as compared to patients of IDA. MCV < 80 fl and MCH < 27 pg were found to be sensitive markers in the detection of traits even in the presence of ID. Of the four discriminant functions studied MCSQ was found to be most sensitive in detection of BTT and it identified 97.9% traits. DF of England and Fraser was most specific for BTT being < 8.4 in only 6.2% patients with IDA. Detection of erythrocytosis especially in the presence of mild anaemia and calculation of discriminant functions derived from red cell indices were found to play an important role in screening for BTT even in the presence of ID and helped identify those patients who required further laboratory evaluation.

  4. Burkholderia glumae: next major pathogen of rice?

    Science.gov (United States)

    Ham, Jong Hyun; Melanson, Rebecca A; Rush, Milton C

    2011-05-01

    Burkholderia glumae causes bacterial panicle blight of rice, which is an increasingly important disease problem in global rice production. Toxoflavin and lipase are known to be major virulence factors of this pathogen, and their production is dependent on the TofI/TofR quorum-sensing system, which is mediated by N-octanoyl homoserine lactone. Flagellar biogenesis and a type III secretion system are also required for full virulence of B. glumae. Bacterial panicle blight is thought to be caused by seed-borne B. glumae; however, its disease cycle is not fully understood. In spite of its economic importance, neither effective control measures for bacterial panicle blight nor rice varieties showing complete resistance to the disease are currently available. A better understanding of the molecular mechanisms underlying B. glumae virulence and of the rice defence mechanisms against the pathogen would lead to the development of better methods of disease control for bacterial panicle blight. Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales; Burkholderiaceae; Burkholderia. Gram-negative, capsulated, motile, lophotrichous flagella, pectolytic. Aborted seed, empty grains as a result of failure of grain filling, brown spots on panicles, seedling rot. Seed sterilization, planting partially resistant lines (no completely resistant line is available). KNOWN VIRULENCE FACTORS: Toxoflavin, lipase, type III effectors. © 2010 LSU AGCENTER. MOLECULAR PLANT PATHOLOGY © 2010 BSPP AND BLACKWELL PUBLISHING LTD.

  5. Cephalosporin resistance in Neisseria gonorrhoeae

    Directory of Open Access Journals (Sweden)

    Manju Bala

    2010-01-01

    Full Text Available Gonorrhea, a disease of public health importance, not only leads to high incidence of acute infections and complications but also plays a major role in facilitating human immunodeficiency virus (HIV acquisition and transmission. One of the major public health needs for gonorrhea control is appropriate, effective treatment. However, treatment options for gonorrhea are diminishing as Neisseria gonorrhoeae have developed resistance to several antimicrobial drugs such as sulfonamides, penicillin, tetracyclines and quinolones. Antimicrobial resistance (AMR surveillance of N. gonorrhoeae helps establish and maintain the efficacy of standard treatment regimens. AMR surveillance should be continuous to reveal the emergence of new resistant strains, monitor the changing patterns of resistance, and be able to update treatment recommendations so as to assist in disease control. Current treatment guidelines recommend the use of single dose injectable or oral cephalosporins. The emergence and spread of cephalosporin resistant and multi drug resistant N. gonorrhoeae strains, represents a worrying trend that requires monitoring and investigation. Routine clinical laboratories need to be vigilant for the detection of such strains such that strategies for control and prevention could be reviewed and revised from time to time. It will be important to elucidate the genetic mechanisms responsible for decreased susceptibility and future resistance. There is also an urgent need for research of safe, alternative anti-gonococcal compounds that can be administered orally and have effective potency, allowing high therapeutic efficacy (greater than 95.0% cure rate.

  6. Anticoagulant Resistance

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte

    Although sewer rat control is carried out in more than 80 % of all Danish municipalities, with usage of large amounts of anticoagulant rodenticides, knowledge on anticoagulant resistance among rats living in the sewers is limited. As rat problems in urban areas are believed to be related to sewer...... problems (70-90 % in UK and DK) unawareness of resistance amongst these populations of Brown rats may constitute a future control problem and knowledge on this issue has become crucial. Rats were captured in sewers from seven different locations in the suburban area of Copenhagen. Locations was chosen...... to represent different sewer rat management strategies i) no anticoagulants for approx. 20 years ii) no anticoagulants for the last 5 years and iii) continuous control for many years. Animals were tested for resistance to bromadiolone by Blood-Clotting Response test, as bromadiolone is the most frequently used...

  7. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  8. Weaving History through the Major

    Science.gov (United States)

    Mayfield, Betty

    2014-01-01

    The benefits of including the study of the history of mathematics in the education of mathematics majors have been discussed at length elsewhere. Many colleges and universities now offer a History of Mathematics course for mathematics majors, for mathematics education majors, or for general credit. At Hood College, we emphasize our commitment to…

  9. TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANCE IN SEWAGE ISOLATES OF ESCHERICHIA COLI

    Science.gov (United States)

    Sewage samples from seven locations in the United States were analyzed for Escherichia coli isolates which were resistant to trimethoprim-sulfamethoxazole (SXT). The prevalence rate of SXT resistant organisms varied between the different geographical locales. The majority of th...

  10. Do Biology Majors Really Differ from Non–STEM Majors?

    Science.gov (United States)

    Cotner, Sehoya; Thompson, Seth; Wright, Robin

    2017-01-01

    Recent calls to action urge sweeping reform in science education, advocating for improved learning for all students—including those majoring in fields beyond the sciences. However, little work has been done to characterize the differences—if any exist—between students planning a career in science and those studying other disciplines. We describe an attempt to clarify, in broad terms, how non–STEM (science, technology, engineering, and mathematics) majors differ from life sciences majors, and how they are similar. Using survey responses and institutional data, we find that non–STEM majors are not unilaterally science averse; non–STEM majors are more likely than biology majors to hold misconceptions about the nature of science, yet they are not completely ignorant of how science works; non–STEM majors are less likely than biology majors to see science as personally relevant; and non–STEM majors populations are likely to be more diverse—with respect to incoming knowledge, perceptions, backgrounds, and skills—than a biology majors population. We encourage science educators to consider these characteristics when designing curricula for future scientists or simply for a well-informed citizenry. PMID:28798210

  11. Resistance welding

    DEFF Research Database (Denmark)

    Bay, Niels; Zhang, Wenqi; Rasmussen, Mogens H.

    2003-01-01

    Resistance welding comprises not only the well known spot welding process but also more complex projection welding operations, where excessive plastic deformation of the weld point may occur. This enables the production of complex geometries and material combinations, which are often not possible...

  12. Shatter resistance in sesame

    International Nuclear Information System (INIS)

    Langham, D.R.

    2001-01-01

    The majority of the world's sesame (probably over 99%) is shattering, and most of the harvest is manual. In a non-mechanized environment the last thing that farmers want is seed retention (''hold''). They want the seed to fall out as easily as possible. The amount of shattering desired is dependent on the method of harvest. By 1944 the first stage of mechanization was initiated. The indehiscent mutant found in 1943 showed in succeeding generations that it was controlled monogenically, and the homozygous recessive (id/id) gave indehiscence. Unfortunately, the id allele had pleiotropic effects including cupped leaves, twisted stems, short seed pods, semi-sterility, and low yield. Improvements in shatter resistance are relative within a specific program. For example, Sesaco has improved its shatter resistance each year, and still for the USA methods of harvest, further improvements are necessary to allow for better retention in adverse weather. This paper presents a methodology for quantifying shatter resistance so researchers can compare levels of shatter resistance between programs. (author)

  13. Background antibiotic resistance patterns in antibiotic-free pastured poultry production

    Science.gov (United States)

    Antibiotic resistance (AR) is a significant public health issue, and agroecosystems are often viewed as major environmental sources of antibiotic resistant foodborne pathogens. While the use of antibiotics in agroecosystems can potentially increase AR, appropriate background resistance levels in th...

  14. Vancomycin Resistance in Staphylococcus aureus


    Science.gov (United States)

    McGuinness, Will A.; Malachowa, Natalia; DeLeo, Frank R.

    2017-01-01

    The evolution of Staphylococcus aureus during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant S. aureus (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. S. aureus strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant S. aureus (VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. S. aureus isolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant S. aureus (VRSA)—they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the vanA gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in S. aureus, with an emphasis on the molecular mechanisms underlying vancomycin resistance. PMID:28656013

  15. Interdisciplinary Project Experiences: Collaboration between Majors and Non-Majors

    Science.gov (United States)

    Smarkusky, Debra L.; Toman, Sharon A.

