Tumor Necrosis Factor B (TNFB) Genetic Variants and Its Increased Expression Are Associated with Vitiligo Susceptibility

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Laddha, Naresh C.; Dwivedi, Mitesh; Gani, Amina R.; Mansuri, Mohmmad Shoab; Begum, Rasheedunnisa

2013-01-01

Genetic polymorphisms in TNFB are involved in the regulation of its expression and are found to be associated with various autoimmune diseases. The aim of the present study was to determine whether TNFB +252A/G (rs909253) and exon 3 C/A (rs1041981) polymorphisms are associated with vitiligo susceptibility, and expression of TNFB and ICAM1 affects the disease onset and progression. We have earlier reported the role of TNFA in autoimmune pathogenesis of vitiligo, and we now show the involvement of TNFB in vitiligo pathogenesis. The two polymorphisms investigated in the TNFB were in strong linkage disequilibrium and significantly associated with vitiligo. TNFB and ICAM1 transcripts were significantly increased in patients compared to controls. Active vitiligo patients showed significant increase in TNFB transcripts compared to stable vitiligo. The genotype-phenotype analysis revealed that TNFB expression levels were higher in patients with GG and AA genotypes as compared to controls. Patients with the early age of onset and female patients showed higher TNFB and ICAM1 expression. Overall, our findings suggest that the increased TNFB transcript levels in vitiligo patients could result, at least in part, from variations at the genetic level which in turn leads to increased ICAM1 expression. For the first time, we show that TNFB +252A/G and exon 3 C/A polymorphisms are associated with vitiligo susceptibility and influence the TNFB and ICAM1 expression. Moreover, the study also emphasizes influence of TNFB and ICAM1 on the disease progression, onset and gender bias for developing vitiligo. PMID:24312346

Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury.

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Velez, Juan Carlos Q; Arif, Ehtesham; Rodgers, Jessalyn; Hicks, Megan P; Arthur, John M; Nihalani, Deepak; Bruner, Evelyn T; Budisavljevic, Milos N; Atkinson, Carl; Fitzgibbon, Wayne R; Janech, Michael G

2017-07-01

Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases. Copyright © 2017 by the American Society of Nephrology.

Placing Antismoking Graphic Warning Posters at Retail Point-of-Sale Locations Increases Some Adolescents' Susceptibility to Future Smoking.

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Shadel, William G; Martino, Steven C; Setodji, Claude; Dunbar, Michael; Kusuke, Daniela; Lanna, Serafina; Meyer, Amanda

2017-12-13

This experiment tested whether introducing graphic antitobacco posters at point-of-sale (POS) had any effect on adolescents' susceptibility to future cigarette smoking and whether these effects were moderated by adolescents' baseline risk of cigarette smoking. The study was conducted in the RAND StoreLab, a life-sized replica of a convenience store that was developed to experimentally evaluate how changing aspects of tobacco advertising displays in retail POS environments influence tobacco use risk and behavior during simulated shopping experiences. In this study, 441 adolescents were randomized to one of the four conditions in a 2 (graphic antismoking poster placed near the tobacco power wall: no, yes) × 2 (graphic antismoking poster placed near the cash register: no, yes) experimental design. The outcome of interest was susceptibility to future cigarette smoking. The addition of antismoking posters at POS led to a significant increase in future smoking susceptibility among those adolescents who already were at high risk for smoking in the future (p posters had no impact on committed never smokers, regardless of poster location; never smokers' susceptibility to future smoking was uniformly low across experimental conditions. Introducing graphic antismoking posters at POS may have the unintended effect of further increasing cigarette smoking susceptibility among adolescents already at risk. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease.

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Wang, Wang; Patel, Vaibhav B; Parajuli, Nirmal; Fan, Dong; Basu, Ratnadeep; Wang, Zuocheng; Ramprasath, Tharmarajan; Kassiri, Zamaneh; Penninger, Josef M; Oudit, Gavin Y

2014-08-01

Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion. Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to

Persistent Salmonella enterica serovar Typhimurium Infection Increases the Susceptibility of Mice to Develop Intestinal Inflammation

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Bárbara M. Schultz

2018-05-01

Full Text Available Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS and interleukin (IL-10−/− mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10−/− mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2. Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10−/− mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.

Analysis of significance of environmental factors in landslide susceptibility modeling: Case study Jemma drainage network, Ethiopia

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Vít Maca

2017-06-01

Full Text Available Aim of the paper is to describe methodology for calculating significance of environmental factors in landslide susceptibility modeling and present result of selected one. As a study area part of a Jemma basin in Ethiopian Highland is used. This locality is highly affected by mass movement processes. In the first part all major factors and their influence are described briefly. Majority of the work focuses on research of other methodologies used in susceptibility models and design of own methodology. This method is unlike most of the methods used completely objective, therefore it is not possible to intervene in the results. In article all inputs and outputs of the method are described as well as all stages of calculations. Results are illustrated on specific examples. In study area most important factor for landslide susceptibility is slope, on the other hand least important is land cover. At the end of article landslide susceptibility map is created. Part of the article is discussion of results and possible improvements of the methodology.

Inhibition of sarcoplasmic Ca2+-ATPase increases caffeine- and halothane-induced contractures in muscle bundles of malignant hyperthermia susceptible and healthy individuals

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Roewer Norbert

2005-06-01

Full Text Available Abstract Background Malignant hyperthermia (MH is triggered by halogenated anaesthetics and depolarising muscle relaxants, leading to an uncontrolled hypermetabolic state of skeletal muscle. An uncontrolled sarcoplasmic Ca2+ release is mediated via the ryanodine receptor. A compensatory mechanism of increased sarcoplasmic Ca2+-ATPase activity was described in pigs and in transfected cell lines. We hypothesized that inhibition of Ca2+ reuptake via the sarcoplasmic Ca2+-ATPase (SERCA enhances halothane- and caffeine-induced muscle contractures in MH susceptible more than in non-susceptible skeletal muscle. Methods With informed consent, surplus muscle bundles of 7 MHS (susceptible, 7 MHE (equivocal and 16 MHN (non-susceptible classified patients were mounted to an isometric force transducer, electrically stimulated, preloaded and equilibrated. Following 15 min incubation with cyclopiazonic acid (CPA 25 μM, the European MH standard in-vitro-contracture test protocol with caffeine (0.5; 1; 1.5; 2; 3; 4 mM and halothane (0.11; 0.22; 0.44; 0.66 mM was performed. Data as median and quartiles; Friedman- and Wilcoxon-test for differences with and without CPA; p Results Initial length, weight, maximum twitch height, predrug resting tension and predrug twitch height of muscle bundles did not differ between groups. CPA increased halothane- and caffeine-induced contractures significantly. This increase was more pronounced in MHS and MHE than in MHN muscle bundles. Conclusion Inhibition of the SERCA activity by CPA enhances halothane- and caffeine-induced contractures especially in MHS and MHE skeletal muscle and may help for the diagnostic assignment of MH susceptibility. The status of SERCA activity may play a significant but so far unknown role in the genesis of malignant hyperthermia.

Knockout of a P-glycoprotein gene increases susceptibility to abamectin and emamectin benzoate in Spodoptera exigua.

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Zuo, Y-Y; Huang, J-L; Wang, J; Feng, Y; Han, T-T; Wu, Y-D; Yang, Y-H

2018-02-01

P-glycoprotein [P-gp or the ATP-binding cassette transporter B1 (ABCB1)] is an important participant in multidrug resistance of cancer cells, yet the precise function of this arthropod transporter is unknown. The aim of this study was to determine the importance of P-gp for susceptibility to insecticides in the beet armyworm (Spodoptera exigua) using clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) gene-editing technology. We cloned an open reading frame (ORF) encoding the S. exigua P-gp protein (SeP-gp) predicted to display structural characteristics common to P-gp and other insect ABCB1 transporters. A knockout line with a frame shift deletion of four nucleotides in the SeP-gp ORF was established using the CRISPR/Cas9 gene-editing system to test its potential role in determining susceptibility to chemical insecticides or insecticidal proteins from the bacterium Bacillus thuringiensis (Bt). Results from comparative bioassays demonstrate that knockout of SeP-gp significantly increases susceptibility of S. exigua by around threefold to abamectin and emamectin benzoate (EB), but not to spinosad, chlorfenapyr, beta-cypermethrin, carbosulfan indoxacarb, chlorpyrifos, phoxim, diafenthiuron, chlorfluazuron, chlorantraniliprole or two Bt toxins (Cry1Ca and Cry1Fa). Our data support an important role for SeP-gp in susceptibility of S. exigua to abamectin and EB and imply that overexpression of SeP-gp may contribute to abamectin and EB resistance in S. exigua. © 2017 The Royal Entomological Society.

Immunological changes at point-of-lay increase susceptibility to Salmonella enterica Serovar enteritidis infection in vaccinated chickens.

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Claire E Johnston

Full Text Available Chicken eggs are the main source of human Salmonella enterica serovar Enteritidis infection. S. Enteritidis infects the oviduct and ovary of the chicken leading to infection of developing eggs. Therefore, control in poultry production is a major public health priority. Vaccination of hens has proved successful in control strategies in United Kingdom leading to a 70% drop in human cases since introduced. However, as hens reach sexual maturity they become immunosuppressed and it has been postulated this leads to increased susceptibility to Salmonella infection. In this study we define the changes to the systemic and reproductive tract-associated immune system of hens throughout sexual development by flow cytometry and histology and determine changes in susceptibility to experimental S. Enteritidis challenge in naive and vaccinated hens. Changes to both systemic and local immune systems occur in chickens at sexual development around 140 days of age. The population of several leukocyte classes drop, with the greatest fall in CD4+ lymphocyte numbers. Within the developing reproductive tract there an organised structure of lymphocytic aggregates with γδ-T lymphocytes associated with the mucosa. At point-of-lay, this organised structure disappears and only scattered lymphocytes remain. Protection against Salmonella challenge is significantly reduced in vaccinated birds at point-of-lay, coinciding with the drop in CD4+ lymphocytes. Susceptibility to reproductive tract infection by Salmonella increased in vaccinated and naïve animals at 140 and 148 days of age. We hypothesise that the drop in γδ-T lymphocytes in the tract leads to decreased innate protection of the mucosa to infection. These findings indicate that systemic and local changes to the immune system increase the susceptibility of hens to S. Enteritidis infection. The loss of protective immunity in vaccinated birds demonstrates that Salmonella control should not rely on vaccination alone

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

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Hals, I. K.; Rokstad, A. M.; Strand, B. L.; Oberholzer, J.; Grill, V.

2013-01-01

Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation. PMID:24364039

HSV-2-Driven Increase in the Expression of α4β7 Correlates with Increased Susceptibility to Vaginal SHIVSF162P3 Infection

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Goode, Diana; Truong, Rosaline; Villegas, Guillermo; Calenda, Giulia; Guerra-Perez, Natalia; Piatak, Michael; Lifson, Jeffrey D.; Blanchard, James; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

2014-01-01

The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase the chances of an otherwise rare transmission event to occur. Expression of α4β7 is required for trafficking of immune cells to gut inductive sites where HIV can expand and it is expressed at high level on cells particularly susceptible to HIV infection. We hypothesized that HSV-2 modulates the expression of α4β7 and other homing receptors in the vaginal tissue and that this correlates with the increased risk of HIV acquisition in HSV-2 positive individuals. To test this hypothesis we used an in vivo rhesus macaque (RM) model of HSV-2 vaginal infection and a new ex vivo model of macaque vaginal explants. In vivo we found that HSV-2 latently infected RMs appeared to be more susceptible to vaginal SHIVSF162P3 infection, had higher frequency of α4β7 high CD4+ T cells in the vaginal tissue and higher expression of α4β7 and CD11c on vaginal DCs. Similarly, ex vivo HSV-2 infection increased the susceptibility of the vaginal tissue to SHIVSF162P3. HSV-2 infection increased the frequencies of α4β7 high CD4+ T cells and this directly correlated with HSV-2 replication. A higher amount of inflammatory cytokines in vaginal fluids of the HSV-2 infected animals was similar to those found in the supernatants of the infected explants. Remarkably, the HSV-2-driven increase in the frequency of α4β7 high CD4+ T cells directly correlated with SHIV replication in the HSV-2 infected tissues. Our results suggest that the HSV-2-driven increase in availability of CD4+ T cells and DCs that express high levels of α4β7 is associated with the increase in susceptibility to SHIV due to HSV-2. This may persists in absence of HSV-2 shedding. Hence, higher availability of α4β7 positive HIV target cells in the vaginal tissue may constitute a risk factor for HIV transmission. PMID:25521298

MDMA Decreases Gluatamic Acid Decarboxylase (GAD) 67-Immunoreactive Neurons in the Hippocampus and Increases Seizure Susceptibility: Role for Glutamate

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Huff, Courtney L.; Morano, Rachel L.; Herman, James P.; Yamamoto, Bryan K.; Gudelsky, Gary A.

2016-01-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37–58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30 days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. PMID:27773601

MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

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Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

2016-12-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

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I. K. Hals

2013-01-01

Full Text Available Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8±3.5% in encapsulated and 42.9±5.2% in nonencapsulated islets (P<0.2. Nonencapsulated islets released 37.7% (median more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P<0.001. Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0±6.1% versus 24.8±5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.

Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

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Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

2016-08-01

We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin

DEFF Research Database (Denmark)

Fosgerau, Keld; Ristagno, Giuseppe; Jayatissa, Magdalena Niepsuj

2010-01-01

Survivors of a cardiac arrest often have persistent cardiovascular derangements following cardiopulmonary resuscitation including decreased cardiac output, arrhythmias and morphological myocardial damage. These cardiovascular derangements may lead to an increased susceptibility towards the extern...

Hypoxia increases susceptibility of Pacific white shrimp to whitespot syndrome virus (WSSV

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M. Lehmann

2016-04-01

Full Text Available The present study aimed to evaluate the mortality, reactive oxygen species production (ROS and total hemocyte counts (THC of the marine shrimp Litopenaeus vannamei infected with the white spot syndrome virus (WSSV at three levels of oxygen saturation. For this, 360 shrimp (20±2g were distributed in 24 tanks (60L, divided in two groups (infected and non-infected, which were subjected to 30, 60 and 100% of dissolved oxygen saturation (in quadruplicate. During 96 hours after infection, daily hemolymph samples were collected for hemato-immunological parameter evaluation (THC and ROS and dead animals were removed and computed to assess cumulative mortality rates. In the infected group, animals subjected to 100% saturation showed higher ROS production (P<0.05 after 48 hours, while THC was significantly reduced (P<0.05, regardless of oxygen saturation. The hypoxia resulted in high mortality when compared to 100% saturation condition. In the uninfected group, no significant differences were observed in all evaluated parameters. Thus, the hypoxia condition increased the susceptibility of shrimp to the infection of WSSV, which may be partly related to the low ROS production showed by the animals subjected to 30% oxygen saturation.

Increasing rate of daptomycin non-susceptible strains of Staphylococcus aureus in patients with atopic dermatitis

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Izabela Błażewicz

2017-12-01

Full Text Available Introduction : Daptomycin is a cyclic lipopeptide that is bactericidal against Staphylococcus aureus , including methicillin-resistant S. aureus (MRSA, vancomycin-intermediate S. aureus (VISA and vancomycin-resistant S. aureus (VRSA strains. Daptomycin exerts its antimicrobial effect by a calcium-dependent interaction with the cytoplasmic membrane resulting in depolarization, ion loss and rapid cell death. Unfortunately, loss of daptomycin susceptibility in S. aureus in the clinical setting has been noted. Aim : To evaluate the susceptibility profile to daptomycin among S. aureus strains isloted from patients with atopic dermatitis (AD. Another point was to correlate the results obtained by broth microdilution method and Etest, which is commonly applied in clinical setting. Material and methods : One hundred patients with the diagnosis of atopic dermatitis were microbiologically assessed for the carriage of S. aureus . Antimicrobial susceptibility tests were performed using broth-microdilution (BMD and Etests for daptomycin. Results : Staphylococcus aureus strains were isolated from the majority of our patients, either from the skin (73% or the anterior nares (75%. Six of the 100 nasal swabs (6% and 5 of the 100 skin swabs (5% were positive for methicillin-resistant Staphylococcus aureus (MRSA. A total of 81 of 148 (54.7% daptomycin non-susceptible isolates of S. aureus were identified by BMD. Only 19 of 81 were also classified as non-susceptible by Etest. Conclusions : Clinicians and microbiologists should be aware of the possibility of the emergence of daptomycin non-susceptibility (or increase in minimal inhibitory concentration during prolonged therapy and closely monitor the susceptibility of persisting isolates that might be recovered during therapy.

HSV-2-driven increase in the expression of α4β7 correlates with increased susceptibility to vaginal SHIV(SF162P3) infection.

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Goode, Diana; Truong, Rosaline; Villegas, Guillermo; Calenda, Giulia; Guerra-Perez, Natalia; Piatak, Michael; Lifson, Jeffrey D; Blanchard, James; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

2014-12-01

The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase the chances of an otherwise rare transmission event to occur. Expression of α4β7 is required for trafficking of immune cells to gut inductive sites where HIV can expand and it is expressed at high level on cells particularly susceptible to HIV infection. We hypothesized that HSV-2 modulates the expression of α4β7 and other homing receptors in the vaginal tissue and that this correlates with the increased risk of HIV acquisition in HSV-2 positive individuals. To test this hypothesis we used an in vivo rhesus macaque (RM) model of HSV-2 vaginal infection and a new ex vivo model of macaque vaginal explants. In vivo we found that HSV-2 latently infected RMs appeared to be more susceptible to vaginal SHIVSF162P3 infection, had higher frequency of α4β7high CD4+ T cells in the vaginal tissue and higher expression of α4β7 and CD11c on vaginal DCs. Similarly, ex vivo HSV-2 infection increased the susceptibility of the vaginal tissue to SHIVSF162P3. HSV-2 infection increased the frequencies of α4β7high CD4+ T cells and this directly correlated with HSV-2 replication. A higher amount of inflammatory cytokines in vaginal fluids of the HSV-2 infected animals was similar to those found in the supernatants of the infected explants. Remarkably, the HSV-2-driven increase in the frequency of α4β7high CD4+ T cells directly correlated with SHIV replication in the HSV-2 infected tissues. Our results suggest that the HSV-2-driven increase in availability of CD4+ T cells and DCs that express high levels of α4β7 is associated with the increase in susceptibility to SHIV due to HSV-2. This may persists in absence of HSV-2 shedding. Hence, higher availability of α4β7 positive HIV target cells in the vaginal tissue may constitute a risk factor for HIV transmission.

HSV-2-driven increase in the expression of α4β7 correlates with increased susceptibility to vaginal SHIV(SF162P3 infection.

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Diana Goode

2014-12-01

Full Text Available The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase the chances of an otherwise rare transmission event to occur. Expression of α4β7 is required for trafficking of immune cells to gut inductive sites where HIV can expand and it is expressed at high level on cells particularly susceptible to HIV infection. We hypothesized that HSV-2 modulates the expression of α4β7 and other homing receptors in the vaginal tissue and that this correlates with the increased risk of HIV acquisition in HSV-2 positive individuals. To test this hypothesis we used an in vivo rhesus macaque (RM model of HSV-2 vaginal infection and a new ex vivo model of macaque vaginal explants. In vivo we found that HSV-2 latently infected RMs appeared to be more susceptible to vaginal SHIVSF162P3 infection, had higher frequency of α4β7high CD4+ T cells in the vaginal tissue and higher expression of α4β7 and CD11c on vaginal DCs. Similarly, ex vivo HSV-2 infection increased the susceptibility of the vaginal tissue to SHIVSF162P3. HSV-2 infection increased the frequencies of α4β7high CD4+ T cells and this directly correlated with HSV-2 replication. A higher amount of inflammatory cytokines in vaginal fluids of the HSV-2 infected animals was similar to those found in the supernatants of the infected explants. Remarkably, the HSV-2-driven increase in the frequency of α4β7high CD4+ T cells directly correlated with SHIV replication in the HSV-2 infected tissues. Our results suggest that the HSV-2-driven increase in availability of CD4+ T cells and DCs that express high levels of α4β7 is associated with the increase in susceptibility to SHIV due to HSV-2. This may persists in absence of HSV-2 shedding. Hence, higher availability of α4β7 positive HIV target cells in the vaginal tissue may constitute a risk factor for HIV transmission.

Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.

LENUS (Irish Health Repository)

O'Shea, Donal

2012-02-01

BACKGROUND: Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independently associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects. METHODOLOGY AND PRINCIPAL FINDINGS: Clinical data and blood were collected from 40 severely obese subjects (BMI>40 kg\\/m(2)) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +\\/- 13% vs 42% +\\/-12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01). CONCLUSIONS\\/SIGNIFICANCE: Obese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.

Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.

LENUS (Irish Health Repository)

O'Shea, Donal

2010-01-01

BACKGROUND: Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independently associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects. METHODOLOGY AND PRINCIPAL FINDINGS: Clinical data and blood were collected from 40 severely obese subjects (BMI>40 kg\\/m(2)) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +\\/- 13% vs 42% +\\/-12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01). CONCLUSIONS\\/SIGNIFICANCE: Obese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.

Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.

Directory of Open Access Journals (Sweden)

Donal O'Shea

Full Text Available BACKGROUND: Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independently associated with increased risk of malignancy. Natural killer cells (NK are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects. METHODOLOGY AND PRINCIPAL FINDINGS: Clinical data and blood were collected from 40 severely obese subjects (BMI>40 kg/m(2 and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008. NK function was also significantly compromised in obese patients (30% +/- 13% vs 42% +/-12%, p = 0.04. Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001. NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01. Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002 and lean controls (p = 0.01. CONCLUSIONS/SIGNIFICANCE: Obese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.

An increasing, potentially measles-susceptible population over time after vaccination in Korea.

Science.gov (United States)

Kang, Hae Ji; Han, Young Woo; Kim, Su Jin; Kim, You-Jin; Kim, A-Reum; Kim, Joo Ae; Jung, Hee-Dong; Eom, Hye Eun; Park, Ok; Kim, Sung Soon

2017-07-24

In Korea, measles occurs mainly in infants measles infection. Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012). The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined. Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cultivar Variation in Hormonal Balance Is a Significant Determinant of Disease Susceptibility to Xanthomonas campestris pv. campestris in Brassica napus

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Md. Tabibul Islam

2017-12-01

Full Text Available This study aimed to directly elucidate cultivar variation in disease susceptibility and disease responses in relation to hormonal status in the interaction of Brassica napus cultivars and Xanthomonas campestris pv. campestris (Xcc, the causal agent of black rot disease. Fully expanded leaves of six B. napus cultivars (cvs. Capitol, Youngsan, Saturnin, Colosse, Tamra, and Mosa were inoculated with Xcc. At 14 days post-inoculation with Xcc, cultivar variation in susceptibility or resistance was interpreted with defense responses as estimated by redox status, defensive metabolites, and expression of phenylpropanoid synthesis-related genes in relation to endogenous hormonal status. Disease susceptibility of six cultivars was distinguished by necrotic lesions in the Xcc-inoculated leaves and characterized concurrently based on the higher increase in reactive oxygen species and lipid peroxidation. Among these cultivars, as the susceptibility was higher, the ratios of abscisic acid (ABA/jasmonic acid (JA and salicylic acid (SA/JA tended to increase with enhanced expression of SA signaling regulatory gene NPR1 and transcriptional factor TGA1 and antagonistic suppression of JA-regulated gene PDF 1.2. In the resistant cultivar (cv. Capitol, accumulation of defensive metabolites with enhanced expression of genes involved in flavonoids (chalcone synthase, proanthocyanidins (anthocyanidin reductase, and hydroxycinnamic acids (ferulate-5-hydroxylase biosynthesis and higher redox status were observed, whereas the opposite results were obtained for susceptible cultivars (cvs. Mosa and Tamra. These results clearly indicate that cultivar variation in susceptibility to infection by Xcc was determined by enhanced alteration of the SA/JA ratio, as a negative regulator of redox status and phenylpropanoid synthesis in the Brasica napus–Xcc pathosystem.

Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

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Knols Bart GJ

2010-06-01

Full Text Available Abstract Background Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously examined the effects of entomopathogenic fungi against adult mosquitoes, most application methods used cannot be readily deployed in the field. Because the fungi are biological organisms it is important to test potential field application methods that will not adversely affect them. The two objectives of this study were to investigate any differences in fungal susceptibility between an insecticide-resistant and insecticide-susceptible strain of Anopheles gambiae sensu stricto, and to test a potential field application method with respect to the viability and virulence of two fungal species Methods Pieces of white polyester netting were dipped in Metarhizium anisopliae ICIPE-30 or Beauveria bassiana IMI391510 mineral oil suspensions. These were kept at 27 ± 1°C, 80 ± 10% RH and the viability of the fungal conidia was recorded at different time points. Tube bioassays were used to infect insecticide-resistant (VKPER and insecticide-susceptible (SKK strains of An. gambiae s.s., and survival analysis was used to determine effects of mosquito strain, fungus species or time since fungal treatment of the net. Results The resistant VKPER strain was significantly more susceptible to fungal infection than the insecticide-susceptible SKK strain. Furthermore, B. bassiana was significantly more virulent than M. anisopliae for both mosquito strains, although this may be linked to the different viabilities of these fungal species. The viability of both fungal species decreased significantly one day after application onto polyester netting when compared to the viability of conidia remaining in suspension. Conclusions The insecticide

Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

Science.gov (United States)

2010-01-01

Background Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously examined the effects of entomopathogenic fungi against adult mosquitoes, most application methods used cannot be readily deployed in the field. Because the fungi are biological organisms it is important to test potential field application methods that will not adversely affect them. The two objectives of this study were to investigate any differences in fungal susceptibility between an insecticide-resistant and insecticide-susceptible strain of Anopheles gambiae sensu stricto, and to test a potential field application method with respect to the viability and virulence of two fungal species Methods Pieces of white polyester netting were dipped in Metarhizium anisopliae ICIPE-30 or Beauveria bassiana IMI391510 mineral oil suspensions. These were kept at 27 ± 1°C, 80 ± 10% RH and the viability of the fungal conidia was recorded at different time points. Tube bioassays were used to infect insecticide-resistant (VKPER) and insecticide-susceptible (SKK) strains of An. gambiae s.s., and survival analysis was used to determine effects of mosquito strain, fungus species or time since fungal treatment of the net. Results The resistant VKPER strain was significantly more susceptible to fungal infection than the insecticide-susceptible SKK strain. Furthermore, B. bassiana was significantly more virulent than M. anisopliae for both mosquito strains, although this may be linked to the different viabilities of these fungal species. The viability of both fungal species decreased significantly one day after application onto polyester netting when compared to the viability of conidia remaining in suspension. Conclusions The insecticide-resistant mosquito strain was susceptible

Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

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Kurt R. Stover

2017-12-01

Full Text Available The incidence of seizures increases with old age. Stroke, dementia and brain tumors are recognized risk factors for new-onset seizures in the aging populations and the incidence of these conditions also increased with age. Whether aging is associated with higher seizure susceptibility in the absence of the above pathologies remains unclear. We used classic kindling to explore this issue as the kindling model is highly reproducible and allows close monitoring of electrographic and motor seizure activities in individual animals. We kindled male young and aging mice (C57BL/6 strain, 2–3 and 18–22 months of age via daily hippocampal CA3 stimulation and monitored seizure activity via video and electroencephalographic recordings. The aging mice needed fewer stimuli to evoke stage-5 motor seizures and exhibited longer hippocampal afterdischarges and more frequent hippocampal spikes relative to the young mice, but afterdischarge thresholds and cumulative afterdischarge durations to stage 5 motor seizures were not different between the two age groups. While hippocampal injury and structural alterations at cellular and micro-circuitry levels remain to be examined in the kindled mice, our present observations suggest that susceptibility to hippocampal CA3 kindling seizures is increased with aging in male C57 black mice.

Susceptibility to hypoxia and breathing control changes after short-term cold exposures

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Lyudmila T. Kovtun

2013-08-01

Full Text Available Background . Hypoxia is the reduction of oxygen availability due to external or internal causes. There is large individual variability of response to hypoxia. Objective . The aim of this study was to define individual and typological features in susceptibility to hypoxia, its interrelation with hypoxic and hypercapnic ventilatory responses (HVR and HCVR, respectively and their changes after cold acclimation. Design . Twenty-four healthy men were tested. HVR and HCVR were measured by the rebreathing method during hypoxic and hypercapnic tests, respectively. These tests were carried out in thermoneutral conditions before and after cold exposures (nude, at 13°C, 2 h daily, for 10 days. Susceptibility to hypoxia (sSaO2 was determined as haemoglobin saturation slope during hypoxic test. Results . It was found that HVR and HCVR significantly increased and susceptibility to hypoxia (sSaO2 tended to decrease after cold acclimation. According to sSaO2 results before cold exposures, the group was divided into 3: Group 1 – with high susceptibility to hypoxia, Group 2 – medium and Group 3 – low susceptibility. Analysis of variances (MANOVA shows the key role of susceptibility to hypoxia and cold exposures and their interrelation. Posterior analysis (Fisher LSD showed significant difference in susceptibility to hypoxia between the groups prior to cold acclimation, while HVR and HCVR did not differ between the groups. After cold acclimation, susceptibility to hypoxia was not significantly different between the groups, while HCVR significantly increased in Groups 1 and 3, HVR significantly increased in Group 3 and HCVR, HVR did not change in Group 2. Conclusions . Short-term cold exposures caused an increase in functional reserves and improved oxygen supply of tissues in Group 1. Cold exposure hypoxia has caused energy loss in Group 3. Group 2 showed the most appropriate energy conservation reaction mode to cold exposures. No relation was found between

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

International Nuclear Information System (INIS)

Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

2011-01-01

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). - Highlights: →Arsenic metabolic genes might be associated with carotid atherosclerosis. → A case

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

2011-08-15

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

Seasonal fluctuation in susceptibility to insecticides within natural populations of Drosophila melanogaster. II. Features of genetic variation in susceptibility to organophosphate insecticides within natural populations of D. melanogaster.

Science.gov (United States)

Miyo, Takahiro; Oguma, Yuzuru; Charlesworth, Brian

2006-08-01

To elucidate genetic variation in susceptibility to organophosphate insecticides within natural populations of Drosophila melanogaster, we conducted an analysis of variance for mortality data sets of isofemale lines (10-286 lines) used in the previous studies. Susceptibility of isofemale lines to the three organophosphate insecticides was continuously distributed within each natural population, ranging from susceptible to resistant. Analysis of variance showed highly significant variation among isofemale lines in susceptibility to each insecticide for each natural population. Significant genetic variances in susceptibility to the three chemicals were estimated for the Katsunuma population; 0.0529-0.2722 for malathion, 0.0492-0.1603 for prothiophos, and 0.0469-0.1696 for fenitrothion. Contrary to the consistent seasonal tendency towards an increase in mean susceptibility in the fall, reported in the previous study, genetic variances in susceptibility to the three organophosphates did not change significantly in 1997 but tended to increase by 2- to 5-times in 1998. We tested whether both the observed situations, maintenance and increase in genetic variance in organophosphate resistance, can be generated under circumstances in which the levels of resistance to the three organophosphates tended to decrease, by conducting a simulation analysis, based on the hypothesis that resistant genotypes have lower fitnesses than susceptible ones under the density-independent condition. The simulation analysis generally explained the pattern in the mean susceptibility and genetic variances in susceptibility to the three organophosphates, observed in the Katsunuma population of D. melanogaster. It was suggested that the differences in the frequencies of resistance genes in the summer population could affect the patterns in genetic variance in organophosphate resistance in the fall population.

Complementation of a pKM101 derivative that decreases resistance to UV killing but increases susceptibility to mutagenesis

International Nuclear Information System (INIS)

Langer, P.J.; Perry, K.L.; Walker, G.C.

1985-01-01

The drug resistance plasmid pKM101 makes Escherichia coli resistant to the lethal effects of ultraviolet (UV) irradiation and more susceptible to mutagenesis by a variety of agents. The plasmid operon responsible for increasing mutagenesis has been termed mucAB (Mutagenesis, UV and chemical). The authors have isolated a derivative of pKM101 called pGW1975 which makes cells more sensitive to killing by UV but which retains the ability of pKM101 to increase susceptibility to methyl methanesulfonate (MMS) mutagenesis. pGW1975 increases UV mutagenesis less than pKM101 in a uvrA + strain but more than pKM101 in a uvrA - strain. muc - point and insertion mutants of pKM101 and pGW1975 complement to restore the plasmid-mediated: (i) ability to reactivate UV-irradiated phage, (ii) resistance to killing by UV, and (iii) level of susceptibility to UV mutagenesis. They have identified a 2.0 kb region of pKM101 which is responsible for the complementation and which maps counterclockwise of mucAB. (Auth)

Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection.

LENUS (Irish Health Repository)

O'Shea, D

2013-02-26

Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m(-2)), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.International Journal of Obesity advance online publication, 26 February 2013; doi:10.1038\\/ijo.2013.16.

Increased susceptibility to infectious salmon anemia virus (ISAv) in Lepeophtheirus salmonis – infected Atlantic salmon

Science.gov (United States)

The salmon louse and infectious salmon anemia virus (ISAv) are the two most significant pathogens of concern to the Atlantic salmon (Salmo salar) aquaculture industry. However, the interactions between sea lice and ISAv, as well as the impact of a prior sea lice infection on the susceptibility of th...

Linear and nonlinear optical susceptibilities in a laterally coupled quantum-dot–quantum-ring system

International Nuclear Information System (INIS)

Zeng, Zaiping; Garoufalis, Christos S.; Baskoutas, Sotirios

2014-01-01

Linear and nonlinear optical susceptibilities in a laterally coupled quantum-dot–quantum-ring system have been theoretically studied. In general, we find that the structure parameters of the coupled system significantly affect the optical susceptibilities. The enhancement of the coupling effects between the dot and ring is found to increase considerably the optical susceptibilities and redshift drastically the transition energies. Comparing to the linear susceptibility, the nonlinear optical susceptibility is found to be more sensitive to the variation of the structure parameters. A comprehensive analysis of the electron probability density movement with respect to the modification of the structure parameters is provided, which offers a unique perspective of the ground-state localization. - Highlights: • Optical susceptibilities in a quantum-dot–quantum-ring system are studied. • The structure parameters significantly affect the optical susceptibilities. • The enhancement of the coupling effects increases the optical susceptibilities. • The nonlinear susceptibility is more sensitive to the change in structure parameters. • A comprehensive analysis of the electron probability density movement is provided

Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis.

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Catherine M Miller

Full Text Available Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis.Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice.Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation.

Aging increases the susceptibility to motor memory interference and reduces off-line gains in motor skill learning

DEFF Research Database (Denmark)

Roig, Marc; Ritterband-Rosenbaum, Anina; Jensen, Jesper Lundbye

2014-01-01

Declines in the ability to learn motor skills in older adults are commonly attributed to deficits in the encoding of sensorimotor information during motor practice. We investigated whether aging also impairs motor memory consolidation by assessing the susceptibility to memory interference and off...... greater susceptibility to memory interference and no off-line gains in motor skill learning. Performing B produced memory interference and reduced off-line gains only in the older group. However, older adults also showed deficits in memory consolidation independent of the interfering effects of B. Age......-related declines in motor skill learning are not produced exclusively by deficits in the encoding of sensorimotor information during practice. Aging also increases the susceptibility to memory interference and reduces off-line gains in motor skill learning after practice....

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

Science.gov (United States)

Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

2015-08-15

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

The histone deacetylase inhibitor vorinostat (SAHA) increases the susceptibility of uninfected CD4+ T cells to HIV by increasing the kinetics and efficiency of postentry viral events.

Science.gov (United States)

Lucera, Mark B; Tilton, Carisa A; Mao, Hongxia; Dobrowolski, Curtis; Tabler, Caroline O; Haqqani, Aiman A; Karn, Jonathan; Tilton, John C

2014-09-01

Latently infected cells remain a primary barrier to eradication of HIV-1. Over the past decade, a better understanding of the molecular mechanisms by which latency is established and maintained has led to the discovery of a number of compounds that selectively reactivate latent proviruses without inducing polyclonal T cell activation. Recently, the histone deacetylase (HDAC) inhibitor vorinostat has been demonstrated to induce HIV transcription from latently infected cells when administered to patients. While vorinostat will be given in the context of antiretroviral therapy (ART), infection of new cells by induced virus remains a clinical concern. Here, we demonstrate that vorinostat significantly increases the susceptibility of CD4(+) T cells to infection by HIV in a dose- and time-dependent manner that is independent of receptor and coreceptor usage. Vorinostat does not enhance viral fusion with cells but rather enhances the kinetics and efficiency of postentry viral events, including reverse transcription, nuclear import, and integration, and enhances viral production in a spreading-infection assay. Selective inhibition of the cytoplasmic class IIb HDAC6 with tubacin recapitulated the effect of vorinostat. These findings reveal a previously unknown cytoplasmic effect of HDAC inhibitors promoting productive infection of CD4(+) T cells that is distinct from their well-characterized effects on nuclear histone acetylation and long-terminal-repeat (LTR) transcription. Our results indicate that careful monitoring of patients and ART intensification are warranted during vorinostat treatment and indicate that HDAC inhibitors that selectively target nuclear class I HDACs could reactivate latent HIV without increasing the susceptibility of uninfected cells to HIV. HDAC inhibitors, particularly vorinostat, are currently being investigated clinically as part of a "shock-and-kill" strategy to purge latent reservoirs of HIV. We demonstrate here that vorinostat increases the

Tobacco Marketing, E-cigarette Susceptibility, and Perceptions among Adults.

Science.gov (United States)

Nicksic, Nicole E; Snell, L Morgan; Rudy, Alyssa K; Cobb, Caroline O; Barnes, Andrew J

2017-09-01

Understanding the impact of tobacco marketing on e-cigarette (EC) susceptibility and perceptions is essential to inform efforts to mitigate tobacco product burden on public health. Data were collected online in 2016 from 634 conventional cigarette (CC) smokers and 393 non-smokers using a convenience sample from Amazon Mechanical Turk. Logistic regression models, stratified by smoking status and adjusted for socio-demographics, examined the relationship among tobacco advertisements and coupons, EC and CC susceptibility, and EC perceptions. Among non-smokers, increased exposure to tobacco advertising and receiving tobacco coupons was significantly related to measures of EC and CC susceptibility (p marketing reduce EC use by decreasing susceptibility.

Future warmer seas: increased stress and susceptibility to grazing in seedlings of a marine habitat-forming species.

Science.gov (United States)

Hernán, Gema; Ortega, María J; Gándara, Alberto M; Castejón, Inés; Terrados, Jorge; Tomas, Fiona

2017-11-01

Increases in seawater temperature are expected to have negative consequences for marine organisms. Beyond individual effects, species-specific differences in thermal tolerance are predicted to modify species interactions and increase the strength of top-down effects, particularly in plant-herbivore interactions. Shifts in trophic interactions will be especially important when affecting habitat-forming species such as seagrasses, as the consequences on their abundance will cascade throughout the food web. Seagrasses are a major component of coastal ecosystems offering important ecosystem services, but are threatened by multiple anthropogenic stressors, including warming. The mechanistic understanding of seagrass responses to warming at multiple scales of organization remains largely unexplored, especially in early-life stages such as seedlings. Yet, these early-life stages are critical for seagrass expansion processes and adaptation to climate change. In this study, we determined the effects of a 3 month experimental exposure to present and predicted mean summer SST of the Mediterranean Sea (25°C, 27°C, and 29°C) on the photophysiology, size, and ecology (i.e., plant-herbivore interactions) of seedlings of the seagrass Posidonia oceanica. Warming resulted in increased mortality, leaf necrosis, and respiration as well as lower carbohydrate reserves in the seed, the main storage organ in seedlings. Aboveground biomass and root growth were also limited with warming, which could hamper seedling establishment success. Furthermore, warming increased the susceptibility to consumption by grazers, likely due to lower leaf fiber content and thickness. Our results indicate that warming will negatively affect seagrass seedlings through multiple direct and indirect pathways: increased stress, reduced establishment potential, lower storage of carbohydrate reserves, and increased susceptibly to consumption. This work provides a significant step forward in understanding the

Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

Science.gov (United States)

DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

2015-02-01

Epilepsy is a family of brain disorders with a largely unknown etiology and high percentage of pharmacoresistance. The clinical manifestations of epilepsy are seizures, which originate from aberrant neuronal synchronization and hyperexcitability. Reactive astrocytosis, a hallmark of the epileptic tissue, develops into loss-of-function of glutamine synthetase, impairment of glutamate-glutamine cycle and increase in extracellular and astrocytic glutamate concentration. Here, we argue that chronically elevated intracellular glutamate level in astrocytes is instrumental to alterations in the metabolism of glycogen and leads to the synthesis of polyglucosans. Unaccessibility of glycogen-degrading enzymes to these insoluble molecules compromises the glycogenolysis-dependent reuptake of extracellular K(+) by astrocytes, thereby leading to increased extracellular K(+) and associated membrane depolarization. Based on current knowledge, we propose that the deterioration in structural homogeneity of glycogen particles is relevant to disruption of brain K(+) homeostasis and increased susceptibility to seizures in epilepsy.

Age-Associated Changes in Estrogen Receptor Ratios Correlate with Increased Female Susceptibility to Coxsackievirus B3-Induced Myocarditis

Directory of Open Access Journals (Sweden)

Andreas Koenig

2017-11-01

Full Text Available Sexual bias is a hallmark in various diseases. This review evaluates sexual dimorphism in clinical and experimental coxsackievirus B3 (CVB3 myocarditis, and how sex bias in the experimental disease changes with increased age. Coxsackieviruses are major causes of viral myocarditis, an inflammation of the heart muscle, which is more frequent and severe in men than women. Young male mice infected with CVB3 develop heart-specific autoimmunity and severe myocarditis. Females infected during estrus (high estradiol develop T-regulatory cells and when infected during diestrus (low estradiol develop autoimmunity similar to males. During estrus, protection depends on estrogen receptor alpha (ERα, which promotes type I interferon, activation of natural killer/natural killer T cells and suppressor cell responses. Estrogen receptor beta has opposing effects to ERα and supports pro-inflammatory immunity. However, the sexual dimorphism of the disease is significantly ameliorated in aged animals when old females become as susceptible as males. This correlates to a selective loss of the ERα that is required for immunosuppression. Therefore, sex-associated hormones control susceptibility in the virus-mediated disease, but their impact can alter with the age and physiological stage of the individual.

Global stability of a susceptible-infected-susceptible epidemic model on networks with individual awareness

International Nuclear Information System (INIS)

Li Ke-Zan; Xu Zhong-Pu; Zhu Guang-Hu; Ding Yong

2014-01-01

Recent research results indicate that individual awareness can play an important influence on epidemic spreading in networks. By local stability analysis, a significant conclusion is that the embedded awareness in an epidemic network can increase its epidemic threshold. In this paper, by using limit theory and dynamical system theory, we further give global stability analysis of a susceptible-infected-susceptible (SIS) epidemic model on networks with awareness. Results show that the obtained epidemic threshold is also a global stability condition for its endemic equilibrium, which implies the embedded awareness can enhance the epidemic threshold globally. Some numerical examples are presented to verify the theoretical results. (interdisciplinary physics and related areas of science and technology)

Identification of highly susceptible individuals in complex networks

Science.gov (United States)

Tang, Shaoting; Teng, Xian; Pei, Sen; Yan, Shu; Zheng, Zhiming

2015-08-01

Identifying highly susceptible individuals in spreading processes is of great significance in controlling outbreaks. In this paper, we explore the susceptibility of people in susceptible-infectious-recovered (SIR) and rumor spreading dynamics. We first study the impact of community structure on people's susceptibility. Although the community structure can reduce the number of infected people for same infection rate, it will not significantly affect nodes' susceptibility. We find the susceptibility of individuals is sensitive to the choice of spreading dynamics. For SIR spreading, since the susceptibility is highly correlated to nodes' influence, the topological indicator k-shell can better identify highly susceptible individuals, outperforming degree, betweenness centrality and PageRank. In contrast, in rumor spreading model, where nodes' susceptibility and influence have no clear correlation, degree performs the best among considered topological measures. Our finding highlights the significance of both topological features and spreading mechanisms in identifying highly susceptible population.

Gas revenue increasingly significant

International Nuclear Information System (INIS)

Megill, R.E.

1991-01-01

This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

Identification of Variants in Breast Cancer Susceptibility Genes and Determination of Functional and Clinical Significance of Novel Mutations

Science.gov (United States)

2014-10-01

to cause other cancer susceptibility (CDKN2A, MLH1, MSH2, MSH6, PMS2 ); 3) genes known or postulated to be moderate penetrance cancer susceptibility...susceptibility (CDKN2A, MLH1, MSH2, MSH6, PMS2 ); 3) genes known or postulated to be moderate penetrance cancer susceptibility genes (ATM, BARD1, BRIP1...three patients in TP53 and 12 patients in MLH1, MSH2, MSH6, or PMS2 ; no VUSs were found in CDH1, CDKN2A, STK11 or PTEN. Three additional patients each

Evaluation of the routine antimicrobial susceptibility testing results of clinically significant anaerobic bacteria in a Slovenian tertiary-care hospital in 2015.

Science.gov (United States)

Jeverica, Samo; Kolenc, Urša; Mueller-Premru, Manica; Papst, Lea

2017-10-01

The aim of our study was to determined antimicrobial susceptibility profiles of 2673 clinically significant anaerobic bacteria belonging to the major genera, isolated in 2015 in a large tertiary-care hospital in Slovenia. The species identification was performed by MALDI-TOF mass spectrometry. Antimicrobial susceptibility was determined immediately at the isolation of the strains against: penicillin, co-amoxiclav, imipenem, clindamycin and metronidazole, using gradient diffusion methodology and EUCAST breakpoints. The most frequent anaerobes were Bacteroides fragilis group with 31% (n = 817), Gram positive anaerobic cocci (GPACs) with 22% (n = 589), Prevotella with 14% (n = 313) and Propionibacterium with 8% (n = 225). Metronidazole has retained full activity (100%) against all groups of anaerobic bacteria intrinsically susceptible to it. Co-amoxiclav and imipenem were active against most tested anaerobes with zero or low resistance rates. However, observed resistance to co-amoxiclav (8%) and imipenem (1%) is worrying especially among B. fragilis group isolates. High overall resistance (23%) to clindamycin was detected in our study and was highest among the genera Prevotella, Bacteroides, Parabacteroides, GPACs and Clostridium. Routine testing of antimicrobial susceptibility of clinically relevant anaerobic bacteria is feasible and provides good surveillance data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

Energy Technology Data Exchange (ETDEWEB)

Li, Jing [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology & Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-NancyUniversité, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

2015-05-01

Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

International Nuclear Information System (INIS)

Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2015-01-01

Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility

Directory of Open Access Journals (Sweden)

Rodrigo de Carvalho Santana

2016-04-01

Full Text Available Abstract: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260. From 2007-2013, this percentage was 18.1% (965/5331. Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

Science.gov (United States)

Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

2014-01-01

Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer's disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels.

Science.gov (United States)

Ruiz, Henry H; Chi, Tiffany; Shin, Andrew C; Lindtner, Claudia; Hsieh, Wilson; Ehrlich, Michelle; Gandy, Sam; Buettner, Christoph

2016-08-01

Epidemiologic studies have demonstrated an association between diabetes and dementia. Insulin signaling within the brain, in particular within the hypothalamus regulates carbohydrate, lipid, and branched chain amino acid (BCAA) metabolism in peripheral organs such as the liver and adipose tissue. We hypothesized that cerebral amyloidosis impairs central nervous system control of metabolism through disruption of insulin signaling in the hypothalamus, which dysregulates glucose and BCAA homeostasis resulting in increased susceptibility to diabetes. We examined whether APP/PS1 mice exhibit increased susceptibility to aging or high-fat diet (HFD)-induced metabolic impairment using metabolic phenotyping and insulin-signaling studies. APP/PS1 mice were more susceptible to high-fat feeding and aging-induced metabolic dysregulation including disrupted BCAA homeostasis and exhibited impaired hypothalamic insulin signaling. Our data suggest that AD pathology increases susceptibility to diabetes due to impaired hypothalamic insulin signaling, and that plasma BCAA levels could serve as a biomarker of hypothalamic insulin action in patients with AD. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Magnetic susceptibility measurements on Bi - Sn alloys

International Nuclear Information System (INIS)

Mustaffa bin Haji Abdullah

1985-01-01

Magnetic susceptibility measurements on eight samples of tin-rich and three samples of bismuth-rich Bi-Sn alloys were made from 85K to 300K by Faraday's method. The susceptibilities of the eight tin-rich samples are positive and greater than the susceptibility of pure tin. The values are approximately constant at low temperatures but decreasing a little bit with increasing temperature. This result is interpreted as due to the predominant contribution of the Pauli spin paramagnetic susceptibility. A small decrease in susceptibility with temperature is interpreted as due to the effect of the second order term in the expression for spin paramagnetic susceptibility. The fluctuation of the susceptibility for alloys of different composition is interpreted as due to the effect of the density of states at the Fermi levels. The three samples of bismuth-rich alloys show a transition to diamagnetic property, where the diamagnetism is increased with temperature. This result is predominant and due to the diamagnetic contribution from the ions. The increase in susceptibility with temperature is interpreted as due to an increase in the effective radii of the ions due to thermal expansion. (author)

Reduced salinity increases susceptibility of zooxanthellate jellyfish to herbicide toxicity during a simulated rainfall event

International Nuclear Information System (INIS)

Klein, Shannon G.; Pitt, Kylie A.; Carroll, Anthony R.

2016-01-01

Accurately predicting how marine biota are likely to respond to changing ocean conditions requires accurate simulation of interacting stressors, exposure regimes and recovery periods. Jellyfish populations have increased in some parts of the world and, despite few direct empirical tests, are hypothesised to be increasing because they are robust to a range of environmental stressors. Here, we investigated the effects of contaminated runoff on a zooxanthellate jellyfish by exposing juvenile Cassiopea sp. medusae to a photosystem II (PSII) herbicide, atrazine and reduced salinity conditions that occur following rainfall. Four levels of atrazine (0ngL"−"1, 10ngL"−"1, 2μgL"−"1, 20μgL"−"1) and three levels of salinity (35 ppt, 25 ppt, 17 ppt) were varied, mimicking the timeline of light, moderate and heavy rainfall events. Normal conditions were then slowly re-established over four days to mimic the recovery of the ecosystem post-rain and the experiment continued for a further 7 days to observe potential recovery of the medusae. Pulse-amplitude modulated (PAM) chlorophyll fluorescence, growth and bell contraction rates of medusae were measured. Medusae exposed to the combination of high atrazine and lowest salinity died. After 3 days of exposure, bell contraction rates were reduced by 88% and medusae were 16% smaller in the lowest salinity treatments. By Day 5 of the experiment, all medusae that survived the initial pulse event began to recover quickly. Although atrazine decreased YII under normal salinity conditions, YII was further reduced when medusae were exposed to both low salinity and atrazine simultaneously. Atrazine breakdown products were more concentrated in jellyfish tissues than atrazine at the end of the experiment, suggesting that although bioaccumulation occurred, atrazine was metabolised. Our results suggest that reduced salinity may increase the susceptibility of medusae to herbicide exposure during heavy rainfall events. - Highlights: �

The association of folate pathway and DNA repair polymorphisms with susceptibility to childhood acute lymphoblastic leukemia.

Science.gov (United States)

Goričar, Katja; Erčulj, Nina; Faganel Kotnik, Barbara; Debeljak, Maruša; Hovnik, Tinka; Jazbec, Janez; Dolžan, Vita

2015-05-15

Genetic factors may play an important role in susceptibility to childhood acute lymphoblastic leukemia (ALL). The aim of our study was to evaluate the associations of genetic polymorphisms in folate pathway and DNA repair genes with susceptibility to ALL. In total, 121 children with ALL and 184 unrelated healthy controls of Slovenian origin were genotyped for 14 polymorphisms in seven genes of folate pathway, base excision repair and homologous recombination repair (TYMS, MTHFR, OGG1, XRCC1, NBN, RAD51, and XRCC3). In addition, the exon 6 of NBN was screened for the presence of mutations using denaturing high performance liquid chromatography. Twelve polymorphisms were in Hardy-Weinberg equilibrium in controls and their genotype frequencies were in agreement with those reported in other Caucasian populations. Among the investigated polymorphisms and mutations, NBN Glu185Gln significantly decreased susceptibility to B-cell ALL (p=0.037), while TYMS 3R allele decreased susceptibility to T-cell ALL (p=0.011). Moreover, significantly decreased susceptibility to ALL was observed for MTHFR TA (p=0.030) and RAD51 GTT haplotypes (p=0.016). Susceptibility to ALL increased with the increasing number of risk alleles (ptrend=0.007). We also observed significant influence of hOGG-RAD51 and NBN-RAD51 interactions on susceptibility to ALL. Our results suggest that combination of several polymorphisms in DNA repair and folate pathways may significantly affect susceptibility to childhood ALL. Copyright © 2015 Elsevier B.V. All rights reserved.

Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility

DEFF Research Database (Denmark)

Fedulov, Alexey V; Leme, Adriana; Yang, Zhiping

2008-01-01

Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles...... inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to "inert" TiO(2......). In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO(2) and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO(2). Neonates of mothers exposed to TiO(2) (and DEP, but not PBS) developed AHR and AI, indicating that pregnancy...

Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice.

Science.gov (United States)

Taylor, Andrew K; Cao, Weiping; Vora, Keyur P; De La Cruz, Juan; Shieh, Wun-Ju; Zaki, Sherif R; Katz, Jacqueline M; Sambhara, Suryaprakash; Gangappa, Shivaprakash

2013-02-01

Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the relevance of PEM as a risk factor for influenza. We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model. We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge. Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.

A standing posture is associated with increased susceptibility to the sound-induced flash illusion in fall-prone older adults.

Science.gov (United States)

Stapleton, John; Setti, Annalisa; Doheny, Emer P; Kenny, Rose Anne; Newell, Fiona N

2014-02-01

Recent research has provided evidence suggesting a link between inefficient processing of multisensory information and incidence of falling in older adults. Specifically, Setti et al. (Exp Brain Res 209:375-384, 2011) reported that older adults with a history of falling were more susceptible than their healthy, age-matched counterparts to the sound-induced flash illusion. Here, we investigated whether balance control in fall-prone older adults was directly associated with multisensory integration by testing susceptibility to the illusion under two postural conditions: sitting and standing. Whilst standing, fall-prone older adults had a greater body sway than the age-matched healthy older adults and their body sway increased when presented with the audio-visual illusory but not the audio-visual congruent conditions. We also found an increase in susceptibility to the sound-induced flash illusion during standing relative to sitting for fall-prone older adults only. Importantly, no performance differences were found across groups in either the unisensory or non-illusory multisensory conditions across the two postures. These results suggest an important link between multisensory integration and balance control in older adults and have important implications for understanding why some older adults are prone to falling.

SCC susceptibility evaluation of plastic deformed austenitic stainless steels

Energy Technology Data Exchange (ETDEWEB)

Kaneshima, Yoshiari; Totsuka, Nobuo; Arioka, Koji [Inst. of Nuclear Safety System Inc., Mihama, Fukui (Japan)

2002-09-01

Slow strain rate temperature (SSRT) tests were carried out to evaluate the SCC susceptibility of deformed SUS316 stainless steel in simulated primary water of pressurized water reactor (PWR). The influence of material hardness and temperature on SCC susceptibility was studied. From these tests following results were obtained. (1) Both of the total SCC and IGSCC susceptibilities increased as the hardness of deformed specimens increased. Especially over 250{approx}300HV area, this tendency remarkably increased. (2) The reduction ratio showed a plateau under 300HV area. However, over 300HV area, it decreased remarkably as the hardness increased, that is, the SCC susceptibility remarkably increased. (3) Based on the SSRT test results conducted at 320, 340 and 360degC, the total SCC susceptibility dependence on temperature was small and the IGSCC susceptibility was dependent on the temperature. From these results, the TGSCC susceptibility dependence on temperature was also small. The activation energy of total SCC and IGSCC susceptibility were calculated. (author)

Characterization of a JAZ7 activation-tagged Arabidopsis mutant with increased susceptibility to the fungal pathogen Fusarium oxysporum

Science.gov (United States)

Thatcher, Louise F.; Cevik, Volkan; Grant, Murray; Zhai, Bing; Jones, Jonathan D.G.; Manners, John M.; Kazan, Kemal

2016-01-01

In Arabidopsis, jasmonate (JA)-signaling plays a key role in mediating Fusarium oxysporum disease outcome. However, the roles of JASMONATE ZIM-domain (JAZ) proteins that repress JA-signaling have not been characterized in host resistance or susceptibility to this pathogen. Here, we found most JAZ genes are induced following F. oxysporum challenge, and screening T-DNA insertion lines in Arabidopsis JAZ family members identified a highly disease-susceptible JAZ7 mutant (jaz7-1D). This mutant exhibited constitutive JAZ7 expression and conferred increased JA-sensitivity, suggesting activation of JA-signaling. Unlike jaz7 loss-of-function alleles, jaz7-1D also had enhanced JA-responsive gene expression, altered development and increased susceptibility to the bacterial pathogen Pst DC3000 that also disrupts host JA-responses. We also demonstrate that JAZ7 interacts with transcription factors functioning as activators (MYC3, MYC4) or repressors (JAM1) of JA-signaling and contains a functional EAR repressor motif mediating transcriptional repression via the co-repressor TOPLESS (TPL). We propose through direct TPL recruitment, in wild-type plants JAZ7 functions as a repressor within the JA-response network and that in jaz7-1D plants, misregulated ectopic JAZ7 expression hyper-activates JA-signaling in part by disturbing finely-tuned COI1-JAZ-TPL-TF complexes. PMID:26896849

Wound-induced pectin methylesterases enhance banana (Musa spp. AAA) susceptibility to Fusarium oxysporum f. sp. cubense.

Science.gov (United States)

Ma, Li; Jiang, Shuang; Lin, Guimei; Cai, Jianghua; Ye, Xiaoxi; Chen, Houbin; Li, Minhui; Li, Huaping; Takác, Tomás; Samaj, Jozef; Xu, Chunxiang

2013-05-01

Recent studies suggest that plant pectin methylesterases (PMEs) are directly involved in plant defence besides their roles in plant development. However, the molecular mechanisms of PME action on pectins are not well understood. In order to understand how PMEs modify pectins during banana (Musa spp.)-Fusarium interaction, the expression and enzyme activities of PMEs in two banana cultivars, highly resistant or susceptible to Fusarium, were compared with each other. Furthermore, the spatial distribution of PMEs and their effect on pectin methylesterification of 10 individual homogalacturonan (HG) epitopes with different degrees of methylesterification (DMs) were also examined. The results showed that, before pathogen treatment, the resistant cultivar displayed higher PME activity than the susceptible cultivar, corresponding well to the lower level of pectin DM. A significant increase in PME expression and activity and a decrease in pectin DM were observed in the susceptible cultivar but not in the resistant cultivar when plants were wounded, which was necessary for successful infection. With the increase of PME in the wounded susceptible cultivar, the JIM5 antigen (low methyestrified HGs) increased. Forty-eight hours after pathogen infection, the PME activity and expression in the susceptible cultivar were higher than those in the resistant cultivar, while the DM was lower. In conclusion, the resistant and the susceptible cultivars differ significantly in their response to wounding. Increased PMEs and thereafter decreased DMs acompanied by increased low methylesterified HGs in the root vascular cylinder appear to play a key role in determination of banana susceptibility to Fusarium.

Thermomechanical processing of 5083 aluminum to increase strength without increasing susceptibility to stress corrosion cracking

International Nuclear Information System (INIS)

Edstrom, C.M.; Blakeslee, J.J.

1980-01-01

5083 aluminium with 25% cold work must be processed above 215 0 C or below 70 0 C to avoid forming continuous precipitate in the grain boundaries which makes the material susceptible to stress corrosion cracking. Time at temperature above 215 0 C should be held to minimum (less than 30 min) to retain some strength from the 25% cold work

Taxonomy and antifungal susceptibility of clinically important Rasamsonia species

DEFF Research Database (Denmark)

Houbraken, J.; Giraud, S.; Meijer, M.

2013-01-01

In recent years, Geosmithia argillacea has been increasingly reported in humans and animals and can be considered an emerging pathogen. The taxonomy of Geosmithia was recently studied, and Geosmithia argillacea and related species were transferred to the new genus Rasamsonia. The diversity among...... reported clinical isolates from animal or human patients. Susceptibility tests showed that the antifungal susceptibility profiles of the four members of the R. argillacea complex are similar, and caspofungin showed significant activity in vitro, followed by amphotericin B and posaconazole. Voriconazole...

antimicrobial susceptibility pattern of Salmonella species

African Journals Online (AJOL)

user

ABSTRACT. Treatment of enteric fever is increasingly becoming very challenging due to the increasing wave of antibiotic resistance. This study is a review of the contemporary antimicrobial susceptibility pattern of. Salmonella species. The antimicrobial susceptibility pattern of Salmonella species to a wide range of.

Immunological bases of increased susceptibility to invasive nontyphoidal Salmonella infection in children with malaria and anaemia.

Science.gov (United States)

Nyirenda, Tonney S; Mandala, Wilson L; Gordon, Melita A; Mastroeni, Pietro

2017-12-15

Malaria and anaemia are key underlying factors for iNTS disease in African children. Knowledge of clinical and epidemiological risk-factors for iNTS disease has not been paralleled by an in-depth knowledge of the immunobiology of the disease. Herein, we review human and animal studies on mechanisms of increased susceptibility to iNTS in children. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis

Science.gov (United States)

Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

2016-01-01

In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia’s gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

Entitlement Can Both Decrease and Increase Consumer Susceptibility to Social Influence

NARCIS (Netherlands)

van der Heide, Martine; Fennis, Bob; van Ittersum, Koert; Trampe, Debra; Diehl, Kristin; Yoon, Carolyn

2015-01-01

Two studies indicate that entitlement—a sense that one deserves special treatment and is exempt from normal social demands—can both buffer and boost consumers’ proneness to social influence. Specifically, Study 1 shows that entitlement reduces susceptibility to consistency appeals. Study 2, however,

Dynamic insecticide susceptibility changes in Florida populations of Diaphorina citri (Hemiptera: Psyllidae).

Science.gov (United States)

Tiwari, Siddharth; Killiny, Nabil; Stelinski, Lukasz L

2013-02-01

Five field populations of Diaphorina citri Kuwayama from various regions of Florida were evaluated in 2011 for resistance to commonly used insecticides. Three diagnostic doses (LD50, LD75, and LD95), developed in 2009 using a laboratory susceptible population, were used to measure changes in susceptibility levels of field-collected populations as compared with a susceptible laboratory population. Further reductions in the susceptibility levels of D. citri to chlorpyriphos and fenpropathrin were determined, compared with results obtained in 2010. Mean percent mortality obtained from all five locations was significantly lower than observed with the laboratory susceptible population for all insecticides tested. Previously, expression of five CYP4 genes was implicated in contributing to insecticide metabolism in D. citri. In the current study, we compared the relative expression of these five CYP4 genes and their associated levels of protein expression among field-collected and laboratory susceptible populations. Expression of all CYP4 genes investigated was higher in field-collected populations when normalized against the laboratory susceptible population. There was an increased signal of a band corresponding to a 45 kDa protein in four of the five field populations as measured by the Western blot assay, which suggests increased production of cytochrome P450 enzymes. The current results indicate that insecticide resistance continues to increase in Florida populations ofD. citri, particularly to chlorpyriphos and fenpropathrin. However, there was no further decrease in susceptibility of Florida populations of D. citri to neonicotinoid insecticides in 2011 as compared with previous years.

Characteristics of Japanese inflammatory bowel disease susceptibility loci.

Science.gov (United States)

Arimura, Yoshiaki; Isshiki, Hiroyuki; Onodera, Kei; Nagaishi, Kanna; Yamashita, Kentaro; Sonoda, Tomoko; Matsumoto, Takayuki; Takahashi, Atsushi; Takazoe, Masakazu; Yamazaki, Keiko; Kubo, Michiaki; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

2014-08-01

There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD. For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn's disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls. We confirmed that the NKX2-3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24). Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

Science.gov (United States)

Laddha, Naresh C.; Dwivedi, Mitesh; Begum, Rasheedunnisa

2012-01-01

Abstract Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates

Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.

Directory of Open Access Journals (Sweden)

Jingbo Liu

Full Text Available It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR increases the susceptibility of offspring to high-fat (HF diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW, and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA, and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH and glucose-6-phosphate dehydrogenase (G6PD. These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.

Intrauterine Growth Retardation Increases the Susceptibility of Pigs to High-Fat Diet-Induced Mitochondrial Dysfunction in Skeletal Muscle

Science.gov (United States)

Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

2012-01-01

It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. PMID:22523560

A Strong Immune Response in Young Adult Honeybees Masks Their Increased Susceptibility to Infection Compared to Older Bees

Science.gov (United States)

Bull, James C.; Ryabov, Eugene V.; Prince, Gill; Mead, Andrew; Zhang, Cunjin; Baxter, Laura A.; Pell, Judith K.; Osborne, Juliet L.; Chandler, Dave

2012-01-01

Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance (“housekeeping”) tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger “house” bees differ in susceptibility to infection. We coupled an infection bioassay with a functional analysis of gene expression in individual bees using a whole genome microarray. Forager bees treated with the entomopathogenic fungus Metarhizium anisopliae s.l. survived for significantly longer than house bees. This was concomitant with substantial differences in gene expression including genes associated with immune function. In house bees, infection was associated with differential expression of 35 candidate immune genes contrasted with differential expression of only two candidate immune genes in forager bees. For control bees (i.e. not treated with M. anisopliae) the development from the house to the forager stage was associated with differential expression of 49 candidate immune genes, including up-regulation of the antimicrobial peptide gene abaecin, plus major components of the Toll pathway, serine proteases, and serpins. We infer that reduced pathogen susceptibility in forager bees was associated with age-related activation of specific immune system pathways. Our findings contrast with the view that the immunocompetence in social insects declines with the onset of foraging as a result of a trade-off in the allocation of resources for foraging. The up-regulation of immune-related genes in young adult bees in response to M. anisopliae infection was an indicator of disease susceptibility; this also challenges previous research in social insects, in which an elevated immune status has been used as a marker of increased disease

Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

Directory of Open Access Journals (Sweden)

Peris Mumbi Munyaka

Full Text Available Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota.Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted.ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels.The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

Science.gov (United States)

Munyaka, Peris Mumbi; Eissa, N; Bernstein, Charles Noah; Khafipour, Ehsan; Ghia, Jean-Eric

2015-01-01

Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

Sleep disruption increases seizure susceptibility: Behavioral and EEG evaluation of an experimental model of sleep apnea.

Science.gov (United States)

Hrnčić, Dragan; Grubač, Željko; Rašić-Marković, Aleksandra; Šutulović, Nikola; Šušić, Veselinka; Bjekić-Macut, Jelica; Stanojlović, Olivera

2016-03-01

Sleep disruption accompanies sleep apnea as one of its major symptoms. Obstructive sleep apnea is particularly common in patients with refractory epilepsy, but causing factors underlying this are far from being resolved. Therefore, translational studies regarding this issue are important. Our aim was to investigate the effects of sleep disruption on seizure susceptibility of rats using experimental model of lindane-induced refractory seizures. Sleep disruption in male Wistar rats with implanted EEG electrodes was achieved by treadmill method (belt speed set on 0.02 m/s for working and 0.00 m/s for stop mode, respectively). Animals were assigned to experimental conditions lasting 6h: 1) sleep disruption (sleep interrupted, SI; 30s working and 90 s stop mode every 2 min; 180 cycles in total); 2) activity control (AC, 10 min working and 30 min stop mode, 9 cycles in total); 3) treadmill chamber control (TC, only stop mode). Afterwards, the animals were intraperitoneally treated with lindane (L, 4 mg/kg, SI+L, AC+L and TC+L groups) or dimethylsulfoxide (DMSO, SIc, ACc and TCc groups). Convulsive behavior was assessed by seizure incidence, latency time to first seizure, and its severity during 30 min after drug administration. Number and duration of ictal periods were determined in recorded EEGs. Incidence and severity of lindane-induced seizures were significantly increased, latency time significantly decreased in animals undergoing sleep disruption (SI+L group) compared with the animals from TC+L. Seizure latency was also significantly decreased in SI+L compared to AC+L groups. Number of ictal periods were increased and duration of it presented tendency to increase in SI+L comparing to AC+L. No convulsive signs were observed in TCc, ACc and SIc groups, as well as no ictal periods in EEG. These results indicate sleep disruption facilitates induction of epileptic activity in rodent model of lindane-epilepsy enabling translational research of this phenomenon. Copyright �

The increased susceptibility of hematopoietic stem cells to Friend leukemia virus in the repopulating period

International Nuclear Information System (INIS)

Hirashima, Kunitake; Kumatori, Toshiyuki

1977-01-01

The present study considers two fundamental problems of leukemia and stem cells: (1) whether the target cells for malignant transformation of Friend leukemia virus (FV) are the pluripotential stem cells; (2) whether the susceptibility of the target cell is changeable depending on the proliferating state of the cell. In the experiments, inbred 8- to 12-week-old C3H/He and BC3Fl hybrid mice were used. As target cells for FV, two candidate cell populations should be considered. These are the pluripotential stem cells expressed as CFUs and the committed stem cells expressed as erythropoietin-responsive cells (ERC). According to our preliminary experiments on the recovery patterns of CFUs or ERC, after a single 150 rads X-irradiation (X) or administration of 215 mg/kg of cyclophosphamide (CY), it was clear that the repopulation of CFUs was quite different from that of ERC. The target cells for FV-induced transformation are the stem cells expressed as CFUs and the susceptibility of these increases under conditions of active repopulation after X-irradiation and cyclophosphamide administration. After the irradiation especially, this effect is dose-dependent for doses over 25 rads at 2 weeks after irradiation. (Auth.)

Susceptibility of irradiated Galleria mellonella F1Larvae to Entomopathogenic Nematodes

International Nuclear Information System (INIS)

Salem, H.M.; Rizk, S.A.; Sayed, R.M.; Hussein, M.A; Hafez, S.E

2008-01-01

Combined effect of substerilizing doses of gamma radiation (40 and 100 Gy) and different concentrations of entomopathogenic nematodes (20, 40, 60, and 80 IJs) on the greater wax moth, Galleria mellonella was studied. The 4th larval instar resulted from irradiated male parent pupae mated with normal female were tested for susceptibility to Heterorhabditis bacteriophora BA1 and Steinernema carpocapsae BA2. The mortality rate of the larvae increased by increrasing radiation dose and nematode concentrations. The reproduction of both nematode strains decreased significantly with increasing the treatments (radiation dose and nematode concentrations). In addition, exposure to gamma radiation and entomopathogenic nematodes significantly decreased the total haemocyte count (THC) of the larvae with increasing radiation doses (40 and 100 Gy) and both nematode strains concentrations (20 and 40 IJs) and reached the minimal count at the combiend effect. Finally, larvae were more susceptible to Steinernema carpocapsa than Heterorhabditis bacteriophora. (author)

Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission

Directory of Open Access Journals (Sweden)

Abusuwwa Raed

2006-06-01

effects that occurred contemporaneously with increased susceptibility were rapid exfoliation and re-growth of epithelial cell layers, entry of macrophages into the vaginal lumen, and release of one or more inflammatory cytokines (Il-1β, KC, MIP 1α, RANTES. The non-detergent microbicides and HEC placebo caused no significant increase in susceptibility or toxic effects. Conclusion This mouse HSV-2 model provides a sensitive method to detect microbicide-induced toxicities that increase susceptibility to infection. In this model, there was no concentration at which detergents provided protection without significantly increasing susceptibility.

Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity.

Science.gov (United States)

Torres, Iviana M; Demirdjian, Sally; Vargas, Jennifer; Goodale, Britton C; Berwin, Brent

2017-07-01

Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is dependent on the acidosis. Investigation of the underlying mechanisms revealed that host cell cytotoxicity correlated with increased bacterial survival during an acidic infection that was due to reduced bactericidal activity of host-derived antimicrobial peptides. These findings extend previous reports that the activities of antimicrobial peptides are pH-dependent and provide novel insights into the consequences of acidosis on infection-derived pathology. Therefore, this report provides the first evidence that physiological levels of acidosis increase the susceptibility of epithelial cells to acute Pseudomonas infection and demonstrates the benefit of maintaining pH homeostasis during a bacterial infection. Copyright © 2017 the American Physiological Society.

Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

Science.gov (United States)

Hitomi, Yuki; Tokunaga, Katsushi

2017-01-01

Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence.

Science.gov (United States)

Yang, Po-Yu; Miao, Nae-Fang; Lin, Chiao-Wen; Chou, Ying-Erh; Yang, Shun-Fa; Huang, Hui-Chuan; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

2016-01-01

The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

International Nuclear Information System (INIS)

Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

2009-01-01

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

Environmentally induced epigenetic transgenerational inheritance of disease susceptibility.

Science.gov (United States)

Nilsson, Eric E; Skinner, Michael K

2015-01-01

Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Penicillin-susceptible Staphylococcus aureus: susceptibility testing, resistance rates and outcome of infection.

Science.gov (United States)

Hagstrand Aldman, Malin; Skovby, Annette; I Påhlman, Lisa

2017-06-01

Staphylococcus aureus (SA) is an important human pathogen that causes both superficial and invasive infections. Penicillin is now rarely used in the treatment of SA infections due to widespread resistance and a concern about the accuracy of existing methods for penicillin susceptibility testing. The aims of the present study were to determine the frequency of penicillin-susceptible SA isolates from blood and wound cultures in Lund, Sweden, and to evaluate methods for penicillin testing in SA. We also wanted to investigate if penicillin-susceptible isolates are associated with higher mortality. Hundred blood culture isolates collected 2008/2009, 140 blood culture isolates from 2014/2015, and 141 superficial wound culture strains from 2015 were examined. Penicillin susceptibility was tested with disk diffusion according to EUCAST guidelines, and results were confirmed with a cloverleaf assay and PCR amplification of the BlaZ gene. Patient data for all bacteraemia cases were extracted from medical records. The disk diffusion method with assessment of both zone size and zone edge appearance had high accuracy in our study. About 57% of bacteraemia isolates from 2008/2009 were sensitive to penicillin compared to 29% in 2014/2015 (p penicillin susceptible. There was no difference in co-morbidity or mortality rates between patients with penicillin resistant and penicillin sensitive SA bacteraemia. Disk-diffusion is a simple and reliable method to detect penicillin resistance in SA, and susceptibility rates are significant. Penicillin has many theoretical advantages and should be considered in the treatment of SA bacteraemia when susceptible.

Effects of different aging statuses and strain rate on the adiabatic shear susceptibility of 2195 aluminum–lithium alloy

International Nuclear Information System (INIS)

Yang, Y.; Tan, G.Y.; Chen, P.X.; Zhang, Q.M.

2012-01-01

The adiabatic shear susceptibility of 2195 aluminum–lithium alloy was investigated by means of split Hopkinson pressure bar. The stress collapse in true stress–true strain curves and true stress–time curves was observed. The adiabatic shear susceptibility of different aging statuses and strain rate were discussed by means of metallography observation. The critical strain, stress collapse time and formation energy of adiabatic shear bands were compared. The results show that different aging statuses and strain rate have significant influences on adiabatic shear behaviors of 2195 aluminum–lithium alloy. The peak-aged specimen has the highest adiabatic shearing susceptibility, while the under-aged specimen has the least adiabatic shear susceptibility. The susceptibility of adiabatic shearing increases with the increases of strain rate.

Effects of different aging statuses and strain rate on the adiabatic shear susceptibility of 2195 aluminum-lithium alloy

Energy Technology Data Exchange (ETDEWEB)

Yang, Y. [School of Materials Science and Engineering, Central South University, Changsha 410083, Hunan (China); State Key Laboratory of Explosion Science and Technology, Beijing 100081 (China); Tan, G.Y., E-mail: yangyanggroup@163.com [School of Materials Science and Engineering, Central South University, Changsha 410083, Hunan (China); Chen, P.X. [School of Materials Science and Engineering, Central South University, Changsha 410083, Hunan (China); Zhang, Q.M. [State Key Laboratory of Explosion Science and Technology, Beijing 100081 (China)

2012-06-01

The adiabatic shear susceptibility of 2195 aluminum-lithium alloy was investigated by means of split Hopkinson pressure bar. The stress collapse in true stress-true strain curves and true stress-time curves was observed. The adiabatic shear susceptibility of different aging statuses and strain rate were discussed by means of metallography observation. The critical strain, stress collapse time and formation energy of adiabatic shear bands were compared. The results show that different aging statuses and strain rate have significant influences on adiabatic shear behaviors of 2195 aluminum-lithium alloy. The peak-aged specimen has the highest adiabatic shearing susceptibility, while the under-aged specimen has the least adiabatic shear susceptibility. The susceptibility of adiabatic shearing increases with the increases of strain rate.

RNA interference of two glutathione S-transferase genes, Diaphorina citri DcGSTe2 and DcGSTd1, increases the susceptibility of Asian citrus psyllid (Hemiptera: Liviidae) to the pesticides fenpropathrin and thiamethoxam.

Science.gov (United States)

Yu, Xiudao; Killiny, Nabil

2018-03-01

The Asian citrus psyllid, Diaphorina citri Kuwayama, is an important agricultural pest of citrus globally. Foliar application of chemical insecticides is the most widely used option for reducing D. citri populations. Knockdown of glutathione S-transferase (GST) in several insect species leads to increased susceptibility to insecticides; however, information about the detoxifying role of GST genes in D. citri is unavailable. Via a sequence homology search, we isolated and characterized three DcGST genes (DcGSTd1, DcGSTe1 and DcGSTe2) from D. citri. Phylogenetic analysis grouped DcGSTd1 into the delta class of GST genes, whereas DcGSTe1 and DcGSTe2 were clustered in the epsilon clade. Gene expression analysis revealed that chlorpyrifos treatment increased the mRNA levels of DcGSTe1 and fenpropathrin enhanced the expression level of DcGSTd1, while DcGSTe2 was significantly up-regulated after exposure to thiamethoxam at a dose of 30% lethal concentration (LC30). RNA interference (RNAi) of DcGSTe2 and DcGSTd1 followed by an insecticide bioassay increased the mortalities of thiamethoxam-treated psyllids by 23.0% and fenpropathrin-treated psyllids by 15.0%. In contrast, knockdown of DcGSTe1 did not significantly increase the susceptibility of D. citri to any of these three insecticides. Further, feeding with double-stranded RNA (dsDcGSTe2-d1) interfusion co-silenced DcGSTe2 and DcGSTd1 expression in D. citri, and led to an increase of susceptibility to both fenpropathrin and thiamethoxam. The findings suggest that DcGSTe2 and DcGSTd1 play unique roles in detoxification of the pesticides thiamethoxam and fenpropathrin. In addition, co-silencing by creating a well-designed dsRNA interfusion against multiple genes was a good RNAi strategy in D. citri. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Manipulation of the Xanthophyll Cycle Increases Plant Susceptibility to Sclerotinia sclerotiorum.

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Jun Zhou

2015-05-01

Full Text Available The xanthophyll cycle is involved in dissipating excess light energy to protect the photosynthetic apparatus in a process commonly assessed from non-photochemical quenching (NPQ of chlorophyll fluorescence. Here, it is shown that the xanthophyll cycle is modulated by the necrotrophic pathogen Sclerotinia sclerotiorum at the early stage of infection. Incubation of Sclerotinia led to a localized increase in NPQ even at low light intensity. Further studies showed that this abnormal change in NPQ was closely correlated with a decreased pH caused by Sclerotinia-secreted oxalate, which might decrease the ATP synthase activity and lead to a deepening of thylakoid lumen acidification under continuous illumination. Furthermore, suppression (with dithiothreitol or a defect (in the npq1-2 mutant of violaxanthin de-epoxidase (VDE abolished the Sclerotinia-induced NPQ increase. HPLC analysis showed that the Sclerotinia-inoculated tissue accumulated substantial quantities of zeaxanthin at the expense of violaxanthin, with a corresponding decrease in neoxanthin content. Immunoassays revealed that the decrease in these xanthophyll precursors reduced de novo abscisic acid (ABA biosynthesis and apparently weakened tissue defense responses, including ROS induction and callose deposition, resulting in enhanced plant susceptibility to Sclerotinia. We thus propose that Sclerotinia antagonizes ABA biosynthesis to suppress host defense by manipulating the xanthophyll cycle in early pathogenesis. These findings provide a model of how photoprotective metabolites integrate into the defense responses, and expand the current knowledge of early plant-Sclerotinia interactions at infection sites.

Initial magnetic susceptibility of the diluted magnetopolymer elastic composites

International Nuclear Information System (INIS)

Borin, D.Yu.; Odenbach, S.

2017-01-01

In this work diluted magnetopolymer elastic composites based on magnetic microparticles are experimentally studied. Considered samples have varied concentration of the magnetic powder and different structural anisotropy. Experimental data on magnetic properties are accomplished by microstructural observations performed using X-Ray tomography. Influence of the particles amount and structuring effects on the initial magnetic susceptibility of the composites as well as the applicability of the Maxwell-Garnett approximation, which is widely used in considerations of magnetopolymer elastic composites, are evaluated. It is demonstrated that the approximation works well for diluted samples containing randomly distributed magnetic particles and for the diluted samples with chain-like structures oriented perpendicular to an externally applied field, while it fails to predict the susceptibility of the samples with structures oriented parallel to the field. Moreover, it is shown, that variation of the chains morphology does not significantly change the composite initial magnetic susceptibility. - Highlights: • The Maxwell-Garnet prediction works well for the diluted isotropic composites. • The Maxwell-Garnet prediction can be used for composites with structures oriented perpendicular to an applied field. • Chains oriented parallel to an applied field significantly increase the composite initial magnetic susceptibility. • The number and thickness of chains is not of the highest importance for the diluted composites. • The crucial reason of the observed effect is expected to be the demagnetisation factor of the chains.

GRAPHICAL USER INTERFACE WITH APPLICATIONS IN SUSCEPTIBLE-INFECTIOUS-SUSCEPTIBLE MODELS.

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Ilea, M; Turnea, M; Arotăriţei, D; Rotariu, Mariana; Popescu, Marilena

2015-01-01

Practical significance of understanding the dynamics and evolution of infectious diseases increases continuously in contemporary world. The mathematical study of the dynamics of infectious diseases has a long history. By incorporating statistical methods and computer-based simulations in dynamic epidemiological models, it could be possible for modeling methods and theoretical analyses to be more realistic and reliable, allowing a more detailed understanding of the rules governing epidemic spreading. To provide the basis for a disease transmission, the population of a region is often divided into various compartments, and the model governing their relation is called the compartmental model. To present all of the information available, a graphical user interface provides icons and visual indicators. The graphical interface shown in this paper is performed using the MATLAB software ver. 7.6.0. MATLAB software offers a wide range of techniques by which data can be displayed graphically. The process of data viewing involves a series of operations. To achieve it, I had to make three separate files, one for defining the mathematical model and two for the interface itself. Considering a fixed population, it is observed that the number of susceptible individuals diminishes along with an increase in the number of infectious individuals so that in about ten days the number of individuals infected and susceptible, respectively, has the same value. If the epidemic is not controlled, it will continue for an indefinite period of time. By changing the global parameters specific of the SIS model, a more rapid increase of infectious individuals is noted. Using the graphical user interface shown in this paper helps achieving a much easier interaction with the computer, simplifying the structure of complex instructions by using icons and menus, and, in particular, programs and files are much easier to organize. Some numerical simulations have been presented to illustrate theoretical

Scalar and pseudoscalar susceptibilities in nuclei

International Nuclear Information System (INIS)

Ericson, Magda; Chanfray, Guy; Chanfray, Guy

2003-01-01

We study the two QCD susceptibilities of the nuclear medium in the linear σ model. The magnitude of the scalar one increases due to the mixing with the softer modes of the nucleon-hole excitations. The pseudoscalar susceptibility, follows the density evolution of the quark condensate and thus decreases in magnitude. At normal nuclear matter density the two susceptibilities become much close than in the vacuum, a consequence of the partial chiral symmetry restoration. (author)

Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy.

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Pleasant, LaTawnya; Ma, Qing; Devarajan, Mahima; Parameswaran, Priyanka; Drake, Keri; Siroky, Brian; Shay-Winkler, Kritton; Robbins, Jeffrey; Devarajan, Prasad

2017-09-01

The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77 ± 0.66 in transgenic mice vs. 2.01 ± 0.58 mg/dl in wild type, P kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. Copyright © 2017 the American Physiological Society.

10′(Z),13′(E)-Heptadecadienylhydroquinone Inhibits Swarming and Virulence Factors and Increases Polymyxin B Susceptibility in Proteus mirabilis

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Wang, Won-Bo; Yuan, Yu-Han; Hsueh, Po-Ren; Liaw, Shwu-Jen

2012-01-01

In this study, we demonstrated that 10′(Z), 13′(E)-heptadecadienylhydroquinone (HQ17-2), isolated from the lacquer tree, could decrease swarming motility and hemolysin activity but increase polymyxin B (PB) susceptibilityof Proteus mirabilis which is intrinsically highly-resistant to PB. The increased PB susceptibility induced by HQ17-2 was also observed in clinical isolates and biofilm-grown cells. HQ17-2 could inhibit swarming in the wild-type and rppA mutant but not in the rcsB mutant, indicating that HQ17-2 inhibits swarming through the RcsB-dependent pathway, a two-component signaling pathway negatively regulating swarming and virulence factor expression. The inhibition of hemolysin activity by HQ17-2 is also mediated through the RcsB-dependent pathway, because HQ17-2 could not inhibit hemolysin activity in the rcsB mutant. Moreover, the finding that HQ17-2 inhibits the expression of flhDC gene in the wild-type and rcsB-complemented strain but not in the rcsB mutant supports the notion. By contrast, HQ17-2 could increase PB susceptibility in the wild-type and rcsB mutant but not in the rppA mutant, indicating that HQ17-2 increases PB susceptibility through the RppA-dependent pathway, a signaling pathway positively regulating PB resistance. In addition, HQ17-2 could inhibit the promoter activities of rppA and pmrI, a gene positively regulated by RppA and involved in PB resistance, in the wild-type but not in the rppA mutant. The inhibition of rppA and pmrI expression caused lipopolysaccharide purified from HQ17-2-treated cells to have higher affinity for PB. Altogether, this study uncovers new biological effects of HQ17-2 and provides evidence for the potential of HQ17-2 in clinical applications. PMID:23029100

Maternal geohelminth infections are associated with an increased susceptibility to geohelminth infection in children: a case-control study.