    2014-01-01

    Students in computer science and information technology should be engaged in solving real-world problems received from government and industry as well as those that expose them to various areas of application. In this paper, we discuss interdisciplinary project experiences between majors and non-majors that offered a creative and innovative…

  16. Molecular Genotype Identification of Different Chickens: Major Histocompatibility Complex

    Directory of Open Access Journals (Sweden)

    Hongzhi Wang

    2014-09-01

    Full Text Available Chicken is a main poultry in China. Molecular breeding for disease resistance plays an important role in the control of diseases, especially infectious diseases. Choice of genes for disease resistance is the key technology of molecular breeding. The major histocompatibility complex (MHC is of great interest to poultry breeding scientists for its extraordinary polymorphism and close relation with traits of resistance against infectious diseases. The MHC-B haplotype plays an important role in the study of disease resistance in chicken. The traditional chicken MHC-B haplotype is commonly defined by serologic reactions of erythrocytes and the majority of studies have been conducted in Leghorn and broiler but study about other chicken breeds is little. In this study, firstly, the microsatellite marker LEI0258 which is located within the MHC was sequenced by using target sequence capture assay in different chicken breeds, and then according to the number of repeated structures and polymorphic sequences in microsatellite, sequence information for the region defined by LEI0258 was obtained for different haplotypes. Afterwards, we identified the relation between MHC-B haplotypes and disease resistance. Collectively, these observed results provided the reference data for disease-resistant breeding association with blood type and for further study of MHC gene function in poultry.

  17. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... video) Animation of Antimicrobial Resistance (text version) Arabic Translation of Animation of Antimicrobial Resistance Chinese Translation of Animation of Antimicrobial Resistance French Translation of ...

  18. Do Biology Majors Really Differ from Non-STEM Majors?

    Science.gov (United States)

    Cotner, Sehoya; Thompson, Seth; Wright, Robin

    2017-01-01

    Recent calls to action urge sweeping reform in science education, advocating for improved learning for all students-including those majoring in fields beyond the sciences. However, little work has been done to characterize the differences-if any exist-between students planning a career in science and those studying other disciplines. We describe an attempt to clarify, in broad terms, how non-STEM (science, technology, engineering, and mathematics) majors differ from life sciences majors, and how they are similar. Using survey responses and institutional data, we find that non-STEM majors are not unilaterally science averse; non-STEM majors are more likely than biology majors to hold misconceptions about the nature of science, yet they are not completely ignorant of how science works; non-STEM majors are less likely than biology majors to see science as personally relevant; and non-STEM majors populations are likely to be more diverse-with respect to incoming knowledge, perceptions, backgrounds, and skills-than a biology majors population. We encourage science educators to consider these characteristics when designing curricula for future scientists or simply for a well-informed citizenry. © 2017 S. Cotner et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Biological substrates underpinning diagnosis of major depression.

    Science.gov (United States)

    Sibille, Etienne; French, Beverly

    2013-09-01

    Major depression is characterized by low mood, a reduced ability to experience pleasure and frequent cognitive, physiological and high anxiety symptoms. It is also the leading cause of years lost due to disability worldwide in women and men, reflecting a lifelong trajectory of recurring episodes, increasing severity and progressive treatment resistance. Yet, antidepressant drugs at best treat only one out of every two patients and have not fundamentally changed since their discovery by chance >50 yr ago. This status quo may reflect an exaggerated emphasis on a categorical disease classification that was not intended for biological research and on oversimplified gene-to-disease models for complex illnesses. Indeed, genetic, molecular and cellular findings in major depression suggest shared risk and continuous pathological changes with other brain-related disorders. So, an alternative is that pathological findings in major depression reflect changes in vulnerable brain-related biological modules, each with their own aetiological factors, pathogenic mechanisms and biological/environment moderators. In this model, pathological entities have low specificity for major depression and instead co-occur, combine and interact within individual subjects across disorders, contributing to the expression of biological endophenotypes and potentially clinical symptom dimensions. Here, we discuss current limitations in depression research, review concepts of gene-to-disease biological scales and summarize human post-mortem brain findings related to pyramidal neurons, γ-amino butyric acid neurons, astrocytes and oligodendrocytes, as prototypical brain circuit biological modules. Finally we discuss nested aetiological factors and implications for dimensional pathology. Evidence suggests that a focus on local cell circuits may provide an appropriate integration point and a critical link between underlying molecular mechanisms and neural network dysfunction in major depression.

  20. Major depression with psychotic features

    Science.gov (United States)

    ... depression References American Psychiatric Association. Major depressive disorder. Diagnostic and Statistical Manual of Mental Disorders: DSM-5 . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013; ...

  1. Antimicrobial resistance

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars

    2014-01-01

    Antimicrobial resistance is a global public health challenge, which has accelerated by the overuse of antibiotics worldwide. Increased antimicrobial resistance is the cause of severe infections, complications, longer hospital stays and increased mortality. Overprescribing of antibiotics......-the-counter sale of antibiotics, the use of antimicrobial stewardship programmes, the active participation of clinicians in audits, the utilization of valid rapid point-of-care tests, the promotion of delayed antibiotic prescribing strategies, the enhancement of communication skills with patients with the aid...... is associated with an increased risk of adverse effects, more frequent re-attendance and increased medicalization of self-limiting conditions. Antibiotic overprescribing is a particular problem in primary care, where viruses cause most infections. About 90% of all antibiotic prescriptions are issued by general...

  2. Resisting dehumanization

    DEFF Research Database (Denmark)

    Lassen, Inger Marie

    2018-01-01

    Recent years have seen an increase in the influx of asylum-seekers in Scandinavia, and in Denmark this has led to ever-tighter immigration control. This article discusses emerging practices of refugee solidarity and resistance to hegemonic migration policy in Danish civil society in the wake of w...... 2015) and appraisal analysis of the incident in focus. Keywords: immigration, discursive discrimination, populism, solidarity, governmentality, topoi, appraisal...

  3. Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae

    NARCIS (Netherlands)

    Rozwandowicz, M.; Brouwer, M.S.M.; Fischer, J.; Wagenaar, J.A.; Gonzalez-Zorn, B.; Guerra, B.; Mevius, D.J.; Hordijk, J.

    2018-01-01

    Bacterial antimicrobial resistance (AMR) is constantly evolving and horizontal gene transfer through plasmids plays a major role. The identification of plasmid characteristics and their association with different bacterial hosts provides crucial knowledge that is essential to understand the

  4. Induced disease resistance signaling in plants

    NARCIS (Netherlands)

    Verhagen, B.W.M.; Loon, L.C. van; Pieterse, C.M.J.

    2006-01-01

    To protect themselves from disease, plants have evolved sophisticated inducible defense mechanisms in which the signal molecules salicylic acid, jasmonic acid and ethylene often play crucial roles. Elucidation of signaling pathways controlling induced disease resistance is a major objective in

  5. Majorization and extremal PH distributions

    NARCIS (Netherlands)

    He, Q.M.; Zhang, H.; Vera, J.C.; Latouche, G.; Ramaswami, V.; Sethuraman, J.; Sigman, K.; Squillante, M.S.; Yao, D.D.

    2013-01-01

    This chapter presents majorization results for PH generators. Based on the majorization results, bounds on the moments and Laplace–Stieltjes transforms of phase-type distributions are found. Exponential distributions and Coxian distributions are identified to be extremal PH distributions with

  6. Do You Have Major Depression?

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Depression Do You Have Major Depression? Past Issues / Fall 2009 Table of Contents Simple ... member may have major depression. —NIMH Types of Depression Just like other illnesses, such as heart disease, ...

  7. Antifolate drug resistance: Novel mutations and haplotype ...

    Indian Academy of Sciences (India)

    N P Sarmah

    2017-09-27

    Sep 27, 2017 ... Malaria is a major public health concern in Northeast India with a preponderance of drug-resistant strains. Until recently the partner drug for artemisinin combination therapy (ACT) was sulphadoxine pyrimethamine (SP). Antifolate drug resistance has been associated with the mutations at dihydropteroate ...