Directory of Open Access Journals (Sweden)

Raaj S Mehta

Full Text Available Children of mothers infected with soil-transmitted helminths (STH may have an increased susceptibility to STH infection.We did a case-control study nested in a birth cohort in Ecuador. Data from 1,004 children aged 7 months to 3 years were analyzed. Cases were defined as children with Ascaris lumbricoides and/or Trichuris trichiura, controls without. Exposure was defined as maternal infection with A. lumbricoides and/or T. trichiura, detected during the third trimester of pregnancy. The analysis was restricted to households with a documented infection to control for infection risk. Children of mothers with STH infections had a greater risk of infection compared to children of uninfected mothers (adjusted OR 2.61, 95% CI: 1.88-3.63, p<0.001. This effect was particularly strong in children of mothers with both STH infections (adjusted OR: 5.91, 95% CI: 3.55-9.81, p<0.001. Newborns of infected mothers had greater levels of plasma IL-10 than those of uninfected mothers (p=0.033, and there was evidence that cord blood IL-10 was increased among newborns who became infected later in childhood (p=0.060.Our data suggest that maternal STH infections increase susceptibility to infection during early childhood, an effect that was associated with elevated IL-10 in cord plasma.

Polymyxin susceptibility testing, interpretative breakpoints and resistance mechanisms: An update.

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Bakthavatchalam, Yamuna Devi; Pragasam, Agila Kumari; Biswas, Indranil; Veeraraghavan, Balaji

2018-03-01

Emerging multidrug-resistant (MDR) nosocomial pathogens are a great threat. Polymyxins, an old class of cationic polypeptide antibiotic, are considered as last-resort drugs in treating infections caused by MDR Gram-negative bacteria. Increased use of polymyxins in treating critically ill patients necessitates routine polymyxin susceptibility testing. However, susceptibility testing both of colistin and polymyxin B (PMB) is challenging. In this review, currently available susceptibility testing methods are briefly discussed. The multicomponent composition of colistin and PMB significantly influences susceptibility testing. In addition, poor diffusion in the agar medium, adsorption to microtitre plates and the synergistic effect of the surfactant polysorbate 80 with polymyxins have a great impact on the performance of susceptibility testing methods This review also describes recently identified chromosomal resistance mechanisms, including modification of lipopolysaccharide (LPS) with 4-amino-4-deoxy-l-arabinose (L-Ara4-N) and phosphoethanolamine (pEtN) resulting in alteration of the negative charge, as well as the plasmid-mediated colistin resistance determinants mcr-1, mcr-1.2, mcr-2 and mcr-3. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

[Significant increase in the colonisation of Staphylococcus aureus among medical students during their hospital practices].

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Rodríguez-Avial, Carmen; Alvarez-Novoa, Andrea; Losa, Azucena; Picazo, Juan J

2013-10-01

Staphylococcus aureus is a pathogen of major concern. The emergence of methicillin-resistant S. aureus (MRSA) has increasingly complicated the therapeutic approach of hospital-acquired infections. Surveillance of MRSA and control measures must be implemented in different healthcare settings, including screening programs for carriers. Our first aim was to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage in medical students from the Clínico San Carlos Hospital (Madrid). As the MRSA carrier rate in healthcare workers is higher than in the general population, we hypothesised that carrier rate could be increased during their clinical practice in their last three years. We performed an epidemiologic al study of the prevalence of S. aureus colonisation among a group of medical students, who were sampled in 2008 in their third-year, and in 2012 when this class was in its sixth year. We have found a significant increase in MSSA carriage, from 27% to 46%. There were no MRSA colonisations in the third-year, but one was found in the sixth-year group. The large majority of strains (89%) of strains were resistant to penicillin, and 27% to erythromycin and clindamycin. As 19 coagulase-negative Staphylococcus MR were also identified, a horizontal transfer of genes, such as mecA gene to S. aureus, could have occurred. Medical students are both, at risk for acquiring, and a potential source of nosocomial pathogens, mainly MSSA. Therefore, they should take special care for hygienic precautions, such as frequent and proper hand washing, while working in the hospital. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Heritable susceptibility factors for the development of cancer

International Nuclear Information System (INIS)

Au, William W.

2006-01-01

High frequencies of inherited DNA sequence variations (polymorphisms) are found in the human population. The involvement of polymorphic genes (especially for chemical metabolism and DNA repair) in the development of cancer is under intensive investigation. In our studies, we have irradiated blood lymphocytes from normal non-smokers with γ-rays or UV-light to investigate genotypes and DNA repair functions. We found that XRCC1 399Gln and XRCC3 241Met were deficient in the repair of γ-ray- but not UV-light-induced DNA damage that led to the expression of chromosome aberrations; therefore the variant genotypes are defective in base excision repair. The reverse was found with XPD 312Asn and XPD 751Gln; therefore they are defective in nucleotide excision repair. XRCC1 194Trp, OGG1 326Cys and APE1 148Glu had no DNA repair deficiency based on our experimental conditions. In another study, we investigated the role of some of these genes on the development of lung cancer. We found a significant increase of chromosome aberrations in patients and controls that had the XPD 751Gln and GSTM1 null genotypes, indicating a mechanistic causation of the disease. Therefore, inheritance of susceptibility genes can have significant impact on disease burden in the population. On the other hand, there are many questions that need to be addressed in order to evaluate the impact of susceptibility on cancer. These questions include the understanding of combinations of different polymorphic genes for susceptibility and of specific disease susceptibility for different ethnic populations. (author)

Genetic control of susceptibility to apoptosis of thymocytes

International Nuclear Information System (INIS)

Mori, N.; Okumoto, M.; Morimoto, J.; Imai, S.; Matsuyama, T.; Takamori, Y.; Yagasaki, O.

1992-01-01

Genetic control of the susceptibility of thymocytes to radiation-induced apoptosis in mice was investigated by counting dead cells in a selected area of thymic cortex on histological specimens after whole-body X-irradiation. The number of dead cells increased almost linearly with doses in BALB/cHeA and STS/A mice. However, dead cell counts in BALB/cHeA mice were more than twice those in STS/A mice at each dose. C57BL/6N and B10.BR mice exhibited a sensitive phenotype similar to BALB/cHeA mice, while C3H/HeMsNrs and NFS/N mice showed a resistant phenotype similar to STS/A mice. Sex difference in the susceptibility of thymocytes to cell death was not recognized in BALB/cHeA and STS/A mice. Resistance was dominant over susceptibility in the progenies of reciprocal crosses between the two strains, indicating an autosomal inheritance. The segregation ratio of susceptible to resistant phenotype in the backcrosses of (BALB/cHeA X STS/A)F 1 with BALB/cHeA was not significantly different from 1 : 1 and all backcrosses of (BALB/cHeA X STS/A)F 1 with STS/A exhibited a resistant phenotype. The results demonstrated that the difference in the susceptibility of thymocytes to radiation-induced apoptosis in the two strains of mice is due to one major autosomal allele. (author)

[Antimicrobial susceptibility in Chile 2012].

Science.gov (United States)

Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

2014-04-01

Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

Risk modification of colorectal cancer susceptibility by interleukin-8 -251T>A polymorphism in Malaysians.

Science.gov (United States)

Mustapha, Mohd Aminudin; Shahpudin, Siti Nurfatimah Mohd; Aziz, Ahmad Aizat Abdul; Ankathil, Ravindran

2012-06-07

To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8 -251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ² tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. On comparing the frequencies of genotypes of patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69, P = 0.003). Variant allele and genotype of IL-8 (-251T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.

Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

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Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

2018-03-15

Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and

Magnetic susceptibility of transition metal alloys with a hcp structure

International Nuclear Information System (INIS)

Volkenshtejn, N.V.; Galoshina, Eh.V.; Gorina, N.B.; Korenovskij, N.L.; Polyakova, V.P.; Savitskij, E.M.

1978-01-01

The angular dependence of the magnetic susceptibility of single crystals of Ru-Nb, Re-W and Os-Re alloys is investigated in the region of the hexagonal closely packed structure. The spin susceptibility is estimated on the basis of available data on the electron specific heat. The principal values of the orbital component of the susceptibility are determined under the assumption of isotopy of the spin contribution to the susceptibility. In Ru-Nb alloys the magnitudes of the orbital contributions and the susceptibility anisotropy are found to increase; in Re-W the spin contribution is noticeably greater whereas the orbital susceptibility is smaller, as is the anistropy. In the Os-Re alloy the orbital contributions increase and the susceptibility anisotropy is constant. It is suggested that the addition of the second component changes the overlapping of the d-electron wave functions

Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection.

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Quispe Calla, N E; Vicetti Miguel, R D; Boyaka, P N; Hall-Stoodley, L; Kaur, B; Trout, W; Pavelko, S D; Cherpes, T L

2016-11-01

Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection.

Drought increases cowpea (Vigna unguiculata [L.] Walp.) susceptibility to cowpea severe mosaic virus (CPSMV) at early stage of infection.

Science.gov (United States)

Silva, Rodolpho G G; Vasconcelos, Ilka M; Martins, Thiago F; Varela, Anna L N; Souza, Pedro F N; Lobo, Ana K M; Silva, Fredy D A; Silveira, Joaquim A G; Oliveira, Jose T A

2016-12-01

The physiological and biochemical responses of a drought tolerant, virus-susceptible cowpea genotype exposed to drought stress (D), infected by Cowpea severe mosaic virus (CPSMV) (V), and to these two combined stresses (DV), at 2 and 6 days post viral inoculation (DPI), were evaluated. Gas exchange parameters (net photosynthesis, transpiration rate, stomatal conductance, and internal CO 2 partial pressure) were reduced in D and DV at 2 and 6 DPI compared to control plants (C). Photosynthesis was reduced by stomatal and biochemical limitations. Water use efficiency increased at 2 DPI in D, DV, and V, but at 6 DPI only in D and DV compared to C. Photochemical parameters (effective quantum efficiency of photosystem II and electron transport rate) decreased in D and DV compared to C, especially at 6 DPI. The potential quantum efficiency of photosystem II did not change, indicating reversible photoinhibition of photosystem II. In DV, catalase decreased at 2 and 6 DPI, ascorbate peroxidase increased at 2 DPI, but decreased at 6 DPI. Hydrogen peroxide increased at 2 and 6 DPI. Peroxidase increased at 6 DPI and chitinase at 2 and 6 DPI. β-1,3-glucanase decreased in DV at 6 DPI compared to V. Drought increased cowpea susceptibility to CPSMV at 2 DPI, as verified by RT-PCR. However, at 6 DPI, the cowpea plants overcome this effect. Likewise, CPSMV increased the negative effects of drought at 2 DPI, but not at 6 DPI. It was concluded that the responses to combined stresses are not additive and cannot be extrapolated from the study of individual stresses. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Trade-offs in disease and bleaching susceptibility among two color morphs of the Hawaiian reef coral, Montipora capitata

Science.gov (United States)

Shore-Maggio, Amanda; Callahan, Sean M.; Aeby, Greta S.

2018-06-01

Two threats impacting coral reefs are bleaching and disease, and differential susceptibility to both exists among and within coral taxa. Bleaching resistance is commonly linked to the clade of endosymbiotic Symbiodinium, but may come at a cost to other biological traits. Montipora capitata is an Indo-Pacific reef-building coral with two color morphs, red and orange, which harbor different clades of Symbiodinium. We explored whether these color morphs displayed differences in bleaching/disease susceptibility and other biological traits (growth rate, reproductive output, and lipid content). We found a trade-off between disease and bleaching susceptibility. The orange morph had significantly higher disease prevalence, whereas the red morph had significantly higher bleaching prevalence. Thermal stress experiments found that bleaching and loss of photochemical efficiency occurred significantly faster in the red morph, but at normal temperatures, the red morph had a significantly higher growth rate. Higher abundance of the red morph in the field suggests that disease resistance is a more successful strategy in the absence of thermal stress events. The orange morph may better tolerate increases in sea temperatures, but may not persist due to decreased growth rate and increased disease susceptibility. Trade-offs in response to stressors highlight the need to consider local and global threats to coral reefs.

Interleukin 1 alpha increases the susceptibility of rabbits to experimental viridans streptococcal endocarditis

NARCIS (Netherlands)

Dankert, J; Joldersma, W; Zaat, SAJ; van der Werff, J.

Major predisposing conditions for infective endocarditis (IE) are the presence of a cardiac platelet-fibrin vegetation and of circulating bacteria with relatively low susceptibility to microbicidal activity of blood platelets. The influence of proinflammatory conditions on development of IE is

Exposure to point-of-sale displays and changes in susceptibility to smoking: findings from a cohort study of school students.

Science.gov (United States)

Bogdanovica, Ilze; Szatkowski, Lisa; McNeill, Ann; Spanopoulos, Dionysis; Britton, John

2015-04-01

To investigate the association between frequency of visiting shops and noticing of tobacco point-of-sale (PoS) displays and the development of susceptibility to smoking, or smoking uptake, in secondary school students. Two surveys of a school based cohort study carried out in 2011 and 2012. Nottinghamshire, UK. A total of 2270 children aged 11-16 years from eight schools in Nottinghamshire. We investigated changes in susceptibility to smoking and smoking status in relation to frequency of visiting shops and noticing PoS displays and number of tobacco brands recognized, controlling for a range of potential confounders. Susceptibility to smoking was defined using a set of three questions covering intentions to try smoking, to smoke within the next year and likelihood of smoking if a best friend offered a cigarette. For the analysis we used multinomial logistic regression. Among non-susceptible never smokers, noticing PoS displays more frequently was associated independently with an increased risk of becoming susceptible to smoking [adjusted relative risk ratio (RRR) = 1.74; 99% confidence interval (CI) = 1.13-2.69], but was not associated with smoking uptake. Recognizing a higher number of brands among non-susceptible never smokers doubled the risk of becoming susceptible to smoking and of becoming a smoker, but this did not have a significant effect on transition to smoking among susceptible never smokers. Frequency of noticing tobacco PoS displays was not associated significantly with smoking uptake among those who were susceptible never smokers at baseline. Noticing tobacco point-of-sale displays more often and recognizing a higher number of tobacco brands is associated with an increased risk of becoming susceptible to smoking among adolescents in the United Kingdom, and recognizing a higher number of brands is associated positively with an increased risk of smoking uptake. © 2014 Society for the Study of Addiction.

Something's missing: need fulfillment and self-expansion as predictors of susceptibility to infidelity.

Science.gov (United States)

Lewandowski, Gary W; Ackerman, Robert A

2006-08-01

The present authors investigated whether an individual's motivations that are related to need fulfillment and self-expansion within a romantic relationship can predict self-reported susceptibility to infidelity. A sample of 109 college students (50 men, 59 women) who were in dating relationships completed questionnaires that assessed 5 types of variables of need fulfillment (i.e., intimacy, companionship, sex, security, and emotional involvement), 3 types of self-expansion variables (i.e., self-expansion, inclusion of the other in the self, and potential for self-expansion), and susceptibility to infidelity. As the present authors predicted, both sets of predictors (need fulfillment and self-expansion) significantly contributed to the variance in susceptibility to infidelity. The present findings indicated the possibility that, when a relationship is not able to fulfill needs or provide ample self-expansion for an individual, his or her susceptibility to infidelity increases.

Analysis of triclosan-selected Salmonella enterica mutants of eight serovars revealed increased aminoglycoside susceptibility and reduced growth rates.

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Ulrike Rensch

Full Text Available The biocide triclosan (TRC is used in a wide range of household, personal care, veterinary, industrial and medical products to control microbial growth. This extended use raises concerns about a possible association between the application of triclosan and the development of antibiotic resistance. In the present study we determined triclosan mutant prevention concentrations (MPC for Salmonella enterica isolates of eight serovars and investigated selected mutants for their mechanisms mediating decreased susceptibility to triclosan. MPCTRC values were 8-64-fold higher than MIC values and ranged between 1-16 µg/ml. The frequencies at which mutants were selected varied between 1.3 x 10(-10-9.9 x 10(-11. Even if MIC values of mutants decreased by 3-7 dilution steps in the presence of the efflux pump inhibitor Phe-Arg-β-naphtylamide, only minor changes were observed in the expression of genes encoding efflux components or regulators, indicating that neither the major multidrug efflux pump AcrAB-TolC nor AcrEF are up-regulated in triclosan-selected mutants. Nucleotide sequence comparisons confirmed the absence of alterations in the regulatory regions acrRA, soxRS, marORAB, acrSE and ramRA of selected mutants. Single bp and deduced Gly93→Val amino acid exchanges were present in fabI, the target gene of triclosan, starting from a concentration of 1 µg/ml TRC used for MPC determinations. The fabI genes were up to 12.4-fold up-regulated. Complementation experiments confirmed the contribution of Gly93→Val exchanges and fabI overexpression to decreased triclosan susceptibility. MIC values of mutants compared to parent strains were even equal or resulted in a more susceptible phenotype (1-2 dilution steps for the aminoglycoside antibiotics kanamycin and gentamicin as well as for the biocide chlorhexidine. Growth rates of selected mutants were significantly lower and hence, might partly explain the rare occurrence of Salmonella field isolates exhibiting

The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.

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Takahashi, Noriyuki; Saitoh, Takayuki; Gotoh, Nanami; Nitta, Yasuhiro; Alkebsi, Lobna; Kasamatsu, Tetsuhiro; Minato, Yusuke; Yokohama, Akihiko; Tsukamoto, Norifumi; Handa, Hiroshi; Murakami, Hirokazu

2017-05-16

T-helper cell type 1 (Th1) polarization in chronic immune thrombocytopenia (cITP) has been reported at the protein and mRNA levels. We evaluated the impact of Th1/Th2 cytokine and cytokine receptor functional polymorphisms on both susceptibility to, and severity of, cITP. We analysed IFN-γ + 874 T/A, IFN-γR -611G/A, IL-4 -590C/T, and IL-4Rα Q576R polymorphisms in 126 cITP patients (male/female: 34/92; median age: 47.7 years) and 202 healthy control donors. Genotyping was determined by PCR and direct sequencing. The Th1/Th2 ratio was detected in peripheral blood mononuclear cells via flow cytometry. cITP patients had a higher frequency of the IL-4Rα 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP patients with the IFN-γ +874 non-AA genotype (high expression type) showed more severe thrombocytopenia than those with the AA genotype (P Th1/Th2 ratio than control patients (P Th1/Th2 ratio (P Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.

Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis

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Meisel, Marlies; Mayassi, Toufic; Fehlner-Peach, Hannah; Koval, Jason C.; O' Brien, Sarah L.; Hinterleitner, Reinhard; Lesko, Kathryn; Kim, Sangman; Bouziat, Romain; Chen, Li; Weber, Christopher R.; Mazmanian, Sarkis K.; Jabri, Bana; Antonopoulos, Dionysios A.

2016-09-20

Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin 15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and play a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). While the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S rRNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (v-IL-15tg mice) shows distinct changes in the composition of the intestinal bacteria. While some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum, and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.

Glucose-6-phosphate dehydrogenase deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2.

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Roshankhah, Shiva; Rostami-Far, Zahra; Shaveisi-Zadeh, Farhad; Movafagh, Abolfazl; Bakhtiari, Mitra; Shaveisi-Zadeh, Jila

2016-12-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. G6PD plays a key role in the pentose phosphate pathway, which is a major source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH provides the reducing equivalents for oxidation-reduction reductions involved in protecting against the toxicity of reactive oxygen species such as H 2 O 2 . We hypothesized that G6PD deficiency may reduce the amount of NADPH in sperms, thereby inhibiting the detoxification of H 2 O 2 , which could potentially affect their motility and viability, resulting in an increased susceptibility to infertility. Semen samples were obtained from four males with G6PD deficiency and eight healthy males as a control. In both groups, motile sperms were isolated from the seminal fluid and incubated with 0, 10, 20, 40, 60, 80, and 120 µM concentrations of H 2 O 2 . After 1 hour incubation at 37℃, sperms were evaluated for motility and viability. Incubation of sperms with 10 and 20 µM H 2 O 2 led to very little decrease in motility and viability, but motility decreased notably in both groups in 40, 60, and 80 µM H 2 O 2 , and viability decreased in both groups in 40, 60, 80, and 120 µM H 2 O 2 . However, no statistically significant differences were found between the G6PD-deficient group and controls. G6PD deficiency does not increase the susceptibility of sperm to oxidative stress induced by H 2 O 2 , and the reducing equivalents necessary for protection against H 2 O 2 are most likely produced by other pathways. Therefore, G6PD deficiency cannot be considered as major risk factor for male infertility.

RSRC1 and CPZ gene polymorphisms with neuroblastoma susceptibility in Chinese children.

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Tang, Jue; Liu, Wei; Zhu, Jinhong; Zhang, Jiao; Wang, Feng-Hua; Liang, Jiang-Hua; Zeng, Jia-Hang; Wang, Hui; Xia, Huimin; He, Jing

2018-07-01

Two new neuroblastoma susceptibility loci at 3q25 (RSRC1 rs6441201 G > A) and 4p16 (CPZ rs3796725 T > C and rs3796727 A > G) were identified by a genome-wide association study (GWAS) involving Italians, African Americans and European Americans. In this case-control study with 393 neuroblastoma cases and 812 controls, we investigated the association between these three polymorphisms and neuroblastoma susceptibility in Chinese population. We found that participants harboring the RSRC1 rs6441201A allele were associated with an increased risk of neuroblastoma (AA vs. GG: adjusted OR = 1.55, 95% CI = 1.03-2.34, P = 0.036). No significant association between the CPZ polymorphisms (rs3796725 T > C and rs3796727A > G) and neuroblastoma susceptibility was observed. In conclusion, our results confirm that the RSRC1 rs6441201A allele is associated with neuroblastoma susceptibility in Chinese population. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of o-aminoazotoluene on liver regeneration and p53 activation in mice susceptible and resistant to hepatocarcinogenesis

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Timofeeva, Olga A.; Eremeev, Artem V.; Goloshchapov, Andrey; Kalashnikova, Eugenia; Ilnitskaya, Svetlana; Setkov, Nikolai A.; Kobzev, Victor; Buzard, Gregory S.; Filipenko, Maxim L.; Kaledin, Vasily I.; Merkulova, Tatyana I.

2008-01-01

The susceptibility to hepatocellular carcinoma (HCC) varies greatly within human populations in response to environmental risk agents. The mechanisms underlying differential susceptibility are still largely unknown and need to be clarified to improve HCC chemoprevention and therapeutic treatment. Inbred rodent strains with established predispositions for hepatocarcinogenesis offer the opportunity to identify intrinsic susceptibility and resistance factors. Previously, we have characterized mouse strains showing differential susceptibility to o-aminoazotoluene (OAT) and established that susceptibility does not result from OAT metabolism or genotoxicity in the livers of resistant and susceptible mice. In this study we have found that OAT differently affects hepatocyte proliferation in mice after partial hepatectomy (PH). OAT inhibited hepatocyte proliferation by 60-80% in the livers of susceptible mice, whereas resistant mice showed less than 15% inhibition. The inhibition resulted in significant delay of hepatic mass recovery in susceptible mice. OAT induced p53 stabilization and transcriptional activation in response to carcinogen treatment to the same degree in both, susceptible and resistant mice. Taken together, our data support inhibition of hepatocyte proliferation as a major cause for increased mouse susceptibility to hepatocarcinogenesis, and acceleration of functional liver recovery may offer a way to increase resistance to hepatic neoplasms. These results may have relevance to clinical observations of HCCs and implications for HCC chemoprevention and treatment

Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

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Shun Yao

2017-08-01

Full Text Available Previous studies have detected abnormal serum ferritin levels in patients with depression; however, the results have been inconsistent. This study used quantitative susceptibility mapping (QSM for the first time to examine brain iron concentration in depressed patients and evaluated whether it is related to severity. We included three groups of age- and gender-matched participants: 30 patients with mild-moderate depression (MD, 14 patients with major depression disorder (MDD and 20 control subjects. All participants underwent MR scans with a 3D gradient-echo sequence reconstructing for QSM and performed the 17-item Hamilton Depression Rating Scale (HDRS test. In MDD, the susceptibility value in the bilateral putamen was significantly increased compared with MD or control subjects. In addition, a significant difference was also observed in the left thalamus in MDD patients compared with controls. However, the susceptibility values did not differ between MD patients and controls. The susceptibility values positively correlated with the severity of depression as indicated by the HDRS scores. Our results provide evidence that brain iron deposition may be associated with depression and may even be a biomarker for investigating the pathophysiological mechanism of depression.

Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal Toll-like receptors in rats.

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Ohno, Kouhei; Kuno, Atsushi; Murase, Hiromichi; Muratsubaki, Shingo; Miki, Takayuki; Tanno, Masaya; Yano, Toshiyuki; Ishikawa, Satoko; Yamashita, Tomohisa; Miura, Tetsuji

2017-12-01

Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined the roles of renal Toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a rat DM model, and Long-Evans-Tokushima-Otsuka (LETO) rats, nondiabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and myeloid differentiation factor 88 (MyD88) were significantly higher in sham-operated OLETF rats than in sham-operated LETO rats, although levels of TLR1, TLR3, and TLR4 were similar. At 12 h after MI, protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the kidney were elevated by 5.3- and 4.0-fold, respectively, and their mRNA levels were increased in OLETF but not LETO rats. The increased KIM-1 and NGAL expression levels after MI in the OLETF kidney were associated with upregulated expression of TLR1, TLR2, TLR4, MyD88, IL-6, TNF-α, chemokine (C-C motif) ligand 2, and transforming growth factor-β 1 and also with activation of p38 MAPK, JNK, and NF-κB. Cu-CPT22, a TLR1/TLR2 antagonist, administered before MI significantly suppressed MI-induced upregulation of KIM-1, TLR2, TLR4, MyD88, and chemokine (C-C motif) ligand 2 levels and activation of NF-κB, whereas NGAL levels and IL-6 and TNF-α expression levels were unchanged. The results suggest that DM increases the susceptibility to AKI after acute MI by augmented activation of renal TLRs and that TLR1/TLR2-mediated signaling mediates KIM-1 upregulation after MI. NEW & NOTEWORTHY This is the first report to demonstrate the involvement of Toll-like recpetors (TLRs) in diabetes-induced susceptibility to acute kidney injury after acute myocardial infarction. We propose that the TLR1/TLR2

Changes in Amino Acid Profile in Roots of Glyphosate Resistant and Susceptible Soybean (Glycine max) Induced by Foliar Glyphosate Application.

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Moldes, Carlos Alberto; Cantarelli, Miguel Angel; Camiña, José Manuel; Tsai, Siu Mui; Azevedo, Ricardo Antunes

2017-10-11

Amino acid profiles are useful to analyze the responses to glyphosate in susceptible and resistant soybean lines. Comparisons of profiles for 10 amino acids (Asp, Asn, Glu, Gln, Ser, His, Gly, Thr, Tyr, Leu) by HPLC in soybean roots were performed in two near isogenic pairs (four varieties). Foliar application of glyphosate was made to soybean plants after 5 weeks of seeding. Roots of four varieties were collected at 0 and 72 h after glyphosate application (AGA) for amino acid analysis by HPLC. Univariate analysis showed a significant increase of several amino acids in susceptible as well as resistant soybean lines; however, amino acids from the major pathways of carbon (C) and nitrogen (N) metabolism, such as Asp, Asn, Glu and Gln, and Ser, increased significantly in susceptible varieties at 72 h AGA. Multivariate analysis using principal component analysis (2D PCA and 3D PCA) allowed different groups to be identified and discriminated based on the soybean genetic origin, showing the amino acid responses on susceptible and resistant varieties. Based on the results, it is possible to infer that the increase of Asn, Asp, Glu, Gln, and Ser in susceptible varieties would be related to the deregulation of C and N metabolism, as well as changes in the growth mechanisms regulated by Ser.

Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis.

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García-Nieto, Pablo E; Schwartz, Erin K; King, Devin A; Paulsen, Jonas; Collas, Philippe; Herrera, Rafael E; Morrison, Ashby J

2017-10-02

The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer. Remarkably, the pattern of carcinogen susceptibility across the genome of primary cells significantly reflects mutation frequency in malignant melanoma. Surprisingly, DNase-accessible euchromatin is protected from UV, while lamina-associated heterochromatin at the nuclear periphery is vulnerable. Many cancer driver genes have an intrinsic increase in carcinogen susceptibility, including the BRAF oncogene that has the highest mutation frequency in melanoma. These findings provide a genome-wide snapshot of DNA injuries at the earliest stage of carcinogenesis. Furthermore, they identify carcinogen susceptibility as an origin of genome instability that is regulated by nuclear architecture and mirrors mutagenesis in cancer. © 2017 The Authors.

In Vitro Antimicrobial Susceptibility of Pathogenic Leptospira Biofilm.

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Vinod Kumar, Kirubakaran; Lall, Chandan; Raj, Ratchagadasse Vimal; Vedhagiri, Kumaresan; Sunish, Ittoop Pulikkottil; Vijayachari, Paluru

2016-10-01

Pathogenic Leptospira spp. are the causative agent of leptospirosis. Biofilm formation in leptospires is a new area of study, and its role in pathogenesis is not fully explored. As in other biofilm-forming bacteria, Leptospira biofilm may play a significant role in antibiotic resistance. In this study, the antimicrobial susceptibility of Leptospira biofilm was investigated by 96-well plate assay using Alamar Blue. Leptospira biofilm showed five to sixfold increase in resistance in all the strains used. The range of minimal bactericidal concentrations for penicillin G, ampicillin, tetracycline, and doxycycline was 1,600 U/ml, 800-1,600 μg/ml, 800-1,600 μg/ml, and 800-1,600 μg/ml, respectively. In agar substrate, the biofilm showed six- to sevenfold increase in resistance to antibiotics compared to planktonic cell. The present study emphasizes the importance of biofilm formation and its antibiotic susceptibility patterns. This could pave the way for devising appropriate strategy to prevent the occurrence of potential chronic leptospirosis in endemic areas and also during an outbreak situation.

Remarkable increase of Neisseria gonorrhoeae with decreased susceptibility of azithromycin and increase in the failure of azithromycin therapy in male gonococcal urethritis in Sendai in 2015.

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Yasuda, Mitsuru; Ito, Shin; Hatazaki, Kyoko; Deguchi, Takashi

2016-12-01

The antimicrobial resistance of Neisseria gonorrhoeae is a serious problem worldwide. In this study, we examined the susceptibility of N. gonorrhoeae isolated from male gonococcal urethritis in Sendai in 2014 and 2015. Furthermore, of all cases, we investigated the clinical efficacy of a single 2-g dose of extended-release azithromycin (AZM-SR) in the treatment of male gonococcal urethritis retrospectively. Sixty N. gonorrhoeae strains in 2014 and 54 strains in 2015 were isolated from male gonococcal urethritis and stored each year. The MIC of AZM was ≥1 mg/L in 4 strains (6.7%) in 2014 and in 13 strains (24.1%) in 2015 and the number of strains having ≥1 mg/L MIC increased significantly (P = 0.016). Microbiological efficacy was evaluated in 32 and 29 of these patients, and the rates of treatment success were 93.8% and 79.3%, respectively. All of the treatment failures were caused by strains having a MIC of AZM of ≥0.5 mg/L. In particular, the increase in the isolates having a MIC of AZM of ≥1 mg/L was remarkable. Therefore, it was thought that the increase in these strains was the reason for the increase in treatment failures in 2015. Because no other drug is effective, it is currently necessary to use AZM-SR to treat gonococcal infections caused by ceftriaxone-resistant strains or patients allergic to ceftriaxone. To prevent a further increase in resistance to AZM, we should not use AZM-SR to treat normal cases of gonococcal infection. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Increased Hypothalamic Inflammation Associated with the Susceptibility to Obesity in Rats Exposed to High-Fat Diet

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Xiaoke Wang

2012-01-01

Full Text Available Inflammation has been implicated in the hypothalamic leptin and insulin resistance resulting defective food intake during high fat diet period. To investigate hypothalamic inflammation in dietary induced obesity (DIO and obesity resistant (DIO-R rats, we established rat models of DIO and DIO-R by feeding high fat diet for 10 weeks. Then we switched half of DIO and DIO-R rats to chow food and the other half to high fat diet for the following 8 weeks to explore hypothalamic inflammation response to the low fat diet intervention. Body weight, caloric intake, HOMA-IR, as well as the mRNA expression of hypothalamic TLR4, NF-κB, TNF-α, IL-1β, and IL-6 in DIO/HF rats were significantly increased compared to DIO-R/HF and CF rats, whereas IL-10 mRNA expression was lower in both DIO/HF and DIO-R/HF rats compared with CF rats. Switching to chow food from high fat diet reduced the body weight and improved insulin sensitivity but not affecting the expressions of studied inflammatory genes in DIO rats. Take together, upregulated hypothalamic inflammation may contribute to the overeating and development of obesity susceptibility induced by high fat diet. Switching to chow food had limited role in correcting hypothalamic inflammation in DIO rats during the intervention period.

A GIS-based extended fuzzy multi-criteria evaluation for landslide susceptibility mapping.

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Feizizadeh, Bakhtiar; Shadman Roodposhti, Majid; Jankowski, Piotr; Blaschke, Thomas

2014-12-01

Landslide susceptibility mapping (LSM) is making increasing use of GIS-based spatial analysis in combination with multi-criteria evaluation (MCE) methods. We have developed a new multi-criteria decision analysis (MCDA) method for LSM and applied it to the Izeh River basin in south-western Iran. Our method is based on fuzzy membership functions (FMFs) derived from GIS analysis. It makes use of nine causal landslide factors identified by local landslide experts. Fuzzy set theory was first integrated with an analytical hierarchy process (AHP) in order to use pairwise comparisons to compare LSM criteria for ranking purposes. FMFs were then applied in order to determine the criteria weights to be used in the development of a landslide susceptibility map. Finally, a landslide inventory database was used to validate the LSM map by comparing it with known landslides within the study area. Results indicated that the integration of fuzzy set theory with AHP produced significantly improved accuracies and a high level of reliability in the resulting landslide susceptibility map. Approximately 53% of known landslides within our study area fell within zones classified as having "very high susceptibility", with the further 31% falling into zones classified as having "high susceptibility".

Genetic variants of STAT4 are associated with ankylosing spondylitis susceptibility and severity in a Chinese Han population.

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Liu, Zhixiang; Zhang, Peisen; Dong, Jie

2014-01-01

Genetic factors play an important role in ankylosing spondylitis (AS) etiology and signal transducer and activator of transcription 4 (STAT4) gene polymorphisms may be involved. The aim of this study was to test whether STAT4 variants were associated with susceptibility to AS in a Chinese population. A total of 175 subjects who were diagnosed as AS and 249 healthy age-matched controls were enrolled in the present study. The rs7574865 G/T SNP in STAT4 gene was genotyped in all the subjects. The SPSS software was used to investigate the association between the rs7574865 genotypes and AS susceptibility or severity. Rs7574865 G/T was found to be significantly associated with increased risk and severity of AS. Our data demonstrated the STAT4 rs7574865 G/T SNP was significantly associated with increased AS susceptibility and severity in Chinese Han Population.

The relationship of motion sickness susceptibility to learned autonomic control for symptom suppression

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Cowings, P. S.; Toscano, W. B.

1982-01-01

Twenty-four men were randomly assigned to four equal groups matched in terms of their Coriolis Sickness Susceptibility Index (CSSI). Two groups of subjects were highly susceptible to motion sickness, and two groups were moderately susceptible. All subjects were given six C551 tests at 5-d intervals. Treatment Groups I (highly susceptible) and II (moderately susceptible) were taught to control their autonomic responses, using a training method called autogenic-feedback training (AFT) before the third, fourth, and fifth CSSI tests. Control groups III (highly susceptible) and IV (moderately susceptible) received no treatment. Results showed that both treatment groups significantly improved performance on CSSI tests after training; neither of the control groups changed significantly. Highly and moderately susceptible subjects in the two treatment groups improved at comparable rates. Highly susceptible control group subjects did not habituate across tests as readily as the moderately susceptible controls.

STrategically Acquired Gradient Echo (STAGE) imaging, part I: Creating enhanced T1 contrast and standardized susceptibility weighted imaging and quantitative susceptibility mapping.

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Chen, Yongsheng; Liu, Saifeng; Wang, Yu; Kang, Yan; Haacke, E Mark

2018-02-01

To provide whole brain grey matter (GM) to white matter (WM) contrast enhanced T1W (T1WE) images, multi-echo quantitative susceptibility mapping (QSM), proton density (PD) weighted images, T1 maps, PD maps, susceptibility weighted imaging (SWI), and R2* maps with minimal misregistration in scanning times creating enhanced GM/WM contrast (the T1WE). The proposed T1WE image was created from a combination of the proton density weighted (6°, PDW) and T1W (24°) images and corrected for RF transmit field variations. Prior to the QSM calculation, a multi-echo phase unwrapping strategy was implemented using the unwrapped short echo to unwrap the longer echo to speed up computation. R2* maps were used to mask deep grey matter and veins during the iterative QSM calculation. A weighted-average sum of susceptibility maps was generated to increase the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). The proposed T1WE image has a significantly improved CNR both for WM to deep GM and WM to cortical GM compared to the acquired T1W image (the first echo of 24° scan) and the T1MPRAGE image. The weighted-average susceptibility maps have 80±26%, 55±22%, 108±33% SNR increases across the ten subjects compared to the single echo result of 17.5ms for the putamen, caudate nucleus, and globus pallidus, respectively. STAGE imaging offers the potential to create a standardized brain imaging protocol providing four pieces of quantitative tissue property information and multiple types of qualitative information in just 5min. Published by Elsevier Inc.

Adolescent Susceptibility to Peer Influence in Sexual Situations.

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Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W; Prinstein, Mitchell J

2016-03-01

One consistent predictor of adolescents' engagement in sexual risk behavior is their belief that peers are engaging in similar behavior; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes. The purpose of this project was to identify predictors of susceptibility to peer influence using a novel performance-based measure of sexual risk taking. Participants were 300 early adolescents (Mage = 12.6 years; 53% female; 44% Caucasian) who completed (1) a pretest assessment of demographics, sexual attitudes, and hypothetical scenarios measuring the likelihood of engaging in sexual risk behavior and (2) a subsequent experimental procedure that simulated an Internet chat room in which youth believed that they were communicating with peers regarding these same hypothetical scenarios. In reality, these "peers" were computer-programmed e-confederates. Changes in responses to the sexual scenarios in the private pretest versus during the public chat room provided a performance-based measure of peer influence susceptibility. In total, 78% of youth provided more risky responses in the chat room than those in pretest. The most robust predictor of this change was gender, with boys significantly more susceptible to peer influence than girls. Significant interactions also were noted, with greater susceptibility among boys with later pubertal development and African-American boys. Results confirm that not all youth are equally susceptible to peer influence. Consistent with sexual script theory, boys evidence greater susceptibility to social pressure regarding sexual behavior than girls. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Exposure to point‐of‐sale displays and changes in susceptibility to smoking: findings from a cohort study of school students

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Szatkowski, Lisa; McNeill, Ann; Spanopoulos, Dionysis; Britton, John

2015-01-01

Abstract Aims To investigate the association between frequency of visiting shops and noticing of tobacco point‐of‐sale (PoS) displays and the development of susceptibility to smoking, or smoking uptake, in secondary school students. Design Two surveys of a school based cohort study carried out in 2011 and 2012. Settings Nottinghamshire, UK. Participants A total of 2270 children aged 11–16 years from eight schools in Nottinghamshire. Measurements We investigated changes in susceptibility to smoking and smoking status in relation to frequency of visiting shops and noticing PoS displays and number of tobacco brands recognized, controlling for a range of potential confounders. Susceptibility to smoking was defined using a set of three questions covering intentions to try smoking, to smoke within the next year and likelihood of smoking if a best friend offered a cigarette. For the analysis we used multinomial logistic regression. Findings Among non‐susceptible never smokers, noticing PoS displays more frequently was associated independently with an increased risk of becoming susceptible to smoking [adjusted relative risk ratio (RRR) = 1.74; 99% confidence interval (CI) = 1.13–2.69], but was not associated with smoking uptake. Recognizing a higher number of brands among non‐susceptible never smokers doubled the risk of becoming susceptible to smoking and of becoming a smoker, but this did not have a significant effect on transition to smoking among susceptible never smokers. Frequency of noticing tobacco PoS displays was not associated significantly with smoking uptake among those who were susceptible never smokers at baseline. Conclusions Noticing tobacco point‐of‐sale displays more often and recognizing a higher number of tobacco brands is associated with an increased risk of becoming susceptible to smoking among adolescents in the United Kingdom, and recognizing a higher number of brands is associated positively with an increased risk of

Does Reactivating a Witnessed Memory Increase Its Susceptibility to Impairment by Subsequent Misinformation?

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Rindal, Eric J.; DeFranco, Rachel M.; Rich, Patrick R.; Zaragoza, Maria S.

2016-01-01

In a recent PNAS article, Chan and LaPaglia (2013) provided arguments and evidence to support the claim that reactivating a witnessed memory (by taking a test) renders the memory labile and susceptible to impairment by subsequent misinformation. In the current article, we argue that Chan and LaPaglia's (2013) findings are open to alternative…

Anaerobic bacteraemia revisited: species and susceptibilities.

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Ng, Lily S Y; Kwang, Lee Ling; Rao, Suma; Tan, Thean Yen

2015-01-01

This retrospective study was performed to evaluate the frequency of anaerobic bacteraemia over a 10-year period, and to provide updated antibiotic susceptibilities for the more clinically relevant anaerobes causing blood stream infection. Data were retrieved from the laboratory information system for the period 2003 to 2012. During this time, blood cultures were inoculated in Bactec™ Plus vials (BD, USA) and continuously monitored in the Bactec™ 9000 blood culture system (BD, USA). Anaerobic organisms were identified using commercial identification kits, predominantly API 20 A (bioMérieux, France) supplemented with Vitek ANC cards (bioMérieux, France) and AN-Ident discs (Oxoid, United Kingdom). A representative subset of isolates were retrieved from 2009 to 2011 and antimicrobial susceptibilities to penicillin, amoxicillin-clavulanate, clindamycin, imipenem, moxifloxacin, piperacillin-tazobactam and metronidazole were determined using the Etest method. Anaerobes comprised 4.1% of all positive blood culture with 727 obligate anaerobes recovered over the 10-year period, representing a positivity rate of 0.35%. The only significant change in anaerobe positivity rates occurred between 2003 and 2004, with an increase of 0.2%. The Bacteroides fragilis group (45%) were the predominant anaerobic pathogens, followed by Clostridium species (12%), Propioniobacterium species (11%) and Fusobacterium species (6%). The most active in vitro antibiotics were imipenem, piperacillin-tazobactam, amoxicillin-clavulanate and metronidazole, with susceptibilities of 95.0%, 93.3%, 90.8% and 90.8% respectively. Resistance was high to penicillin, clindamycin and moxifl oxacin. However, there were apparent differences for antibiotic susceptibilities between species. This study indicates that the anaerobes comprise a small but constant proportion of bloodstream isolates. Antibiotic resistance was high to some antibiotics, but metronidazole, the beta-lactam/beta-lactamase inhibitors and

Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle During Adulthood

Directory of Open Access Journals (Sweden)

Fiona B Mcdonald

2016-03-01

Full Text Available Intermittent hypoxia is a feature of apnea of prematurity, chronic lung disease and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH during postnatal development (pCIH causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 hours of delivery, pups and their respective dams were exposed to CIH: 90s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 hrs per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH, where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

Early life exposure to chronic intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during adulthood.

LENUS (Irish Health Repository)

McDonald, Fiona B

2016-03-01

Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and\\/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

The Interaction of TXNIP and AFq1 Genes Increases the Susceptibility of Schizophrenia.

Science.gov (United States)

Su, Yousong; Ding, Wenhua; Xing, Mengjuan; Qi, Dake; Li, Zezhi; Cui, Donghong

2017-08-01

Although previous studies showed the reduced risk of cancer in patients with schizophrenia, whether patients with schizophrenia possess genetic factors that also contribute to tumor suppressor is still unknown. In the present study, based on our previous microarray data, we focused on the tumor suppressor genes TXNIP and AF1q, which differentially expressed in patients with schizophrenia. A total of 413 patients and 578 healthy controls were recruited. We found no significant differences in genotype, allele, or haplotype frequencies at the selected five single nucleotide polymorphisms (SNPs) (rs2236566 and rs7211 in TXNIP gene; rs10749659, rs2140709, and rs3738481 in AF1q gene) between patients with schizophrenia and controls. However, we found the association between the interaction of TXNIP and AF1q with schizophrenia by using the MDR method followed by traditional statistical analysis. The best gene-gene interaction model identified was a three-locus model TXNIP (rs2236566, rs7211)-AF1q (rs2140709). After traditional statistical analysis, we found the high-risk genotype combination was rs2236566 (GG)-rs7211(CC)-rs2140709(CC) (OR = 1.35 [1.03-1.76]). The low-risk genotype combination was rs2236566 (GT)-rs7211(CC)-rs2140709(CC) (OR = 0.67 [0.49-0.91]). Our finding suggested statistically significant role of interaction of TXNIP and AF1q polymorphisms (TXNIP-rs2236566, TXNIP-rs7211, and AF1q-rs2769605) in schizophrenia susceptibility.

Susceptibility-Weighted Imaging and Quantitative Susceptibility Mapping in the Brain

Science.gov (United States)

Liu, Chunlei; Li, Wei; Tong, Karen A.; Yeom, Kristen W.; Kuzminski, Samuel

2015-01-01

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging. PMID:25270052

Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain.

Science.gov (United States)

Liu, Chunlei; Li, Wei; Tong, Karen A; Yeom, Kristen W; Kuzminski, Samuel

2015-07-01

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging. © 2014 Wiley Periodicals, Inc.

Accuracy of magnetic resonance based susceptibility measurements

Science.gov (United States)

Erdevig, Hannah E.; Russek, Stephen E.; Carnicka, Slavka; Stupic, Karl F.; Keenan, Kathryn E.

2017-05-01

Magnetic Resonance Imaging (MRI) is increasingly used to map the magnetic susceptibility of tissue to identify cerebral microbleeds associated with traumatic brain injury and pathological iron deposits associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Accurate measurements of susceptibility are important for determining oxygen and iron content in blood vessels and brain tissue for use in noninvasive clinical diagnosis and treatment assessments. Induced magnetic fields with amplitude on the order of 100 nT, can be detected using MRI phase images. The induced field distributions can then be inverted to obtain quantitative susceptibility maps. The focus of this research was to determine the accuracy of MRI-based susceptibility measurements using simple phantom geometries and to compare the susceptibility measurements with magnetometry measurements where SI-traceable standards are available. The susceptibilities of paramagnetic salt solutions in cylindrical containers were measured as a function of orientation relative to the static MRI field. The observed induced fields as a function of orientation of the cylinder were in good agreement with simple models. The MRI susceptibility measurements were compared with SQUID magnetometry using NIST-traceable standards. MRI can accurately measure relative magnetic susceptibilities while SQUID magnetometry measures absolute magnetic susceptibility. Given the accuracy of moment measurements of tissue mimicking samples, and the need to look at small differences in tissue properties, the use of existing NIST standard reference materials to calibrate MRI reference structures is problematic and better reference materials are required.

Quantitative Susceptibility Mapping in Parkinson's Disease.

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Langkammer, Christian; Pirpamer, Lukas; Seiler, Stephan; Deistung, Andreas; Schweser, Ferdinand; Franthal, Sebastian; Homayoon, Nina; Katschnig-Winter, Petra; Koegl-Wallner, Mariella; Pendl, Tamara; Stoegerer, Eva Maria; Wenzel, Karoline; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen Rainer; Schmidt, Reinhold; Schwingenschuh, Petra

2016-01-01

Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

Influence of preexisting pulmonary emphysema on susceptibility of rats to inhaled diesel exhaust

International Nuclear Information System (INIS)

Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Griffith, W.C.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K.

1990-01-01

The susceptibilities of normal rats and rats with preexisting pulmonary emphysema to chronically inhaled diesel exhaust were compared. Rats were exposed 7 h/day, 5 days/wk for 24 months to diesel exhaust at 3.5 mg soot/m3, or to clean air as controls. Emphysema was induced in one-half of the rats by intratracheal instillation of elastase 6 wk before exhaust exposure. Measurements included lung burdens of diesel soot, respiratory function, bronchoalveolar lavage, clearance of radiolabeled particles, pulmonary immune responses, lung collagen, excised lung weight and volume, histopathology, and mean linear intercept of terminal air spaces. Parameters indicated by analysis of variance to exhibit significant interactions between the influences of emphysema and exhaust were examined to determine if the effects were more than additive (indicating increased susceptibility). Although 14 of 63 parameters demonstrated emphysema-exhaust interactions, none indicated increased susceptibility. Less soot accumulated in lungs of emphysematous rats than in those of nonemphysematous rats, and the reduced accumulation had a sparing effect in the emphysematous rats. The results did not support the hypothesis that emphysematous lungs are more susceptible than are normal lungs to chronic exposure to high levels of diesel exhaust. The superimposition of effects of emphysema and exhaust, however, might still warrant special concern for heavy exposures of emphysematous subjects

High-frequency, transient magnetic susceptibility of ferroelectrics

Science.gov (United States)

Grimes, Craig A.

1996-10-01

A significant high-frequency magnetic susceptibility was measured both in weakly polarized and nonpolarized samples of barium titanate, lead zirconate titanate, and carnauba wax. Magnetic susceptibility measurements were made from 10 to 500 MHz using a thin film permeameter at room temperature; initial susceptibilities ranged from 0.1 to 2.5. These values are larger than expected for paramagnets and smaller than expected for ferromagnets. It was found that the magnetic susceptibility decreases rapidly with exposure to the exciting field. The origin of the magnetic susceptibility is thought to originate with the applied time varying electric field associated with the susceptibility measurements. An electric field acts to rotate an electric dipole, creating a magnetic quadrupole if the two moments are balanced, and a net magnetic dipole moment if imbalanced. It is thought that local electrostatic fields created at ferroelectric domain discontinuities associated with grain boundaries create an imbalance in the anion rotation that results in a net, measurable, magnetic moment. The origin of the magnetic aftereffect may be due to the local heating of the material through the moving charges associated with the magnetic moment.

Endogenous and Exogenous KdpF Peptide Increases Susceptibility of Mycobacterium bovis BCG to Nitrosative Stress and Reduces Intramacrophage Replication

Science.gov (United States)

Rosas Olvera, Mariana; Vivès, Eric; Molle, Virginie; Blanc-Potard, Anne-Béatrice; Gannoun-Zaki, Laila

2017-01-01

Emerging antibiotic resistance in pathogenic bacteria like Mycobacterium sp., poses a threat to human health and therefore calls for the development of novel antibacterial strategies. We have recently discovered that bacterial membrane peptides, such as KdpF, possess anti-virulence properties when overproduced in pathogenic bacterial species. Overproduction of the KdpF peptide in Mycobacterium bovis BCG decreased bacterial replication within macrophages, without presenting antibacterial activity. We propose that KdpF functions as a regulatory molecule and interferes with bacterial virulence, potentially through interaction with the PDIM transporter MmpL7. We demonstrate here that KdpF overproduction in M. bovis BCG, increased bacterial susceptibility to nitrosative stress and thereby was responsible for lower replication rate within macrophages. Moreover, in a bacterial two-hybrid system, KdpF was able to interact not only with MmpL7 but also with two membrane proteins involved in nitrosative stress detoxification (NarI and NarK2), and a membrane protein of unknown function that is highly induced upon nitrosative stress (Rv2617c). Interestingly, we showed that the exogenous addition of KdpF synthetic peptide could affect the stability of proteins that interact with this peptide. Finally, the exogenous KdpF peptide presented similar biological effects as the endogenously expressed peptide including nitrosative stress susceptibility and reduced intramacrophage replication rate for M. bovis BCG. Taken together, our results establish a link between high levels of KdpF and nitrosative stress susceptibility to further highlight KdpF as a potent molecule with anti-virulence properties. PMID:28428950

Real-Time Optical Antimicrobial Susceptibility Testing

DEFF Research Database (Denmark)

Fredborg, Marlene; Andersen, Klaus R; Jørgensen, Erik

2013-01-01

Rapid antibiotic susceptibility testing is in highly demand in health-care fields as antimicrobial resistant bacterial strains emerge and spread. Here we describe an optical screening system (oCelloScope), which based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time......, introduces real-time detection of bacterial growth and antimicrobial susceptibility, with imaging material to support the automatically generated graphs. Automated antibiotic susceptibility tests of a monoculture showed statistically significant antibiotic effect within 6 minutes and within 30 minutes...... from multidrug-resistant pathogenic bacteria. The oCelloScope system can be employed for a broad range of applications within bacteriology and may present new vistas as a point-of-care instrument in both clinical and veterinarian settings....

Female Nur77-deficient mice show increased susceptibility to diet-induced obesity.

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Sonia Perez-Sieira

Full Text Available Adipose tissue is essential in the regulation of body weight. The key process in fat catabolism and the provision of energy substrate during times of nutrient deprivation or enhanced energy demand is the hydrolysis of triglycerides and the release of fatty acids and glycerol. Nur77 is a member of the NR4A subfamily of nuclear receptors that plays an important metabolic role, modulating hepatic glucose metabolism and lipolysis in muscle. However, its endogenous role on white adipose tissue, as well as the gender dependency of these mechanisms, remains largely unknown. Male and female wild type and Nur77 deficient mice were fed with a high fat diet (45% calories from fat for 4 months. Mice were analyzed in vivo with the indirect calorimetry system, and tissues were analyzed by real-time PCR and Western blot analysis. Female, but not male Nur77 deficient mice, gained more weight and fat mass when compared to wild type mice fed with high fat diet, which can be explained by decreased energy expenditure. The lack of Nur77 also led to a decreased pHSL/HSL ratio in white adipose tissue and increased expression of CIDEA in brown adipose tissue of female Nur77 deficient mice. Overall, these findings suggest that Nur77 is an important physiological modulator of lipid metabolism in adipose tissue and that there are gender differences in the sensitivity to deletion of the Nur77 signaling. The decreased energy expenditure and the actions of Nur77 on liver, muscle, brown and white adipose tissue contribute to the increased susceptibility to diet-induced obesity in females lacking Nur77.

Role of vanadium carbide traps in reducing the hydrogen embrittlement susceptibility of high strength alloy steels. Final report

Energy Technology Data Exchange (ETDEWEB)

Spencer, G.L.; Duquette, D.J.

1998-08-01

High strength alloy steels typically used for gun steel were investigated to determine their susceptibility to hydrogen embrittlement. Although AISI grade 4340 was quite susceptible to hydrogen embrittlement, ASTM A723 steel, which has identical mechanical properties but slightly different chemistries, was not susceptible to hydrogen embrittlement when exposed to the same conditions. The degree of embrittlement was determined by conducting notched tensile testing on uncharged and cathodically charged specimens. Chemical composition was modified to isolate the effect of alloying elements on hydrogen embrittlement susceptibility. Two steels-Modified A723 (C increased from 0.32% to 0.40%) and Modified 4340 (V increased from 0 to O.12%) were tested. X-ray diffraction identified the presence of vanadium carbide, V{sub 4}C{sub 3}, in A-23 steels, and subsequent hydrogen extraction studies evaluated the trapping effect of vanadium carbide. Based on these tests, it was determined that adding vanadium carbide to 4340 significantly decreased hydrogen embrittlement susceptibility because vanadium carbide traps ties up diffusible hydrogen. The effectiveness of these traps is examined and discussed in this paper.

Risk factors for tobacco susceptibility in an orthodontic population: An exploratory study.

Science.gov (United States)

Jashinsky, Jared Michael; Liles, Sandy; Schmitz, Katy; Ding, Ding; Hovell, Melbourne

2017-08-01

Tobacco use is related to increased periodontal disease, tooth loss, and decreased success of orthodontic appliances, and it may inhibit orthodontic tooth movement. Most smokers start during adolescence. Since most cessation attempts fail, prevention appears necessary. A cross-sectional sample of orthodontic patients reported hypothesized risk factors for smoking and susceptibility to tobacco use initiation. Exploratory analyses regressed susceptibility to tobacco initiation on each hypothesized predictor variable in a separate logistic model that included a standard set of covariates. Significant odds ratios (OR) were found for the presence of a smoker in the home (OR, 2.168; 95% confidence interval [CI], 1.144-4.107), a friend having no-smoking rules in his or her home and car (OR, 0.337; 95% CI, 0.128-0.886), having been offered a cigarette (OR, 4.526; 95% CI, 1.190-17.207), and exposure to tobacco advertisements (OR, 1.910; 95% CI, 1.044-3.496). Peer, family, and environmental factors appear to increase children's susceptibility to smoking in orthodontic populations. Attention to such factors could help dental clinicians to more effectively identify susceptible young patients in need of antismoking advice. Prospective and experimental studies are required to confirm the role that dental clinicians might play in youth smoking prevention. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibility to knee osteoarthritis.

Science.gov (United States)

Yigit, Serbulent; Inanir, Ahmet; Tekcan, Akın; Tural, Ercan; Ozturk, Gokhan Tuna; Kismali, Gorkem; Karakus, Nevin

2014-03-01

Interleukin-4 (IL-4) is a strong chondroprotective cytokine and polymorphisms within this gene may be a risk factor for osteoarthritis (OA). We aimed to investigate genotype and allele frequencies of IL-4 gene intron 3 variable number of tandem repeats (VNTR) polymorphism in patients with knee OA in a Turkish population. The study included 202 patients with knee OA and 180 healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers followed by restriction fragment length polymorphism (RFLP) analysis. Our result show that there was statistically significant difference between knee OA patients and control group with respect to IL-4 genotype distribution and allele frequencies (p=0.000, OR: 0.20, 95% CI: 0.10-0.41, OR: 0.22, 95% CI: 0.12-0.42, respectively). Our findings suggest that there is an association of IL-4 gene intron 3 VNTR polymorphism with susceptibility of a person for development of knee OA. As a result, IL-4 gene intron 3 VNTR polymorphism could be a genetic marker in OA in a Turkish study population. This is the first association study that evaluates the associations between IL-4 gene VNTR polymorphism and knee OA. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Role of T cell receptor delta gene in susceptibility to celiac disease.

Science.gov (United States)

Roschmann, E; Wienker, T F; Volk, B A

1996-02-01

There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.

Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

Science.gov (United States)

Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

2014-04-10

In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

The association between miR-499 polymorphism and cancer susceptibility: a meta-analysis.

Science.gov (United States)

Xu, Zhongfei; Zhang, Enjiao; Duan, Weiyi; Sun, Changfu; Bai, Shuang; Tan, Xuexin

2015-01-01

MicroRNAs are a class of new noncoding RNA that play important roles in the pathogenesis of tumor. Rs3746444 in miR-499 is suggested to be associated with cancer susceptibility. In the present study, we assess the association between miR-499 rs3746444 polymorphism and cancer susceptibility through a meta-analysis. We searched relevant articles from the PubMed and Embase databases. We screened all the resulting articles for adherence to the inclusion and exclusion criteria. The associations between miR-499 polymorphism and cancer susceptibility were estimated by computing the odds ratios (ORs) and 95% confidence intervals (CIs). All analyses were performed using Stata software. There are 18 datasets included in the analysis. Statistically significant associations were found between the miR-499 rs3746444 polymorphism and susceptibility to cancer (GG versus AA: OR =1.24, 95% CI: 1.01-1.52; G versus A: OR =1.11, 95% CI: 1.01-1.23). A subsequent analysis, on the basis of ethnicity for the population characteristic, showed that Asians had increased susceptibility to cancer (GG versus AA: OR =1.32, 95% CI: 1.09-1.59; GG + AG versus AA: OR = 1.17, 95% CI: 1.01-1.37). In the subgroup analysis of tumor type, none of the genetic models had statistically significant results. The meta-regression suggested that race and cancer types are not the source of heterogeneity in the present meta-analysis. No publication bias was detected by either the inverted funnel plot or Egger's test. Rs3746444 in miR-499 might be related to susceptibility to cancer.

Susceptibility of pathogenic and nonpathogenic Naegleria ssp

International Nuclear Information System (INIS)

Whiteman, L.Y.

1988-01-01

The susceptibility of four species of Naegleria amoebae to complement-mediated lysis was determined. The amoebicidal activity of normal human serum (NHS) and normal guinea pig serum (NGPS) for Naegleria amoebae was measured by an in vitro cytotoxicity assay. Release of radioactivity from amoebae labeled with 3 H-uridine and visual observation with a compound microscope were used as indices of lysis. Susceptibility or resistance to complement-mediated lysis in vitro correlated with the in vivo pathogenic potential. Nonpathogenic Naegleria amoebae were lysed at a faster rate and at higher cell concentrations than were pathogenic amoebae. Electrophoretic analysis of NHS incubated with pathogenic or nonpathogenic Naegleria spp. demonstrated that amoebae activate the complement cascade resulting in the production of C3 and C5 complement cleavage products. Treatment with papain or trypsin for 1 h, but not with sialidase, increase the susceptibility of highly pathogenic, mouse-passaged N. fowleri to lysis. Treatment with actinomycin D, cycloheximide or various protease inhibitors for 4 h did not increase susceptibility to lysis. Neither a repair process involving de novo protein synthesis nor a complement-inactivating protease appear to account for the increase resistance of N. fowleri amoebae to complement-mediated lysis. A binding study with 125 I radiolabeled C9 indicated that the terminal complement component does not remain stably bound to the membrane of pathogenic amoebae

Increased susceptibility of dystrophin-deficient brain to mild hypoxia

International Nuclear Information System (INIS)

Wallis, T.; Rae, C.; Bubb, W.A.; Head, S.I.

2002-01-01

Full text: Duchenne muscular dystrophy is an X-linked disorder resulting from total absence of the 427 kDa protein dystrophin. Dystrophin is normally expressed in the brain mainly in a neuronal subpopulation: cortical pyramidal cells, hippocampal CA1 neurons and cerebellar Purkinje cells. One suggested role for dystrophin is in colocalising mitochondrial creatine kinase with ADP translocase and ATP synthase in mitochondria. Brain tissue slices in the murine model of Duchenne dystrophy, the mdx mouse, have been shown to be more sensitive to hypoxia than control. In this work, we used 13 C NMR to monitor the metabolic response of mdx cortical brain tissue slices to normoxia (95%O 2 /5% CO 2 ) and mild hypoxia (95%air/5% CO 2 ). Under normoxic conditions, mdx cortical slices displayed increased net flux through the Krebs cycle and glutamate/glutamine cycle, consistent with the proposed GABA A lesion which results in decreased inhibitory input. By contrast, mild hypoxia resulted in a significant increase in the total pool size of lactate and decreased net flux of 13 C from [3- 13 C]pyruvate into glutamate C4, GABA C2 and Ala C2, as well as decreased anaplerotic activity as measured by the ratio of Asp C2: Asp C3 label. Mild hypoxia has a significantly greater effect on brain oxidative metabolism in mdx mice, than in control

The interaction of BDNF and NTRK2 gene increases the susceptibility of paranoid schizophrenia.

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Zheng Lin

Full Text Available The association between BDNF gene functional Val66Met polymorphism rs6265 and the schizophrenia is far from being consistent. In addition to the heterogeneous in schizophrenia per se leading to the inconsistent results, the interaction among multi-genes is probably playing the main role in the pathogenesis of schizophrenia, but not a single gene. Neurotrophic tyrosine kinase receptor 2 (NTRK2 is the high-affinity receptor of BDNF, and was reported to be associated with mood disorders, though no literature reported the association with schizophrenia. Thus, in the present study, total 402 patients with paranoid schizophrenia (the most common subtype of schizophrenia and matched 406 healthy controls were recruited to investigate the role of rs6265 in BDNF, three polymorphisms in NTRK2 gene (rs1387923, rs2769605 and rs1565445 and their interaction in the susceptibility to paranoid schizophrenia in a Chinese Han population. We did not observe significant differences in allele and genotype frequencies between patients and healthy controls for all four polymorphisms separately. The haplotype analysis also showed no association between haplotype of NTRK2 genes (rs1387923, rs2769605, and rs1565445 and paranoid schizophrenia. However, we found the association between the interaction of BDNF and NTRK2 with paranoid schizophrenia by using the MDR method followed by conventional statistical analysis. The best gene-gene interaction model was a three-locus model (BDNF rs6265, NTRK2 rs1387923 and NTRK2 rs2769605, in which one low-risk and three high-risk four-locus genotype combinations were identified. Our findings implied that single polymorphism of rs6265 rs1387923, rs2769605, and rs1565445 in BDNF and NTRK2 were not associated with the development of paranoid schizophrenia in a Han population, however, the interaction of BDNF and NTRK2 genes polymorphisms (BDNF-rs6265, NTRK2-rs1387923 and NTRK2-rs2769605 may be involved in the susceptibility to paranoid

The interaction of BDNF and NTRK2 gene increases the susceptibility of paranoid schizophrenia.

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Lin, Zheng; Su, Yousong; Zhang, Chengfang; Xing, Mengjuan; Ding, Wenhua; Liao, Liwei; Guan, Yangtai; Li, Zezhi; Cui, Donghong

2013-01-01

The association between BDNF gene functional Val66Met polymorphism rs6265 and the schizophrenia is far from being consistent. In addition to the heterogeneous in schizophrenia per se leading to the inconsistent results, the interaction among multi-genes is probably playing the main role in the pathogenesis of schizophrenia, but not a single gene. Neurotrophic tyrosine kinase receptor 2 (NTRK2) is the high-affinity receptor of BDNF, and was reported to be associated with mood disorders, though no literature reported the association with schizophrenia. Thus, in the present study, total 402 patients with paranoid schizophrenia (the most common subtype of schizophrenia) and matched 406 healthy controls were recruited to investigate the role of rs6265 in BDNF, three polymorphisms in NTRK2 gene (rs1387923, rs2769605 and rs1565445) and their interaction in the susceptibility to paranoid schizophrenia in a Chinese Han population. We did not observe significant differences in allele and genotype frequencies between patients and healthy controls for all four polymorphisms separately. The haplotype analysis also showed no association between haplotype of NTRK2 genes (rs1387923, rs2769605, and rs1565445) and paranoid schizophrenia. However, we found the association between the interaction of BDNF and NTRK2 with paranoid schizophrenia by using the MDR method followed by conventional statistical analysis. The best gene-gene interaction model was a three-locus model (BDNF rs6265, NTRK2 rs1387923 and NTRK2 rs2769605), in which one low-risk and three high-risk four-locus genotype combinations were identified. Our findings implied that single polymorphism of rs6265 rs1387923, rs2769605, and rs1565445 in BDNF and NTRK2 were not associated with the development of paranoid schizophrenia in a Han population, however, the interaction of BDNF and NTRK2 genes polymorphisms (BDNF-rs6265, NTRK2-rs1387923 and NTRK2-rs2769605) may be involved in the susceptibility to paranoid schizophrenia.

Detection of superparamagnetic particles in soils developed on basalts using frequency- and amplitude-dependent magnetic susceptibility

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Grison, H.; Petrovsky, E.; Kapicka, A.

2016-12-01

In rock, soil and environmental studies dealing with magnetic methods, the frequency-dependent magnetic susceptibility (κFD%) is parameter generally accepted as a tool for identification of ultrafine superparamagnetic (SP) particles. This parameter became an indicator of pedogenic magnetic fraction (increased pedogenesis). Despite the number of studies using this parameter, knowledge about threshold values of κFD% is not clear enough and this parameter may be misinterpreted. Moreover, in strongly magnetic soils, magnetic signal of the SP (mostly pedogenic) minerals may be masked by dominant lithological signal, carried by coarse-grain mineral fraction; therefore, influence of pedogenesis is hard to detect. The aim of this contribution is to compare results in determination of ultrafine SP magnetic particles in soils determined using different instruments: (a) Bartington MS2B dual-frequency meter, and (b) more sensitive AGICO Kappameter MFK1-FA. The values of the κFD % obtained by the Bartington MS2B varied from 0.9 to 5.8% (mass-specific magnetic susceptibility from 119 to 1533 × 10-8 m3/kg) while the AGICO MFK1-FA varied from 3.7 to 8.2% (mass-specific magnetic susceptibility from 295 to 1843 × 10-8 m3/kg). Although both instruments suggest significant portion of SP magnetic particles, the results can't be interpreted using the generally accepted threshold values based on Bartington data. However, our results suggest that relation between the mass-specific magnetic susceptibility and κFD% along whole soil profile may serve as suitable tool in discriminating between lithogenic and pedogenic control of magnetic fraction in the soil profile. Moreover, we propose new concept of identification of SP particles, based on field-dependent magnetic susceptibility. Its behaviour shows distinct features with significant change at amplitudes of about 100 A/m. Below this value, susceptibility decreases with increasing amplitude, reflecting saturation of magnetization due

Definition of a magnetic susceptibility of conglomerates with magnetite particles. Particularities of defining single particle susceptibility

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Sandulyak, A. A.; Sandulyak, A. V.; Ershova, V.; Pamme, N.; Ngmasom, B.; Iles, A.

2017-11-01

Data of a magnetic susceptibility of ferro-and the ferrimagnetic particles of many technogenic, natural, special media are especially demanded for the solution of various tasks connected with purposeful magnetic impact on these particles. One of productive approaches to definition of a magnetic susceptibility χ of these particles consists in receiving experimental data of a susceptibility of disperse samples 〈 χ 〉 with a disperse phase of these particles. The paper expounds and analyses the results of experiments on defining (by Faraday method in a magnetic field with intensity H = 90-730 kA/m) the magnetic susceptibility 〈 χ 〉 of disperse samples (conglomerates) with a given volume ratio γ of magnetite particles (γ = 0.0065-0.25). The corresponding families of concentration and field dependences are provided alongside with discussing the applicability of linear and exponential functions to describe these dependences. We consider the possibility of defining single particles susceptibility χ (with simultaneous obtaining field dependence of this susceptibility) by the commonly used relation χ = 〈 χ 〉 /γ both at relatively small (preferable for accuracy reasons) values γ - to γ = 0.02…0.025, as well as at increased values γ - up to γ = 0.25. The data χ are provided depending on H and correlating with known data at H matter magnetic susceptibility χm (for the case when the particles are traditionally likened to balls with the characteristic for them demagnetising factor equalling 1/3) complies with the anticipated inverse function χm ∼ 1/H in the studied area H (where magnetization M expressed as M = χH reaches saturation M = Const).

Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

NARCIS (Netherlands)

Plant, Darren; Flynn, Edward; Mbarek, Hamdi; Dieudé, Philippe; Cornelis, François; Arlestig, Lisbeth; Dahlqvist, Solbritt Rantapää; Goulielmos, George; Boumpas, Dimitrios T; Sidiropoulos, Prodromos; Johansen, Julia S; Ørnbjerg, Lykke M; Hetland, Merete Lund; Klareskog, Lars; Filer, Andrew; Buckley, Christopher D; Raza, Karim; Witte, Torsten; Schmidt, Reinhold E; Worthington, Jane

BACKGROUND: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with

Mitochondrial vulnerability and increased susceptibility to nutrient-induced cytotoxicity in fibroblasts from leigh syndrome French canadian patients.

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Yan Burelle

Full Text Available Mutations in LRPPRC are responsible for the French Canadian variant of Leigh Syndrome (LSFC, a severe disorder characterized biochemically by a tissue-specific deficiency of cytochrome c oxidase (COX and clinically by the occurrence of severe and deadly acidotic crises. Factors that precipitate these crises remain unclear. To better understand the physiopathology and identify potential treatments, we performed a comprehensive analysis of mitochondrial function in LSFC and control fibroblasts. Furthermore, we have used this cell-based model to screen for conditions that promote premature cell death in LSFC cells and test the protective effect of ten interventions targeting well-defined aspects of mitochondrial function. We show that, despite maintaining normal ATP levels, LSFC fibroblasts present several mitochondrial functional abnormalities under normal baseline conditions, which likely impair their capacity to respond to stress. This includes mitochondrial network fragmentation, impaired oxidative phosphorylation capacity, lower membrane potential, increased sensitivity to Ca2+-induced permeability transition, but no changes in reactive oxygen species production. We also show that LSFC fibroblasts display enhanced susceptibility to cell death when exposed to palmitate, an effect that is potentiated by high lactate, while high glucose or acidosis alone or in combination were neutral. Furthermore, we demonstrate that compounds that are known to promote flux through the electron transport chain independent of phosphorylation (methylene blue, dinitrophenol, or modulate fatty acid (L-carnitine or Krebs cycle metabolism (propionate are protective, while antioxidants (idebenone, N-acetyl cysteine, resveratrol exacerbate palmitate plus lactate-induced cell death. Collectively, beyond highlighting multiple alterations in mitochondrial function and increased susceptibility to nutrient-induced cytotoxicity in LSFC fibroblasts, these results raise

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

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Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

2016-01-01

Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

Mean magnetic susceptibility regularized susceptibility tensor imaging (MMSR-STI) for estimating orientations of white matter fibers in human brain.

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Li, Xu; van Zijl, Peter C M

2014-09-01

An increasing number of studies show that magnetic susceptibility in white matter fibers is anisotropic and may be described by a tensor. However, the limited head rotation possible for in vivo human studies leads to an ill-conditioned inverse problem in susceptibility tensor imaging (STI). Here we suggest the combined use of limiting the susceptibility anisotropy to white matter and imposing morphology constraints on the mean magnetic susceptibility (MMS) for regularizing the STI inverse problem. The proposed MMS regularized STI (MMSR-STI) method was tested using computer simulations and in vivo human data collected at 3T. The fiber orientation estimated from both the STI and MMSR-STI methods was compared to that from diffusion tensor imaging (DTI). Computer simulations show that the MMSR-STI method provides a more accurate estimation of the susceptibility tensor than the conventional STI approach. Similarly, in vivo data show that use of the MMSR-STI method leads to a smaller difference between the fiber orientation estimated from STI and DTI for most selected white matter fibers. The proposed regularization strategy for STI can improve estimation of the susceptibility tensor in white matter. © 2014 Wiley Periodicals, Inc.

Assessing increasing susceptibility to wildfire at the wildland-urban fringe in the western United States

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Kinoshita, A. M.; Hogue, T. S.

2013-05-01

Much of the western U.S. is increasingly susceptible to wildfire activity due to drier conditions, elevated fuel loads, and expanding urbanization. As population increases, development pushes the urban boundary further into wildlands, creating more potential for human interaction at the wildland-urban interface (WUI), primarily from human ignitions and fire suppression policies. The immediate impacts of wildfires include vulnerability to debris flows, flooding, and impaired water quality. Fires also alter longer-term hydrological and ecosystem behavior. The current study utilizes geospatial datasets to investigate historical wildfire size and frequency relative to the WUI for a range of cities across western North America. California, the most populous state in the U.S., has an extensive fire history. The decennial population and acres burned for four major counties (Los Angeles, San Bernardino, San Diego, and Shasta) in California show that increasing wildfire size and frequency follow urbanization trends, with high correlation between the last decade of burned area, urban-fringe proximity, and increasing population. Ultimately, results will provide information on urban fringe communities that are most vulnerable to the risks associated with wildfire and post-fire impacts. In light of evolving land use policies (i.e. forest management and treatment, development at the urban-fringe) and climate change, it is critical to advance our knowledge of the implications that these conditions pose to urban centers, communicate risks to the public, and ultimately provide guidance for wildfire management.

Calcium handling by platelets from normal and malignant hyperthermia-susceptible pigs

International Nuclear Information System (INIS)

Miller, K.E.; Brooks, R.R.; Bonk, K.R.; Carpenter, J.F.

1991-01-01

Platelets from normal and malignant hyperthermia (MH)-susceptible pigs were evaluated for differences in 45 calcium uptake in the absence or presence of caffeine, halothane, or halothane and caffeine together. There were no statistically significant differences in basal or halothane-inhibited calcium uptake by platelets from either source. There was a small statistically significant difference in calcium uptake between platelets from normal and MH-susceptible pigs in the presence of 16 mM caffeine and 0.5% halothane. Calcium uptake by platelets from one pedigree of MH-susceptible pigs were stimulated in a concentration-dependent manner by caffeine. These data suggest that exposure of platelets to caffeine may have potential for identifying MH-susceptibility

Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

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Isabella M. Fuentes

2016-12-01

Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

Magnetic susceptibility in the edged topological disordered nanoscopic cylinder

International Nuclear Information System (INIS)

Faizabadi, Edris; Omidi, Mahboubeh

2011-01-01

The effects of edged topological disorder on magnetic susceptibility are investigated in a nanoscopic cylinder threaded by a magnetic flux. Persistent current versus even or odd number of electrons shows different signs in ordered and disordered cylinders and also in short or long ones. In addition, temperature-averaged susceptibility has only diamagnetic signs in strong regimes and it is associated with paramagnetic signs in ordered and weak disordered ones. Besides, in an edged topological disordered cylinder, the temperature-averaged susceptibility decreases by raising the temperature somewhat and then increasing initiates and finally at high temperature tends to zero as the ordered one. - Research highlights: → Magnetic susceptibility in one-dimensional topological disordered quantum ring. → Edged topological disorder effect on magnetic susceptibility in nanoscopic cylinder. → Edged topological disorder effect on temperature-averaged susceptibility in cylinder.

Effects of phase constitution of Zr-Nb alloys on their magnetic susceptibilities

International Nuclear Information System (INIS)

Nomura, Naoyuki; Tanaka, Yuko; Suyalatu; Kondo, Ryota; Doi, Hisashi; Tsutsumi, Yusuke; Hanawa, Takao

2009-01-01

The magnetic susceptibilities and microstructures of Zr-Nb binary alloys were investigated to develop a new metallic biomaterial with a low magnetic susceptibility for magnetic resonance imaging (MRI). The magnetic susceptibility was measured with a magnetic susceptibility balance, and the microstructure was evaluated with an X-ray diffractometer (XRD), an optical microscope (OM), and a transmission electron microscope (TEM). Zr-Nb alloys as-cast showed a minimum value of magnetic susceptibility between 3 and 9 mass% Nb, and the value abruptly increased up to 20 mass% Nb, followed by a gradual increase with the increase of the Nb content. XRD, OM, and TEM revealed that the minimum value of the susceptibility was closely related to the appearance of the athermal ω phase in the β phase. Since the magnetic susceptibility of Zr-3Nb alloy consisting of an α' phase was as low as that of Zr-9Nb alloy consisting of the β and ω phases, that of the ω phase was lower than that of the α' and β phases. When Zr-16Nb alloy was heat-treated, the isothermal ω phase appeared, and, simultaneously, the magnetic susceptibility decreased. Therefore, the ω phase contributes to the decrease of the magnetic susceptibility, independently of the formation process of the ω phase. The magnetic susceptibility of the Zr-3Nb alloy as-cast was almost one-third that of Ti-6Al-4V alloy, which is commonly used for medical implant devices. Zr-Nb alloys are useful for medical devices used under MRI. (author)

Nanotoxicity overview: nano-threat to susceptible populations.

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Li, Yang; Zhang, Yi; Yan, Bing

2014-02-28

Due to the increasing applications of nanomaterials and nanotechnology, potential danger of nanoparticle exposure has become a critical issue. However, recent nanotoxicity studies have mainly focused on the health risks to healthy adult population. The nanotoxicity effects on susceptible populations (such as pregnant, neonate, diseased, and aged populations) have been overlooked. Due to the alterations in physiological structures and functions in susceptible populations, they often suffer more damage from the same exposure. Thus, it is urgent to understand the effects of nanoparticle exposure on these populations. In order to fill this gap, the potential effects of nanoparticles to pregnant females, neonate, diseased, and aged population, as well as the possible underlying mechanisms are reviewed in this article. Investigations show that responses from susceptible population to nanoparticle exposure are often more severe. Reduced protection mechanism, compromised immunity, and impaired self-repair ability in these susceptible populations may contribute to the aggravated toxicity effects. This review will help minimize adverse effects of nanoparticles to susceptible population in future nanotechnology applications.

Nanotoxicity Overview: Nano-Threat to Susceptible Populations

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Yang Li

2014-02-01

Full Text Available Due to the increasing applications of nanomaterials and nanotechnology, potential danger of nanoparticle exposure has become a critical issue. However, recent nanotoxicity studies have mainly focused on the health risks to healthy adult population. The nanotoxicity effects on susceptible populations (such as pregnant, neonate, diseased, and aged populations have been overlooked. Due to the alterations in physiological structures and functions in susceptible populations, they often suffer more damage from the same exposure. Thus, it is urgent to understand the effects of nanoparticle exposure on these populations. In order to fill this gap, the potential effects of nanoparticles to pregnant females, neonate, diseased, and aged population, as well as the possible underlying mechanisms are reviewed in this article. Investigations show that responses from susceptible population to nanoparticle exposure are often more severe. Reduced protection mechanism, compromised immunity, and impaired self-repair ability in these susceptible populations may contribute to the aggravated toxicity effects. This review will help minimize adverse effects of nanoparticles to susceptible population in future nanotechnology applications.

Secondhand smoke exposure and other correlates of susceptibility to smoking: a propensity score matching approach.

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McIntire, Russell K; Nelson, Ashlyn A; Macy, Jonathan T; Seo, Dong-Chul; Kolbe, Lloyd J

2015-09-01

Secondhand smoke (SHS) exposure is responsible for numerous diseases of the lungs and other bodily systems among children. In addition to the adverse health effects of SHS exposure, studies show that children exposed to SHS are more likely to smoke in adolescence. Susceptibility to smoking is a measure used to identify adolescent never-smokers who are at risk for smoking. Limited research has been conducted on the influence of SHS on susceptibility to smoking. The purpose of this study was to determine a robust measure of the strength of correlation between SHS exposure and susceptibility to smoking among never-smoking U.S. adolescents. This study used data from the 2009 National Youth Tobacco Survey to identify predictors of susceptibility to smoking in the full (pre-match) sample of adolescents and a smaller (post-match) sample created by propensity score matching. Results showed a significant association between SHS exposure and susceptibility to smoking among never-smoking adolescents in the pre-match (OR=1.47) and post-match (OR=1.52) samples. The odds ratio increase after matching suggests that the strength of the relationship was underestimated in the pre-match sample. Other significant correlates of susceptibility to smoking identified include: gender, race/ethnicity, personal income, smoke-free home rules, number of smoking friends, perception of SHS harm, perceived benefits of smoking, and exposure to pro-tobacco media messages. The use of propensity score matching procedures reduced bias in the post-match sample, and provided a more robust estimate of the influence of SHS exposure on susceptibility to smoking, compared to the pre-match sample estimates. Copyright © 2015 Elsevier Ltd. All rights reserved.

A landslide susceptibility map of Africa

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Broeckx, Jente; Vanmaercke, Matthias; Duchateau, Rica; Poesen, Jean

2017-04-01

Studies on landslide risks and fatalities indicate that landslides are a global threat to humans, infrastructure and the environment, certainly in Africa. Nonetheless our understanding of the spatial patterns of landslides and rockfalls on this continent is very limited. Also in global landslide susceptibility maps, Africa is mostly underrepresented in the inventories used to construct these maps. As a result, predicted landslide susceptibilities remain subject to very large uncertainties. This research aims to produce a first continent-wide landslide susceptibility map for Africa, calibrated with a well-distributed landslide dataset. As a first step, we compiled all available landslide inventories for Africa. This data was supplemented by additional landslide mapping with Google Earth in underrepresented regions. This way, we compiled 60 landslide inventories from the literature (ca. 11000 landslides) and an additional 6500 landslides through mapping in Google Earth (including 1500 rockfalls). Various environmental variables such as slope, lithology, soil characteristics, land use, precipitation and seismic activity, were investigated for their significance in explaining the observed spatial patterns of landslides. To account for potential mapping biases in our dataset, we used Monte Carlo simulations that selected different subsets of mapped landslides, tested the significance of the considered environmental variables and evaluated the performance of the fitted multiple logistic regression model against another subset of mapped landslides. Based on these analyses, we constructed two landslide susceptibility maps for Africa: one for all landslide types and one excluding rockfalls. In both maps, topography, lithology and seismic activity were the most significant variables. The latter factor may be surprising, given the overall limited degree of seismicity in Africa. However, its significance indicates that frequent seismic events may serve as in important

Curiosity predicts smoking experimentation independent of susceptibility in a US national sample.

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Nodora, Jesse; Hartman, Sheri J; Strong, David R; Messer, Karen; Vera, Lisa E; White, Martha M; Portnoy, David B; Choiniere, Conrad J; Vullo, Genevieve C; Pierce, John P

2014-12-01

To improve smoking prevention efforts, better methods for identifying at-risk youth are needed. The widely used measure of susceptibility to smoking identifies at-risk adolescents; however, it correctly identifies only about one third of future smokers. Adding curiosity about smoking to this susceptibility index may allow us to identify a greater proportion of future smokers while they are still pre-teens. We use longitudinal data from a recent national study on parenting to prevent problem behaviors. Only oldest children between 10 and 13years of age were eligible. Participants were identified by RDD survey and followed for 6years. All baseline never smokers with at least one follow-up assessment were included (n=878). The association of curiosity about smoking with future smoking behavior was assessed. Then, curiosity was added to form an enhanced susceptibility index and sensitivity, specificity and positive predictive value were calculated. Among committed never smokers at baseline, those who were 'definitely not curious' were less likely to progress toward smoking than both those who were 'probably not curious' (ORadj=1.89; 95% CI=1.03-3.47) or 'probably/definitely curious' (ORadj=2.88; 95% CI=1.11-7.45). Incorporating curiosity into the susceptibility index increased the proportion identified as at-risk to smoke from 25.1% to 46.9%. The sensitivity (true positives) for this enhanced susceptibility index for both experimentation and established smoking increased from 37-40% to over 50%, although the positive predictive value did not improve. The addition of curiosity significantly improves the identification and classification of which adolescents will experiment with smoking or become established smokers. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential Susceptibility: The Genetic Moderation of Peer Pressure on Alcohol Use.

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Griffin, Amanda M; Cleveland, H Harrington; Schlomer, Gabriel L; Vandenbergh, David J; Feinberg, Mark E

2015-10-01

Although peer pressure can influence adolescents' alcohol use, individual susceptibility to these pressures varies across individuals. The dopamine receptor D4 gene (DRD4) is a potential candidate gene that may influence adolescents' susceptibility to their peer environment due to the role dopamine plays in reward sensation during social interaction. We hypothesized that DRD4 genotype status would moderate the impact of 7th-grade antisocial peer pressure on 12th-grade lifetime alcohol use (n = 414; 58.7% female; 92.8% White). The results revealed significant main effects for antisocial peer pressure, but no main effects for DRD4 genotype on lifetime alcohol use. Adolescent DRD4 genotype moderated the association between peer pressure and lifetime alcohol use. For individuals who carried at least one copy of the DRD4 7-repeat allele (7+), antisocial peer pressure was associated with increased lifetime alcohol use. These findings indicate that genetic sensitivity to peer pressure confers increased alcohol use in late adolescence.