  8. Patterns of Resistance in Managing Assessment Change

    Science.gov (United States)

    Deneen, Christopher; Boud, David

    2014-01-01

    Achieving change in assessment practices in higher education is difficult. One of the reasons for this is resistance among those responsible for teaching and assessing. This paper seeks to explore this resistance through an analysis of staff dialogue during a major attempt to change the assessment practices at one institution. An institution-wide…

  9. Synergy between verapamil and other multidrug -resistance ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Synergy between verapamil and other multidrug-resistance modulators in model membranes. 737. J. Biosci. 32(4), June 2007. 1. Introduction. A major problem in the treatment of cancer is that of multidrug resistance, which remains imperfectly understood, though in some instances it certainly involves altered membrane ...

  10. Strategies to Minimize Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Sang Hee Lee

    2013-09-01

    Full Text Available Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs and various data such as pharmacokinetic (PK and pharmacodynamic (PD properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST, clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care, the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing. The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.

  11. [Staphylococcus aureus and antibiotic resistance].

    Science.gov (United States)

    Sancak, Banu

    2011-07-01

    After the report of first case of methicillin-resistant Staphylococcus aureus (MRSA) in 1961, MRSA become a major problem worldwide. Over the last decade MRSA strains have emerged as serious pathogens in nosocomial and community settings. Glycopeptides (vancomycin and teicoplanin) are still the current mainstay of therapy for infections caused by MRSA. In the last decade dramatic changes have occurred in the epidemiology of MRSA infections. The isolates with reduced susceptibility and in vitro resistance to vancomycin have emerged. Recently, therapeutic alternatives such as quinupristin/dalfopristin, linezolid, tigecycline and daptomycin have been introduced into clinical practice for treating MRSA infections. Nevertheless, these drugs are only approved for certain indication and resistance has already been reported. In this review, the new information on novel drugs for treating MRSA infections and the resistance mechanisms of these drugs were discussed.

  12. Insulin resistance and chronic inflammation

    Directory of Open Access Journals (Sweden)

    Natalia Matulewicz

    2016-12-01

    Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

  13. Antibiotics and Resistance: Glossary

    Science.gov (United States)

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network ...

  14. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... of Animation of Antimicrobial Resistance More in Antimicrobial ... Antimicrobial Resistance Monitoring System About NARMS 2015 NARMS Integrated ...

  15. Animation of Antimicrobial Resistance

    Science.gov (United States)

    ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... of Animation of Antimicrobial Resistance More in Antimicrobial ... Antimicrobial Resistance Monitoring System About NARMS 2015 NARMS Integrated ...

  16. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... in the normal range. What happens with insulin resistance? In insulin resistance, muscle, fat, and liver cells do not ... they do not usually test specifically for insulin resistance. Insulin resistance can be assessed by measuring the level ...

  17. Emerging antidepressants to treat major depressive disorder.

    Science.gov (United States)

    Block, Samantha G; Nemeroff, Charles B

    2014-12-01

    Depression is a common disorder with an annual risk of a depressive episode in the United States of 6.6%. Only 30-40% of patients remit with antidepressant monotherapy, leaving 60-70% of patients who do not optimally respond to therapy. Unremitted depressive patients are at increased risk for suicide. Considering the prevalence of treatment resistant depression and its consequences, treatment optimization is imperative. This review summarizes the latest treatment modalities for major depressive disorder including pharmacotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation and psychotherapy. Through advancements in research to better understand the pathophysiology of depression, advances in treatment will be realized. Copyright © 2014. Published by Elsevier B.V.

  18. Major neutrophil functions subverted by Porphyromonas gingivalis

    Science.gov (United States)

    Olsen, Ingar; Hajishengallis, George

    2016-01-01

    Polymorphonuclear leukocytes (neutrophils) constitute an integrated component of the innate host defense in the gingival sulcus/periodontal pocket. However, the keystone periodontal pathogen Porphyromonas gingivalis has in the course of evolution developed a number of capacities to subvert this defense to its own advantage. The present review describes the major mechanisms that P. gingivalis uses to subvert neutrophil homeostasis, such as impaired recruitment and chemotaxis, resistance to granule-derived antimicrobial agents and to the oxidative burst, inhibition of phagocytic killing while promoting a nutritionally favorable inflammatory response, and delay of neutrophil apoptosis. Studies in animal models have shown that at least some of these mechanisms promote the dysbiotic transformation of the periodontal polymicrobial community, thereby leading to inflammation and bone loss. It is apparent that neutrophil–P. gingivalis interactions and subversion of innate immunity are key contributing factors to the pathogenesis of periodontal disease. PMID:26993626

  19. Major neutrophil functions subverted by Porphyromonas gingivalis

    Directory of Open Access Journals (Sweden)

    Ingar Olsen

    2016-03-01

    Full Text Available Polymorphonuclear leukocytes (neutrophils constitute an integrated component of the innate host defense in the gingival sulcus/periodontal pocket. However, the keystone periodontal pathogen Porphyromonas gingivalis has in the course of evolution developed a number of capacities to subvert this defense to its own advantage. The present review describes the major mechanisms that P. gingivalis uses to subvert neutrophil homeostasis, such as impaired recruitment and chemotaxis, resistance to granule-derived antimicrobial agents and to the oxidative burst, inhibition of phagocytic killing while promoting a nutritionally favorable inflammatory response, and delay of neutrophil apoptosis. Studies in animal models have shown that at least some of these mechanisms promote the dysbiotic transformation of the periodontal polymicrobial community, thereby leading to inflammation and bone loss. It is apparent that neutrophil–P. gingivalis interactions and subversion of innate immunity are key contributing factors to the pathogenesis of periodontal disease.

  20. Preventing and managing antiretroviral drug resistance.

    Science.gov (United States)

    Kuritzkes, Daniel R

    2004-05-01

    Development of resistance to antiretroviral drugs (ARVs) is a major impediment to optimum treatment of HIV-1 infection. Although resistance testing can help to select subsequent regimens when virologic failure occurs, cross-resistance, which affects all classes of ARVs, may make it more difficult to achieve optimum control of HIV. We have known for some time that our first choice of antiretroviral therapy offers the best chance to control HIV replication and that initial therapy should be selected with an eye on future options. Potency is the first line of defense against the development of resistance. Other factors that affect resistance development include: tolerability, potential for optimum adherence, and genetic and pharmacologic barriers to development of resistance. If resistance emerges, only a single drug may be affected initially, and a rapid change in ARVs may preserve the efficacy of other components. One cautionary note is that we can no longer assume that a patient's HIV is fully susceptible to all ARVs even in the initial regimen. Transmission of drug-resistant HIV means that the genetic composition may be that of an "experienced" virus with reduced susceptibility to ARVs. Resistance testing at the time of transmission is most likely to reveal this resistance, but over time the dominant genetic pattern may revert to wild-type, and be missed by resistance testing. Because "archived" resistant HIV may emerge quickly once treatment is initiated, we need to keep this in mind when selecting initial therapy.

  1. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  2. Resistance profiles and risk factors of resistant microorganisms in bacteraemia of abdominal origin.

    Science.gov (United States)

    Martín Jaramago, J; Armero Ibáñez, R; Camarena Miñana, J J; Morales Suárez-Varela, M

    2017-11-01

    The presence of resistant microorganisms is a major cause of failure in initial empirical antimicrobial therapy. The objectives of this study are to determine the resistance profile of microorganisms that cause bacteraemia of abdominal origin and to identify whether the previous use of antibiotics and the place of acquisition of bacteraemia are risk factors associated with the presence of resistant organisms. A clinical, observational, epidemiological, retrospective cohort study was conducted with all the adult patients admitted to a university hospital from 2011-2013. Antimicrobial resistance profiles were described and a 95% confidence interval chi-square test was used to determine whether the variables studied were risk factors in the isolation of resistant microorganisms. Of the 1245 patients with bacteraemia, 212 (17%) presented bacteraemia of abdominal origin. The resistance profile highlights the incidence of methicillin resistant Staphylococcus aureus (50%), coagulase-negative staphylococci resistant to linezolid (20.58%), enterococci resistant to vancomycin (3.12%), Escherichia coli resistant to third-generation cephalosporins (9.9%) and fluoroquinolones (35.64%), Klebsiella pneumoniae resistant to third-generation cephalosporins (8.33%), Pseudomonas aeruginosa resistant to fluoroquinolones and carbapenem (25% and 25% respectively) and Acinetobacter baumanii resistant to fluoroquinolones and carbapenem (100% and 100% respectively), Candida albicans resistant to fluconazole (11.11%), single Candida krusei isolate resistant to fluconazole and Candida parapsilosis resistant to echinocandins (12.5%). In our study, previous use of antibiotics had a statistically significant association with the isolation of resistant microorganisms (P=.013) but not the place of acquisition of bacteraemia (P=.239). Establishing the incidence of resistant organisms can improve empirical antimicrobial therapy in patients with bacteraemia of abdominal origin. Previous use of

  3. Staphylococcus aureus: resistance pattern and risk factors

    Directory of Open Access Journals (Sweden)

    Mohammad Naghavi-Behzad

    2015-03-01

    Full Text Available Introduction: Methicillin resistant Staphylococcus aureus (MRSA has emerged as a nosocomial pathogen of major worldwide importance and is an increasingly frequent cause of community-acquired infections. In this study, different risk factors and MRSA resistance pattern were investigated. Methods: In a 24 months period, all of the patients who were confined to bed in the surgery ward were included in the study. Then they were assessed to find out as if they had MRSA infection when hospitalized and once when they were discharged. Almost 48 h after admission, when patients were discharged, social and medical histories were acquired. Acquired samples were examined. Results: During the present study of 475 patients, 108 patients (22.8% had S. aureus. About frequency of antibiotic resistance among collected S. aureus colonies, erythromycin resistance, was the most frequent antibiotic resistance, also resistance to vancomycin was 0.4% that was the least. Only hospitalization duration had statistically significant correlation with antibiotic resistance, also resistance to erythromycin had statistically significant relation with history of surgery and alcohol consumption. Of all 34 MRSA species, 22 (64.7% samples were resistant to erythromycin, 17 (50.0% resistant to cefoxitin, 5 (14.7% resistant to mupirocin, 1 (2.9% resistant to vancomycin and 1 (2.9% resistant to linezolid. Conclusion: The results of the current study show that among hospitalized patients, there is resistance against methicillin. Since based on results of the study there is resistance against oxacillin and erythromycin in most cases, administering appropriate antibiotics have an important role in minimizing the resistance burden among bacterial species.

  4. Strategies for improving rust resistance in oats

    International Nuclear Information System (INIS)

    Harder, D.E.; McKenzie, R.I.H.; Martens, J.W.; Brown, P.D.

    1977-01-01

    During the history of breeding oats for rust resistance in Canada the known sources of resistance proved inadequate to counter the virulence potential of both stem rust (Puccinia graminis avenae) and crown rust (P. coronata avenae). A major programme to overcome the rust problem was undertaken at Winnipeg, involving four alternate approaches: (1) A search for new resistance in wild oat species, particularly Avena sterilis, has provided a wealth of good resistance to crown rust, but less to stem rust. Much of the A. sterilis-derived crown rust resistance is now being used world-wide; (2) Efforts at synthesizing new resistance by mutation breeding methods have not been successful. Of about seven million plants examined, only one showed significant new resistance, but this was associated with poor plant type; (3) Resistance with low levels of expression but which appears broadly effective has been observed against both stem and crown rusts. It appears that numbers of these low-level genes exist, and that they can be accumulated to provide increasingly effective resistance. Problems in using this type of resistance in a practical way are discussed; (4) Excellent rust resistance has been found in lower ploidy species such as A. barbata, but it was not previously possible to stabilize this resistance in hexaploid species. By using mutagenic treatments attempts have been made to translocate smaller portions of the A. barbata chromosome carrying the resistance to the hexaploid cultivar Rodney. In conclusion, mutation breeding methods at present appear to have limited application in synthesizing new rust-resistant genotypes in oats. The search for already existing genetic resistance and its synthesis into multi-genic resistant lines appears to be the most effective way at present of resolving the rust problem in oats. (author)

  5. Stenting of major airway constriction

    International Nuclear Information System (INIS)

    Wu Xiaomei

    2002-01-01

    Objective: To investigate the correlated issues in the stenting treatment of major airway constriction. Methods: Nineteen cases of major airway stenting procedure were studied retrospectively. The clinical choice of stents of different advantages or deficiencies were discussed. The importance of intravenous anesthesia supporting, life-parameters monitoring during the procedures and the prevention of complications were analysed. Results: Under intravenous and local anesthesia, 19 Wallstents had been successively placed and relieved 19 cases of major airway constrictions due to malignant or benign diseases (15 of tumors, 3 of tuberculosis, 1 of tracheomalacia). Intravenous anesthesia and life-parameters monitoring had made the procedures more safe and precise. Conclusions: Major airway stenting is an reliable method for relieving tracheobronchial stenosis; and intravenous anesthesia supporting and life-parameters monitoring guarantee the satisfactions of procedures

  6. Major hazards onshore and offshore

    International Nuclear Information System (INIS)

    1992-01-01

    This symposium continues the tradition of bringing together papers on a topic of current interest and importance in terms of process safety - in this case, Major Hazards Onshore and Offshore. Lord Cullen in his report on the Piper Alpha disaster has, in effect, suggested that the experience gained in the control of major hazards onshore during the 1980s should be applied to improve safety offshore during the 1990s. This major three-day symposium reviews what has been learned so far with regard to major hazards and considers its present and future applications both onshore and offshore. The topics covered in the programme are wide ranging and deal with all aspects of legislation, the application of regulations, techniques for evaluating hazards and prescribing safety measures in design, construction and operation, the importance of the human factors, and recent technical developments in protective measures, relief venting and predicting the consequences of fires and explosions. (author)

  7. Cake Division by Majority Decision

    OpenAIRE

    Hans Gersbach; Bernhard Pachl

    2006-01-01

    We consider a collective choice process where three players make proposals sequentially on how to divide a given quantity of resources. Afterwards, one of the proposals is chosen by majority decision. If no proposal obtains a majority, a proposal is drawn by lot. We establish the existence of the set of subgame perfect equilibria, using a suitable refinement concept. In any equilibrium, the first agent offers the whole cake to the second proposal-maker, who in turn offers the whole cake back ...

  8. Resistant hypertension.

    Science.gov (United States)

    Armario, P; Oliveras, A; de la Sierra, A

    2013-11-01

    A 53 year old woman with hypercholesterolemia treated with statins, with no history of cardiovascular disease, was referred to the Hypertension and Vascular Risk Unit for management of hypertension resistant to 4 antihypertensive agents at full doses. The patient had obesity, with a body mass index of 36.3kg/m(2) and office blood pressure 162/102mm Hg. Physical examination showed no data of interest. glucose 120mg/dl, glycated Hb: 6.4%, albuminuria 68mg/g, kidney function and study of the renin angiotensin system and other biochemical parameters were normal. Echocardiography: left ventricular mass, 131g/m(2) (normal, <110g/m(2)). True resistant hypertension was confirmed by ambulatory monitoring of blood pressure during 24h (153/89mm Hg). Spironolactone treatment (25mg/day) was added and was well tolerated, with no change in renal function and kaliemia within normal (4.1mmol/l) following the treatment. After 8 weeks, blood pressure was well controlled: office blood pressure 132/86mm Hg and 24h-ambulatory blood pressure: 128/79mm Hg. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  9. Retroviral superinfection resistance

    Directory of Open Access Journals (Sweden)

    van der Kuyl Antoinette C

    2005-08-01

    Full Text Available Abstract The retroviral phenomenon of superinfection resistance (SIR defines an interference mechanism that is established after primary infection, preventing the infected cell from being superinfected by a similar type of virus. This review describes our present understanding of the underlying mechanisms of SIR established by three characteristic retroviruses: Murine Leukaemia Virus (MuLV, Foamy Virus (FV, and Human Immunodeficiency Virus (HIV. In addition, SIR is discussed with respect to HIV superinfection of humans. MuLV resistant mice exhibit two genetic resistance traits related to SIR. The cellular Fv4 gene expresses an Env related protein that establishes resistance against MuLV infection. Another mouse gene (Fv1 mediates MuLV resistance by expression of a sequence that is distantly related to Gag and that blocks the viral infection after the reverse transcription step. FVs induce two distinct mechanisms of superinfection resistance. First, expression of the Env protein results in SIR, probably by occupancy of the cellular receptors for FV entry. Second, an increase in the concentration of the viral Bet (Between-env-and-LTR-1-and-2 protein reduces proviral FV gene expression by inhibition of the transcriptional activator protein Tas (Transactivator of spumaviruses. In contrast to SIR in FV and MuLV infection, the underlying mechanism of SIR in HIV-infected cells is poorly understood. CD4 receptor down-modulation, a major characteristic of HIV-infected cells, has been proposed to be the main mechanism of SIR against HIV, but data have been contradictory. Several recent studies report the occurrence of HIV superinfection in humans; an event associated with the generation of recombinant HIV strains and possibly with increased disease progression. The role of SIR in protecting patients from HIV superinfection has not been studied so far. The phenomenon of SIR may also be important in the protection of primates that are vaccinated with live