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

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Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

2016-02-29

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

Changes of deep gray matter magnetic susceptibility over 2years in multiple sclerosis and healthy control brain

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Jesper Hagemeier

Full Text Available In multiple sclerosis, pathological changes of both tissue iron and myelin occur, yet these factors have not been characterized in a longitudinal fashion using the novel iron- and myelin-sensitive quantitative susceptibility mapping (QSM MRI technique. We investigated disease-relevant tissue changes associated with myelin loss and iron accumulation in multiple sclerosis deep gray matter (DGM over two years. One-hundred twenty (120 multiple sclerosis patients and 40 age- and sex-matched healthy controls were included in this prospective study. Written informed consent and local IRB approval were obtained from all participants. Clinical testing and QSM were performed both at baseline and at follow-up. Brain magnetic susceptibility was measured in major DGM structures. Temporal (baseline vs. follow-up and cross-sectional (multiple sclerosis vs. controls differences were studied using mixed factorial ANOVA analysis and appropriate t-tests. At either time-point, multiple sclerosis patients had significantly higher susceptibility in the caudate and globus pallidus and lower susceptibility in the thalamus. Over two years, susceptibility increased significantly in the caudate of both controls and multiple sclerosis patients. Inverse thalamic findings among MS patients suggest a multi-phase pathology explained by simultaneous myelin loss and/or iron accumulation followed by iron depletion and/or calcium deposition at later stages. Keywords: Quantitative susceptibility mapping, QSM, Iron, Multiple sclerosis, Longitudinal study

Understanding susceptibility of in-core components to irradiation-assisted stress corrosion cracking

International Nuclear Information System (INIS)

Chung, H.M.; Ruther, W.E.; Sanecki, J.E.; Kassner, T.F.

1991-03-01

As nuclear plants age and accumulated fluences of core structural components increase, susceptibility of the components to irradiation-assisted stress corrosion cracking (IASCC) is also expected to increase. Irradiation-induced sensitization, commonly associated with an IASCC failure, was investigated in this study to provide a better understanding of long-term structural integrity of safety-significant in-core components. Irradiation-induced sensitization of high- and commercial-purity Type 304 stainless steels irradiated in BWRs was analyzed. 7 refs., 8 figs

Antimicrobial Non-Susceptibility of Escherichia coli from Outpatients and Patients Visiting Emergency Rooms in Taiwan.

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Jann-Tay Wang

Full Text Available Longitudinal nationwide surveillance data on antimicrobial non-susceptibility and prevalence of extended-spectrum β-lactamases (ESBLs as well as AmpC β-lactamases producers among Escherichia coli from different sources in the community settings are limited. Such data may impact treatment practice. The present study investigated E. coli from outpatients and patients visiting emergency rooms collected by the Taiwan Surveillance of Antimicrobial Resistance (TSAR program. A total of 3481 E. coli isolates were studied, including 2153 (61.9% from urine and 1125 (32.3% from blood samples. These isolates were collected biennially between 2002 and 2012 from a total of 28 hospitals located in different geographic regions of Taiwan. Minimum inhibitory concentrations (MIC were determined using methods recommended by the Clinical Laboratory Standards Institute (CLSI. The prevalence and factors associated with the presence of ESBL and AmpC β-lactamase-producers were determined. Significant increases in non-susceptibility to most β-lactams and ciprofloxacin occurred during the study period. By 2012, non-susceptibility to cefotaxime and ciprofloxacin reached 21.1% and 26.9%, respectively. The prevalence of ESBL- and AmpC- producers also increased from 4.0% and 5.3%, respectively, in 2002-2004, to 10.7% for both in 2010-2012 (P < 0.001. The predominant ESBL and AmpC β-lactamase genes were CTX-M and CMY-types, respectively. Non-susceptibility of urine isolates to nitrofurantoin remained at around 8% and to fosfomycin was low (0.7% but to cefazolin (based on the 2014 CLSI urine criteria increased from 11.5% in 2002-2004 to 23.9% in 2010-2012 (P <0.001. Non-susceptibility of isolates from different specimen types was generally similar, but isolates from elderly patients were significantly more resistant to most antimicrobial agents and associated with the presence of ESBL- and AmpC- β-lactamases. An additional concern is that decreased ciprofloxacin

High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

DEFF Research Database (Denmark)

Bottley, G; Watherston, O G; Hiew, Y-L

2007-01-01

a role for E7 in tumour immune evasion. We show that knockdown of E7 expression in HPV16- and HPV18-transformed cervical carcinoma cells by RNA interference increased expression of major histocompatibility complex (MHC) class I at the cell surface and reduced susceptibility of these cells to natural...... killer (NK) cells. Tetracycline-regulated induction of HPV16 E7 resulted in reduced expression of cell surface MHC class I molecules and increased NK cell killing. Our results suggest that, for HPV-associated malignancies, reduced MHC class I expression is the result of an active immune evasion strategy...

Susceptibility, likelihood to be diagnosed, worry and fear for contracting Lyme disease.

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Fogel, Joshua; Chawla, Gurasees S

Risk perception and psychological concerns are relevant for understanding how people view Lyme disease. This study investigates the four separate outcomes of susceptibility, likelihood to be diagnosed, worry, and fear for contracting Lyme disease. University students (n=713) were surveyed about demographics, perceived health, Lyme disease knowledge, Lyme disease preventive behaviors, Lyme disease history, and Lyme disease miscellaneous variables. We found that women were associated with increased susceptibility and fear. Asian/Asian-American race/ethnicity was associated with increased worry and fear. Perceived good health was associated with increased likelihood to be diagnosed, worry, and fear. Correct knowledge was associated with increased susceptibility and likelihood to be diagnosed. Those who typically spend a lot of time outdoors were associated with increased susceptibility, likelihood to be diagnosed, worry, and fear. In conclusion, healthcare providers and public health campaigns should address susceptibility, likelihood to be diagnosed, worry, and fear about Lyme disease, and should particularly target women and Asians/Asian-Americans to address any possible misconceptions and/or offer effective coping strategies. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Ertapenem susceptibility of extended spectrum beta-lactamase-producing organisms

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Selby Edward B

2007-06-01

Full Text Available Abstract Background Infections caused by multiply drug resistant organisms such as extended spectrum beta-lactamase (ESBL-producing Escherichia coli and Klebsiella pneumoniae are increasing. Carbapenems (imipenem and meropenem are the antibiotics commonly used to treat these agents. There is limited clinical data regarding the efficacy of the newest carbapenem, ertapenem, against these organisms. Ertapenem susceptibility of ESBL-producing E. coli and K. pneumoniae clinical isolates were evaluated and compared to imipenem to determine if imipenem susceptibility could be used as a surrogate for ertapenem susceptibility. Methods 100 ESBL isolates (n = 34 E. coli and n = 66 K. pneumoniae collected from 2005–2006 clinical specimens at WRAMC were identified and tested for susceptibility by Vitek Legacy [bioMerieux, Durham, NC]. Ertapenem susceptibility was performed via epsilometer test (E-test [AB Biodisk, Solna, Sweden]. Results 100% of ESBL isolates tested were susceptible to ertapenem. 100% of the same isolates were also susceptible to imipenem. Conclusion These results, based on 100% susceptibility, suggest that ertapenem may be an alternative to other carbapenems for the treatment of infections caused by ESBL-producing E. coli and K. pneumoniae. Clinical outcomes studies are needed to determine if ertapenem is effective for the treatment of infection caused by these organisms. However, due to lack of resistant isolates, we are unable to conclude whether imipenem susceptibility accurately predicts ertapenem susceptibility.

Clinico-mycological and Antifungal Susceptibility Profiles of Candiduria in A Tertiary Care Hospital From South India

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Dinoop Korol Ponnambath

2017-10-01

Full Text Available Introduction: Candida is one of the common causative agent of Urinary Tract Infections (UTI worldwide. The most common reported species causing UTI is Candida albicans. Incidence of UTI due to non-albicans Candida species. is on rise in recent years because of their better adaptability and increased resistance to antifungals. Susceptibility profile reports of various Candida species. to newer azoles like voriconazole and betaglucan inhibitors (e.g., caspofungin are deficient in India, since the reference broth microdilution method is not widely utilized. In this study, a rapid reliable and easier alternative, VITEK 2 compact system was utilized to determine the antifungal susceptibility profile. Aim: To analyse the clinical and mycological profile with determination of drug susceptibility pattern of Candida isolates from urine samples. Materials and Methods: This observational study was conducted in PSG Institute of Medical Sciences and Research, during April to September 2015. Candida isolated with a colony count of ≥103 CFU/ml of urine from clinically suspected cases of UTI were included in the study. Urine samples (n=3821 from clinically suspected UTI cases (n=3821 were subjected to microscopic examination and semi quantitative estimation of yeast culture obtained by inoculated of calibrated volume of urine onto blood, Mac-conkey and HiCrome UTI agar. Clinical parameters of the cases were obtained for analysis. Speciation of Candida was performed using germ tube test, observation of morphology in corn-meal agar and pigment production in HiChrome Candida differential agar. Confirmation of the species identification and anti-fungal susceptibility profile were obtained using VITEK-2 compact system. Results: Total 101 patients were identified with significant candiduria. Community-Acquired Candiduria (CAC was seen in 11 (10.8% of the cases. 23 (22.7% cases of candiduria were associated with pyuria. Concomitant candidemia was observed in 4 (3

Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

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2011-01-01

Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) S. aureus strains. Methods Transcriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry. Results Growth of S. aureus strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (σB), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σB-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to DcRS did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation. Conclusions The results of

Chimpanzees show a developmental increase in susceptibility to contagious yawning: a test of the effect of ontogeny and emotional closeness on yawn contagion.

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Elainie Alenkær Madsen

Full Text Available Contagious yawning has been reported for humans, dogs and several non-human primate species, and associated with empathy in humans and other primates. Still, the function, development and underlying mechanisms of contagious yawning remain unclear. Humans and dogs show a developmental increase in susceptibility to yawn contagion, with children showing an increase around the age of four, when also empathy-related behaviours and accurate identification of others' emotions begin to clearly evince. Explicit tests of yawn contagion in non-human apes have only involved adult individuals and examined the existence of conspecific yawn contagion. Here we report the first study of heterospecific contagious yawning in primates, and the ontogeny of susceptibility thereto in chimpanzees, Pan troglodytes verus. We examined whether emotional closeness, defined as attachment history with the yawning model, affected the strength of contagion, and compared the contagiousness of yawning to nose-wiping. Thirty-three orphaned chimpanzees observed an unfamiliar and familiar human (their surrogate human mother yawn, gape and nose-wipe. Yawning, but not nose-wiping, was contagious for juvenile chimpanzees, while infants were immune to contagion. Like humans and dogs, chimpanzees are subject to a developmental trend in susceptibility to contagious yawning, and respond to heterospecific yawn stimuli. Emotional closeness with the model did not affect contagion. The familiarity-biased social modulatory effect on yawn contagion previously found among some adult primates, seem to only emerge later in development, or be limited to interactions with conspecifics. The influence of the 'chameleon effect', targeted vs. generalised empathy, perspective-taking and visual attention on contagious yawning is discussed.

Alzheimer skin fibroblasts show increased susceptibility to free radicals.

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Tesco, G; Latorraca, S; Piersanti, P; Piacentini, S; Amaducci, L; Sorbi, S

1992-11-01

We have studied the response to toxic oxygen metabolites of fibroblasts derived from skin biopsies of 5 patients with familial (FAD) and 4 with sporadic (AD) Alzheimer's disease compared with those derived from 4 normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 munits of xanthine-oxidase (Xo). To quantify cell damage we measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures. We found a significant increase in LDH activity in the FAD vs. controls and also in the AD vs. controls.

Effect of structural transition on magnetic susceptibility of tantalum carbide

International Nuclear Information System (INIS)

Lipatnikov, V.N.; Gusev, A.I.; Rempel', A.A.; Shvejkin, G.P.

1987-01-01

Ordering of carbon atoms and vacancies in nonmetal sublattice of TaC y is investigated for the first time by methods of magnetic susceptibility and structural neutron diffraction analysis. Measurements of magnetic susceptibility were conducted on high-sensitive magnetic scales in temperature interval of 300 - 1300 K with holding at each temperature up to the establishment of constant, nonchanging in the course of time value of susceptibility x. When investigating x-hardened tantalum carbide within the interval of TaC 0.82 - TaC 0.85 compositions under the conditions of slow heating, it was observed nonrecorded earlier irreversible decrease of susceptibility at temperature of 960 - 1000 K. With further temperature increase T>T tr it was observed at first even and than uneven increase of x value at a temperature of T tr equal to 1090, 1130 and 1150 K for TaC 0.82 , TaC 0.83 and TaC 0.85 respectively. The measuring of magnetic susceptibility of the same samples at temperature decrease reveals the presence of susceptibility temperature hysteresis in the interval of 1070 - 1090, 1100 - 1130 and 1120 - 1150 for TaC 0.82 , TaC 0.83 and TaC 0.85 . Reversible susceptibility jump corresponding to the temperature hysteresis range at dependences of x(T), is connected with equilibrium structural phase transition of order-disorder

Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections

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Lipner, Ettie M.; Garcia, Benjamin J.; Strong, Michael

2016-01-01

Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects. PMID:26751573

Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

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Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

2013-10-15

Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

Increased susceptibility to otitis media in a Splunc1-deficient mouse model

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Bartlett, Jennifer A.; Meyerholz, David K.; Wohlford-Lenane, Christine L.; Naumann, Paul W.; Salzman, Nita H.; McCray, Paul B.

2015-01-01

ABSTRACT Otitis media (inflammation of the middle ear) is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and examined whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by the accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid and mucus in the middle ear lumens. Furthermore, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1−/− mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear. PMID:25765466

Effect of inoculum size on the antibiotic susceptibilities of β-lactamase positive isolates of Moraxella catarrhalis

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J. Vraneš

2005-08-01

Full Text Available It is well known that bacteria producing β-lactamases in general show marked inoculum effect in susceptibility testing. The aim of this study is to determine the effect of inoculum size on the susceptibility of β-lactamase positive strains of M. catarrhalis to oral β-lactam and non β-lactam antibiotics. MICs of antibiotics were determined by a twofold microdilution technique with two different inoculum sizes were tested: 5x 105 CFU/ml -standard inoculum and 5 x107 CFU/ml -high inoculum. The highest increase (4-fold was observed with penicillins alone (amoxycillin and ampicillin or combined with inhibitor and ceftibuten, followed by older cephalosporins, erithromycine and chloramphenicol ( 2-fold. Tetracycline did not show a significant increase in MIC when a higher inoculum size was applied. In spite of the increase in MIC with high inoculum all strains were still susceptible to amoxycillin combined with clavulanate. MICs of cephalosporins were also below the resistance breakpoint for most of the strains at the higher inoculum. Based on that, we can conclude that therapeutic implications of the inoculum effect were not significant.These data suggest that high inocula should be used to determine MICs of ampicillin and amoxycillin for M. catarrhalis but that this precaution is unnecessary with the cephalosporins tested or with amoxycillin/clavulanate

Receptivity to Tobacco Advertising and Susceptibility to Tobacco Products.

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Pierce, John P; Sargent, James D; White, Martha M; Borek, Nicolette; Portnoy, David B; Green, Victoria R; Kaufman, Annette R; Stanton, Cassandra A; Bansal-Travers, Maansi; Strong, David R; Pearson, Jennifer L; Coleman, Blair N; Leas, Eric; Noble, Madison L; Trinidad, Dennis R; Moran, Meghan B; Carusi, Charles; Hyland, Andrew; Messer, Karen

2017-06-01

Non-cigarette tobacco marketing is less regulated and may promote cigarette smoking among adolescents. We quantified receptivity to advertising for multiple tobacco products and hypothesized associations with susceptibility to cigarette smoking. Wave 1 of the nationally representative PATH (Population Assessment of Tobacco and Health) study interviewed 10 751 adolescents who had never used tobacco. A stratified random selection of 5 advertisements for each of cigarettes, e-cigarettes, smokeless products, and cigars were shown from 959 recent tobacco advertisements. Aided recall was classified as low receptivity, and image-liking or favorite ad as higher receptivity. The main dependent variable was susceptibility to cigarette smoking. Among US youth, 41% of 12 to 13 year olds and half of older adolescents were receptive to at least 1 tobacco advertisement. Across each age group, receptivity to advertising was highest for e-cigarettes (28%-33%) followed by cigarettes (22%-25%), smokeless tobacco (15%-21%), and cigars (8%-13%). E-cigarette ads shown on television had the highest recall. Among cigarette-susceptible adolescents, receptivity to e-cigarette advertising (39.7%; 95% confidence interval [CI]: 37.9%-41.6%) was higher than for cigarette advertising (31.7%; 95% CI: 29.9%-33.6%). Receptivity to advertising for each tobacco product was associated with increased susceptibility to cigarette smoking, with no significant difference across products (similar odds for both cigarette and e-cigarette advertising; adjusted odds ratio = 1.22; 95% CI: 1.09-1.37). A large proportion of US adolescent never tobacco users are receptive to tobacco advertising, with television advertising for e-cigarettes having the highest recall. Receptivity to advertising for each non-cigarette tobacco product was associated with susceptibility to smoke cigarettes. Copyright © 2017 by the American Academy of Pediatrics.

Magnetic susceptibility characterisation of superparamagnetic microspheres

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Grob, David Tim; Wise, Naomi; Oduwole, Olayinka; Sheard, Steve

2018-04-01

The separation of magnetic materials in microsystems using magnetophoresis has increased in popularity. The wide variety and availability of magnetic beads has fuelled this drive. It is important to know the magnetic characteristics of the microspheres in order to accurately use them in separation processes integrated on a lab-on-a-chip device. To investigate the magnetic susceptibility of magnetic microspheres, the magnetic responsiveness of three types of Dynabeads microspheres were tested using two different approaches. The magnetophoretic mobility of individual microspheres is studied using a particle tracking system and the magnetization of each type of Dynabeads microsphere is measured using SQUID relaxometry. The magnetic beads' susceptibility is obtained at four different applied magnetic fields in the range of 38-70 mT for both the mobility and SQUID measurements. The susceptibility values in both approaches show a consistent magnetic field dependence.

Influence of deformation on SCC susceptibility of austenitic stainless steel in PWR primary water

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Kaneshima, Yoshiari; Totsuka, Nobuo; Nakajima, Nobuo [Institute of Nuclear Safety System Inc., Mihama, Fukui (Japan)

2001-09-01

Slow strain rate tests (SSRT) were carried out to evaluate the SCC susceptibility of four types of austenitic stainless steels (SUS304, SUS316, SUS304L and SUS316L) in PWR primary water. The influence of deformation on SCC susceptibility of SUS316 was studied. All types of stainless steel were susceptible to SCC, and the SCC susceptibility varied depending on the steel type. The comparison of the SSRT results and tensile test in air based on the reduction of area measurement showed that the SCC susceptibility increased with increasing the degree of deformation. For explaining the influence of deformation on SCC susceptibility, it is necessary to evaluate both intergranular and transgranular fractures. (author)

Tobacco marketing awareness on youth smoking susceptibility and perceived prevalence before and after an advertising ban.

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Moodie, Crawford; MacKintosh, Anne Marie; Brown, Abraham; Hastings, Gerard B

2008-10-01

The Tobacco Advertising and Promotion Act (TAPA) was implemented in the United Kingdom in 2003. This study is the first to assess its impact on young people, examining smoking susceptibility (intention to smoke among never smokers) and perceived prevalence across three British cross-sectional samples (aged 11-16) before and after the introduction of the ban. Three in-home surveys (n = 1078, 1121 and 1121) were conducted before (1999 and 2002) and after (2004) the implementation of the TAPA. Significant declines in awareness of tobacco marketing and perceived prevalence occurred across the three waves. Higher levels of awareness and perceived prevalence were associated with increased susceptibility, but direct measures of susceptibility remained stable. The TAPA is protecting young people in United Kingdom from tobacco marketing and reducing perceived prevalence, both of which are linked to susceptibility. The stability of susceptibility across the three waves is probably best explained by both the partial implementation of TAPA at the final survey point and the time such effects take to emerge. The evidence from this and previous studies is, however, that, ultimately, they will appear.

Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis

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M. Costagli

2016-01-01

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurological disorder that entails degeneration of both upper and lower motor neurons. The primary motor cortex (M1 in patients with upper motor neuron (UMN impairment is pronouncedly hypointense in Magnetic Resonance (MR T2* contrast. In the present study, 3D gradient-recalled multi-echo sequences were used on a 7 Tesla MR system to acquire T2*-weighted images targeting M1 at high spatial resolution. MR raw data were used for Quantitative Susceptibility Mapping (QSM. Measures of magnetic susceptibility correlated with the expected concentration of non-heme iron in different regions of the cerebral cortex in healthy subjects. In ALS patients, significant increases in magnetic susceptibility co-localized with the T2* hypointensity observed in the middle and deep layers of M1. The magnetic susceptibility, hence iron concentration, of the deep cortical layers of patients' M1 subregions corresponding to Penfield's areas of the hand and foot in both hemispheres significantly correlated with the clinical scores of UMN impairment of the corresponding limbs. QSM therefore reflects the presence of iron deposits related to neuroinflammatory reaction and cortical microgliosis, and might prove useful in estimating M1 iron concentration, as a possible radiological sign of severe UMN burden in ALS patients.

Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

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Jesus Perez-Losada

Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

Does obesity increase susceptibility to ozone? Respiratory, behavioral, and metabolic assessments in Brown Norway rats

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There may be a link between obesity and susceptibility to the respiratory, cardiovascular, and other health effects of air pollutants. Furthermore, it has been proposed that some air pollutants are obesogenic and may contribute to obesity. In view of the epidemic growth of obesit...

Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.

Science.gov (United States)

Sakakibara, Yasufumi; Sekiya, Michiko; Fujisaki, Naoki; Quan, Xiuming; Iijima, Koichi M

2018-01-01

Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER)-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.

Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.

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Yasufumi Sakakibara

2018-01-01

Full Text Available Wolfram syndrome (WS, caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1, is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.

Intramuscular injection of malignant hyperthermia trigger agents induces hypermetabolism in susceptible and nonsusceptible individuals.

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Metterlein, Thomas; Schuster, Frank; Kranke, Peter; Roewer, Norbert; Anetseder, Martin

2010-01-01

A new minimally invasive metabolic test for the diagnosis of susceptibility for malignant hyperthermia measuring intramuscular p(CO(2)) and lactate following local application of caffeine and halothane in humans was recently proposed. The present study tested the hypothesis that a more simplified test protocol allows a differentiation between malignant hyperthermia susceptible (MHS) and malignant hyperthermia nonsusceptible (MHN) and control individuals. With approval of the local ethics committee and informed consent, microdialysis and p(CO(2)) probes with attached microtubing were placed into the lateral vastus muscle of six MHS, seven MHN and seven control individuals. Following equilibration, boluses of 500 microl caffeine 80 mmol l(-1) and halothane 10 vol% dissolved in soybean oil were injected locally. p(CO(2)) and lactate were measured spectrophotometrically. The maximal rate of p(CO(2)) increase was significantly higher in MHS than in MHN and control individuals following application of halothane and caffeine, respectively. Intramuscular caffeine injection leads to a significantly higher increase of local lactate levels in MHS than in MHN and control individuals, whereas halothane increased local lactate levels in all investigated groups. Haemodynamic and systemic metabolic parameters did not differ between the investigated groups. Local caffeine and halothane injection increased intramuscular metabolism in MHS individuals significantly more than in the two other groups. In contrast to previous investigations, direct injection of the concentrations of halothane described here increased lactate and p(CO(2)) even in MHN skeletal muscle.

Magnetic susceptibility of molecular carbon: nanotubes and fullerite

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Ramirez, A P; Haddon, R C; Zhou, O; Fleming, R M; Zhang, J; McClure, S M; Smalley, R E [AT T Bell Laboratories, Murray Hill, NJ (United States)

1994-07-01

Elemental carbon can be synthesized in a variety of geometrical forms, from three-dimensional extended structures (diamond) to finite molecules (C[sub 60] fullerite). Results are presented here on the magnetic susceptibility of the least well-understood members of this family, nanotubes and C[sub 60] fullerite. (1) Nanotubes represent the cylindrical form of carbon, intermediate between graphite and fullerite. They are found to have significantly larger orientation-averaged susceptibility, on a per carbon basis, than any other form of elemental carbon. This susceptibility implies an average band structure among nanotubes similar to that of graphite. (2) High-resolution magnetic susceptibility data on C[sub 60] fullerite near the molecular orientational-ordering transition at 259 K show a sharp jump corresponding to 2.5 centimeter-gram-second parts per million per mole of C[sub 60]. This jump directly demonstrates the effect of an intermolecular cooperative transition on an intramolecular electronic property, where the susceptibility jump may be ascribed to a change in the shape of the molecule due to lattice forces.

Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

Science.gov (United States)

Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2015-10-01

Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

Science.gov (United States)

Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

2011-09-01

Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations. © 2011 The Author(s).

Examining the role of components of Slc11a1 (Nramp1 in the susceptibility of New Zealand sea lions (Phocarctos hookeri to disease.

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Amy J Osborne

Full Text Available The New Zealand sea lion (NZSL, Phocarctos hookeri is a Threatened marine mammal with a restricted distribution and a small, declining, population size. The species is susceptible to bacterial pathogens, having suffered three mass mortality events since 1998. Understanding the genetic factors linked to this susceptibility is important in mitigating population decline. The gene solute carrier family 11 member a1 (Slc11a1 plays an important role in mammalian resistance or susceptibility to a wide range of bacterial pathogens. At present, Slc11a1 has not been characterised in many taxa, and despite its known roles in mediating the effects of infectious disease agents, has not been examined as a candidate gene in susceptibility or resistance in any wild population of conservation concern. Here we examine components of Slc11a1 in NZSLs and identify: i a polymorphic nucleotide in the promoter region; ii putative shared transcription factor binding motifs between canids and NZSLs; and iii a conserved polymorphic microsatellite in the first intron of Slc11a1, which together suggest conservation of Slc11a1 gene structure in otariids. At the promoter polymorphism, we demonstrate a shift away from normal allele frequency distributions and an increased likelihood of death from infectious causes with one allelic variant. While this increased likelihood is not statistically significant, lack of significance is potentially due to the complexity of genetic susceptibility to disease in wild populations. Our preliminary data highlight the potential significance of this gene in disease resistance in wild populations; further exploration of Slc11a1 will aid the understanding of susceptibility to infection in mammalian species of conservation significance.

Low-field susceptibilities of rare earth spin glass alloys

International Nuclear Information System (INIS)

Sarkissian, B.V.B.

1977-01-01

Static susceptibility in various applied fields and AC susceptibility data on Sc 13% Gd and Sc 4.5% Tb spin glass alloys are reported. The data show that the sharp peak at the freezing temperature, Tsub(g), normally observed in the low-field susceptibility of spin glasses containing 3d magnetic impurities is observed here in the case of Gd, which is an S state solute, but not for Tb. On the contrary, for the Sc-Tb alloy a rather rounded maximum is observed which becomes slightly sharper with increasing applied magnetic fields. (author)

Antimicrobial resistance and susceptibility testing of anaerobic bacteria.

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Schuetz, Audrey N

2014-09-01

Infections due to anaerobic bacteria can be severe and life-threatening. Susceptibility testing of anaerobes is not frequently performed in laboratories, but such testing is important to direct appropriate therapy. Anaerobic resistance is increasing globally, and resistance trends vary by geographic region. An overview of a variety of susceptibility testing methods for anaerobes is provided, and the advantages and disadvantages of each method are reviewed. Specific clinical situations warranting anaerobic susceptibility testing are discussed. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Predictive susceptibility analysis of typhoon induced landslides in Central Taiwan

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Shou, Keh-Jian; Lin, Zora

2017-04-01

Climate change caused by global warming affects Taiwan significantly for the past decade. The increasing frequency of extreme rainfall events, in which concentrated and intensive rainfalls generally cause geohazards including landslides and debris flows. The extraordinary, such as 2004 Mindulle and 2009 Morakot, hit Taiwan and induced serious flooding and landslides. This study employs rainfall frequency analysis together with the atmospheric general circulation model (AGCM) downscaling estimation to understand the temporal rainfall trends, distributions, and intensities in the adopted Wu River watershed in Central Taiwan. To assess the spatial hazard of the landslides, landslide susceptibility analysis was also applied. Different types of rainfall factors were tested in the susceptibility models for a better accuracy. In addition, the routes of typhoons were also considered in the predictive analysis. The results of predictive analysis can be applied for risk prevention and management in the study area.

Patient Susceptibility to Candidiasis—A Potential for Adjunctive Immunotherapy

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Davidson, Linda; Netea, Mihai G.; Kullberg, Bart Jan

2018-01-01

Candida spp. are colonizing fungi of human skin and mucosae of the gastrointestinal and genitourinary tract, present in 30–50% of healthy individuals in a population at any given moment. The host defense mechanisms prevent this commensal fungus from invading and causing disease. Loss of skin or mucosal barrier function, microbiome imbalances, or defects of immune defense mechanisms can lead to an increased susceptibility to severe mucocutaneous or invasive candidiasis. A comprehensive understanding of the immune defense against Candida is essential for developing adjunctive immunotherapy. The important role of underlying genetic susceptibility to Candida infections has become apparent over the years. In most patients, the cause of increased susceptibility to fungal infections is complex, based on a combination of immune regulation gene polymorphisms together with other non-genetic predisposing factors. Identification of patients with an underlying genetic predisposition could help determine which patients could benefit from prophylactic antifungal treatment or adjunctive immunotherapy. This review will provide an overview of patient susceptibility to mucocutaneous and invasive candidiasis and the potential for adjunctive immunotherapy. PMID:29371502

Patient Susceptibility to Candidiasis—A Potential for Adjunctive Immunotherapy

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Linda Davidson

2018-01-01

Full Text Available Candida spp. are colonizing fungi of human skin and mucosae of the gastrointestinal and genitourinary tract, present in 30–50% of healthy individuals in a population at any given moment. The host defense mechanisms prevent this commensal fungus from invading and causing disease. Loss of skin or mucosal barrier function, microbiome imbalances, or defects of immune defense mechanisms can lead to an increased susceptibility to severe mucocutaneous or invasive candidiasis. A comprehensive understanding of the immune defense against Candida is essential for developing adjunctive immunotherapy. The important role of underlying genetic susceptibility to Candida infections has become apparent over the years. In most patients, the cause of increased susceptibility to fungal infections is complex, based on a combination of immune regulation gene polymorphisms together with other non-genetic predisposing factors. Identification of patients with an underlying genetic predisposition could help determine which patients could benefit from prophylactic antifungal treatment or adjunctive immunotherapy. This review will provide an overview of patient susceptibility to mucocutaneous and invasive candidiasis and the potential for adjunctive immunotherapy.

Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

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Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

2016-01-01

Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID:26870082

Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase.

Science.gov (United States)

Shiraishi, A; Sakumi, K; Sekiguchi, M

2000-10-01

O(6)-methylguanine-DNA methyltransferase plays vital roles in preventing induction of mutations and cancer as well as cell death related to alkylating agents. Mice defective in the MGMT: gene, encoding the methyltransferase, were used to evaluate cell death-inducing and tumorigenic activities of therapeutic agents which have alkylation potential. MGMT(-/-) mice were considerably more sensitive to dacarbazine, a monofunctional triazene, than were wild-type mice, in terms of survival. When dacarbazine was administered i.p. to 6-week-old mice and survival at 30 days was enumerated, LD(50) values of MGMT(-/-) and MGMT(+/+) mice were 20 and 450 mg/kg body wt, respectively. Increased sensitivity of MGMT(-/-) mice to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosou rea (ACNU), a bifunctional nitrosourea, was also noted. On the other hand, there was no difference in survival of MGMT(+/+) and MGMT(-/-) mice exposed to cyclophosphamide, a bifunctional nitrogen mustard. It appears that dacarbazine and ACNU produce O(6)-alkylguanine as a major toxic lesion, while cyclophosphamide yields other types of modifications in DNA which are not subjected to the action of the methyltransferase. MGMT(-/-) mice seem to be less refractory to the tumor-inducing effect of dacarbazine than are MGMT(+/+) mice. Thus, the level of O(6)-methylguanine-DNA methyltransferase activity is an important factor when determining susceptibility to drugs with the potential for alkylation.

Field-impressed anisotropy of susceptibility in iron-terbium thin films

International Nuclear Information System (INIS)

Stephenson, A.; Booth, N.A.

1995-01-01

Two thin films of Fe 1-x Tb x where x=0.17 and 0.23 are shown to exhibit the effect of field-impressed anisotropy. After application of a direct field of 80 mT, which gives them an isothermal remanent magnetization (IRM) in their plane, the anisotropy of initial susceptibility differs from that measured after the films have been tumble-demagnetized. By subtracting the susceptibility results of the tumble-demagnetized state from those obtained after the application of the 80 mT direct field, it is shown that the effect of this field is to decrease the susceptibility measured along the former applied field direction and to increase the susceptibility at right angles to this. The effect is almost certainly due to changes in domain alignment. Even though these films contain many domains, the above results are similar to those previously obtained for single-domain γFe 2 O 3 and magnetite particles. The sense of the effect is opposite to that for multi-domain magnetite particles where the susceptibility has been found to increase along the previously applied field direction. ((orig.))

Sixteen-Day Bedrest Significantly Increases Plasma Colloid Osmotic Pressure

Science.gov (United States)

Hargens, Alan R.; Hsieh, S. T.; Murthy, G.; Ballard, R. E.; Convertino, V. A.; Wade, Charles E. (Technical Monitor)

1994-01-01

Upon exposure to microgravity, astronauts lose up to 10% of their total plasma volume, which may contribute to orthostatic intolerance after space flight. Because plasma colloid osmotic pressure (COP) is a primary factor maintaining plasma volume, our objective was to measure time course changes in COP during microgravity simulated by 6 deg. head-down tilt (HDT). Seven healthy male subjects (30-55 years of age) were placed in HDT for 16 days. For the purpose of another study, three of the seven subjects were chosen to exercise on a cycle ergometer on day 16. Blood samples were drawn immediately before bedrest on day 14 of bedrest, 18-24 hours following exercise while all subjects were still in HDT and 1 hour following bedrest termination. Plasma COP was measured in all 20 microliter EDTA-treated samples using an osmometer fitted with a PM 30 membrane. Data were analyzed with paired and unpaired t-tests. Plasma COP on day 14 of bedrest (29.9 +/- 0.69 mmHg) was significantly higher (p less than 0.005) than the control, pre-bedrest value (23.1 +/- 0.76 mmHg). At one hour of upright recovery after HDT, plasma COP remained significantly elevated (exercise: 26.9 +/- 0.87 mmHg; no exercise: 26.3 +/- 0.85 mmHg). Additionally, exercise had no significant effect on plasma COP 18-24 hours following exercise (exercise: 27.8 +/- 1.09 mmHg; no exercise: 27.1 +/- 0.78 mmHg). Our results demonstrate that plasma COP increases significantly with microgravity simulated by HDT. However, preliminary results indicate exercise during HDT does not significantly affect plasma COP.

Genetic architecture of intrinsic antibiotic susceptibility.

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Hany S Girgis

2009-05-01

Full Text Available Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired.To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance.Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect.

Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing Loss in CBA/CaJ Mice

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Xiaolong Fu

2016-01-01

Full Text Available MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14−/− mice and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14−/− mice did not exhibit significant hearing loss until five months of age. In addition, Myh14−/− mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14−/− mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice.

Susceptibility profiles of Nocardia isolates based on current taxonomy.

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Schlaberg, Robert; Fisher, Mark A; Hanson, Kimberley E

2014-01-01

The genus Nocardia has undergone rapid taxonomic expansion in recent years, and an increasing number of species are recognized as human pathogens. Many established species have predictable antimicrobial susceptibility profiles, but sufficient information is often not available for recently described organisms. Additionally, the effectiveness of sulfonamides as first-line drugs for Nocardia has recently been questioned. This led us to review antimicrobial susceptibility patterns for a large number of molecularly identified clinical isolates. Susceptibility results were available for 1,299 isolates representing 39 different species or complexes, including 11 that were newly described, during a 6-year study period. All tested isolates were susceptible to linezolid. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) was rare (2%) except among Nocardia pseudobrasiliensis (31%) strains and strains of the N. transvalensis complex (19%). Imipenem susceptibility varied for N. cyriacigeorgica and N. farcinica, as did ceftriaxone susceptibility of the N. nova complex. Resistance to more than one of the most commonly used drugs (amikacin, ceftriaxone, TMP-SMX, and imipenem) was highest for N. pseudobrasiliensis (100%), N. transvalensis complex (83%), N. farcinica (68%), N. puris (57%), N. brasiliensis (51%), N. aobensis (50%), and N. amikacinitolerans (43%). Thus, while antimicrobial resistance can often be predicted, susceptibility testing should still be considered when combination therapy is warranted, for less well characterized species or those with variable susceptibility profiles, and for patients with TMP-SMX intolerance.

Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni.

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Sandra D Melman

2009-08-01

Full Text Available The near exclusive use of praziquantel (PZQ for treatment of human schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes.We measured susceptibility to PZQ of isolates of Schistosoma mansoni obtained from patients from Kisumu, Kenya continuously exposed to infection as a consequence of their occupations as car washers or sand harvesters. We used a an in vitro assay with miracidia, b an in vivo assay targeting adult worms in mice and c an in vitro assay targeting adult schistosomes perfused from mice. In the miracidia assay, in which miracidia from human patients were exposed to PZQ in vitro, reduced susceptibility was associated with previous treatment of the patient with PZQ. One isolate ("KCW" that was less susceptible to PZQ and had been derived from a patient who had never fully cured despite multiple treatments was studied further. In an in vivo assay of adult worms, the KCW isolate was significantly less susceptible to PZQ than two other isolates from natural infections in Kenya and two lab-reared strains of S. mansoni. The in vitro adult assay, based on measuring length changes of adults following exposure to and recovery from PZQ, confirmed that the KCW isolate was less susceptible to PZQ than the other isolates tested. A sub-isolate of KCW maintained separately and tested after three years was susceptible to PZQ, indicative that the trait of reduced sensitivity could be lost if selection was not maintained.Isolates of S. mansoni from some patients in Kisumu have lower susceptibility to PZQ, including one from a patient who was never fully cured after repeated rounds of treatment administered over several years. As use of PZQ continues, continued selection for worms with diminished susceptibility is possible, and the probability of emergence of resistance will increase as large reservoirs of untreated worms diminish. The potential for rapid emergence of resistance should be an important

Variations in Endosymbiont Infection Between Buprofezin-Resistant and Susceptible Strains of Laodelphax striatellus (Fallén).

Science.gov (United States)

Li, Yongteng; Liu, Xiangdong; Guo, Huifang

2018-06-01

The endosymbionts Wolbachia and Rickettsia have been shown to be correlated with the insecticide resistance of mosquito and whitefly. The small brown planthopper (SBPH), Laodelphax striatellus, harbours many species of endosymbionts, and has developed a high resistance to buprofezin in China. In this study, we examined the species and the infection incidences of endosymbionts in a buprofezin-resistant (BR) strain, a buprofezin-susceptible (BS) strain, and the BR strain after exposure to buprofezin, and we also investigated the change in buprofezin susceptibility after removal of Wolbachia from the BR strain. The results showed that Wolbachia infection incidences were 100% in both the BR and BS strains, but the Wolbachia density in the BR strain was significantly higher than that in the BS strain. There were no significant differences in Arsenophonus infection incidence between the two strains. However, the infection incidence of Serratia and double infection incidence of Serratia + Wolbachia in the BR strain were significantly higher than that in the BS strain. After the BR strain was exposed to 1200 mg/L buprofezin, the infection incidence of Arsenophonus in the surviving individuals increased, and the infection rate of Serratia did not differ, but the double infection incidence of Serratia + Wolbachia decreased. And when a Wolbachia-infected line originating from the BR strain was cleared of Wolbachia, its susceptibility to buprofezin increased. The results suggest that Serratia and Wolbachia infection might improve the buprofezin resistance of SBPH.

Identification and Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Rubik's Cube of Clinical Microbiology?

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Gajdács, Márió; Spengler, Gabriella; Urbán, Edit

2017-11-07

Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria.

Interventions on Metabolism: Making Antibiotic-Susceptible Bacteria

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Fernando Baquero

2017-11-01

Full Text Available Antibiotics act on bacterial metabolism, and antibiotic resistance involves changes in this metabolism. Interventions on metabolism with drugs might therefore modify drug susceptibility and drug resistance. In their recent article, Martin Vestergaard et al. (mBio 8:e01114-17, 2017, https://doi.org/10.1128/mBio.01114-17 illustrate the possibility of converting intrinsically resistant bacteria into susceptible ones. They reported that inhibition of a central metabolic enzyme, ATP synthase, allows otherwise ineffective polymyxin antibiotics to act on Staphylococcus aureus. The study of the intrinsic resistome of bacterial pathogens has shown that several metabolic genes, including multigene transcriptional regulators, contribute to antibiotic resistance. In some cases, these genes only marginally increase antibiotic resistance, but reduced levels of susceptibility might be critical in the evolution or resistance under low antibiotic concentrations or in the clinical response of highly resistant bacteria. Drug interventions on bacterial metabolism might constitute a critical adjuvant therapy in combination with antibiotics to ensure susceptibility of pathogens with intrinsic or acquired antimicrobial resistance.

Structural properties and magnetic susceptibility of iron-intercalated titanium ditelluride

International Nuclear Information System (INIS)

Pleshchev, V.G.; Titov, A.N.; Titova, S.G.; Kuranov, A.V.

1997-01-01

Structural peculiarities and magnetic susceptibility of titanium ditelluride, intercalated by iron, are studied. It is established that the basic motive of crystal structure by intercalation is preserved and the iron atoms are locates in the van der Waals gaps in positions with octahedral coordination. It is shown that the magnetic susceptibility of the Fe 0.25 TiT 2 sample increases approximately by 20 times. The magnetic susceptibility for the Fe 0.33 TiTe 2 samples becomes even much higher

Exposure to Advertisements and Susceptibility to Electronic Cigarette Use Among Youth.

Science.gov (United States)

Dai, Hongying; Hao, Jianqiang

2016-12-01

Despite the rapid increase in e-cigarette use among youth, little is known about the social and behavioral factors that have contributed to this rise. We investigated whether young e-cigarette users are susceptible to e-cigarette advertisements. Estimates of e-cigarette use and exposure to e-cigarette advertisements from the 2014 National Young Tobacco Survey were investigated. Factors associated with the prevalence and levels of e-cigarette use were analyzed using multinomial logistic regression. Of all respondents (n = 21,491), 19.8% had tried e-cigarettes and 9.4% were current e-cigarette users. Exposure to e-cigarette ads was prevalent among youth, with 38.6%/29.6%/53.2%/35.4% having medium to high exposure to e-cigarette ads from the Internet/newspapers/stores/TV, respectively. Current use of e-cigarettes among youth was associated with frequent exposure (high vs. low) to e-cigarette advertising from the Internet (odd ratio [OR] = 3.1, p < .0001), newspapers/magazines (OR = 2.5, p < .0001), stores (OR = 2.8, p < .0001), and TV/movies (OR = 2.1, p < .0001). In the multivariate analysis that joint analyzed four advertisement channels and covariates, greater exposure to e-cigarette ads on the Internet (adjusted OR = 1.9, p < .0001) and in retail stores (adjusted OR = 1.9, p < .0001) remained to be significantly associated with increased odds of using e-cigarettes. Vaping by other household members significantly increased the risk of adolescent e-cigarette use (OR = 8.7, p < .0001). Exposure to e-cigarette ads significantly increased susceptibility to e-cigarette use among adolescents. E-cigarette advertising regulations and educational campaigns are critically needed. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

The association between miR-499 polymorphism and cancer susceptibility: a meta-analysis

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Xu Z

2015-08-01

Full Text Available Zhongfei Xu, Enjiao Zhang, Weiyi Duan, Changfu Sun, Shuang Bai, Xuexin Tan Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, People’s Republic of China Background: MicroRNAs are a class of new noncoding RNA that play important roles in the pathogenesis of tumor. Rs3746444 in miR-499 is suggested to be associated with cancer susceptibility. In the present study, we assess the association between miR-499 rs3746444 polymorphism and cancer susceptibility through a meta-analysis. Methods: We searched relevant articles from the PubMed and Embase databases. We screened all the resulting articles for adherence to the inclusion and exclusion criteria. The associations between miR-499 polymorphism and cancer susceptibility were estimated by computing the odds ratios (ORs and 95% confidence intervals (CIs. All analyses were performed using Stata software. Results: There are 18 datasets included in the analysis. Statistically significant associations were found between the miR-499 rs3746444 polymorphism and susceptibility to cancer (GG versus AA: OR =1.24, 95% CI: 1.01–1.52; G versus A: OR =1.11, 95% CI: 1.01–1.23. A subsequent analysis, on the basis of ethnicity for the population characteristic, showed that Asians had increased susceptibility to cancer (GG versus AA: OR =1.32, 95% CI: 1.09–1.59; GG + AG versus AA: OR = 1.17, 95% CI: 1.01–1.37. In the subgroup analysis of tumor type, none of the genetic models had statistically significant results. The meta-regression suggested that race and cancer types are not the source of heterogeneity in the present meta-analysis. No publication bias was detected by either the inverted funnel plot or Egger’s test. Conclusion: Rs3746444 in miR-499 might be related to susceptibility to cancer. Keywords: microRNA, single-nucleotide polymorphism, tumor, risk factor

Design and development of novel MRI compatible zirconium- ruthenium alloys with ultralow magnetic susceptibility

Science.gov (United States)

Li, H.F.; Zhou, F.Y.; Li, L.; Zheng, Y.F.