  10. Developmentally regulated sphingolipid degradation in Leishmania major.

    Directory of Open Access Journals (Sweden)

    Ou Zhang

    Full Text Available Leishmania parasites alternate between extracellular promastigotes in sandflies and intracellular amastigotes in mammals. These protozoans acquire sphingolipids (SLs through de novo synthesis (to produce inositol phosphorylceramide and salvage (to obtain sphingomyelin from the host. A single ISCL (Inositol phosphoSphingolipid phospholipase C-Like enzyme is responsible for the degradation of both inositol phosphorylceramide (the IPC hydrolase or IPCase activity and sphingomyelin (the SMase activity. Recent studies of a L. major ISCL-null mutant (iscl(- indicate that SL degradation is required for promastigote survival in stationary phase, especially under acidic pH. ISCL is also essential for L. major proliferation in mammals. To further understand the role of ISCL in Leishmania growth and virulence, we introduced a sole IPCase or a sole SMase into the iscl(- mutant. Results showed that restoration of IPCase only complemented the acid resistance defect in iscl(- promastigotes and improved their survival in macrophages, but failed to recover virulence in mice. In contrast, a sole SMase fully restored parasite infectivity in mice but was unable to reverse the promastigote defects in iscl(-. These findings suggest that SL degradation in Leishmania possesses separate roles in different stages: while the IPCase activity is important for promastigote survival and acid tolerance, the SMase activity is required for amastigote proliferation in mammals. Consistent with these findings, ISCL was preferentially expressed in stationary phase promastigotes and amastigotes. Together, our results indicate that SL degradation by Leishmania is critical for parasites to establish and sustain infection in the mammalian host.

  11. Is Glutathione the Major Cellular Target of Cisplatin?

    DEFF Research Database (Denmark)

    Kasherman, Yonit; Stürup, Stefan; gibson, dan

    2009-01-01

    Cisplatin is an anticancer drug whose efficacy is limited because tumors develop resistance to the drug. Resistant cells often have elevated levels of cellular glutathione (GSH), believed to be the major cellular target of cisplatin that inactivates the drug by binding to it irreversibly, forming...... [Pt(SG)2] adducts. We show by [1H,15N] HSQC that the half-life of 15N labeled cisplatin in whole cell extracts is 75 min, but no Pt-GSH adducts were observed. When the low molecular mass fraction (cisplatin, binding to GSH was observed probably due to removal...

  12. Major Decisions: Motivations for Selecting a Major, Satisfaction, and Belonging

    Science.gov (United States)

    Soria, Krista M.; Stebleton, Michael

    2013-01-01

    In this paper, we analyzed the relationship between students' motivations for choosing academic majors and their satisfaction and sense of belonging on campus. Based on a multi-institutional survey of students who attended large, public, research universities in 2009, the results suggest that external extrinsic motivations for selecting a major…

  13. Pectoralis major fascia in rhinoplasty.

    Science.gov (United States)

    Xavier, Rui

    2015-06-01

    Fascia is frequently used in rhinoplasty, for several different purposes. The deep temporalis fascia is most often chosen, though harvesting this fascia requires a separate surgical field that adds surgical time to the procedure and morbidity to the patient. In augmentation rhinoplasty cases as well as in many revision rhinoplasty cases, costal cartilage may be required. In these cases, when costal cartilage is harvested from the 5(th) to 7(th) ribs, pectoralis major fascia is in the surgical field and must be incised to provide access to the costal cartilage. Pectoralis major fascia is similar to the deep temporalis fascia, sharing many physical and histological characteristics with it. Pectoralis major fascia can be harvested from the same surgical field as costal cartilage and used in the nose whenever autologous costal cartilage is harvested, thus precluding the need for a separate surgical field for fascia harvest. The surgical technique for harvesting pectoralis major fascia is demonstrated, and two clinical cases of patients in whom this fascia was harvested and used in the nose are presented. Pectoralis major fascia may be considered an alternative option for use in rhinoplasty cases whenever autologous costal cartilage is used. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  14. CHARACTERISTICS OF METHICILLIN-RESISTANT STAPHYLOCOCCI

    Science.gov (United States)

    Sutherland, R.; Rolinson, G. N.

    1964-01-01

    Sutherland, R. (Beecham Research Laboratories Ltd., Betchworth, Surrey, England), and G. N. Rolinson. Characteristics of methicillin-resistant staphylococci. J. Bacteriol. 87:887–899. 1964.—Cultures of naturally occurring methicillin-resistant staphylococci obtained from a number of hospitals were examined for the nature and degree of resistance to methicillin and other antibiotics. All the cultures tested were similar in that they consisted of mixed populations in which the majority of cells were of normal sensitivity to methicillin with a minority showing methicillin resistance. The resistant members also differed from the rest of the population in that they grew more slowly even in the absence of methicillin. Pure cultures of the resistant minority were obtained readily but, on repeated transfer in the absence of methicillin, resistance was lost and the cultures reverted to mixed populations similar to the original naturally occurring strains. When methicillin-sensitive staphylococci were repeatedly subcultured in the presence of methicillin, a mixed population was obtained in which only a minority of cells were resistant to the antibiotic; in this respect, the cultures of methicillin-resistant staphylococci selected in vitro resembled the naturally occurring strains. The original cultures of methicillin-resistant staphylococci comprised populations of cells with uniform sensitivity or insensitivity to other antibiotics. The resistance of these staphylococci to methicillin was not due to increased ability to inactivate the drug but to intrinsic insensitivity to methicillin. PMID:14137628

  15. Resisting dehumanization

    DEFF Research Database (Denmark)

    Lassen, Inger Marie

    2018-01-01

    Recent years have seen an increase in the influx of asylum-seekers in Scandinavia, and in Denmark this has led to ever-tighter immigration control. This article discusses emerging practices of refugee solidarity and resistance to hegemonic migration policy in Danish civil society in the wake...... of an incident from September 2015, when a member of a Danish City Council offered private shelter to immigrants who were on their way to Norway. The incident led to legal proceedings in August 2016 for what the defendant referred to as ‘the offense of helping fellow human beings in need’. The study is informed...... 2015) and appraisal analysis of the incident in focus. Keywords: immigration, discursive discrimination, populism, solidarity, governmentality, topoi, appraisal...

  16. Reduction of cellular cisplatin resistance by hyperthermia - a review

    NARCIS (Netherlands)

    Hettinga, JVE; Konings, AWT; Kampinga, HH

    1997-01-01

    Resistance to cisplatin (cDDP) is a major limitation to its clinical effectiveness. Review of literature data indicates that cDDP resistance is a multifactorial phenomenon. This provides an explanation why attempts to reverse or circumvent resistance using cDDP-analogues or combination therapy with

  17. Antibiotic resistance in community-acquired urinary tract infections

    African Journals Online (AJOL)

    the treatment of other infections would inevitably lead to the development of resistance. S Afr Med J 1994; 84: 600-602. Antibiotic resistance is a major problem in developing countries.' There are many reasons for this, including antibiotic use in animal feeds, inappropriate prescribing and poor sanitation. Resistance rates in ...

  18. Incidence of cephalosporin resistance among clinical isolates of ...

    African Journals Online (AJOL)

    Background: The emergence of beta-lactam resistance in Pseudomonas aeruginosa is a major global challenge, particularly, the rise in the resistance to 3rd and 4th generation cephalosporins. Aim: This study was carried out to determine the resistance pattern of Pseudomonas aeruginosa to different generations of ...

  19. Incidence of cephalosporin resistance among clinical isolates of ...

    African Journals Online (AJOL)

    MJP

    2015-12-12

    Dec 12, 2015 ... Background: The emergence of beta-lactam resistance in Pseudomonas aeruginosa is a major global challenge, particularly, the rise in the resistance to 3rd and 4th generation cephalosporins. Aim: This study was carried out to determine the resistance pattern of Pseudomonas aeruginosa to different ...

  20. Methicillin-Susceptible, Vancomycin-Resistant Staphylococcus aureus, Brazil

    OpenAIRE

    Panesso , Diana; Planet , Paul J.; Diaz , Lorena; Hugonnet , Jean-Emannuel; Tran , Truc T.; Narechania , Apurva; Munita , José M.; Rincon , Sandra; Carvajal , Lina P.; Reyes , Jinnethe; Londono , Alejandra; Smith , Hannah; Sebra , Robert; Deikus , Gintaras; Weinstock , George M

    2015-01-01

    International audience; We report characterization of a methicillin-susceptible, vancomycin-resistant bloodstream isolate of Staphylococcus aureus recovered from a patient in Brazil. Emergence of vancomycin resistance in methicillin-susceptible S. aureus would indicate that this resistance trait might be poised to disseminate more rapidly among S. aureus and represents a major public health threat.

  1. Comparative Analysis Of Antibiotic Resistance And R-Plasmids Of ...

    African Journals Online (AJOL)

    Bacterial resistance to antibiotics constitutes a major cause of failure in the treatment of bacterial infections. The genetic exchange of plasmids containing antibiotic resistant determinants between bacteria is believed to play a critical role in the evolution of antibiotics resistant bacteria and this has been shown in S. aureus.

  2. Personality, academic majors and performance

    DEFF Research Database (Denmark)

    Vedel, Anna; Thomsen, Dorthe Kirkegaard; Larsen, Lars

    2015-01-01

    Personality–performance research typically uses samples of psychology students without questioning their representativeness. The present article reports two studies challenging this practice. Study 1: group differences in the Big Five personality traits were explored between students (N = 1067......) in different academic majors (medicine, psychology, law, economics, political science, science, and arts/humanities), who were tested immediately after university enrolment. Study 2: six and a half years later the students’ academic records were obtained, and predictive validity of the Big Five personality...... traits and their subordinate facets was examined in the various academic majors in relation to Grade Point Average (GPA). Significant group differences in all Big Five personality traits were found between students in different academic majors. Also, variability in predictive validity of the Big Five...

  3. Candida Species Biofilms’ Antifungal Resistance

    Science.gov (United States)

    Silva, Sónia; Rodrigues, Célia F.; Araújo, Daniela; Rodrigues, Maria Elisa; Henriques, Mariana

    2017-01-01

    Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent growth form of Candida cells and a strong causative agent of the intensification of antifungal resistance. As yet, no specific resistance factor has been identified as the sole responsible for the increased recalcitrance to antifungal agents exhibited by biofilms. Instead, biofilm antifungal resistance is a complex multifactorial phenomenon, which still remains to be fully elucidated and understood. The different mechanisms, which may be responsible for the intrinsic resistance of Candida species biofilms, include the high density of cells within the biofilm, the growth and nutrient limitation, the effects of the biofilm matrix, the presence of persister cells, the antifungal resistance gene expression and the increase of sterols on the membrane of biofilm cells. Thus, this review intends to provide information on the recent advances about Candida species biofilm antifungal resistance and its implication on intensification of the candidiasis. PMID:29371527

  4. Effect of electrode shape on grounding resistances - Part 1

    DEFF Research Database (Denmark)

    Ingeman-Nielsen, Thomas; Tomaskovicova, Sonia; Dahlin, Torleif

    2016-01-01

    Electrode grounding resistance is a major factor affecting measurement quality in electric resistivity tomography (ERT) measurements for cryospheric applications. Still, little information is available on grounding resistances in the geophysical literature, mainly because it is difficult to measure....... The focus-one protocol is a new method for estimating single electrode grounding resistances by measuring the resistance between a single electrode in an ERT array and all the remaining electrodes connected in parallel. For large arrays, the measured resistance is dominated by the grounding resistance...... of the electrode under test, the focus electrode. We have developed an equivalent circuit model formulation for the resistance measured when applying the focus-one protocol. Our model depends on the individual grounding resistances of the electrodes of the array, the mutual resistances between electrodes...

  5. Antimicrobial resistance of Staphylococcus aureus isolates from dairy cows and genetic diversity of resistant isolates

    Science.gov (United States)

    Staphylococcus aureus is a frequent and major contagious mastitis bacterial pathogen. The antibiotic treatment cure rates vary considerably from 4% to 92%. Staphylococcus aureus readily becomes resistant to antibiotics, resulting in persistent noncurable intramammary infection that usually results i...

  6. Major Appliance Repair. Teacher Edition.

    Science.gov (United States)

    Smreker, Eugene; Calvert, King

    This module is a comprehensive text on basic appliance repair, designed to prepare students for entry-level jobs in this growing field. Ensuring a firm grounding in electrical knowledge, the module contains 13 instructional units that cover the following topics: (1) major appliance repair orientation; (2) safety and first aid; (3) fundamentals of…

  7. Dirichlet polynomials, majorization, and trumping

    International Nuclear Information System (INIS)

    Pereira, Rajesh; Plosker, Sarah

    2013-01-01

    Majorization and trumping are two partial orders which have proved useful in quantum information theory. We show some relations between these two partial orders and generalized Dirichlet polynomials, Mellin transforms, and completely monotone functions. These relations are used to prove a succinct generalization of Turgut’s characterization of trumping. (paper)

  8. Endocrinopathies in thalassemia major patient

    Science.gov (United States)

    Lubis, D. A.; Yunir, E. M.

    2018-03-01

    Advanced in chelation therapy and regular blood transfusion have marked improvements in the life expectancy of patients with thalassemia major, however these patients still have to deal with several complications. We report a 19-year-old male, presented with multiple endocrine complication-related thalassemia; hypogonadism, short stature, osteoporosis with history of fracture, and subclinical hypothyroid.

  9. Major purchasers view customer service.

    Science.gov (United States)

    Darling, H; Kerr, V; Lynn, D

    1998-01-01

    While managed care organizations may select a variety of strategies toward customer service, the most successful will be adapting their approach to the expectation and requirements of major purchasers. In order to better understand the perspective of the individuals who are responsible for policy decisions at that level, Managed Care Quarterly (MCQ) conducted interviews with three highly respected representatives.

  10. Physics momentum 'stars' draw majors

    CERN Multimedia

    Lindström, I

    2003-01-01

    Over the past decade, the number of University of Arizona students declaring physics as their major has doubled, amid a national decline. According to a recent report by the National Task Force on Undergraduate Physics, it is the university's dedication to its undergraduate physics program which draws students in (1 page).

  11. Suppression of Drug Resistance in Dengue Virus

    Science.gov (United States)

    Mateo, Roberto; Nagamine, Claude M.

    2015-01-01

    ABSTRACT Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due to the high error rates of RNA-dependent RNA synthesis. Indeed, treatment of dengue virus infection with a nucleoside analog resulted in the expected genetic selection of resistant viruses in tissue culture and in mice. However, when the function of the oligomeric core protein was inhibited, no detectable selection of drug resistance in tissue culture or in mice was detected, despite the presence of drug-resistant variants in the population. Suppressed selection of drug-resistant virus correlated with cooligomerization of the targeted drug-susceptible and drug-resistant core proteins. The concept of “dominant drug targets,” in which inhibition of oligomeric viral assemblages leads to the formation of drug-susceptible chimeras, can therefore be used to prevent the outgrowth of drug resistance during dengue virus infection. PMID:26670386

  12. Action and resistance mechanisms of antibiotics: A guide for clinicians

    Directory of Open Access Journals (Sweden)

    Garima Kapoor

    2017-01-01

    Full Text Available Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.

  13. Examining the evidence for major histocompatibility complex-dependent mate selection in humans and nonhuman primates

    Czech Academy of Sciences Publication Activity Database

    Winternitz, Jamie Caroline; Abbate, J. L.