2016-01-01

In the present study, novel MRI compatible zirconium-ruthenium alloys with ultralow magnetic susceptibility were developed for biomedical and therapeutic devices under MRI diagnostics environments. The results demonstrated that alloying with ruthenium into pure zirconium would significantly increase the strength and hardness properties. The corrosion resistance of zirconium-ruthenium alloys increased significantly. High cell viability could be found and healthy cell morphology observed when culturing MG 63 osteoblast-like cells and L-929 fibroblast cells with zirconium-ruthenium alloys, whereas the hemolysis rates of zirconium-ruthenium alloys are alloys and Ti-based alloys, the magnetic susceptibilities of the zirconium-ruthenium alloys (1.25 × 10−6 cm3·g−1–1.29 × 10−6 cm3·g−1 for zirconium-ruthenium alloys) are ultralow, about one-third that of Ti-based alloys (Ti–6Al–4V, ~3.5 × 10−6 cm3·g−1, CP Ti and Ti–6Al–7Nb, ~3.0 × 10−6 cm3·g−1), and one-sixth that of Co–Cr alloys (Co–Cr–Mo, ~7.7 × 10−6 cm3·g−1). Among the Zr–Ru alloy series, Zr–1Ru demonstrates enhanced mechanical properties, excellent corrosion resistance and cell viability with lowest magnetic susceptibility, and thus is the optimal Zr–Ru alloy system as therapeutic devices under MRI diagnostics environments. PMID:27090955

Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia

DEFF Research Database (Denmark)

Nissen, Jette Lindbjerg; Skov, Robert; Knudsen, Inge Jenny Dahl

2013-01-01

OBJECTIVES: Penicillin-susceptible Staphylococcus aureus isolates account for a fifth of cases of S. aureus bacteraemia (SAB) in Denmark, but little is known about treatment outcomes with penicillins or other antimicrobials. Here we compare penicillin, dicloxacillin and cefuroxime as definitive...... treatments in relation to 30 day mortality. METHODS: A retrospective chart review of 588 penicillin-susceptible S. aureus cases at five centres from January 1995 to December 2010. Data on demographics, antimicrobial treatment, clinical signs and symptoms, and mortality at day 30 were collected. Hazard ratios...... compared with penicillin (adjusted HR 2.54, 95% CI 1.49-4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other...

NMR Spectroscopy Identifies Metabolites Translocated from Powdery Mildew Resistant Rootstocks to Susceptible Watermelon Scions.

Science.gov (United States)

Mahmud, Iqbal; Kousik, Chandrasekar; Hassell, Richard; Chowdhury, Kamal; Boroujerdi, Arezue F

2015-09-16

Powdery mildew (PM) disease causes significant loss in watermelon. Due to the unavailability of a commercial watermelon variety that is resistant to PM, grafting susceptible cultivars on wild resistant rootstocks is being explored as a short-term management strategy to combat this disease. Nuclear magnetic resonance-based metabolic profiles of susceptible and resistant rootstocks of watermelon and their corresponding susceptible scions (Mickey Lee) were compared to screen for potential metabolites related to PM resistance using multivariate principal component analysis. Significant score plot differences between the susceptible and resistant groups were revealed through Mahalanobis distance analysis. Significantly different spectral buckets and their corresponding metabolites (including choline, fumarate, 5-hydroxyindole-3-acetate, and melatonin) have been identified quantitatively using multivariate loading plots and verified by volcano plot analyses. The data suggest that these metabolites were translocated from the powdery mildew resistant rootstocks to their corresponding powdery mildew susceptible scions and can be related to PM disease resistance.

Immunogenetics and genetic susceptibility in the pathogenesis of autoimmune hepatitis

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Das Anup K

2014-11-01

Full Text Available vAutoimmune hepatitis is a progressive liver disease. Its pathogenesis is unclear, but needs a ‘trigger’ to initiate the disease in a genetically susceptible person. The susceptibility is partly related to MHCII class genes, and more so with human leukocyte antigen (HLA. Several mechanisms have been proposed which, however, cannot fully explain the immunologic findings in autoimmune hepatitis. The susceptibility to any autoimmune disease is determined by several factors where genetic and immunological alterations, along with, environmental factor are active. MHCII antigens as a marker for AIH, or a predictor of treatment response and prognosis has been investigated. Since MHCII antigens show significant ethnic heterogeneity, mutations in MHCII may merely act as only precursors of the surface markers of immune cells, which can be of significance, because the changes in HLA and MHC are missing in certain populations. One such marker is the CTLA-4 (CD152 gene mutation, reported in the phenotypes representing susceptibility to AIH. Other candidate genes of cytokines, TNF, TGF-beta1 etc, have also been investigated but with unvalidated results. Paediatric AIH show differences in genetic susceptibility. Genetic susceptibility or resistance to AIH may be associated with polypeptides in DRB1 with certain amino-acid sequences. Understanding which genes are implicated in genesis and/or disease progression will obviously help to identify key pathways in AIH and provide better insights into its pathogenesis. But studies to identify responsible genes are complex because of the complex trait of AIH.

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults.

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Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

2016-01-01

Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (Pstrategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults

Science.gov (United States)

Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

2016-01-01

Background Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. Objective To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. Methods This study used the 2005–2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. Results The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (Phepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme. PMID:27093614

CISH and susceptibility to infectious diseases.

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Khor, Chiea C; Vannberg, Fredrik O; Chapman, Stephen J; Guo, Haiyan; Wong, Sunny H; Walley, Andrew J; Vukcevic, Damjan; Rautanen, Anna; Mills, Tara C; Chang, Kwok-Chiu; Kam, Kai-Man; Crampin, Amelia C; Ngwira, Bagrey; Leung, Chi-Chiu; Tam, Cheuk-Ming; Chan, Chiu-Yeung; Sung, Joseph J Y; Yew, Wing-Wai; Toh, Kai-Yee; Tay, Stacey K H; Kwiatkowski, Dominic; Lienhardt, Christian; Hien, Tran-Tinh; Day, Nicholas P; Peshu, Nobert; Marsh, Kevin; Maitland, Kathryn; Scott, J Anthony; Williams, Thomas N; Berkley, James A; Floyd, Sian; Tang, Nelson L S; Fine, Paul E M; Goh, Denise L M; Hill, Adrian V S

2010-06-03

The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling. Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya, Malawi, and Vietnam. We had previously tested 20 other immune-related genes in one or more of these sample collections. We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five single-nucleotide polymorphisms (SNPs) (at positions -639, -292, -163, +1320, and +3415 [all relative to CISH]) within the CISH-associated locus were considered together in a multiple-SNP score, we found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P=3.8x10(-11) for all comparisons), with -292 accounting for most of the association signal (P=4.58x10(-7)). Peripheral-blood mononuclear cells obtained from adult subjects carrying the -292 variant, as compared with wild-type cells, showed a muted response to the stimulation of interleukin-2 production--that is, 25 to 40% less CISH expression. Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signaling have a role in immunity against various infectious diseases. The overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles. 2010 Massachusetts Medical Society

Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis.

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Yanagimachi, Masakatsu; Naruto, Takuya; Miyamae, Takako; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Sato, Hidenori; Goto, Hiroaki; Yokota, Shumpei

2011-04-01

Systemic-onset juvenile idiopathic arthritis (systemic JIA) and macrophage activation syndrome (MAS), the most devastating complication of systemic JIA, are characterized by abnormal levels of proinflammatory cytokines. Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, and acts as a master transcription factor in the activation of genes encoding proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Our aim was to assess associations of IRF5 gene polymorphisms with susceptibility to systemic JIA and MAS. Three IRF5 single-nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 81 patients with systemic JIA (33 with MAS, 48 without) and 190 controls. There were no associations of the IRF5 gene polymorphisms or haplotypes under study with susceptibility to systemic JIA. There was a significant association of the rs2004640 T allele with MAS susceptibility (OR 4.11; 95% CI 1.84, 9.16; p = 0.001). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T), which was reported as conferring an increased risk of SLE, was significantly associated with MAS susceptibility in patients with systemic JIA (OR 4.61; 95% CI 1.73, 12.3; p < 0.001). IRF5 gene polymorphism is a genetic factor influencing susceptibility to MAS in patients with systemic JIA, and IRF5 contributes to the pathogenesis of MAS in these patients.

Bleaching Gels Containing Calcium and Fluoride: Effect on Enamel Erosion Susceptibility

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Alessandra B. Borges

2012-01-01

Full Text Available This in vitro study evaluated the effect of 35% hydrogen peroxide (HP bleaching gel modified or not by the addition of calcium and fluoride on enamel susceptibility to erosion. Bovine enamel samples (3 mm in diameter were divided into four groups (n=15 according to the bleaching agent: control—without bleaching (C; 35% hydrogen peroxide (HP; 35% HP with the addition of 2% calcium gluconate (HP + Ca; 35% HP with the addition of 0.6% sodium fluoride (HP + F. The bleaching gels were applied on the enamel surface for 40 min, and the specimens were subjected to erosive challenge with Sprite Zero and remineralization with artificial saliva for 5 days. Enamel wear was assessed using profilometry. The data were analyzed by ANOVA/ Tukey’s test (P<0.05. There were significant differences among the groups (P=0.009. The most enamel wear was seen for C (3.37±0.80 μm, followed by HP (2.89 ± 0.98 μm and HP + F (2.72 ± 0.64 μm. HP + Ca (2.31 ± 0.92 μm was the only group able to significantly reduce enamel erosion compared to C. The application of HP bleaching agent did not increase the enamel susceptibility to erosion. However, the addition of calcium gluconate to the HP gel resulted in reduced susceptibility of the enamel to erosion.

Assessment of oxidant susceptibility of red blood cells in various species based on cell deformability.

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Simmonds, Michael J; Meiselman, Herbert J; Marshall-Gradisnik, Sonya M; Pyne, Michael; Kakanis, Michael; Keane, James; Brenu, Ekua; Christy, Rhys; Baskurt, Oguz K

2011-01-01

The present study was designed to investigate the oxidant susceptibility of red blood cells (RBC) from four species (echidna, human, koala, Tasmanian devil) based on changes in cellular deformability. These species were specifically chosen based on differences in lifestyle and/or biology associated with varied levels of oxidative stress. The major focus was the influence of superoxide radicals generated within the cell (phenazine methosulfate, PMS, 50 μM) or in the extracellular medium (xanthine oxidase-hypoxanthine, XO-HX, 0.1 U/ml XO) on RBC deformability at various shear stresses (SS). RBC deformability was assessed by laser-diffraction analysis using a "slit-flow ektacytometer". Both superoxide-generating treatments resulted in significant increases of methemoglobin for all species (p koala cells exhibited a similar sigmoid-like response to SS, short-beaked echidna values were markedly lower and only increased slightly with SS, while Tasmanian devil RBC were extremely rigid. The effect of XO-HX on RBC deformability was less when compared with PMS (i.e., smaller increase in rigidity) with the exception of Tasmanian devil RBC which exhibited essentially no deformation even at the highest SS; Tasmanian devil RBC response to XO-HX was thus comparable to that observed with PMS. Our findings indicate that ektacytometry can be used to determine the oxidant susceptibility of RBC from different species which varies significantly among mammals representing diverse lifestyles and evolutionary histories. These differences in susceptibility are consistent with species-specific discrepancies between observed and allometrically-predicted life spans and are compatible with the oxidant theory of aging.

Neisseria gonorrhoeae strain with reduced susceptibilities to extended-spectrum cephalosporins.

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Nguyen, Duylinh; Gose, Severin; Castro, Lina; Chung, Kathleen; Bernstein, Kyle; Samuel, Micheal; Bauer, Heidi; Pandori, Mark

2014-07-01

The spread of Neisseria gonorrhoeae strains with reduced susceptibility to extended-spectrum cephalosporins is an increasing public health threat. Using Etest and multiantigen sequence typing, we detected sequence type 1407, which is associated with reduced susceptibilities to extended-spectrum cephalosporins, in 4 major populated regions in California, USA, in 2012.

Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals

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Partha Pratim Das

2016-01-01

Results: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candidaalbicans (n=47, 77.0%, C. dubliniensis (n=9, 14.7%, C. parapsilosis (n=2, 3.2%, C. glabrata (n=2, 3.2%, and C. famata (n=1, 1.6%. Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control group. Antifungal susceptibility testing revealed (n=6, 9.3% C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. Interpretation & conclusions: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country.

Reappearance and treatment of penicillin-susceptible Staphylococcus aureus in a tertiary medical centre.

Science.gov (United States)

Chabot, Matthew R; Stefan, Mihaela S; Friderici, Jennifer; Schimmel, Jennifer; Larioza, Julius

2015-12-01

The purpose of this study was to describe trends in the prevalence and treatment patterns of penicillin-susceptible Staphylococcus aureus (SA) infections. This was a cross-sectional study of MSSA isolates from blood cultures at a tertiary-care centre between 1 January 2003 and 31 December 2012. All blood cultures positive for MSSA drawn during the study period were used to calculate the prevalence of penicillin-susceptible SA. Repeat cultures were excluded if they were isolated within 6 weeks of the index culture. The analysis was then restricted to inpatient blood cultures to assess treatment patterns. Antibiotics administered 48-96 h after the culture were analysed. A total of 446 blood cultures positive for MSSA were included in the analysis. There was a distinct trend showing an increase in the percentage of penicillin-susceptible SA over 10 years from 13.2% (95% CI 4.1%-22.3%) in 2003 to 32.4% (95% CI 17.3%-47.5%) in 2012 (P trend penicillin use for penicillin-susceptible SA bacteraemia increased from 0.0% in 2003-04 to 50.0% in 2011-12 (P trend = 0.007). Over a decade, there was an ∼3-fold increase in penicillin susceptibility among MSSA blood cultures at a large tertiary-care facility. Although treatment with penicillin increased over the study period, only 50% of penicillin-susceptible SA was treated with penicillin in the final study period. This study suggests that while susceptibility to penicillin appears to be returning in SA, the use of penicillin for penicillin-susceptible SA bacteraemia is low. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus

DEFF Research Database (Denmark)

Garred, P; Madsen, H O; Halberg, P

1999-01-01

To determine whether variant alleles in the coding portion of the mannose-binding lectin (MBL) gene are associated with increased susceptibility to systemic lupus erythematosus (SLE) and concomitant infections.......To determine whether variant alleles in the coding portion of the mannose-binding lectin (MBL) gene are associated with increased susceptibility to systemic lupus erythematosus (SLE) and concomitant infections....

Transforming Growth Factor β/Activin signaling in neurons increases susceptibility to starvation.

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Wen-Bin Alfred Chng

Full Text Available Animals rely on complex signaling network to mobilize its energy stores during starvation. We have previously shown that the sugar-responsive TGFβ/Activin pathway, activated through the TGFβ ligand Dawdle, plays a central role in shaping the post-prandial digestive competence in the Drosophila midgut. Nevertheless, little is known about the TGFβ/Activin signaling in sugar metabolism beyond the midgut. Here, we address the importance of Dawdle (Daw after carbohydrate ingestion. We found that Daw expression is coupled to dietary glucose through the evolutionarily conserved Mio-Mlx transcriptional complex. In addition, Daw activates the TGFβ/Activin signaling in neuronal populations to regulate triglyceride and glycogen catabolism and energy homeostasis. Loss of those neurons depleted metabolic reserves and rendered flies susceptible to starvation.

Transforming Growth Factor β/Activin signaling in neurons increases susceptibility to starvation.

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Chng, Wen-Bin Alfred; Koch, Rafael; Li, Xiaoxue; Kondo, Shu; Nagoshi, Emi; Lemaitre, Bruno

2017-01-01

Animals rely on complex signaling network to mobilize its energy stores during starvation. We have previously shown that the sugar-responsive TGFβ/Activin pathway, activated through the TGFβ ligand Dawdle, plays a central role in shaping the post-prandial digestive competence in the Drosophila midgut. Nevertheless, little is known about the TGFβ/Activin signaling in sugar metabolism beyond the midgut. Here, we address the importance of Dawdle (Daw) after carbohydrate ingestion. We found that Daw expression is coupled to dietary glucose through the evolutionarily conserved Mio-Mlx transcriptional complex. In addition, Daw activates the TGFβ/Activin signaling in neuronal populations to regulate triglyceride and glycogen catabolism and energy homeostasis. Loss of those neurons depleted metabolic reserves and rendered flies susceptible to starvation.

Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

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Marie Desnos-Ollivier

Full Text Available New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes. Interestingly, geometric mean minimum inhibitory concentrations (MICs of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001. Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens.

Grey matter correlates of susceptibility to scams in community-dwelling older adults.

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Duke Han, S; Boyle, Patricia A; Yu, Lei; Arfanakis, Konstantinos; James, Bryan D; Fleischman, Debra A; Bennett, David A

2016-06-01

Susceptibility to scams is a significant issue among older adults, even among those with intact cognition. Age-related changes in brain macrostructure may be associated with susceptibility to scams; however, this has yet to be explored. Based on previous work implicating frontal and temporal lobe functioning as important in decision making, we tested the hypothesis that susceptibility to scams is associated with smaller grey matter volume in frontal and temporal lobe regions in a large community-dwelling cohort of non-demented older adults. Participants (N = 327, mean age = 81.55, mean education = 15.30, 78.9 % female) completed a self-report measure used to assess susceptibility to scams and an MRI brain scan. Results indicated an inverse association between overall grey matter and susceptibility to scams in models adjusted for age, education, and sex; and in models further adjusted for cognitive function. No significant associations were observed for white matter, cerebrospinal fluid, or total brain volume. Models adjusted for age, education, and sex revealed seven clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, left middle temporal, left orbitofrontal, right ventromedial prefrontal, right middle temporal, right precuneus, and right dorsolateral prefrontal regions. In models further adjusted for cognitive function, results revealed three significant clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, right hippocampal, and right middle temporal regions. Lower grey matter concentration in specific brain regions may be associated with susceptibility to scams, even after adjusting for cognitive ability. Future research is needed to determine whether grey matter reductions in these regions may be a biomarker for susceptibility to scams in old age.

Density-independent population projection trajectories of chromosome-substituted lines resistant and susceptible to organophosphate insecticides in Drosophila melanogaster

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Miyo Takahiro

2004-11-01

Full Text Available Abstract Background Seasonal fluctuations in susceptibility to organophosphate insecticides were observed in the Katsunuma population of Drosophila melanogaster for two consecutive years; susceptibility to three organophosphates tended to increase in the fall. To examine the hypothesis that variation in fitness among resistant and susceptible genotypes could trigger the change of genetic constitution within the fall population, we investigated density-independent population projection trajectories starting from single adult females with characteristics of chromosome-substituted lines resistant and susceptible to the three organophosphates. Results Density-independent population projection trajectories, expressed as the ratios of the number of each chromosome-substituted line to that of line SSS, for which all chromosomes were derived from the susceptible line, showed significant declines in numbers with time for all the resistant chromosome-substituted lines. Conclusion The declining tendency in the density-independent population projection trajectories of the resistant chromosome-substituted lines could explain the simultaneous decline in the levels of resistance to the three organophosphates, observed in the Katsunuma population in the fall.

Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

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Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha; Lionakis, Michail S; Ding, Li; Hsu, Amy P; Zelazny, Adrian M; Moutsopoulos, Niki M; Kuhns, Douglas B; Deming, Clay; Quiñones, Mariam; Segre, Julia A; Bryant, Clare E; Holland, Steven M

2016-04-05

Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.

Susceptibility of clinical isolates of uropathogenic bacteria from ...

African Journals Online (AJOL)

Resistance of uropathogens to antibiotics has been on increase and responsible for increased mortality and morbidity among patients. Clinical isolates (22) of uropathogenic bacteria comprising Escherichia coli, Klebsiella Pneumoniae, Proteus mirabilis and Staphylococcus aureus were tested for susceptibility to standard ...

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

Science.gov (United States)

McKay, James D.; Hung, Rayjean J.; Han, Younghun; Zong, Xuchen; Carreras-Torres, Robert; Christiani, David C.; Caporaso, Neil E.; Johansson, Mattias; Xiao, Xiangjun; Li, Yafang; Byun, Jinyoung; Dunning, Alison; Pooley, Karen A.; Qian, David C.; Ji, Xuemei; Liu, Geoffrey; Timofeeva, Maria N.; Bojesen, Stig E.; Wu, Xifeng; Le Marchand, Loic; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C.; Bush, William S.; Tardon, Adonina; Rennert, Gad; Teare, M. Dawn; Field, John K.; Kiemeney, Lambertus A.; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B.; Andrew, Angeline S.; Shen, Hongbing; Hong, Yun-Chul; Yuan, Jian-Min; Bertazzi, Pier Alberto; Pesatori, Angela C.; Ye, Yuanqing; Diao, Nancy; Su, Li; Zhang, Ruyang; Brhane, Yonathan; Leighl, Natasha; Johansen, Jakob S.; Mellemgaard, Anders; Saliba, Walid; Haiman, Christopher A.; Wilkens, Lynne R.; Fernandez-Somoano, Ana; Fernandez-Tardon, Guillermo; van der Heijden, Henricus F.M.; Kim, Jin Hee; Dai, Juncheng; Hu, Zhibin; Davies, Michael PA; Marcus, Michael W.; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C.; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Doherty, Jennifer A.; Barnett, Matt P.; Chen, Chu; Goodman, Gary E.; Cox, Angela; Taylor, Fiona; Woll, Penella; Brüske, Irene; Wichmann, H.-Erich; Manz, Judith; Muley, Thomas R.; Risch, Angela; Rosenberger, Albert; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances A.; Tsao, Ming-Sound; Arnold, Susanne M.; Haura, Eric B.; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M.; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J.; Butler, Lesley M.; Koh, Woon-Puay; Gao, Yu-Tang; Houlston, Richard S.; McLaughlin, John; Stevens, Victoria L.; Joubert, Philippe; Lamontagne, Maxime; Nickle, David C.; Obeidat, Ma’en; Timens, Wim; Zhu, Bin; Song, Lei; Kachuri, Linda; Artigas, María Soler; Tobin, Martin D.; Wain, Louise V.; Rafnar, Thorunn; Thorgeirsson, Thorgeir E.; Reginsson, Gunnar W.; Stefansson, Kari; Hancock, Dana B.; Bierut, Laura J.; Spitz, Margaret R.; Gaddis, Nathan C.; Lutz, Sharon M.; Gu, Fangyi; Johnson, Eric O.; Kamal, Ahsan; Pikielny, Claudio; Zhu, Dakai; Lindströem, Sara; Jiang, Xia; Tyndale, Rachel F.; Chenevix-Trench, Georgia; Beesley, Jonathan; Bossé, Yohan; Chanock, Stephen; Brennan, Paul; Landi, Maria Teresa; Amos, Christopher I.

2017-01-01

Summary While several lung cancer susceptibility loci have been identified, much of lung cancer heritability remains unexplained. Here, 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated GWAS analysis of lung cancer on 29,266 patients and 56,450 controls. We identified 18 susceptibility loci achieving genome wide significance, including 10 novel loci. The novel loci highlighted the striking heterogeneity in genetic susceptibility across lung cancer histological subtypes, with four loci associated with lung cancer overall and six with lung adenocarcinoma. Gene expression quantitative trait analysis (eQTL) in 1,425 normal lung tissues highlighted RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes, OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer. PMID:28604730

Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress

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Qiu-Qin Han

2017-05-01

Full Text Available While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT, increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.

Barley yellow dwarf virus Infection Leads to Higher Chemical Defense Signals and Lower Electrophysiological Reactions in Susceptible Compared to Tolerant Barley Genotypes.

Science.gov (United States)

Paulmann, Maria K; Kunert, Grit; Zimmermann, Matthias R; Theis, Nina; Ludwig, Anatoli; Meichsner, Doreen; Oelmüller, Ralf; Gershenzon, Jonathan; Habekuss, Antje; Ordon, Frank; Furch, Alexandra C U; Will, Torsten

2018-01-01

Barley yellow dwarf virus (BYDV) is a phloem limited virus that is persistently transmitted by aphids. Due to huge yield losses in agriculture, the virus is of high economic relevance. Since the control of the virus itself is not possible, tolerant barley genotypes are considered as the most effective approach to avoid yield losses. Although several genes and quantitative trait loci are known and used in barley breeding for virus tolerance, little is known about molecular and physiological backgrounds of this trait. Therefore, we compared the anatomy and early defense responses of a virus susceptible to those of a virus-tolerant cultivar. One of the very early defense responses is the transmission of electrophysiological reactions. Electrophysiological reactions to BYDV infection might differ between susceptible and tolerant cultivars, since BYDV causes disintegration of sieve elements in susceptible cultivars. The structure of vascular bundles, xylem vessels and sieve elements was examined using microscopy. All three were significantly decreased in size in infected susceptible plants where the virus causes disintegration of sieve elements. This could be associated with an uncontrolled ion exchange between the sieve-element lumen and apoplast. Further, a reduced electrophysiological isolation would negatively affect the propagation of electrophysiological reactions. To test the influence of BYDV infection on electrophysiological reactions, electropotential waves (EPWs) induced by leaf-tip burning were recorded using aphids as bioelectrodes. EPWs in infected susceptible plants disappeared already after 10 cm in contrast to those in healthy susceptible or infected tolerant or healthy tolerant plants. Another early plant defense reaction is an increase in reactive oxygen species (ROS). Using a fluorescent dye, we found a significant increase in ROS content in infected susceptible plants but not in infected tolerant plants. Similar results were found for the

Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

DEFF Research Database (Denmark)

Henningsen, Kim; Johannesen, Mads Dyrvig; Bouzinova, Elena

2012-01-01

In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

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Wójtowicz, Agnieszka; Gresnigt, Mark S; Lecompte, Thanh; Bibert, Stephanie; Manuel, Oriol; Joosten, Leo A B; Rüeger, Sina; Berger, Christoph; Boggian, Katia; Cusini, Alexia; Garzoni, Christian; Hirsch, Hans H; Weisser, Maja; Mueller, Nicolas J; Meylan, Pascal R; Steiger, Jürg; Kutalik, Zoltan; Pascual, Manuel; van Delden, Christian; van de Veerdonk, Frank L; Bochud, Pierre-Yves

2015-05-15

Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Significance in the increase of women psychiatrists in Korea.

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Kim, Ha Kyoung; Kim, Soo In

2008-01-01

The number of female doctors has increased in Korea; 18.9% (13,083) of the total medical doctors registered (69,097) were women in 2006, compared to 13.6% (2,216) in 1975. The proportion of female doctors will jump up by 2010 considering that nearly 40% of the medical students are women as of today. This trend has had strong influence on the field of psychiatry; the percentage of women psychiatrists rose from 1.6 (6)% to 18% (453), from 1975 to 2006 and now women residents comprise 39% (206) of all. This is not only a reflection of a social phenomenon of the increase in professional women but also attributed to some specific characteristics of the psychiatry. Psychiatric practice may come more natural to women. While clinical activities of women psychiatrists are expanding, there are few women leaders and much less women are involving in academic activities in this field as yet. Though there is less sexual discrimination in the field of psychiatry, women psychiatrists are still having a lot of difficulties in balancing work and family matters. Many women psychiatrists also report they've ever felt an implied discrimination in their careers. In this study, we are to identify the characteristics of women psychiatrists and to explore the significance of the increase in women psychiatrists in Korea and the situation in which they are.

School bullying and susceptibility to smoking among never-tried cigarette smoking students.

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Azagba, Sunday

2016-04-01

Bullying involvement has been linked with substance use; however, less is known about its relationship with pre-initiation stages of adolescent cigarette smoking behavior. This study examined the association between bullying involvement and smoking susceptibility among never tried or experimented with cigarette smoking students. Susceptibility to cigarette smoking in adolescence is a strong predictor of subsequent smoking initiation. A cross-sectional data on Canadian adolescent and youth were drawn from the 2012/2013 Youth Smoking Survey (n=28,843). Logistic regression analysis was used to examine the association between bullying and smoking susceptibility among never-smoking students. About 21% self-reported involvement in bullying (as a bully, victim or both). Middle school students (grades 6-8) reported more involvement in bullying (24%) than those in grades 9-12 (16%). The multivariable analyses showed that the association between bullying and smoking susceptibility was significantly different by grade level. Middle school students involved in bullying had higher odds of smoking susceptibility compared to uninvolved students (bully, adjusted odds ratio [AOR]=2.54, 95% CI=1.73-3.74; victim, AOR=1.29, 95% CI=1.11-1.48; bully-victim, AOR=2.19, 95% CI=1.75-2.74). There were no significant associations between all subgroups of bullying and smoking susceptibility for grades 9-12 students. Students involved in bullying were more susceptible to smoking, although patterns of association varied by grade level. In particular, the findings highlight that non-smoking middle school students involved in bullying were susceptible to future smoking. Copyright © 2016 Elsevier Inc. All rights reserved.

Change in antimicrobial susceptibility of Mycoplasma gallisepticum field isolates.

Science.gov (United States)

Gharaibeh, Saad; Al-Rashdan, Mohammad

2011-06-02

This study compares the antimicrobial susceptibility over time between two groups of Mycoplasma gallisepticum (MG) isolates from the same geographical area. Minimum inhibitory concentration of 13 antimicrobials was determined against two groups of MG isolates from chickens. Group 1 strains (n=22) were isolated in 2004-2005 while group 2 strains (n=7) were isolated in 2007-2008. Minimum inhibitory concentration 50 for group 1 versus group 2 was 4/4, 0.5/0.5, ≤ 0.031/≥ 64, ≤ 0.031/2, ≤ 0.031/0.125, 1/0.5, 1/1, ≤ 0.031/≤ 0.031, ≤ 0.031/2, ≤ 0.031/2, 1/4, ≤ 0.031/0.062, and 0.062/2 μg/ml against gentamicin, spectinomycin, erythromycin, tilmicosin, tylosin, florfenicol, thiamphenicol, tiamulin, ciprofloxacin, enrofloxacin, chlortetracycline, doxycycline, and oxytetracycline, respectively. There was a statistically significant increase in resistance of group 2 to erythromycin, tilmicosin, tylosin, ciprofloxacin, enrofloxacin, chlortetracycline, doxycycline, and oxytetracycline. This dramatic increase in resistance against 8 antimicrobials belonging to three different families of antimicrobials in a relatively short period of time appears to be rare and of concern. The cause of this increased resistance observed in group 2 of MG isolates was not determined and should be further investigated. Monitoring of MG field strain susceptibility is highly recommended to implement successful treatment and prophylaxis programs in endemic areas. Copyright © 2011 Elsevier B.V. All rights reserved.

Defense response of susceptible and resistant Biomphalaria alexandrina snails against Schistosoma mansoni infection

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Iman F. Abou-El-Naga

2012-09-01

Full Text Available In Egypt, Biomphalaria alexandrina is the intermediate host for Schistosoma mansoni. The fates of Schistosoma miracidia in the snails varies between different species of Biomphalaria. The internal defense system is one of the factors that influence the susceptibility pattern of the snails. The interaction between Biomphalaria snails and S. mansoni needs to be identified for each species, and even between the members of the same species with different degrees of susceptibility. In the present study, the first generation of susceptible and resistant parents of B. alexandrina was examined histologically at the 30th day post exposure. The study includes the characterization of the immune response, as expressed by tissue reactions, of susceptible and resistant B. alexandrina snails against S. mansoni. It was also designed to determine the impact of the resistance increase in parent snails, on the mechanisms of interaction of their offspring against infection. The results showed that the infection rate of the offspring from the susceptible parents was 92%. No susceptible offspring was produced from the resistant parents. When the parents were of equal number of susceptible and resistant snails, they gave an offspring with an infection rate of 20%. Susceptible snails that had susceptible parents showed a higher degree of susceptibility than those that had both susceptible and resistant parents. A common feature of the resistant snails was the absence of any viable parasites. The tissue reactions of the resistant snails having only resistant parents occurred at the site of miracidial penetration. In resistant snails for which susceptible ones were included in their parents, the reactions occurred in the deep tissues. These results characterized the immune response of B. alexandrina snails against Schistosoma infection which was found to occur by two different mechanisms. One type of defense occurs in highly resistant snails, and employs direct

CISH and Susceptibility to Infectious Diseases

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Khor, Chiea C.; Vannberg, Fredrik O.; Chapman, Stephen J.; Guo, Haiyan; Wong, Sunny H.; Walley, Andrew J.; Vukcevic, Damjan; Rautanen, Anna; Mills, Tara C.; Chang, Kwok-Chiu; Kam, Kai-Man; Crampin, Amelia C.; Ngwira, Bagrey; Leung, Chi-Chiu; Tam, Cheuk-Ming; Chan, Chiu-Yeung; Sung, Joseph J.Y.; Yew, Wing-Wai; Toh, Kai-Yee; Tay, Stacey K.H.; Kwiatkowski, Dominic; Lienhardt, Christian; Hien, Tran-Tinh; Day, Nicholas P.; Peshu, Nobert; Marsh, Kevin; Maitland, Kathryn; Scott, J. Anthony; Williams, Thomas N.; Berkley, James A.; Floyd, Sian; Tang, Nelson L.S.; Fine, Paul E.M.; Goh, Denise L.M.; Hill, Adrian V.S.

2013-01-01

Background The interleukin-2 (IL2)-mediated immune response is critical for host defence against infectious pathogens. CISH, a suppressor of cytokine signalling, controls IL2 signalling. Methods We tested for association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis and severe malaria) in 8402 persons from the Gambia, Hong Kong, Kenya, Malawi, and Vietnam using a case-control design. We have previously tested twenty other immune-related genes in one or more of these sample collections. Results We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five SNPs (CISH −639, −292, −163, +1320 and +3415) within the CISH-associated locus were considered together in a multi-SNP score, we found substantial support for an effect of CISH genetic variants on susceptibility to bacteremia, malaria, and tuberculosis (overall P=3.8 × 10−11) with CISH −292 being “responsible” for the majority of the association signal (P=4.58×10−7). Peripheral blood mononuclear cells of adult volunteers carrying the CISH −292 variant showed a muted response to IL2 stimulation — in the form of 25-40% less CISH — when compared with “control” cells lacking the −292 variant. Conclusions Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signalling may play a major role in immunity against various infectious diseases. The overall risk of having one of these infectious diseases was found to be increased by at least 18 percent in individuals carrying the variant CISH alleles. PMID:20484391

Identification and Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Rubik’s Cube of Clinical Microbiology?

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Gajdács, Márió; Spengler, Gabriella; Urbán, Edit

2017-01-01

Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria. PMID:29112122

Effects of white matter microstructure on phase and susceptibility maps.

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Wharton, Samuel; Bowtell, Richard

2015-03-01

To investigate the effects on quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI) of the frequency variation produced by the microstructure of white matter (WM). The frequency offsets in a WM tissue sample that are not explained by the effect of bulk isotropic or anisotropic magnetic susceptibility, but rather result from the local microstructure, were characterized for the first time. QSM and STI were then applied to simulated frequency maps that were calculated using a digitized whole-brain, WM model formed from anatomical and diffusion tensor imaging data acquired from a volunteer. In this model, the magnitudes of the frequency contributions due to anisotropy and microstructure were derived from the results of the tissue experiments. The simulations suggest that the frequency contribution of microstructure is much larger than that due to bulk effects of anisotropic magnetic susceptibility. In QSM, the microstructure contribution introduced artificial WM heterogeneity. For the STI processing, the microstructure contribution caused the susceptibility anisotropy to be significantly overestimated. Microstructure-related phase offsets in WM yield artifacts in the calculated susceptibility maps. If susceptibility mapping is to become a robust MRI technique, further research should be carried out to reduce the confounding effects of microstructure-related frequency contributions. © 2014 Wiley Periodicals, Inc.

Protein energy malnutrition increases arginase activity in monocytes and macrophages.

Science.gov (United States)

Corware, Karina; Yardley, Vanessa; Mack, Christopher; Schuster, Steffen; Al-Hassi, Hafid; Herath, Shanthi; Bergin, Philip; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Kropf, Pascale

2014-01-01

Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases. In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication. Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth. Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

Effects of dissolved calcium and magnesium ions on lead-induced stress corrosion cracking susceptibility of nuclear steam generator tubing alloy in high temperature crevice solutions

International Nuclear Information System (INIS)

Lu, B.T.; Tian, L.P.; Zhu, R.K.; Luo, J.L.; Lu, Y.C.

2011-01-01

The effects of Ca 2+ and Mg 2+ ions on the stress corrosion cracking (SCC) susceptibility of UNS N08800 are investigated using constant extension rate tensile (CERT) tests at 300 o C in simulated crevice chemistries. The presence of lead contamination in the crevice chemistries increases significantly the SCC susceptibility of the alloy. The lead-assisted SCC (PbSCC) susceptibility is reduced markedly by the addition of Ca 2+ and Mg 2+ ions into the solution and this mitigating effect is enhanced by increasing the total concentration of Ca 2+ + Mg 2+ . The CERT test results are consistent with the types of fracture surfaces shown by Scanning Electron Microscopy (SEM). There is a reasonable correlation between the SCC susceptibility and the donor densities in the anodic films in accord with the role of lead-induced passivity degradation in PbSCC.

Polymyxins: Antimicrobial susceptibility concerns and therapeutic options

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V Balaji

2011-01-01

Full Text Available The increasing prevalence of multidrug-resistant nosocomial pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae poses a great challenge to the treating physicians. The paucity of newer effective antimicrobials has led to renewed interest in the polymyxin group of drugs, as a last resort for treatment of gram-negative bacterial infections. There is a dearth of information on the pharmacological properties of colistin, leading to difficulties in selecting the right dose, dosing interval, and route of administration for treatment, especially in critically-ill patients. The increasing use of colistin over the last few years necessitates the need for accurate and reliable in vitro susceptibility testing methods. Development of heteroresistant strains as a result of colistin monotherapy is also a growing concern. There is a compelling need from the clinicians to provide options for probable and possible colistin combination therapy for multidrug-resistant bacterial infections in the ICU setting. Newer combination drug synergy determination tests are being developed and reported. There are no standardized recommendations from antimicrobial susceptibility testing reference agencies for the testing and interpretation of these drug combinations. Comparison and analysis of these reported methodologies may help to understand and assist the microbiologist to choose the best method that produces accurate results at the earliest. This will help clinicians to select the appropriate combination therapy. In this era of multidrug resistance it is important for the microbiology laboratory to be prepared, by default, to provide timely synergistic susceptibility results in addition to routine susceptibility, if warranted. Not as a favour or at request, but as a responsibility.

[Susceptibility of natural populations of dengue vector to insecticides in Colombia].

Science.gov (United States)

Santacoloma, Liliana; Chaves, Bernardo; Brochero, Helena Luisa

2012-09-01

Physiological resistance of natural population of Aedes aegypti to insecticides contribute to the decreased efficacy of chemical control as a main control strategy during dengue outbreaks. The susceptibility status of Ae. aegypti was assessed for the carbamate propoxur, the adulticide malathion and the larvicide temephos on 13 natural populations of Ae. aegypti immature forms were taken from 8 Colombian localities. These included the following: Bucaramanga (1), Sabana de Torres (2), Girardot (2), La Mesa (2), Villavicencio (2), Puerto López (2), San José del Guaviare (1) and Florencia (1). Susceptibility tests mainly consisted of the standardized bioassay outlined by WHO (1981) and CDC bottles (1998). Colorimetric tests were undertaken to determine enzyme levels possibly responsible for the reduction of susceptibility to organophosphate and carbamate insecticides. All specimens demonstrated susceptibility to malathion and propoxur insecticides. Four of the 13 populations revealed susceptibility to the temephos larvicide. Seven of 11 populations showed a limited increase in values for nonspecific esterase enzymes. The Bucaramanga population was the only one which showed an increase in the cytochrome P450 monooxygenases enzymes. Neither population was found with modified acetilcolinesterase. The widespread susceptibility to organophosphates used as adulticides indicated that malathion, the most used insecticide in Colombia, remains effective in interrupting the transmission of dengue. Physiological resistance to insecticides occurring in communities of a single township proved to be a localized phenomenon.

Quark number density and susceptibility calculation with one correction in mean field potential

International Nuclear Information System (INIS)

Singh, S. Somorendro

2016-01-01

We calculate quark number density and susceptibility of a model which has one loop correction in mean field potential. The calculation shows continuous increasing in the number density and susceptibility up to the temperature T = 0.4 GeV. Then the value of number density and susceptibility approach to the lattice result for higher value of temperature. The result indicates that the calculated values of the model fit well and the result increase the temperature to reach the lattice data with the one loop correction in the mean field potential. (author)

Antimicrobial Susceptibility Patterns of Environmental Streptococci Recovered from Bovine Milk Samples in the Maritime Provinces of Canada

Directory of Open Access Journals (Sweden)

Marguerite Cameron

2016-09-01

Full Text Available Determination of antimicrobial susceptibility of bovine mastitis pathogens is important for guiding antimicrobial treatment decisions and for the detection of emerging resistance. Environmental streptococci are ubiquitous in the farm environment and are a frequent cause of mastitis in dairy cows. The aim of the study was to determine patterns of antimicrobial susceptibility among species of environmental streptococci isolated from dairy cows in the Maritime Provinces of Canada. The collection consisted of 192 isolates identified in milk samples collected from 177 cows originating from 18 dairy herds. Results were aggregated into: 1 Streptococcus uberis (n = 70, 2 Streptococcus dysgalactiae (n = 28, 3 other Streptococci spp. (n = 35, 4, Lactococcus spp. (n = 32, and 5 Enterococcus spp. (n = 27. Minimum inhibitory concentrations (MIC were determined using the Sensititre microdilution system and mastitis plate format. Multilevel logistic regression models were used to analyze the data, with antimicrobial susceptibility as the outcome. The proportion of susceptible Streptococcus uberis ranged from 23% (for penicillin to 99% (for penicillin/novobiocin, with a median of 82%. All Streptococcus dysgalactiae were susceptible to all antimicrobials except for penicillin (93% susceptible and tetracycline (18% susceptible. The range of susceptibility for other Streptococcus spp. was 43% (for tetracycline to 100%, with a median percent susceptibility of 92%. Lactococcus spp. isolates displayed percent susceptibilities ranging from 0% (for penicillin to 97% (for erythromycin, median 75%. For the antimicrobials tested, the MIC were higher for Enterococcus spp. than for the other species. According to the multilevel models, there was a significant interaction between antimicrobial and bacterial species, indicating that susceptibility against a particular antimicrobial varied among the species of environmental streptococci and vice versa. Generally

Influence of chlorine on the susceptibility of striped bass (Morone saxatilis) to Vibrio anguillarum

Energy Technology Data Exchange (ETDEWEB)

Hetrick, F M; Hall, Jr, L W; Wolski, S; Graves, W C; Roberson, B S

1984-09-01

The subtle effects that low levels of pollutants have on fish populations are probably more important than the effects of large spills, since the effects are less likely to be obvious and the source more difficult to detect in time to save the environment. An experiment was carried out to determine if exposure of striped bass to sublethal concentrations of chlorine affected their susceptibility to bacterial infection. Exposure of striped bass for 96 h to sublethal concentrations of total residual chlorine (TRC) (0.05-0.23 mg/L) did not increase their susceptibility to infection with the bacterial pathogen Vibrio anguillarum. Variables examined were TRC concentrations, length of exposure to chlorine, and the order of exposure to chlorine and the pathogen. Mortalities in the groups exposed to both chlorine and pathogen were not significantly different from those seen in groups receiving the bacteria only. Smaller fish are more susceptible than larger fish, and the LD50 is markedly affected by the ambient temperature in that fewer bacteria are needed to kill fish at lower temperatures. One contributing factor to this increased resistance of fish at higher water temperatures appears to be related to their immune status. 29 references, 5 tables.

MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts.

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Waring, Barbara M; Sjaastad, Louisa E; Fiege, Jessica K; Fay, Elizabeth J; Reyes, Ismarc; Moriarity, Branden; Langlois, Ryan A

2018-01-15

Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs. IMPORTANCE Influenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. Micro

Ranking alloys for susceptibility to MIC

International Nuclear Information System (INIS)

Scott, P.J.B.; Davies, M.; Goldie, J.

1991-01-01

This paper reports that laboratory experiments demonstrate that alloys containing 6 to 9% Mo are susceptible to microbiologically influenced corrosion attack. They also demonstrate that corrosion behavior in batch cultures do not correlate well with standard ferric chloride and pitting potential tests of the same alloys. In recent years, there has been an increasing awareness of the incidence of plant equipment failures caused by microbiologically influenced corrosion (MIC). This has led to the search for suitable testing techniques to look for MIC, which, in turn, has expanded the list of known susceptible alloys. Faced with field failures, the normal response has been to upgrade the alloy of construction. There is, for example, a common belief that the addition of more molybdenum to austenitic stainless steels conveys immunity (or at least increased resistance) to MIC. The basis for this is an extrapolation of localized corrosion data. The supposed correlation between molybdenum content and resistance to MIC has not yet been supported by a comprehensive testing program

Nodal infection in Markovian susceptible-infected-susceptible and susceptible-infected-removed epidemics on networks are non-negatively correlated.

Science.gov (United States)

Cator, E; Van Mieghem, P

2014-05-01

By invoking the famous Fortuin, Kasteleyn, and Ginibre (FKG) inequality, we prove the conjecture that the correlation of infection at the same time between any pair of nodes in a network cannot be negative for (exact) Markovian susceptible-infected-susceptible (SIS) and susceptible-infected-removed (SIR) epidemics on networks. The truth of the conjecture establishes that the N-intertwined mean-field approximation (NIMFA) upper bounds the infection probability in any graph so that network design based on NIMFA always leads to safe protections against malware spread. However, when the infection or/and curing are not Poisson processes, the infection correlation between two nodes can be negative.

Nodal infection in Markovian susceptible-infected-susceptible and susceptible-infected-removed epidemics on networks are non-negatively correlated

Science.gov (United States)

Cator, E.; Van Mieghem, P.

2014-05-01

By invoking the famous Fortuin, Kasteleyn, and Ginibre (FKG) inequality, we prove the conjecture that the correlation of infection at the same time between any pair of nodes in a network cannot be negative for (exact) Markovian susceptible-infected-susceptible (SIS) and susceptible-infected-removed (SIR) epidemics on networks. The truth of the conjecture establishes that the N-intertwined mean-field approximation (NIMFA) upper bounds the infection probability in any graph so that network design based on NIMFA always leads to safe protections against malware spread. However, when the infection or/and curing are not Poisson processes, the infection correlation between two nodes can be negative.

Hypnotic susceptibility and affective states in bipolar I and II disorders.

Science.gov (United States)

Zhang, Bingren; Wang, Jiawei; Zhu, Qisha; Ma, Guorong; Shen, Chanchan; Fan, Hongying; Wang, Wei

2017-11-09

Highly hypnotizable individuals have impaired executive function, elevated motor impulsivity and increased emotional sensitivity, which are sometimes found in bipolar disorder patients. It is then reasonable to assume that certain aspects of hypnotic susceptibility differ with the types of bipolar disorder. The Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) test, the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32) and the Plutchick-van Praag Depression Inventory (PVP) were applied to 62 patients with bipolar I disorder, 33 bipolar II disorder, and 120 healthy volunteers. The passing rate of the SHSS:C 'Moving hands apart' item was higher in bipolar I patients than in controls, whereas for 'Mosquito hallucination' the rate was lower. Bipolar I and II patients scored significantly higher on MDQ, HCL-32 and PVP scales than controls. The passing rates of 'Mosquito hallucination' in controls, 'Arm rigidity' in bipolar I, and 'Age regression' in bipolar II predicted the respective MDQ scores. In contrast to cognitive suggestions, bipolar I patients followed motor suggestions more often under hypnosis. Furthermore, both bipolar disorder patients and healthy volunteers demonstrated associations between mania levels and certain hypnotic susceptibility features. Our study aids in better understanding the altered conscious states in bipolar disorders, and encourages the use of related psychotherapy for these patients.

Susceptibility of anaerobic bacteria in Auckland: 1991-1996.

Science.gov (United States)

Shore, K P; Pottumarthy, S; Morris, A J

1999-11-12

To determine the antimicrobial susceptibility of local anaerobic bacteria. The antimicrobial susceptibility of 357 obligate anaerobes collected between 1991 and 1997 was determined by a standard agar dilution method. Isolates tested included Bacteroides spp. 131, Fusobacterium spp. 12, Prevotella spp. 13, Veillonella spp. 5, Clostridium perfringens 27, other Clostridium spp. 29, Propionibacterium spp. 57, Actinomyces spp. 7, other non-sporing gram-positive bacilli 28 and Peptostreptococcus spp. 48. Ten antimicrobials were tested: penicillin, amoxycillin/ clavulanic acid, pipercillin/tazobactam, ceftriaxone, cefoxitin, cefotetan, imipenem, meropenem, clindamycin and metronidazole. Imipenem, pipercillin/tazobactam, meropenem and amoxycillin/clavulanic acid were active against virtually all anaerobes tested. Metronidazole was active against all anaerobic gram-negative bacteria and Clostridium spp., but had variable activity against other anaerobes. Cefoxitin was the most active cephalosporin against Bacteroides spp., with 76%, 64% and 15% of Bacteroides spp. being susceptible to cefoxitin, cefotetan and ceftriaxone, respectively. Penicillin had poor activity against anaerobic gram negative bacilli. Actinomyces and Propionibacterium spp. were susceptible to all antimicrobials tested except metronidazole. Variable results were obtained with other antimicrobial-organism combinations. Comparison of results with data from a previously published survey showed little change in susceptibility except for increased resistance of Bacteroides fragilis to ceftriaxone and Clostridium species (not C perfringens) to clindamycin. Our results update the local susceptibility profile of anaerobic bacteria and may be considered when choosing an antimicrobial agent for prophylaxis or treatment of anaerobic infections.

Discrete time Markov chains (DTMC) susceptible infected susceptible (SIS) epidemic model with two pathogens in two patches

Science.gov (United States)

Lismawati, Eka; Respatiwulan; Widyaningsih, Purnami

2017-06-01

The SIS epidemic model describes the pattern of disease spread with characteristics that recovered individuals can be infected more than once. The number of susceptible and infected individuals every time follows the discrete time Markov process. It can be represented by the discrete time Markov chains (DTMC) SIS. The DTMC SIS epidemic model can be developed for two pathogens in two patches. The aims of this paper are to reconstruct and to apply the DTMC SIS epidemic model with two pathogens in two patches. The model was presented as transition probabilities. The application of the model obtain that the number of susceptible individuals decreases while the number of infected individuals increases for each pathogen in each patch.

Landslide Susceptibility Statistical Methods: A Critical and Systematic Literature Review

Science.gov (United States)

Mihir, Monika; Malamud, Bruce; Rossi, Mauro; Reichenbach, Paola; Ardizzone, Francesca

2014-05-01

Landslide susceptibility assessment, the subject of this systematic review, is aimed at understanding the spatial probability of slope failures under a set of geomorphological and environmental conditions. It is estimated that about 375 landslides that occur globally each year are fatal, with around 4600 people killed per year. Past studies have brought out the increasing cost of landslide damages which primarily can be attributed to human occupation and increased human activities in the vulnerable environments. Many scientists, to evaluate and reduce landslide risk, have made an effort to efficiently map landslide susceptibility using different statistical methods. In this paper, we do a critical and systematic landslide susceptibility literature review, in terms of the different statistical methods used. For each of a broad set of studies reviewed we note: (i) study geography region and areal extent, (ii) landslide types, (iii) inventory type and temporal period covered, (iv) mapping technique (v) thematic variables used (vi) statistical models, (vii) assessment of model skill, (viii) uncertainty assessment methods, (ix) validation methods. We then pulled out broad trends within our review of landslide susceptibility, particularly regarding the statistical methods. We found that the most common statistical methods used in the study of landslide susceptibility include logistic regression, artificial neural network, discriminant analysis and weight of evidence. Although most of the studies we reviewed assessed the model skill, very few assessed model uncertainty. In terms of geographic extent, the largest number of landslide susceptibility zonations were in Turkey, Korea, Spain, Italy and Malaysia. However, there are also many landslides and fatalities in other localities, particularly India, China, Philippines, Nepal and Indonesia, Guatemala, and Pakistan, where there are much fewer landslide susceptibility studies available in the peer-review literature. This

Experimental susceptibility of Wood Ducks (Aix sponsa) for West Nile virus

Science.gov (United States)

Hofmeister, Erik K.; Porter, Robert E.; Franson, J. Christian

2015-01-01

Detection of West Nile virus (WNV) has been reported in a variety of wild ducks in the US, but little is known about the pathogenesis and outcome of exposure of the disease in these species. Previous experimental studies of WNV in ducks either have challenged a small number of ducks with WNV or have tested domesticated ducks. To determine susceptibility and immune response, we challenged 7-wk-old Wood Ducks (Aix sponsa) with a 1999 American Crow (Corvus brachyrhynchos) isolate of WNV. Wood Ducks were susceptible to infection with the virus, and, although clinical signs or mortality were not observed, microscopic lesions were noted, particularly in the heart and brain. West Nile virus viremia peaked on day 2 postinfection (pi) at 104.54 plaque-forming units (PFU) of virus/mL serum and WNV was shed orally (between 102and 102.9 PFU per swab) and cloacally. Specific anti-WNV antibody response was rapid, with anti-WNV IgM detected on day 3 pi followed on day 5 pi by anti-WNV IgG. Neutralizing antibodies were detected by plaque-reduction neutralization assay in one duck on day 4 pi, and in all sampled ducks on day 5. These results indicate that Wood Ducks are susceptible to WNV, but it is unlikely that significant WNV mortality events occur in Wood Ducks or that ducks play a significant role in transmission. However, WNV viremia was sufficient, in theory, to infect mosquitoes, and oral and cloacal shedding of the virus may increase the risk of infection to other waterbirds.

Alloy and composition dependence of hydrogen embrittlement susceptibility in high-strength steel fasteners

Science.gov (United States)

Brahimi, S. V.; Yue, S.; Sriraman, K. R.

2017-06-01

High-strength steel fasteners characterized by tensile strengths above 1100 MPa are often used in critical applications where a failure can have catastrophic consequences. Preventing hydrogen embrittlement (HE) failure is a fundamental concern implicating the entire fastener supply chain. Research is typically conducted under idealized conditions that cannot be translated into know-how prescribed in fastener industry standards and practices. Additionally, inconsistencies and even contradictions in fastener industry standards have led to much confusion and many preventable or misdiagnosed fastener failures. HE susceptibility is a function of the material condition, which is comprehensively described by the metallurgical and mechanical properties. Material strength has a first-order effect on HE susceptibility, which increases significantly above 1200 MPa and is characterized by a ductile-brittle transition. For a given concentration of hydrogen and at equal strength, the critical strength above which the ductile-brittle transition begins can vary due to second-order effects of chemistry, tempering temperature and sub-microstructure. Additionally, non-homogeneity of the metallurgical structure resulting from poorly controlled heat treatment, impurities and non-metallic inclusions can increase HE susceptibility of steel in ways that are measurable but unpredictable. Below 1200 MPa, non-conforming quality is often the root cause of real-life failures. This article is part of the themed issue 'The challenges of hydrogen and metals'.

Magnetic susceptibility measuring probe utilizing a compensation coil

International Nuclear Information System (INIS)

Bonnet, Jean; Fournet, Julien.

1978-01-01

This invention concerns a magnetic susceptibility measuring probe. It is used, inter alia, in logging, to wit continuous logging of the magnetic susceptibility of the ground throughout the length of a bore hole. The purpose of this invention is to increase the sensitivity of this type of probe by creating a side focusing effect . To this end, it provides for the use of a compensation winding, coaxial with the measurement winding and arranged symmetrically to the latter with respect to the centre of the induction windings [fr

The Role of Hydrogen-Enhanced Strain-Induced Lattice Defects on Hydrogen Embrittlement Susceptibility of X80 Pipeline Steel

Science.gov (United States)

Hattori, M.; Suzuki, H.; Seko, Y.; Takai, K.

2017-08-01

Studies to date have not completely determined the factors influencing hydrogen embrittlement of ferrite/bainite X80 pipeline steel. Hydrogen embrittlement susceptibility was evaluated based on fracture strain in tensile testing. We conducted a thermal desorption analysis to measure the amount of tracer hydrogen corresponding to that of lattice defects. Hydrogen embrittlement susceptibility and the amount of tracer hydrogen significantly increased with decreasing crosshead speed. Additionally, a significant increase in the formation of hydrogen-enhanced strain-induced lattice defects was observed immediately before the final fracture. In contrast to hydrogen-free specimens, the fracture surface of the hydrogen-charged specimens exhibited shallower dimples without nuclei, such as secondary phase particles. These findings indicate that the presence of hydrogen enhanced the formation of lattice defects, particularly just prior to the occurrence of final fracture. This in turn enhanced the formation of shallower dimples, thereby potentially causing premature fracture of X80 pipeline steel at lower crosshead speeds.

Comparison of antibiotic susceptibility of Escherichia coli in urinary isolates from an emergency department with other institutional susceptibility data.

Science.gov (United States)

Zatorski, Catherine; Jordan, Jeanne A; Cosgrove, Sara E; Zocchi, Mark; May, Larissa

2015-12-15

The antibiotic susceptibility of Escherichia coli in isolates from patients with uncomplicated urinary tract infection (UTI) in an emergency department (ED) was compared with susceptibility data from the associated hospital. Patients eligible for study participation included women age 18-65 years with one or more symptoms consistent with a UTI for whom a urine dipstick, urinalysis, or urine culture was ordered. Clinical decision-making, including the decision to order a urine culture, was at the discretion of the individual healthcare provider; however, a deidentified urine culture and antimicrobial susceptibility testing were performed for those study participants for whom a urine culture was not ordered. We compared the E. coli-specific antibiogram for uncomplicated UTI to the antibiogram based on all urine cultures in the ED regardless of patient disposition, non-intensive care unit (ICU) hospital inpatients, and the hospitalwide antibiogram. Of the 578 ED patients screened for study eligibility, 119 met the inclusion criteria. E. coli, detected in 53 (74%) of the 72 pathogen-positive cultures, was the most common pathogen isolated. For E. coli, ciprofloxacin nonsusceptibility was significantly less common in isolates from ED patients with uncomplicated cystitis and pyelonephritis than in isolates from non-ICU inpatients or from the hospitalwide population. E. coli nonsusceptibility to ciprofloxacin was significantly less common in ED isolates from patients with uncomplicated UTI than in isolates from all ED patients with clinician-ordered urine cultures. Antibiotic susceptibility of E. coli in an ED and its associated hospital depended on factors such as whether patients were hospitalized and whether ED isolates were from patients with uncomplicated UTI. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Hot tearing susceptibility of binary Mg–Y alloy castings

International Nuclear Information System (INIS)

Wang, Zhi; Huang, Yuanding; Srinivasan, Amirthalingam; Liu, Zheng; Beckmann, Felix; Kainer, Karl Ulrich; Hort, Norbert

2013-01-01

Highlights: ► Quantitatively and qualitatively assessing hot tearing susceptibility for different alloys. ► Monitoring the hot tearing propagation process. ► Detecting the hot tearing initiation/onset temperature. ► Recording the stress and strain evolution during the casting solidification and the subsequent cooling. - Abstract: The influence of Y content on the hot tearing susceptibility (HTS) of binary Mg–Y alloys has been predicted using thermodynamic calculations based on Clyne and Davies model. The calculated results are compared with experimental results determined using a constrained rod casting (CRC) apparatus with a load cell and data acquisition system. Both thermodynamic calculations and experimental measurements indicate that the hot tearing susceptibility as a function of Y content follows the “λ” shape. The experimental results show that HTS first increases with increase in Y content, reaches the maximum at about 0.9 wt.%Y and then decreases with further increase the Y content. The maximum susceptibility observed in Mg–0.9 wt.%Y alloy is attributed to its coarsened columnar microstructure, large solidification range and small amount of eutectic at the time of hot tearing. The initiation of hot cracks is monitored during CRC experiments. It corresponds to a drop in load increment on the force curves. The critical solid fractions at which the hot cracks are initiated are in the range from 0.9 to 0.99. It is also found that it decreases with increasing the content of Y. The hot cracks propagate along the dendritic or grain boundaries through the interdendritic separation or tearing of interconnected dendrites. Some of the formed cracks are possible to be healed by the subsequent refilling of the remained liquids

Formulation of Biocides Increases Antimicrobial Potency and Mitigates the Enrichment of Nonsusceptible Bacteria in Multispecies Biofilms

Science.gov (United States)

Forbes, Sarah; Cowley, Nicola; Mistry, Hitesh; Amézquita, Alejandro

2017-01-01

ABSTRACT The current investigation aimed to generate data to inform the development of risk assessments of biocide usage. Stabilized domestic drain biofilm microcosms were exposed daily over 6 months to increasing concentrations (0.01% to 1%) of the biocide benzalkonium chloride (BAC) in a simple aqueous solution (BAC-s) or in a complex formulation (BAC-f) representative of a domestic cleaning agent. Biofilms were analyzed by culture, differentiating by bacterial functional group and by BAC or antibiotic susceptibility. Bacterial isolates were identified by 16S rRNA sequencing, and changes in biofilm composition were assessed by high-throughput sequencing. Exposure to BAC-f resulted in significantly larger reductions in levels of viable bacteria than exposure to BAC-s, while bacterial diversity greatly decreased during exposure to both BAC-s and BAC-f, as evidenced by sequencing and viable counts. Increases in the abundance of bacteria exhibiting reduced antibiotic or BAC susceptibility following exposure to BAC at 0.1% were significantly greater for BAC-s than BAC-f. Bacteria with reduced BAC and antibiotic susceptibility were generally suppressed by higher BAC concentrations, and formulation significantly enhanced this effect. Significant decreases in the antimicrobial susceptibility of bacteria isolated from the systems before and after long-term BAC exposure were not detected. In summary, dose-dependent suppression of bacterial viability by BAC was enhanced by formulation. Biocide exposure decreased bacterial diversity and transiently enriched populations of organisms with lower antimicrobial susceptibility, and the effects were subsequently suppressed by exposure to 1% BAC-f, the concentration most closely reflecting deployment in formulated products. IMPORTANCE Assessment of the risks of biocide use has been based mainly on the exposure of axenic cultures of bacteria to biocides in simple aqueous solutions. The current investigation aimed to assess the

Possible Association of IL-4 VNTR Polymorphism with Susceptibility to Preeclampsia

Directory of Open Access Journals (Sweden)

Saeedeh Salimi

2014-01-01

Full Text Available Preeclampsia (PE is a pregnancy-specific disorder that results in maternal mortality and morbidity. Growing evidence indicated that cytokines are involved in the pathogenesis of PE and interleukin-4 VNTR polymorphism could be implicated in altering the PE risk. The aim of this study was to evaluate the possible association between IL-4 VNTR polymorphism and susceptibility to PE in Iranian population for the first time. Genetic polymorphism was evaluated in 192 PE and 186 healthy control women by polymerase chain reaction method. We found that the VNTR polymorphism of IL-4 gene has significantly increased the risk of preeclampsia (RP2/RP1 versus RP1/RP1, OR, 2.8 [95% CI, 1.7 to 8.8]; P=0.0001 and RP2/RP2 versus RP1/RP1; P=0.002. The results showed that carriage of IL-4 VNTR RP2 allele has positive association with preeclampsia susceptibility.

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation

NARCIS (Netherlands)

Wojtowicz, A.; Gresnigt, M.S.; Lecompte, T.; Bibert, S.; Manuel, O.; Joosten, L.A.B.; Rueger, S.; Berger, C.; Boggian, K.; Cusini, A.; Garzoni, C.; Hirsch, H.H.; Weisser, M.; Mueller, N.J.; Meylan, P.R.; Steiger, J.; Kutalik, Z.; Pascual, M.; Delden, C. van; Veerdonk, F.L. van de; Bochud, P.Y.

2015-01-01

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped

Estimating susceptibility and magnetization within the Earth's continental crust: Petrophysical and Satellite approaches

Science.gov (United States)

Purucker, M. E.; McEnroe, S. A.

2014-12-01

Magnetic models (Xchaos) made from Champ and Orsted data are used to place constraints on the average magnetic susceptibility and its variability in the continental crust. Estimates of magnetic crustal thickness are made in a two-step process. The first step uses a recent seismic model (Crust1.0) to estimate the thickness of crystalline crust above the Moho, modified in the Andes and the Himalayas to account for the non-magnetic lower crust there. The second step calculates the magnetic field expected from such a layer of crystalline rock assuming the magnetization is solely induced in the earth's main field by rock of constant magnetic susceptibility, and modifies the starting crustal thickness to bring it into agreement with the Xchaos model. This global model removes spherical harmonic degrees less than 15 to account for the core field mask. We restrict our attention to the continental crust, in particular to Australia, western North America, and Scandinavia. Petrophysical and petrological data from Scandinavian rocks that have been deep in the crust help place limits on susceptibility values. Our simulations use two susceptibilities, 0.02 and 0.04 SI. The mean crystalline crustal thickness from the seismic model is 42 and 37 km in western North America and Australia, respectively, and the modification with the magnetic data makes little change to the mean crustal thickness, irrespective of whether the susceptibility is 0.02 or 0.04 SI. However, the modification with the magnetic data does make a significant difference to the standard deviation of the crustal thickness, increasing it by a factor of two in the case of a susceptibility of 0.04, and by a factor of four in the case of a susceptibility of 0.02. The changes to the standard deviation of the crustal thickness are also evident in the Scandinavian data, but the mean crystalline crustal thickness of 45 km is significantly larger than that found from either magnetic model (33 and 30 km). The differences

Estimating Fitness by Competition Assays between Drug Susceptible and Resistant Mycobacterium tuberculosis of Predominant Lineages in Mumbai, India

Science.gov (United States)

Bhatter, Purva; Chatterjee, Anirvan; D'souza, Desiree; Tolani, Monica; Mistry, Nerges

2012-01-01

Background Multi Drug Resistant Tuberculosis (MDR TB) is a threat to global tuberculosis control. A significant fitness cost has been associated with DR strains from specific lineages. Evaluation of the influence of the competing drug susceptible strains on fitness of drug resistant strains may have an important bearing on understanding the spread of MDR TB. The aim of this study was to evaluate the fitness of MDR TB strains, from a TB endemic region of western India: Mumbai, belonging to 3 predominant lineages namely CAS, Beijing and MANU in the presence of drug susceptible strains from the same lineages. Methodology Drug susceptible strains from a single lineage were mixed with drug resistant strain, bearing particular non synonymous mutation (rpoB D516V; inhA, A16G; katG, S315T1/T2) from the same or different lineages. Fitness of M.tuberculosis (M.tb) strains was evaluated using the difference in growth rates obtained by using the CFU assay system. Conclusion/Significance While MANU were most fit amongst the drug susceptible strains of the 3 lineages, only Beijing MDR strains were found to grow in the presence of any of the competing drug susceptible strains. A disproportionate increase in Beijing MDR could be an alarm for an impending epidemic in this locale. In addition to particular non synonymous substitutions, the competing strains in an environment may impact the fitness of circulating drug resistant strains. PMID:22479407

Strain, Sex, and Open-Field Behavior: Factors Underlying the Genetic Susceptibility to Helplessness

Science.gov (United States)

Padilla, Eimeira; Barrett, Douglas W.; Shumake, Jason D.; Gonzalez-Lima, F.

2009-01-01

Learned helplessness represents a failure to escape after exposure to inescapable stress and may model human psychiatric disorders related to stress. Previous work has demonstrated individual differences in susceptibility to learned helplessness. In this study, we assessed different factors associated with this susceptibility, including strain, sex, and open-field behavior. Testing of three rat strains (Holtzman, Long-Evans, and Sprague-Dawley) revealed that Holtzman rats were the most susceptible to helplessness. Holtzman rats not only had the longest escape latencies following inescapable shock, but also showed spontaneous escape deficits in the absence of prior shock when tested with a fixed-ratio 2 (FR2) running response. Moreover, when tested with fixed-ratio 1 (FR1) running—an easy response normally unaffected by helplessness training in rats—inescapable shock significantly increased the escape latencies of Holtzman rats. Within the Holtzman strain, we confirmed recent findings that females showed superior escape performance and therefore appeared more resistant to helplessness than males. However, regression and covariance analyses suggest that this sex difference may be explained by more baseline ambulatory activity among females. In addition, some indices of novelty reactivity (greater exploration of novel vs. familiar open-field) predicted subsequent helpless behavior. In conclusion, Holtzman rats, and especially male Holtzman rats, have a strong predisposition to become immobile when stressed which interferes with their ability to learn active escape responses. The Holtzman strain therefore appears to be a commercially available model for studying susceptibility to helplessness in males, and novelty-seeking may be a marker of this susceptibility. PMID:19428642

The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan

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Cheng Hsiao-Hsu

2005-11-01

Full Text Available Abstract Background Candida species have various degrees of susceptibility to common antifungal drugs. The extent of resistance to amphotericin B and fluconazole of Candida glabrata isolates causing candidemia has been reported. Active surveillance may help us to monitor the trend of susceptibility to antifungal drugs and to determine if there is an emerging co-resistance to both drugs of Candida species, specifically, of C. glabrata in Taiwan. Methods The susceptibilities to amphotericin B and fluconazole of Candida species collected in 1999 and 2002 of the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY were determined by the microdilution method. Results The antifungal susceptibilities of 342 and 456 isolates collected from 11 hospitals participating in both TSARY 1999 and TSARY 2002, respectively, have been determined. The resistance rate to amphotericin B has increased from 0.3% in the TSARY1999 to 2.2% in the TSARY 2002. In contrast, the resistance rate to fluconazole has decreased from 8.8% to 2.2%. Nevertheless, significantly more C. glabrata isolates were not susceptible to fluconazole in the TSARY 2002 (47.4% than that in the TSARY 1999 (20.8%. There were 9.8% and 11% of C. glabrata isolates having susceptible-dose dependent and resistant phenotype to fluconazole in the TSARY 1999, verse 45.3% and 2.1% in the TSARY 2002. Conclusion There was an increase of resistance rate to amphotericin B in C. glabrata. On the other hand, although the resistance rate to fluconazole has decreased, almost half of C. glabrata isolates were not susceptible to this drug. Hence, continuous monitoring the emerging of co-resistance to both amphotericin B and fluconazole of Candida species, specifically, of C. glabrata, will be an important early-warning system.

Changing attitudes toward smoking and smoking susceptibility through peer crowd targeting: more evidence from a controlled study.

Science.gov (United States)

Moran, Meghan Bridgid; Sussman, Steve

2015-01-01

Peer crowd identification consistently predicts an adolescent's smoking behavior. As such, several interventions have targeted adolescents and young adults based on their identification with a specific crowd (e.g., Hipsters). This study uses a controlled experimental design to isolate and test the effect of peer crowd targeting in an antismoking ad on antismoking attitudes and smoking susceptibility. Two hundred and thirty-nine adolescents, age 13-15 years, completed a baseline survey and then viewed an antismoking ad targeting one of eight crowds; 1 week later they completed a posttest. Participants were assessed on antismoking attitudes and smoking susceptibility. Adolescents who strongly identified with the crowd targeted by the ad reported stronger antismoking attitudes and lower levels of smoking susceptibility. Those who disidentified with the crowd targeted in the ad exhibited not statistically significant increases in smoking susceptibility and weaker antismoking attitudes at posttest. These findings indicate that targeting youths based on their peer crowd is a useful strategy for antismoking interventions. Additional research should further examine whether youths who disidentify with the targeted crowd in an ad exhibit reactance against the message.

Effects of tissue susceptibility on brain temperature mapping.

Science.gov (United States)

Maudsley, Andrew A; Goryawala, Mohammed Z; Sheriff, Sulaiman

2017-02-01

A method for mapping of temperature over a large volume of the brain using volumetric proton MR spectroscopic imaging has been implemented and applied to 150 normal subjects. Magnetic susceptibility-induced frequency shifts in gray- and white-matter regions were measured and included as a correction in the temperature mapping calculation. Additional sources of magnetic susceptibility variations of the individual metabolite resonance frequencies were also observed that reflect the cellular-level organization of the brain metabolites, with the most notable differences being attributed to changes of the N-Acetylaspartate resonance frequency that reflect the intra-axonal distribution and orientation of the white-matter tracts with respect to the applied magnetic field. These metabolite-specific susceptibility effects are also shown to change with age. Results indicate no change of apparent brain temperature with age from 18 to 84 years old, with a trend for increased brain temperature throughout the cerebrum in females relative for males on the order of 0.1°C; slightly increased temperatures in the left hemisphere relative to the right; and a lower temperature of 0.3°C in the cerebellum relative to that of cerebral white-matter. This study presents a novel acquisition method for noninvasive measurement of brain temperature that is of potential value for diagnostic purposes and treatment monitoring, while also demonstrating limitations of the measurement due to the confounding effects of tissue susceptibility variations. Copyright © 2016 Elsevier Inc. All rights reserved.

acetyltransferases: Influence on Lung Cancer Susceptibility

African Journals Online (AJOL)

Lung cancer remains a major health challenge in the world. It is the commonest cause of cancer mortality in men, it has been suggested that genetic susceptibility may contribute to the major risk factor, with increasing prevalence of smoking. Lung cancer has reached epidemic proportions in India. Recently indoor air ...

THE SMALL BUT SIGNIFICANT AND NONTRANSITORY INCREASE IN PRICES (SSNIP TEST

Directory of Open Access Journals (Sweden)

Liviana Niminet

2008-12-01

Full Text Available The Small but Significant Nontransitory Increase in Price Test was designed to define the relevant market by concepts of product, geographical area and time. This test, also called the ,,hypothetical monopolistic test” is the subject of many researches both economical and legal as it deals with economic concepts as well as with legally aspects.

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Science.gov (United States)

McKay, James D; Hung, Rayjean J; Han, Younghun; Zong, Xuchen; Carreras-Torres, Robert; Christiani, David C; Caporaso, Neil E; Johansson, Mattias; Xiao, Xiangjun; Li, Yafang; Byun, Jinyoung; Dunning, Alison; Pooley, Karen A; Qian, David C; Ji, Xuemei; Liu, Geoffrey; Timofeeva, Maria N; Bojesen, Stig E; Wu, Xifeng; Le Marchand, Loic; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C; Bush, William S; Tardon, Adonina; Rennert, Gad; Teare, M Dawn; Field, John K; Kiemeney, Lambertus A; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B; Andrew, Angeline S; Shen, Hongbing; Hong, Yun-Chul; Yuan, Jian-Min; Bertazzi, Pier Alberto; Pesatori, Angela C; Ye, Yuanqing; Diao, Nancy; Su, Li; Zhang, Ruyang; Brhane, Yonathan; Leighl, Natasha; Johansen, Jakob S; Mellemgaard, Anders; Saliba, Walid; Haiman, Christopher A; Wilkens, Lynne R; Fernandez-Somoano, Ana; Fernandez-Tardon, Guillermo; van der Heijden, Henricus F M; Kim, Jin Hee; Dai, Juncheng; Hu, Zhibin; Davies, Michael P A; Marcus, Michael W; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Doherty, Jennifer A; Barnett, Matt P; Chen, Chu; Goodman, Gary E; Cox, Angela; Taylor, Fiona; Woll, Penella; Brüske, Irene; Wichmann, H-Erich; Manz, Judith; Muley, Thomas R; Risch, Angela; Rosenberger, Albert; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances A; Tsao, Ming-Sound; Arnold, Susanne M; Haura, Eric B; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J; Butler, Lesley M; Koh, Woon-Puay; Gao, Yu-Tang; Houlston, Richard S; McLaughlin, John; Stevens, Victoria L; Joubert, Philippe; Lamontagne, Maxime; Nickle, David C; Obeidat, Ma'en; Timens, Wim; Zhu, Bin; Song, Lei; Kachuri, Linda; Artigas, María Soler; Tobin, Martin D; Wain, Louise V; Rafnar, Thorunn; Thorgeirsson, Thorgeir E; Reginsson, Gunnar W; Stefansson, Kari; Hancock, Dana B; Bierut, Laura J; Spitz, Margaret R; Gaddis, Nathan C; Lutz, Sharon M; Gu, Fangyi; Johnson, Eric O; Kamal, Ahsan; Pikielny, Claudio; Zhu, Dakai; Lindströem, Sara; Jiang, Xia; Tyndale, Rachel F; Chenevix-Trench, Georgia; Beesley, Jonathan; Bossé, Yohan; Chanock, Stephen; Brennan, Paul; Landi, Maria Teresa; Amos, Christopher I

2017-07-01

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

Susceptibility to chemical insecticides of two Brazilian populations of the visceral leishmaniasis vector Lutzomyia longipalpis (Diptera: Psychodidae).

Science.gov (United States)

Alexander, B; Barros, V C; de Souza, S F; Barros, S S; Teodoro, L P; Soares, Z R; Gontijo, N F; Reithinger, R

2009-10-01

To investigate the insecticide susceptibility of two geographically separated Lutzomyia longipalpis populations (Lapinha and Montes Claros) with different histories of insecticide exposure (i.e. no exposure and repeated exposure, respectively). (i) Bioassay monitoring of sand fly survival over time when exposed to a range of insecticides; and (ii) analysis of the level of insecticide detoxification enzymes in individual sand flies caught at both study sites. Insecticides tested were the organophosphates malathion and fenitrothion and the pyrethroids lambda-cyhalothrin, permethrin and deltamethrin. Survival analyses showed that whilst there was no overall significant difference in susceptibility of both populations to organophosphates, Lapinha sand flies were significantly more susceptible to pyrethroids than those from Montes Claros. Multiple regression analyses also showed that insecticide susceptibility in both locations varied with sand fly sex. The relative susceptibilities of the two sand fly populations to tested insecticides were also compared. Thus, Montes Claros sand flies were most susceptible to malathion, followed by fenitrothion, deltamethrin and permethrin. Those from Lapinha were most susceptible to lambda-cyhalothrin, followed by malathion, permethrin, deltamethrin and fenitrothion. Biochemical analyses demonstrated that Montes Claros sand flies had significantly lower insecticide detoxification enzyme activity than Lapinha sand flies. Our results are the first record of significantly reduced susceptibility to the insecticides used in control of wild populations of Lu. longipalpis. They demonstrate the importance of evaluating chemicals against this species by conventional bioassay and microplate assays before and during spraying programmes.

Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

Science.gov (United States)

Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

2018-03-01

Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Susceptibility of ternary aluminum alloys to cracking during solidification

International Nuclear Information System (INIS)

Liu, Jiangwei; Kou, Sindo

2017-01-01

The crack susceptibility map of a ternary Al alloy system provides useful information about which alloy compositions are most susceptible to cracking and thus should be avoided by using a filler metal with a significantly different composition. In the present study the crack susceptibility maps of ternary Al alloy systems were calculated based on the maximum |dT/d(f S ) 1/2 | as an index for the crack susceptibility, where T is temperature and f S fraction solid. Due to the complexity associated with ternary alloy solidification, commercial thermodynamic software Pandat and Al database PanAluminum, instead of analytical equations, were used to calculate f S as a function of T and hence the maximum |dT/d(f S ) 1/2 | for ternary Al-Mg-Si, Al-Cu-Mg and Al-Cu-Si alloy systems. A crack susceptibility map covering 121 alloy compositions was constructed for each of the three ternary alloy systems at each of the following three levels of back diffusion: no back diffusion, back diffusion under a 100 °C/s cooling rate, and back diffusion under 20° C/s. The location of the region of high crack susceptibility, which is the most important part of the map, was shown in each of the nine calculated maps. These locations were compared with those observed in crack susceptibility tests by previous investigators. With back diffusion considered, either under 20 or 100 °C/s, the agreement between the calculated and observed maps was good especially for Al-Mg-Si and Al-Cu-Mg. Thus, the maximum |dT/d(f S ) 1/2 | can be used as a crack susceptibility index to construct crack susceptibility maps for ternary Al alloys and to evaluate the effect of back diffusion on their crack susceptibility. - Graphical abstract: The crack susceptibility map of a ternary alloy system indicates the composition range most susceptible to cracking, which should be avoided in welding or casting. The crack susceptibility maps of ternary Al alloy systems Al-Mg-Si, Al-Cu-Mg and Al-Cu-Si were calculated based

Nonlinear electromagnetic susceptibilities of unmagnetized plasmas

International Nuclear Information System (INIS)

Yoon, Peter H.

2005-01-01

Fully electromagnetic nonlinear susceptibilities of unmagnetized plasmas are analyzed in detail. Concrete expressions of the second-order nonlinear susceptibility are found in various forms in the literature, usually in connection with the discussions of various three-wave decay processes, but the third-order susceptibilities are rarely discussed. The second-order susceptibility is pertinent to nonlinear wave-wave interactions (i.e., the decay/coalescence), whereas the third-order susceptibilities affect nonlinear wave-particle interactions (i.e., the induced scattering). In the present article useful approximate analytical expressions of these nonlinear susceptibilities that can be readily utilized in various situations are derived

Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles - a retrospective chart review.

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Mushtaq, Ammara; Chen, Derrick J; Strand, Gregory J; Dylla, Brenda L; Cole, Nicolynn C; Mandrekar, Jayawant; Patel, Robin

2016-07-01

With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), most Gram-positive rods (GPRs) are readily identified; however, their clinical relevance in blood cultures remains unclear. Herein, we assessed the clinical significance of GPRs isolated from blood and identified in the era of MALDI-TOF MS. A retrospective chart review of patients presenting to the Mayo Clinic, Rochester, MN, from January 1, 2013, to October 13, 2015, was performed. Any episode of a positive blood culture for a GPR was included. We assessed the number of bottles positive for a given isolate, time to positivity of blood cultures, patient age, medical history, interpretation of culture results by the healthcare team and whether infectious diseases consultation was obtained. We also evaluated the susceptibility profiles of a larger collection of GPRs tested in the clinical microbiology laboratory of the Mayo Clinic, Rochester, MN from January 1, 2013, to October 31, 2015. There were a total of 246 GPRs isolated from the blood of 181 patients during the study period. 56% (n = 101) were deemed contaminants by the healthcare team and were not treated; 33% (n = 59) were clinically determined to represent true bacteremia and were treated; and 8% (n = 14) were considered of uncertain significance, with patients prescribed treatment regardless. Patient characteristics associated with an isolate being treated on univariate analysis included younger age (P = 0.02), identification to the species level (P = 0.02), higher number of positive blood culture sets (P < 0.0001), lower time to positivity (P < 0.0001), immunosuppression (P = 0.03), and recommendation made by an infectious disease consultant (P = 0.0005). On multivariable analysis, infectious diseases consultation (P = 0.03), higher number of positive blood culture sets (P = 0.0005) and lower time to positivity (P = 0.03) were associated with an isolate being treated. 100, 83, 48 and 34% of GPRs

Has the emergence of community-associated methicillin-resistant Staphylococcus aureus increased trimethoprim-sulfamethoxazole use and resistance?: a 10-year time series analysis.

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Wood, Jameson B; Smith, Donald B; Baker, Errol H; Brecher, Stephen M; Gupta, Kalpana

2012-11-01

There are an increasing number of indications for trimethoprim-sulfamethoxazole use, including skin and soft tissue infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Assessing the relationship between rates of use and antibiotic resistance is important for maintaining the expected efficacy of this drug for guideline-recommended conditions. Using interrupted time series analysis, we aimed to determine whether the 2005 emergence of CA-MRSA and recommendations of trimethoprim-sulfamethoxazole as the preferred therapy were associated with changes in trimethoprim-sulfamethoxazole use and susceptibility rates. The data from all VA Boston Health Care System facilities, including 118,863 inpatient admissions, 6,272,661 outpatient clinic visits, and 10,138 isolates were collected over a 10-year period. There was a significant (P = 0.02) increase in trimethoprim-sulfamethoxazole prescriptions in the post-CA-MRSA period (1,605/year) compared to the pre-CA-MRSA period (1,538/year). Although the overall susceptibility of Escherichia coli and Proteus spp. to trimethoprim-sulfamethoxazole decreased over the study period, the rate of change in the pre- versus the post-CA-MRSA period was not significantly different. The changes in susceptibility rates of S. aureus to trimethoprim-sulfamethoxazole and to methicillin were also not significantly different. The CA-MRSA period is associated with a significant increase in use of trimethoprim-sulfamethoxazole but not with significant changes in the rates of susceptibilities among clinical isolates. There is also no evidence for selection of organisms with increased resistance to other antimicrobials in relation to increased trimethoprim-sulfamethoxazole use.

[Bacterial diversity in the oral cavity of adolescents with different caries susceptibilities].

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Yangyang, Zhang; Jinzhi, He; Xin, Xu; Xuedong, Zhou

2015-12-01

To analyze the differences between the bacterial diversities in the saliva of caries-free and caries-susceptible adolescents through polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE). Twenty adolescent subjects aged 12-18 years were recruited and subdivided into two groups: caries-free adolescents (n = 10) and caries-susceptible adolescents (n = 10). Saliva samples were collected. Total DNA was isolated directly from each sample. A portion of the 16S rRNA gene locus was PCR-amplified by using universal primers. Microbial diversity was analyzed through PCR-DGGE. Analyzing the DGGE profile, we found that the composition of the saliva microbiome exhibited great intra-individual differences; the average band numbers of the caries-free adolescent group and the caries-susceptible adolescent group were 32.5 ± 3.7 and 27.3 ± 3.4, respectively. The differences between the groups were statistically significant (P = 0.008). Shannon-Wiener's indexes of the caries-susceptible adolescent group and the caries-free adolescent group were 2.5 ± 0.2 and 2.6 ± 0.2, respectively, but the differences between the groups were not significant (P = 0.405). Clustering analysis results suggested that most of the samples in the same group clustered together; this observation showed a high community structure similarity. The microbial diversity and complexity of bacteria in saliva are significantly higher in caries-free adolescents than in caries-susceptible adolescents. During caries development, bacterial diversity in the saliva likely decreases.