    2015-01-01

    Roč. 6, 13 May (2015), s. 73-88 ISSN 1179-7274 Institutional support : RVO:68081766 Keywords : major histocompatibility complex * sexual selection * olfaction * facial attraction * parasite resistance * inbreeding avoidance Subject RIV: EB - Genetics ; Molecular Biology

  14. Pyramiding for Resistance Durability: Theory and Practice.

    Science.gov (United States)

    Mundt, Chris

    2018-04-12

    Durable disease resistance is a key component of global food security, and combining resistance genes into "pyramids" is an important way to increase durability of resistance. The mechanisms by which pyramids impact durability are not well known. The traditional view of resistance pyramids considers the use of major resistance gene (R-gene) combinations deployed against pathogens that are primarily asexual. Interestingly, published examples of the successful use of pyramids in the traditional sense are rare. In contrast, most published descriptions of durable pyramids in practice are for cereal rusts, and tend to indicate an association between durability and cultivars combining major R-genes with incompletely expressed, adult plant resistance genes. Pyramids have been investigated experimentally for a diversity of pathogens, and many reduce disease levels below that of the single best gene. Resistance gene combinations have been identified through phenotypic reactions, molecular markers, and challenge against effector genes. As resistance genes do not express equally in all genetic backgrounds, however, a combination of genetic information and phenotypic analyses provide the ideal scenario for testing of putative pyramids. Not all resistance genes contribute equally to pyramids, and approaches have been suggested to identify the best genes and combinations of genes for inclusion. Combining multiple resistance genes into a single plant genotype quickly is a challenge that is being addressed through alternative breeding approaches, as well as through genomics tools such as resistance gene cassettes and gene editing. Experimental and modeling tests of pyramid durability are in their infancy, but have promise to help direct future studies of pyramids. Several areas for further work on resistance gene pyramids are suggested.

  15. Overview perspective of bacterial resistance.

    Science.gov (United States)

    Furtado, Guilherme H; Nicolau, David P

    2010-10-01

    The rapidly escalating prevalence of antimicrobial resistance is a global concern. This reduced susceptibility to currently available antimicrobial agents coupled with the progressive shortage of newly approved compounds is a worrisome situation. Major problems are encountered for a growing number of Gram-positive (i.e., Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp.) and Gram-negative pathogens (i.e., Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae). We provide an overview of bacterial resistance focusing on the most common pathogens responsible for infection in both the community and healthcare settings. In addition, several strategies to curb antimicrobial resistance are also discussed. It is increasingly evident that without the introduction of novel antimicrobial agents, a return to the clinical outcomes associated with the pre-antibiotic era are inevitable.

  16. DRUG RESISTANCE IN HELICOBACTER PYLORI

    Directory of Open Access Journals (Sweden)

    Júlia Silveira VIANNA

    Full Text Available ABSTRACT Background Helicobacter pylori has a worldwide distribution and is associated with the pathogenesis of various diseases of the digestive system. Treatment to eradicate this microorganism involves the use of a combination of antimicrobials, such as amoxicillin, metronidazole, clarithromycin, and levofloxacin, combined with proton pump inhibitors. Although the current therapy is effective, a high rate of treatment failure has been observed, mainly because of the acquisition of point mutations, one of the major resistance mechanisms developed by H. pylori. This phenomenon is related to frequent and/or inappropriate use of antibiotics. Conclusion This review reported an overview of the resistance to the main drugs used in the treatment of H. pylori, confirming the hypothesis that antibacterial resistance is a highly local phenomenon and genetic characteristics of a given population can influence which therapy is the most appropriate.

  17. Resistance mechanisms in Campylobacter jejuni

    Science.gov (United States)

    Iovine, Nicole M.

    2013-01-01

    Campylobacter jejuni is a major cause of food-borne gastroenteritis worldwide. While mortality is low, morbidity imparted by post-infectious sequelae such as Guillain-Barré syndrome, Reiter syndrome/reactive arthritis and irritable bowel syndrome is significant. In addition, the economic cost is high due to lost productivity. Food animals, particularly poultry, are the main reservoirs of C. jejuni. The over-use of antibiotics in the human population and in animal husbandry has led to an increase in antibiotic-resistant infections, particularly with fluoroquinolones. This is problematic because C. jejuni gastroenteritis is clinically indistinguishable from that caused by other bacterial pathogens, and such illnesses are usually treated empirically with fluoroquinolones. Since C. jejuni is naturally transformable, acquisition of additional genes imparting antibiotic resistance is likely. Therefore, an understanding of the antibiotic resistance mechanisms in C. jejuni is needed to provide proper therapy both to the veterinary and human populations. PMID:23406779

  18. Cross-resistance to herbicides in annual ryegrass (lolium rigidum)

    International Nuclear Information System (INIS)

    Christopher, J.T.; Powles, S.B.; Liljegren, D.R.; Holtum, J.A.M.

    1991-01-01

    Lolium rigidum Gaud. biotype SLR31 is resistant to the herbicide diclofop-methyl and cross-resistant to several sulfonylurea herbicides. Wheat and the cross-resistant ryegrass exhibit similar patterns of resistance to sulfonylurea herbicides, suggesting that the mechanism of resistance may be similar. Cross-resistant ryegrass is also resistant to the wheat-selective imidazolinone herbicide imazamethabenz. The cross-resistant biotype SLR31 metabolized [phenyl-U- 14 C]chlorsulfuron at a faster rate than a biotype which is susceptible to both diclofop-methyl and chlorsulfuron. A third biotype which is resistant to diclofop-methyl but not to chlorsulfuron metabolized chlorsulfuron at the same rate as the susceptible biotype. The increased metabolism of chlorsulfuron observed in the cross-resistant biotype is, therefore, correlated with the patterns of resistance observed in these L. rigidum biotypes. During high performance liquid chromatography analysis the major metabolite of chlorsulfuron in both susceptible and cross-resistant ryegrass coeluted with the major metabolite produced in wheat. The major product is clearly different from the major product in the tolerant dicot species, flax (Linium usitatissimum). The elution pattern of metabolites of chlorsulfuron was the same for both the susceptible and cross-resistant ryegrass but the cross-resistant ryegrass metabolized chlorsulfuron more rapidly. The investigation of the dose response to sulfonylurea herbicides at the whole plant level and the study of the metabolism of chlorsulfuron provide two independent sets of data which both suggest that the resistance to chlorsulfuron in cross-resistant ryegrass biotype SLR31 involves a wheat-like detoxification system

  19. Discussion on the origin of sedimentary rock resistivity

    International Nuclear Information System (INIS)

    Dong Gangjian

    2012-01-01

    Conduction current way of sedimentary rock sedimentary rock is caused by the internal structure of sedimentary rock sedimentary rock pore resistance depends on the salinity of pore water and clay content and distribution. Resistivity of sedimentary rock sedimentary rock major factor in mineral composition, water resistance, oil resistance. and sedimentary structures. In practice, we should give full attention to the difference between lithology and physical properties. (author)

  20. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  1. HIV Resistance Testing

    Science.gov (United States)

    ... 14, 2016 Select a Language: Fact Sheet 126 HIV Resistance Testing WHAT IS RESISTANCE? HOW DOES RESISTANCE ... ARVs. If you miss doses of your medications, HIV will multiply more easily. More mutations will occur. ...

  2. Combating Antibiotic Resistance

    Science.gov (United States)

    ... in Farm Animals FDA: Cutting-Edge Technology Sheds Light on Antibiotic Resistance For More Information Antibiotics and Antibiotic Resistance Antimicrobial Resistance Information for Consumers and Health Professionals CDC: Get Smart: Know When Antibiotics Work More in Consumer Updates ...

  3. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it ... Veterinary Medicine is cited as the corporate author. Animation Animation of Antimicrobial Resistance (video) Animation of Antimicrobial ...

  4. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Antimicrobial Resistance More in Antimicrobial Resistance National Antimicrobial Resistance Monitoring System About NARMS 2015 NARMS Integrated Report Data Meetings and Publications Resources Judicious Use of Antimicrobials Page Last Updated: ...

  5. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  6. Beta thalassaemiatriat in western Nigeria | Kotila | African Health ...

    African Journals Online (AJOL)

    Background: Genes for thalassaemia, haemoglobin S, Glucose-6-phosphate dehydrogenase which confer resistance to malaria are found in high frequencies in Nigeria, 25% of the population being carriers of the sickle cell trait while another 25% are hemizygous for the G6PD gene. The frequency of alpha thalassaemia is ...

  7. An agent-based model for Leishmania major infection

    Science.gov (United States)

    Dancik, Garrett M.; Jones, Douglas E.; Dorman, Karin S.

    Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a CD4+ Thl immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. Amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004].

  8. Neurobiology of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Rosa Villanueva

    2013-01-01

    Full Text Available We survey studies which relate abnormal neurogenesis to major depressive disorder. Clinically, descriptive gene and protein expression analysis and genetic and functional studies revised here show that individual alterations of a complex signaling network, which includes the hypothalamic-pituitary-adrenal axis; the production of neurotrophins and growth factors; the expression of miRNAs; the production of proinflammatory cytokines; and, even, the abnormal delivery of gastrointestinal signaling peptides, are able to induce major mood alterations. Furthermore, all of these factors modulate neurogenesis in brain regions involved in MDD, and are functionally interconnected in such a fashion that initial alteration in one of them results in abnormalities in the others. We highlight data of potential diagnostic significance and the relevance of this information to develop new therapeutic approaches. Controversial issues, such as whether neurogenesis is the basis of the disease or whether it is a response induced by antidepressant treatments, are also discussed.

  9. Hypogonadism in thalassemia major patients

    Directory of Open Access Journals (Sweden)

    Sasima Srisukh

    2016-09-01

    Full Text Available Despite recent advances in iron chelation therapy, excess iron deposition in pituitary gonadotropic cells remains one of the major problems in thalassemic patients. Hypogonadism, mostly hypogonadotropic hypogonadism, is usually detected during puberty. Early diagnosis and treatment are crucial for normal pubertal development and to reduce the complications of hypogonadism. The risks and benefits of hormonal replacement therapy, especially regarding the thromboembolic event, remain a challenge for providers caring for thalassemic patients.

  10. Cancers of major salivary glands.

    Science.gov (United States)

    Panwar, Aru; Kozel, Jessica A; Lydiatt, William M

    2015-07-01

    Major salivary gland malignancies are a rare but histologically diverse group of entities. Establishing the diagnosis of a malignant salivary neoplasm may be challenging because of the often minimally symptomatic nature of the disease, and limitations of imaging modalities and cytology. Treatment is centered on surgical therapy and adjuvant radiation in selected scenarios. Systemic therapy with chemotherapeutic agents and monoclonal antibodies lacks evidence in support of its routine use. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Induced resistance: an enhancement of basal resistance?

    NARCIS (Netherlands)

    Vos, M. de; Robben, C.; Pelt, J.A. van; Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    Upon primary pathogen attack, plants activate resistance mechanisms at the site of infection. Besides this so-called basal resistance, plants have also the ability to enhance their defensive capacity against future pathogen attack. There are at least two types of biologically induced resistance.

  12. Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study

    Directory of Open Access Journals (Sweden)

    Silpi Basak

    2016-01-01

    Full Text Available Background and Objective. Antimicrobial resistance is now a major challenge to clinicians for treating patients. Hence, this short term study was undertaken to detect the incidence of multidrug-resistant (MDR, extensively drug-resistant (XDR, and pandrug-resistant (PDR bacterial isolates in a tertiary care hospital. Material and Methods. The clinical samples were cultured and bacterial strains were identified in the department of microbiology. The antibiotic susceptibility profile of different bacterial isolates was studied to detect MDR, XDR, and PDR bacteria. Results. The antibiotic susceptibility profile of 1060 bacterial strains was studied. 393 (37.1% bacterial strains were MDR, 146 (13.8% strains were XDR, and no PDR was isolated. All (100% Gram negative bacterial strains were sensitive to colistin whereas all (100% Gram positive bacterial strains were sensitive to vancomycin. Conclusion. Close monitoring of MDR, XDR, or even PDR must be done by all clinical microbiology laboratories to implement effective measures to reduce the menace of antimicrobial resistance.

  13. Computational Studies of Drug Resistance

    DEFF Research Database (Denmark)

    da Silva Martins, João Miguel

    Drug resistance has been an increasing problem in patient treatment and drug development. Starting in the last century and becoming a major worry in the medical and scienti c communities in the early part of the current millennium, major research must be performed to address the issues of viral...... is of the utmost importance in developing better and less resistance-inducing drugs. A drug's in uence can be characterized in many diff erent ways, however, and the approaches I take in this work re ect those same different in uences. This is what I try to achieve in this work, through seemingly unrelated...... approaches that come together in the study of drug's and their in uence on proteins and vice-versa. In part I, I aim to understand through combined theoretical ensemble analysis and free energy calculations the e ects mutations have over the binding anity and function of the M2 proton channel. This research...

  14. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... More in Antimicrobial Resistance National Antimicrobial Resistance Monitoring System About NARMS 2015 NARMS Integrated Report Data Meetings and Publications Resources Judicious Use of ...

  15. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... More in Antimicrobial Resistance National Antimicrobial Resistance Monitoring System ... If you need help accessing information in different file formats, see Instructions for Downloading ...

  16. Antibiotic resistance: the Iowa experience.

    Science.gov (United States)

    Bell, Nancy

    2002-11-01

    In the past 10 years, the number of strains of Streptococcus pneumoniae and other common respiratory pathogens that are resistant to penicillin has increased. The Iowa Department of Public Health convened a multidisciplinary task force in January 1998 to develop strategies to combat antibiotic resistance in the state because they were alarmed by these reports. Within 18 months, the task force implemented statewide surveillance of resistant organisms and posted information about the surveillance on the Internet, distributed a public health guide on judicious antibiotic use and infection control measures to 7500 healthcare providers, and held a press conference to inform the public about antibiotic resistance. The task force collaborated with several major insurers in the state to profile the top prescribers of antibiotic agents in their plan. The profiling and educational interventions led to a substantial decrease in both overall antibiotic prescribing and drug costs. Other states may want to undertake similar programs to help protect their citizens from infections caused by resistant pathogens.

  17. Drug-resistant spinal tuberculosis

    Directory of Open Access Journals (Sweden)

    Anil K Jain

    2018-01-01

    Full Text Available Drug-resistant spinal tuberculosis (TB is an emerging health problem in both developing and developed countries. In this review article, we aim to define management protocols for suspicion, diagnosis, and treatment of such patients. Spinal TB is a deep-seated paucibacillary lesion, and the demonstration of acid-fast bacilli on Ziehl-Neelsen staining is possible only in 10%–30% of cases. Drug resistance is suspected in patients showing the failure of clinicoradiological improvement or appearance of a fresh lesion of osteoarticular TB while on anti tubercular therapy (ATT for a minimum period of 5 months. The conventional culture of Mycobacterium tuberculosis remains the gold standard for both bacteriological diagnosis and drug sensitivity testing (DST; however, the high turn around time of 2–6 weeks for detection with added 3 weeks for DST is a major limitation. To overcome this problem, rapid culture methods and molecular methods have been introduced. From a public health perspective, reducing the period between diagnosis and treatment initiation has direct benefits for both the patient and the community. For all patients of drug-resistant spinal TB, a complete Drug-O-Gram should be prepared which includes details of all drugs, their doses, and duration. Patients with confirmed multidrug-resistant TB strains should receive a regimen with at least five effective drugs, including pyrazinamide and one injectable. Patients with resistance to additional antitubercular drugs should receive individualized ATT as per their DST results.

  18. Drug-resistant Spinal Tuberculosis.

    Science.gov (United States)

    Jain, Anil K; Jaggi, Karan Raj; Bhayana, Himanshu; Saha, Rumpa

    2018-01-01

    Drug-resistant spinal tuberculosis (TB) is an emerging health problem in both developing and developed countries. In this review article, we aim to define management protocols for suspicion, diagnosis, and treatment of such patients. Spinal TB is a deep-seated paucibacillary lesion, and the demonstration of acid-fast bacilli on Ziehl-Neelsen staining is possible only in 10%-30% of cases. Drug resistance is suspected in patients showing the failure of clinicoradiological improvement or appearance of a fresh lesion of osteoarticular TB while on anti tubercular therapy (ATT) for a minimum period of 5 months. The conventional culture of Mycobacterium tuberculosis remains the gold standard for both bacteriological diagnosis and drug sensitivity testing (DST); however, the high turn around time of 2-6 weeks for detection with added 3 weeks for DST is a major limitation. To overcome this problem, rapid culture methods and molecular methods have been introduced. From a public health perspective, reducing the period between diagnosis and treatment initiation has direct benefits for both the patient and the community. For all patients of drug-resistant spinal TB, a complete Drug-O-Gram should be prepared which includes details of all drugs, their doses, and duration. Patients with confirmed multidrug-resistant TB strains should receive a regimen with at least five effective drugs, including pyrazinamide and one injectable. Patients with resistance to additional antitubercular drugs should receive individualized ATT as per their DST results.

  19. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  20. Selective Insulin Resistance in Adipocytes*

    Science.gov (United States)

    Tan, Shi-Xiong; Fisher-Wellman, Kelsey H.; Fazakerley, Daniel J.; Ng, Yvonne; Pant, Himani; Li, J