Antibiotic susceptibility profiles for mastitis treatment.

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Hinckley, L S; Benson, R H; Post, J E; DeCloux, J C

1985-10-01

Susceptibility tests were performed on milk samples representing prevalent mastitis infections in certain herds. Susceptibility patterns of the same bacterial species from several mastitis infections in the same herd were consistent. The herd antibiotic susceptibility profiles were used as a basis for selecting antibiotics for treatment of all such mastitis cases in that herd. A high degree of correlation was seen between the susceptibility test results and treatment results. Susceptibility patterns of the same bacterial species from mastitis infections in different herds varied greatly, which indicated that any one antibiotic would not work equally well against the same bacterial infection in every herd. Therefore, treatment should be selected on the basis of susceptibility test results. When both Streptococcus and Staphylococcus mastitis occurred in the same herd, the susceptibility patterns for the 2 bacterial species varied widely. Therefore, for herds that experienced both streptococcal and staphylococcal mastitis, antibiotics to which both bacterial species were susceptible were used for treatment.

Do parasitic trematode cercariae demonstrate a preference for susceptible host species?

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Brittany F Sears

Full Text Available Many parasites are motile and exhibit behavioural preferences for certain host species. Because hosts can vary in their susceptibility to infections, parasites might benefit from preferentially detecting and infecting the most susceptible host, but this mechanistic hypothesis for host-choice has rarely been tested. We evaluated whether cercariae (larval trematode parasites prefer the most susceptible host species by simultaneously presenting cercariae with four species of tadpole hosts. Cercariae consistently preferred hosts in the following order: Anaxyrus ( = Bufo terrestris (southern toad, Hyla squirella (squirrel tree frog, Lithobates ( = Rana sphenocephala (southern leopard frog, and Osteopilus septentrionalis (Cuban tree frog. These host species varied in susceptibility to cercariae in an order similar to their attractiveness with a correlation that approached significance. Host attractiveness to parasites also varied consistently and significantly among individuals within a host species. If heritable, this individual-level host variation would represent the raw material upon which selection could act, which could promote a Red Queen "arms race" between host cues and parasite detection of those cues. If, in general, motile parasites prefer to infect the most susceptible host species, this phenomenon could explain aggregated distributions of parasites among hosts and contribute to parasite transmission rates and the evolution of virulence. Parasite preferences for hosts belie the common assumption of disease models that parasites seek and infect hosts at random.

Antimicrobial susceptibility of anaerobic bacteria in New Zealand: 1999-2003.

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Roberts, Sally A; Shore, Keith P; Paviour, Susan D; Holland, David; Morris, Arthur J

2006-05-01

Routine susceptibility testing of all anaerobic organisms is not advocated, but it is useful for laboratories to test periodically for anaerobic organisms and provide local susceptibility data to guide therapy. This study reports the national trend of antibiotic susceptibility of clinically significant anaerobes in New Zealand. Clinical isolates were tested using standardized methods against a range of antibiotics commonly used to treat anaerobic infections. Susceptibility was determined using NCCLS criteria. The change in susceptibility trends between this study and earlier studies was measured by comparing the geometric mean of the MIC. A total of 364 anaerobes were tested. Penicillin had poor activity against Bacteroides spp., Prevotella spp., Eubacterium spp., Clostridium tertium and Veillonella spp. In general, Fusobacterium spp., Bacteroides ureolyticus, Propionibacterium spp., Clostridium perfringens and anaerobic streptococci isolates, with the exception of Peptostreptococcus anaerobius, were penicillin susceptible. Amoxicillin/clavulanate showed good activity against most anaerobes, but resistance was seen with Bacteroides fragilis group and P. anaerobius isolates. Cefoxitin was more active than cefotetan, particularly against non-B. fragilis species, Eubacterium spp. and P. anaerobius. Meropenem and imipenem showed good activity against all anaerobes, with only 2 and 4% of Bacteroides spp., respectively, showing resistance. With the exception of Propionibacterium acnes isolates, which are predictably resistant, metronidazole was active against all anaerobes tested. There has been little change in susceptibility since 1997. Metronidazole, cefoxitin, piperacillin/tazobactam and amoxicillin/clavulanate remain good empirical choices when anaerobes are expected in our setting. No clinically relevant changes in susceptibility over time were found.

Risk of leukemia in susceptible children exposed to preconception, in utero, and postnatal radiation

International Nuclear Information System (INIS)

Bross, I.D.J.; Natarajan, N.

1974-01-01

Further statistical analysis has clarified the hypothesis that there exists a susceptible subgroup of children who are prone to develop leukemia after exposure to low doses of diagnostic radiation which have no effect on normal insusceptible children. The susceptible group does not show marked increase in relative risk when there is no report of exposure. The risk of developing leukemia among the susceptible children with any of the three types of radiation exposure is markedly increased in the appropriate age groups. The data are concordant with a latent period of 4 to 7 years. (auth)

Working memory in schizophrenia: behavioral and neural evidence for reduced susceptibility to item-specific proactive interference.

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Kaller, Christoph P; Loosli, Sandra V; Rahm, Benjamin; Gössel, Astrid; Schieting, Stephan; Hornig, Tobias; Hennig, Jürgen; Tebartz van Elst, Ludger; Weiller, Cornelius; Katzev, Michael

2014-09-15

Susceptibility to item-specific proactive interference (PI) contributes to interindividual differences in working memory (WM) capacity and complex cognition relying on WM. Although WM deficits are a well-recognized impairment in schizophrenia, the underlying pathophysiological effects on specific WM control functions, such as the ability to resist item-specific PI, remain unknown. Moreover, opposing hypotheses on increased versus reduced PI susceptibility in schizophrenia are both justifiable by the extant literature. To provide first insights into the behavioral and neural correlates of PI-related WM control in schizophrenia, a functional magnetic resonance imaging experiment was conducted in a sample of 20 patients and 20 well-matched control subjects. Demands on item-specific PI were experimentally manipulated in a recent-probes task (three runs, 64 trials each) requiring subjects to encode and maintain a set of four target items per trial. Compared with healthy control subjects, schizophrenia patients showed a significantly reduced PI susceptibility in both accuracy and latency measures. Notably, reduced PI susceptibility in schizophrenia was not associated with overall WM impairments and thus constituted an independent phenomenon. In addition, PI-related activations in inferior frontal gyrus and anterior insula, typically assumed to support PI resistance, were reduced in schizophrenia, thus ruling out increased neural efforts as a potential cause of the patients' reduced PI susceptibility. The present study provides first evidence for a diminished vulnerability of schizophrenia patients to item-specific PI, which is presumably a consequence of the patients' more efficient clearing of previously relevant WM traces and the accordingly reduced likelihood for item-specific PI to occur. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Evaluation of Significance of Diffusely Increased Bilateral Renal Uptake on Bone Scan

International Nuclear Information System (INIS)

Sung, Mi Sook; Yang, Woo Jin; Byun, Jae Young; Park, Jung Mi; Shinn, Kyung Sub; Bahk, Yong Whee

1990-01-01

Unexpected renal abnormality can be detected on bone scan using 99m Tc-MDP. The purpose of the study is to evaluate the diagnostic significance of diffusely increased bilateral renal uptake on bone scan. 1,500 bone scan were reviewed and 43 scans which showed diffusely increased bilateral renal uptake were selected for analysis. Laboratory findings for renal and liver function tests including routine urinalysis were reviewed in 43 patients. 26 of 43 case showed abnormality in urinalysis and renal function study. 20 of 43 cases showed abnormal liver function study and 3 of these cases were diagnosed as hepatorenal syndrome later. 13 of those 20 cases had liver cirrhosis with or without hepatoma. 12 of 43 cases showed abnormality both in renal and liver function studies. 2 of 43 cases showed diffusely increased bilateral renal uptake after chemotherapy for cancer but not on previous scans before chemotherapy. 2 of 43 cases showed hypercalcaemia and 8 of 43 cases had multifocal bone uptake due to metastasis or benign bone lesion. But the latter showed no hypercalcaemia at all. There was no significant correlation between increased renal uptake and MDP uptake in soft tissue other than kidneys. This study raised the possibility that the impaired liver and/or renal function may result in diffuse increase of bilateral renal uptake of MDP of unknown mechanism. It seems to need further study on this correlation.

Evaluation of Significance of Diffusely Increased Bilateral Renal Uptake on Bone Scan

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Sung, Mi Sook; Yang, Woo Jin; Byun, Jae Young; Park, Jung Mi; Shinn, Kyung Sub; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

1990-03-15

Unexpected renal abnormality can be detected on bone scan using {sup 99m}Tc-MDP. The purpose of the study is to evaluate the diagnostic significance of diffusely increased bilateral renal uptake on bone scan. 1,500 bone scan were reviewed and 43 scans which showed diffusely increased bilateral renal uptake were selected for analysis. Laboratory findings for renal and liver function tests including routine urinalysis were reviewed in 43 patients. 26 of 43 case showed abnormality in urinalysis and renal function study. 20 of 43 cases showed abnormal liver function study and 3 of these cases were diagnosed as hepatorenal syndrome later. 13 of those 20 cases had liver cirrhosis with or without hepatoma. 12 of 43 cases showed abnormality both in renal and liver function studies. 2 of 43 cases showed diffusely increased bilateral renal uptake after chemotherapy for cancer but not on previous scans before chemotherapy. 2 of 43 cases showed hypercalcaemia and 8 of 43 cases had multifocal bone uptake due to metastasis or benign bone lesion. But the latter showed no hypercalcaemia at all. There was no significant correlation between increased renal uptake and MDP uptake in soft tissue other than kidneys. This study raised the possibility that the impaired liver and/or renal function may result in diffuse increase of bilateral renal uptake of MDP of unknown mechanism. It seems to need further study on this correlation.

[Susceptibility and resistence of Pseudomonas aeruginosa to antimicrobial agents].

Science.gov (United States)

Gamero Delgado, M C; García-Mayorgas, A D; Rodríguez, F; Ibarra, A; Casal, M

2007-06-01

Pseudomonas aeruginosa is an opportunistic microorganism that is frequently the cause of nosocomial infections. Multiple mechanisms are involved in its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. The objective of this study was to assess the susceptibility and resistance patterns of P. aeruginosa strains isolated in Hospital Reina Sofia between 2000 and 2005, as well as to analyze the differences between intrahospital and extrahospital isolates in 2005 and to compare the results with those obtained in other studies. A total of 3,019 strains of P. aeruginosa from different hospitals and nonhospital settings were evaluated, taking into consideration their degree of sensitivity to different antibiotics. The MICs were determined by means of the Wider I automated system (Soria Melguizo), taking into consideration the criteria of susceptibility and resistance recommended by MENSURA. Results of the analysis showed that P. aeruginosa maintained similar levels of antimicrobial susceptibility during the period 2000-2005, with increased susceptibility to amikacin, gentamicin and tobramycin. There were also important differences in the degree of susceptibility between intrahospital and extrahospital strains, except for imipenem and fosfomycin. The intrahospital difference in susceptibility was also evaluated, emphasizing the importance of periodically studying susceptibility and resistance patterns of P. aeruginosa in each setting in order to evaluate different therapeutic guidelines, as it is not always advisable to extrapolate data from different regions. These differences can be explained by the different use of antibiotics in each center and the geographic variations of the resistance mechanisms of P. aeruginosa.

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

International Nuclear Information System (INIS)

Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

2012-01-01

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC 0−t and C max of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC 0−t of MTX by 55%. In addition, diclofenac enhanced the C max of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC 0−t and C max of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

Quantitative Susceptibility Mapping of Human Brain Reflects Spatial Variation in Tissue Composition

Science.gov (United States)

Li, Wei; Wu, Bing; Liu, Chunlei

2011-01-01

Image phase from gradient echo MRI provides a unique contrast that reflects brain tissue composition variations, such as iron and myelin distribution. Phase imaging is emerging as a powerful tool for the investigation of functional brain anatomy and disease diagnosis. However, the quantitative value of phase is compromised by its nonlocal and orientation dependent properties. There is an increasing need for reliable quantification of magnetic susceptibility, the intrinsic property of tissue. In this study, we developed a novel and accurate susceptibility mapping method that is also phase-wrap insensitive. The proposed susceptibility mapping method utilized two complementary equations: (1) the Fourier relationship of phase and magnetic susceptibility; and (2) the first-order partial derivative of the first equation in the spatial frequency domain. In numerical simulation, this method reconstructed the susceptibility map almost free of streaking artifact. Further, the iterative implementation of this method allowed for high quality reconstruction of susceptibility maps of human brain in vivo. The reconstructed susceptibility map provided excellent contrast of iron-rich deep nuclei and white matter bundles from surrounding tissues. Further, it also revealed anisotropic magnetic susceptibility in brain white matter. Hence, the proposed susceptibility mapping method may provide a powerful tool for the study of brain physiology and pathophysiology. Further elucidation of anisotropic magnetic susceptibility in vivo may allow us to gain more insight into the white matter microarchitectures. PMID:21224002

Low-temperature susceptibility of concentrated magnetic fluids

Science.gov (United States)

Pshenichnikov, Alexander F.; Lebedev, Alexander V.

2004-09-01

The initial susceptibility of concentrated magnetic fluids (ferrocolloids) has been experimentally investigated at low temperatures. The results obtained indicate that the interparticle dipole-dipole interactions can increase the susceptibility by several times as compared to the Langevin value. It is shown that good agreement between recent theoretical models and experimental observations can be achieved by introducing a correction for coefficients in the series expansion of susceptibility in powers of density and aggregation parameter. A modified equation for equilibrium susceptibility is offered to sum over corrections made by Kalikmanov (Statistical Physics of Fluids, Springer-Verlag, Berlin, 2001) and by B. Huke and M. Lücke (Phys. Rev. E 67, 051403, 2003). The equation gives good quantitative agreement with the experimental data in the wide range of temperature and magnetic particles concentration. It has been found that in some cases the magnetic fluid solidification occurs at temperature several tens of kelvins higher than the crystallization temperature of the carrier liquid. The solidification temperature of magnetic fluids is independent of particle concentration (i.e., magneto-dipole interparticle interactions) and dependent on the surfactant type and carrier liquid. This finding allows us to suggest that molecular interactions and generation of some large-scale structure from colloidal particles in magnetic fluids are responsible for magnetic fluid solidification. If the magnetic fluid contains the particles with the Brownian relaxation mechanism of the magnetic moment, the solidification manifests itself as the peak on the "susceptibility-temperature" curve. This fact proves the dynamic nature of the observed peak: it arises from blocking the Brownian mechanism of the magnetization relaxation.

Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

Science.gov (United States)

Dobón, Albor; Canet, Juan Vicente; García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

2015-04-01

Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

Directory of Open Access Journals (Sweden)

Albor Dobón

2015-04-01

Full Text Available Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

An uncertainty and sensitivity analysis approach for GIS-based multicriteria landslide susceptibility mapping

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Feizizadeh, Bakhtiar; Blaschke, Thomas

2014-01-01

GIS-based multicriteria decision analysis (MCDA) methods are increasingly being used in landslide susceptibility mapping. However, the uncertainties that are associated with MCDA techniques may significantly impact the results. This may sometimes lead to inaccurate outcomes and undesirable consequences. This article introduces a new GIS-based MCDA approach. We illustrate the consequences of applying different MCDA methods within a decision-making process through uncertainty analysis. Three GIS-MCDA methods in conjunction with Monte Carlo simulation (MCS) and Dempster–Shafer theory are analyzed for landslide susceptibility mapping (LSM) in the Urmia lake basin in Iran, which is highly susceptible to landslide hazards. The methodology comprises three stages. First, the LSM criteria are ranked and a sensitivity analysis is implemented to simulate error propagation based on the MCS. The resulting weights are expressed through probability density functions. Accordingly, within the second stage, three MCDA methods, namely analytical hierarchy process (AHP), weighted linear combination (WLC) and ordered weighted average (OWA), are used to produce the landslide susceptibility maps. In the third stage, accuracy assessments are carried out and the uncertainties of the different results are measured. We compare the accuracies of the three MCDA methods based on (1) the Dempster–Shafer theory and (2) a validation of the results using an inventory of known landslides and their respective coverage based on object-based image analysis of IRS-ID satellite images. The results of this study reveal that through the integration of GIS and MCDA models, it is possible to identify strategies for choosing an appropriate method for LSM. Furthermore, our findings indicate that the integration of MCDA and MCS can significantly improve the accuracy of the results. In LSM, the AHP method performed best, while the OWA reveals better performance in the reliability assessment. The WLC

Comparison of the landslide susceptibility models in Taipei Water Source Domain, Taiwan

Science.gov (United States)

WU, C. Y.; Yeh, Y. C.; Chou, T. H.

2017-12-01

Taipei Water Source Domain, locating at the southeast of Taipei Metropolis, is the main source of water resource in this region. Recently, the downstream turbidity often soared significantly during the typhoon period because of the upstream landslides. The landslide susceptibilities should be analysed to assess the influence zones caused by different rainfall events, and to ensure the abilities of this domain to serve enough and quality water resource. Generally, the landslide susceptibility models can be established based on either a long-term landslide inventory or a specified landslide event. Sometimes, there is no long-term landslide inventory in some areas. Thus, the event-based landslide susceptibility models are established widely. However, the inventory-based and event-based landslide susceptibility models may result in dissimilar susceptibility maps in the same area. So the purposes of this study were to compare the landslide susceptibility maps derived from the inventory-based and event-based models, and to interpret how to select a representative event to be included in the susceptibility model. The landslide inventory from Typhoon Tim in July, 1994 and Typhoon Soudelor in August, 2015 was collected, and used to establish the inventory-based landslide susceptibility model. The landslides caused by Typhoon Nari and rainfall data were used to establish the event-based model. The results indicated the high susceptibility slope-units were located at middle upstream Nan-Shih Stream basin.

Personality traits as potential susceptibility markers : Differential susceptibility to support among parents

NARCIS (Netherlands)

Slagt, M.; Dubas, J.S.; Denissen, J.J.A.; Deković, M.; van Aken, M.A.G.

2015-01-01

In this study, we examined whether parents are differentially susceptible to support from their spouse and adolescent child depending on their personality traits, and whether differences in susceptibility to support among parents, in turn, are linked to the quality of support parents give to their

Combined MRI and MRS in prostate cancer: improvement of spectral quality by susceptibility matching.

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Scheidler, J; Vogel, M; Gross, P; Heuck, A

2009-06-01

Local magnetic field inhomogeneity caused by susceptibility artifacts due to air in the endorectal coil substantially degrades the quality of 3D MR spectroscopic imaging (3D-MRSI). Perflubron (PFB) has magnetic susceptibility similar to that of human tissue. We prospectively assessed the effect of susceptibility matching using PFB on in vivo prostate (1)H-3D-MRSI. Ninety-one consecutive patients referred for 3D-MRSI were examined using air and PFB as the filling agent for endorectal coils at 1.5T with an identically placed PRESS box and sat bands. Solely auto-shim without additional manual shimming was used. The full width at half maximum (FWHM) of the water peak was statistically compared with a paired t-test. The spectral quality was visually evaluated for the definition of metabolite peaks and for the citrate peak split (duplet). The MR image quality was rated on a five-point scale. FWHM was significantly less (p PFB (mean 9.0 +/- 3.3, range 3 - 20) than air (mean 14.9 +/- 4.2, range 6 - 26) in 85/91 patients (93%). The spectral quality markedly improved using PFB and frequently the duplet of the citrate peak was able to be identified. Image quality ratings were similar (mean rating PFB 4.2, air 4.3 points). Omitting manual shimming led to a time savings of 4 min. per study. 3D-MRSI using PFB for susceptibility matching benefits from significantly better local field homogeneity, thus providing improved spectra quality. Combined with a substantial time savings in data acquisition, this may increase the clinical utilization of 3D-MRSI in patients with prostate cancer.

Studies on the Identification of Constituents in Ethanol Extract of Radix Glycyrrhizae and Their Anti-Primary Hepatoma Cell Susceptibility

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Jie Liu

2014-01-01

Full Text Available The objective of this paper is to study the chemical constituents of Radix Glycyrrhizae and to apply the resulting natural products in the study of drug susceptibility of hepatoma cells so as to provide a scientific basis for quality standards and clinical application of medicinal Radix Glycyrrhizae. Chromatographic materials were used for isolation and purification; structural identification was performed based on physicochemical properties and spectral data. MTT colorimetry was used to detect the proliferation inhibition rate against primary hepatoma cells by natural products, and flow cytometry was used to detect the changes in cell cycle progression. Five compounds were isolated and identified, namely, liquiritigenin (1, liquiritin (2, isoliquiritigenin (3, betulinic acid (4, and oleanolic acid (5. In the study, 5-FU (5-fluorouracil is used as a positive control to the hepatoma cells. Primary hepatoma cells were highly susceptible to 5-FU and liquiritigenin, both of which markedly inhibited the proliferation of hepatoma cells; flow cytometry results showed an increase in G0/G1 phase cells, a decrease in S phase cells, and a relative increase in G2/M phase cells. Primary hepatoma cells are highly susceptible to liquiritigenin, a natural product; the testing of tumor cell susceptibility is of important significance to the improvement of therapeutic effect of cancer.

Effect of Chemical Composition on Susceptibility to Weld Solidification Cracking in Austenitic Weld Metal

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Kadoi, Kota; Shinozaki, Kenji

2017-12-01

The influence of the chemical composition, especially the niobium content, chromium equivalent Creq, and nickel equivalent Nieq, on the weld solidification cracking susceptibility in the austenite single-phase region in the Schaeffler diagram was investigated. Specimens were fabricated using the hot-wire laser welding process with widely different compositions of Creq, Nieq, and niobium in the region. The distributions of the susceptibility, such as the crack length and brittle temperature range (BTR), in the Schaeffler diagram revealed a region with high susceptibility to solidification cracking. Addition of niobium enhanced the susceptibility and changed the distribution of the susceptibility in the diagram. The BTR distribution was in good agreement with the distribution of the temperature range of solidification (Δ T) calculated by solidification simulation based on Scheil model. Δ T increased with increasing content of alloying elements such as niobium. The distribution of Δ T was dependent on the type of alloying element owing to the change of the partitioning behavior. Thus, the solidification cracking susceptibility in the austenite single-phase region depends on whether the alloy contains elements. The distribution of the susceptibility in the region is controlled by the change in Δ T and the segregation behavior of niobium with the chemical composition.

Pregnancy and Susceptibility to Infectious Diseases

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Elisabeth Sappenfield

2013-01-01

Full Text Available To summarize the literature regarding susceptibility of pregnant women to infectious diseases and severity of resulting disease, we conducted a review using a PubMed search and other strategies. Studies were included if they reported information on infection risk or disease outcome in pregnant women. In all, 1454 abstracts were reviewed, and a total of 85 studies were included. Data were extracted regarding number of cases in pregnant women, rates of infection, risk factors for disease severity or complications, and maternal outcomes. The evidence indicates that pregnancy is associated with increased severity of some infectious diseases, such as influenza, malaria, hepatitis E, and herpes simplex virus (HSV infection (risk for dissemination/hepatitis; there is also some evidence for increased severity of measles and smallpox. Disease severity seems higher with advanced pregnancy. Pregnant women may be more susceptible to acquisition of malaria, HIV infection, and listeriosis, although the evidence is limited. These results reinforce the importance of infection prevention as well as of early identification and treatment of suspected influenza, malaria, hepatitis E, and HSV disease during pregnancy.

A strabismus susceptibility locus on chromosome 7p

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Parikh, Vaishali; Shugart, Yin Yao; Doheny, Kimberly F.; Zhang, Jie; Li, Lan; Williams, John; Hayden, David; Craig, Brian; Capo, Hilda; Chamblee, Denise; Chen, Cathy; Collins, Mary; Dankner, Stuart; Fiergang, Dean; Guyton, David; Hunter, David; Hutcheon, Marcia; Keys, Marshall; Morrison, Nancy; Munoz, Michelle; Parks, Marshall; Plotsky, David; Protzko, Eugene; Repka, Michael X.; Sarubbi, Maria; Schnall, Bruce; Siatkowski, R. Michael; Traboulsi, Elias; Waeltermann, Joanne; Nathans, Jeremy

2003-01-01

Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes. PMID:14519848

A GIS-based extended fuzzy multi-criteria evaluation for landslide susceptibility mapping

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Feizizadeh, Bakhtiar; Shadman Roodposhti, Majid; Jankowski, Piotr; Blaschke, Thomas

2014-01-01

Landslide susceptibility mapping (LSM) is making increasing use of GIS-based spatial analysis in combination with multi-criteria evaluation (MCE) methods. We have developed a new multi-criteria decision analysis (MCDA) method for LSM and applied it to the Izeh River basin in south-western Iran. Our method is based on fuzzy membership functions (FMFs) derived from GIS analysis. It makes use of nine causal landslide factors identified by local landslide experts. Fuzzy set theory was first integrated with an analytical hierarchy process (AHP) in order to use pairwise comparisons to compare LSM criteria for ranking purposes. FMFs were then applied in order to determine the criteria weights to be used in the development of a landslide susceptibility map. Finally, a landslide inventory database was used to validate the LSM map by comparing it with known landslides within the study area. Results indicated that the integration of fuzzy set theory with AHP produced significantly improved accuracies and a high level of reliability in the resulting landslide susceptibility map. Approximately 53% of known landslides within our study area fell within zones classified as having “very high susceptibility”, with the further 31% falling into zones classified as having “high susceptibility”. PMID:26089577

Susceptibility analysis of landslide in Chittagong City Corporation Area, Bangladesh

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Sourav Das

2015-06-01

Full Text Available In Chittagong city, landslide phenomena is the most burning issue which causes great problems to the life and properties and it is increasing day by day and becoming one of the main problems of city life. On 11 June 2007, a massive landslide happened in Chittagong City Corporation (CCC area, a large number of foothill settlements and slums were demolished; more than 90 people died and huge resource destruction took place. It is therefore essential to analyze the landslide susceptibility for CCC area to prepare mitigation strategies as well as assessing the impacts of climate change. To assess community susceptibility of landslide hazard, a landslide susceptibility index map has been prepared using analytical hierarchy process (AHP model based on geographic information system (GIS and remote sensing (RS and its susceptibility is analyzed through community vulnerability assessment tool (CVAT. The major findings of the research are 27% of total CCC area which is susceptible to landslide hazard and whereas 6.5 sq.km areas are found very highly susceptible. The landslide susceptible areas of CCC have also been analyzed in respect of physical, social, economic, environmental and critical facilities and it is found that the overall CCC area is highly susceptible to landslide hazard. So the findings of the research can be utilized to prioritize risk mitigation investments, measures to strengthen the emergency preparedness and response mechanisms for reducing the losses and damages due to future landslide events. DOI: http://dx.doi.org/10.3126/ije.v4i2.12635 International Journal of Environment Vol.4(2 2015: 157-181

Enhanced susceptibility to seizures modulated by high interleukin-1β levels during early life malnutrition.

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Simão, Fabrício; Habekost Oliveira, Victória; Lahorgue Nunes, Magda

2016-10-01

Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1β (IL-1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1β, IL-1R1, PSD-95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1β and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1β and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016. © 2016 Wiley Periodicals, Inc.

Diagenetic versus detrital origin of the magnetic susceptibility variations in some carbonate Frasnian-Famennian boundary sections from Northern Africa and Western Europe: implications for paleoenvironmental reconstructions

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Riquier, Laurent; Averbuch, Olivier; Devleeschouwer, Xavier; Tribovillard, Nicolas

2010-10-01

To provide a new insight into the diagenetic versus detrital origin of the magnetic susceptibility variations in ancient carbonate sequences, a study was conducted within four Frasnian-Famennian platform carbonate sections from Germany, France and Morocco. The study includes along-section magnetic susceptibility and carbonate content measurements complemented by analyses of magnetic hysteresis parameters, inorganic geochemistry and clay mineralogy. Our results show that the magnetic susceptibility evolution is dominantly controlled by the variations in the concentration of low-coercivity ferromagnetic magnetite grains and, to a lesser extent, of paramagnetic clays. In more detail, hysteresis ratios suggest the coexistence of two magnetite populations with significantly different grain size: (1) a dominantly coarse-grained detrital fraction including a mixture of multi-domain and single-domain particles (2) an authigenic fine-grained fraction composed of a mixture of single-domain and superparamagnetic particles. Despite a diagenetic imprint on the clay assemblages, no relationship is established between magnetic susceptibility and illite crystallinity, therefore discarding a noticeable distortion of primary within-section magnetic susceptibility evolution. The overall inherited character of the magnetic susceptibility fluctuations is corroborated by a significant correlation of magnetic susceptibility with terrigenous proxies (Zr, Th). The poorer correlation of magnetic susceptibility with the Fe content is consistent with the existence of a very fine-grained authigenic magnetite component that possibly induces a global magnetic susceptibility increase at the section scale, but no distortion of the within-section evolution. The magnetic susceptibility curves presented here provide a general record of climate-driven detrital influx and carbonate productivity through Frasnian-Lower Famennian times.

Reversion of High-level Mecillinam Resistance to Susceptibility in Escherichia coli During Growth in Urine

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Elisabeth Thulin

2017-09-01

This is the first example describing conditional resistance where a genetically stable antibiotic resistance can be phenotypically reverted to susceptibility by metabolites present in urine. These findings have several important clinical implications regarding the use of mecillinam to treat UTIs. First, they suggest that mecillinam can be used to treat also those clinical strains that are identified as MecR in standard laboratory tests. Second, the results suggest that testing of mecillinam susceptibility in the laboratory ought to be performed in media that mimics urine to obtain clinically relevant susceptibility testing results. Third, these findings imply that changes in patient behavior, such as increased water intake or use of diuretics to reduce urine osmolality and increased intake of cysteine, might induce antibiotic susceptibility in an infecting MecR E. coli strain and thereby increase treatment efficiency.

Endogenous MMTV proviruses induce susceptibility to both viral and bacterial pathogens.

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Sanchita Bhadra

2006-12-01

Full Text Available Most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (MMTV (called Mtvs, which have multiple replication defects. A BALB/c congenic mouse strain lacking all endogenous Mtvs (Mtv-null was resistant to MMTV oral and intraperitoneal infection and tumorigenesis compared to wild-type BALB/c mice. Infection of Mtv-null mice with an MMTV-related retrovirus, type B leukemogenic virus, also resulted in severely reduced viral loads and failure to induce T-cell lymphomas, indicating that resistance is not dependent on expression of a superantigen (Sag encoded by exogenous MMTV. Resistance to MMTV in Mtv-null animals was not due to neutralizing antibodies. Further, Mtv-null mice were resistant to rapid mortality induced by intragastric inoculation of the Gram-negative bacterium, Vibrio cholerae, but susceptibility to Salmonella typhimurium was not significantly different from BALB/c mice. Susceptibility to both MMTV and V. cholerae was reconstituted by the presence of any one of three endogenous Mtvs located on different chromosomes and was associated with increased pathogen load. One of these endogenous proviruses is known to encode only Sag. Therefore, Mtv-encoded Sag appears to provide a unique genetic susceptibility to specific viruses and bacteria. Since human endogenous retroviruses also encode Sags, these studies have broad implications for pathogen-induced responses in mice and humans.

The Epidemiological And Susceptibility Study Of Inpatient Blood Cultures In Amir Alam Hospital 1998 - 2000

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Karimi Shahidi M

2002-07-01

Full Text Available Sepsis is one of the most critical medical emergency situations. Treatment with anti microbial drugs should be initiated as soon as samples of blood and other relevant sites have been cultured. Available information about patterns of anti microbial Susceptibility among bacterial isolates from the community, the hospital, and the patient should be taken in to account. It is important, pending culture results, to initiate empirical anti microbial therapy."nMaterials and methods: In a descriptive study during 3 years (1377-1379, microbial and anti microbial susceptibility patterns evaluated in Amir alam clinical laboratory on 2000 specimen of blood culture received from 765 hospitalized patients at Amir Alam hospital wards."nResults: 113 specimens from 77 patient (10 percent were positive for microbial growth. Enterobacter, S. aureus, S.epidermidis, Pneumococci, Ecoli, and Pseudomonas were the most common isolated etiologic agents(80 percent . The most common organism was Entenobacter in 1377, S.aureus in 1378 and pseudomonas in 1379 There were significant change in patlern of organisms, increase resistance to some important available antibiotics and change in antibiotic susceptibility pattern during three years (disc diffusion method."nConclusions: According to Results of this study due to change in pattern of organism and their antibiotic susceptibility, dynamic microbiological study provide important data for Ordering empirical and culture oriented treatment of patients with bacteremia, Sepsis, anti microbial Chemotherapy, anti microbial susceptibility empirical anti microbial therapy, microbial pattern.

Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System (KARMS) Data From 2013 to 2015.

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Kim, Dokyun; Ahn, Ji Young; Lee, Chae Hoon; Jang, Sook Jin; Lee, Hyukmin; Yong, Dongeun; Jeong, Seok Hoon; Lee, Kyungwon

2017-05-01

National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66-72% and 29-31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38-41%, 33-41%, and carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains. © The Korean Society for Laboratory Medicine

Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species.

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Andrade, Juvana M; Baba, Elio H; Machado-de-Avila, Ricardo A; Chavez-Olortegui, Carlos; Demicheli, Cynthia P; Frézard, Frédéric; Monte-Neto, Rubens L; Murta, Silvane M F

2016-08-01

Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in Leishmania, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing Leishmania guyanensis and L. braziliensis mutants and investigated their susceptibility to the trivalent form of Sb (Sb(III)) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased Sb(III) susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to Sb(III) exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, Sb(III)-sodium nitrate or Sb(III)-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of Sb(III) alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to Sb(III) and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated Sb(III) susceptibility modulation by silver in Leishmania and suggests the potential antileishmanial activity of the combination of nitrate salts and Sb(III). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Mechanisms of induced susceptibility to Diplodia tip blight in drought-stressed Austrian pine.

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Sherwood, Patrick; Villari, Caterina; Capretti, Paolo; Bonello, Pierluigi

2015-05-01

Plants experiencing drought stress are frequently more susceptible to pathogens, likely via alterations in physiology that create favorable conditions for pathogens. Common plant responses to drought include the production of reactive oxygen species (ROS) and the accumulation of free amino acids (AAs), particularly proline. These same phenomena also frequently occur during pathogenic attack. Therefore, drought-induced perturbations in AA and ROS metabolism could potentially contribute to the observed enhanced susceptibility. Furthermore, nitrogen (N) availability can influence AA accumulation and affect plant resistance, but its contributions to drought-induced susceptibility are largely unexplored. Here we show that drought induces accumulation of hydrogen peroxide (H2O2) in Austrian pine (Pinus nigra Arnold) shoots, but that shoot infection by the blight and canker pathogen Diplodia sapinea (Fr.) Fuckel leads to large reductions in H2O2 levels in droughted plants. In in vitro assays, H2O2 was toxic to D. sapinea, and the fungus responded to this oxidative stress by increasing catalase and peroxidase activities, resulting in substantial H2O2 degradation. Proline increased in response to drought and infection when examined independently, but unlike all other AAs, proline further increased in infected shoots of droughted trees. In the same tissues, the proline precursor, glutamate, decreased significantly. Proline was found to protect D. sapinea from H2O2 damage, while also serving as a preferred N source in vitro. Fertilization increased constitutive and drought-induced levels of some AAs, but did not affect plant resistance. A new model integrating interactions of proline and H2O2 metabolism with drought and fungal infection of plants is proposed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Quantitative influence of minor and impurity elements on hot cracking susceptibility of extra high-purity type 310 stainless steel

International Nuclear Information System (INIS)

Saida, Kazuyoshi; Matsushita, Hideki; Nishimoto, Kazutoshi; Kiuchi, Kiyoshi; Nakayama, Junpei

2013-01-01

To evaluate the influence of minor and impurity elements such as C, Mn, P and S on the solidification and ductility-dip cracking susceptibilities of extra high-purity type 310 stainless steels, the transverse-Varestraint test was conducted by using several type 310 stainless steels with different amounts of C, Mn, P and S. Two types of hot cracks occurred in these steels by Varestraint test; solidification and ductility-dip cracks. The solidification cracking susceptibility was significantly reduced as the amounts of C, P and S decreased. The ductility-dip cracking susceptibility also reduced with a decrease in P and S contents. It adversely, however, increased as the C content of the steels was reduced. Mn didn't greatly affect the hot cracking susceptibility of the extra high-purity steels. The characteristic influence on solidification cracking was the ratio of P:S:C=1:1.3:0.56, while Mn negligibly ameliorated solidification cracking in the extra low S (and P) steels. The numerical analysis on the solidification brittle temperature range (BTR) revealed that the reduced solidification cracking susceptibility with decreasing the amounts of C, P and S in steel could be attributed to the reduced BTR due to the suppression of solidification segregation of minor and impurity elements in the finally solidified liquid film between dendrites. On the other hand, a molecular orbital analysis to estimate the binding strength of the grain boundary suggested that the increased ductility-dip cracking susceptibility in extra high-purity steels was caused by grain boundary embrittlement due to the refining of beneficial elements for grain boundary strengthening such as C. (author)

In vivo Host Environment Alters Pseudomonas aeruginosa Susceptibility to Aminoglycoside Antibiotics

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Pan, Xiaolei; Dong, Yuanyuan; Fan, Zheng; Liu, Chang; Xia, Bin; Shi, Jing; Bai, Fang; Jin, Yongxin; Cheng, Zhihui; Jin, Shouguang; Wu, Weihui

2017-01-01

During host infection, Pseudomonas aeruginosa coordinately regulates the expression of numerous genes to adapt to the host environment while counteracting host clearance mechanisms. As infected patients take antibiotics, the invading bacteria encounter antibiotics in the host milieu. P. aeruginosa is highly resistant to antibiotics due to multiple chromosomally encoded resistant determinants. And numerous in vitro studies have demonstrated the regulatory mechanisms of antibiotic resistance related genes in response to antibiotics. However, it is not well-known how host environment affects bacterial response to antibiotics. In this study, we found that P. aeruginosa cells directly isolated from mice lungs displayed higher susceptibility to tobramycin than in vitro cultured bacteria. In vitro experiments demonstrated that incubation with A549 and differentiated HL60 (dHL60) cells sensitized P. aeruginosa to tobramycin. Further studies revealed that reactive oxygen species produced by the host cells contributed to the increased bacterial susceptibility. At the same concentration of tobramycin, presence of A549 and dHL60 cells resulted in higher expression of heat shock proteins, which are known inducible by tobramycin. Further analyses revealed decreased membrane potential upon incubation with the host cells and modification of lipopolysaccharide, which contributed to the increased susceptibility to tobramycin. Therefore, our results demonstrate that contact with host cells increased bacterial susceptibility to tobramycin. PMID:28352614

Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility.

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Barrera, Maria Claudia; Rojas, Laura Jimena; Weiss, Austin; Fernandez, Olga; McMahon-Pratt, Diane; Saravia, Nancy G; Gomez, Maria Adelaida

2017-12-01

The mechanisms of Leishmania resistance to antimonials have been primarily determined in experimentally derived Leishmania strains. However, their participation in the susceptibility phenotype in field isolates has not been conclusively established. Being an intracellular parasite, the activity of antileishmanials is dependent on internalization of drugs into host cells and effective delivery to the intracellular compartments inhabited by the parasite. In this study we quantified and comparatively analyzed the gene expression of nine molecules involved in mechanisms of xenobiotic detoxification and Leishmania resistance to antimonial drugs in resistant and susceptible laboratory derived and clinical L.(Viannia) panamensis strains(n=19). In addition, we explored the impact of Leishmania susceptibility to antimonials on the expression of macrophage gene products having putative functions in transport, accumulation and metabolism of antimonials. As previously shown for other Leishmania species, a trend of increased abcc3 and lower aqp-1 expression was observed in the laboratory derived Sb-resistant L.(V.) panamensis line. However, this was not found in clinical strains, in which the expression of abca2 was significantly higher in resistant strains as both, promastigotes and intracellular amastigotes. The effect of drug susceptibility on host cell gene expression was evaluated on primary human macrophages from patients with cutaneous leishmaniasis (n=17) infected ex-vivo with the matched L.(V.) panamensis strains isolated at diagnosis, and in THP-1 cells infected with clinical strains (n=6) and laboratory adapted L.(V.) panamensis lines. Four molecules, abcb1 (p-gp), abcb6, aqp-9 and mt2a were differentially modulated by drug resistant and susceptible parasites, and among these, a consistent and significantly increased expression of the xenobiotic scavenging molecule mt2a was observed in macrophages infected with Sb-susceptible L. (V.) panamensis. Our results

AGING AND SUSCEPTIBILITY TO TOLUENE IN RATS: A PHARMACOKINETIC, BIOMARKER, AND PHYSIOLOGICAL APPROACH.

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Aging adults are a growing segment of the U.S. population and are likely to exhibit increased susceptibility to many environmental toxicants. However, there is little information on the susceptibility of the aged to toxicants. The toxicity of toluene has been well characterized i...

Susceptibility Tensor Imaging (STI) of the Brain

Science.gov (United States)

Li, Wei; Liu, Chunlei; Duong, Timothy Q.; van Zijl, Peter C.M.; Li, Xu

2016-01-01

Susceptibility tensor imaging (STI) is a recently developed MRI technique that allows quantitative determination of orientation-independent magnetic susceptibility parameters from the dependence of gradient echo signal phase on the orientation of biological tissues with respect to the main magnetic field. By modeling the magnetic susceptibility of each voxel as a symmetric rank-2 tensor, individual magnetic susceptibility tensor elements as well as the mean magnetic susceptibility (MMS) and magnetic susceptibility anisotropy (MSA) can be determined for brain tissues that would still show orientation dependence after conventional scalar-based quantitative susceptibility mapping (QSM) to remove such dependence. Similar to diffusion tensor imaging (DTI), STI allows mapping of brain white matter fiber orientations and reconstruction of 3D white matter pathways using the principal eigenvectors of the susceptibility tensor. In contrast to diffusion anisotropy, the main determinant factor of susceptibility anisotropy in brain white matter is myelin. Another unique feature of susceptibility anisotropy of white matter is its sensitivity to gadolinium-based contrast agents. Mechanistically, MRI-observed susceptibility anisotropy is mainly attributed to the highly ordered lipid molecules in myelin sheath. STI provides a consistent interpretation of the dependence of phase and susceptibility on orientation at multiple scales. This article reviews the key experimental findings and physical theories that led to the development of STI, its practical implementations, and its applications for brain research. PMID:27120169

Evaluation of Local Wheat Cultivars Susceptibility to infection with Black Stem Rust

International Nuclear Information System (INIS)

Batta, Y.A.

2007-01-01

The present study was conducted to assess the susceptibility of seven local wheat cultivars from Palestine to infection with black stem rust caused by Puccinia graminis f. sp. tritici. Two techniques of disease inoculation were applied during bioassays: global inoculation of entire wheat plants with urediospores and localized inoculation with urediospores and localized inoculation with urediospores on wheat leaf-pieces incubated under humid conditions. Susceptibility of tested cultivars was evaluated according to disease scale based on number and size of typical unredial pustules that appeared after inoculation on entire plants or leaf pieces. Results obtained on bioassay of susceptibility and disease rating on entire plants indicated that Anbar, Kamata and Hetiya safra cultivars were the least susceptible to P. g. tritici infection, whereas Debiya beda cultivar was the most susceptible. The other tested cultivars such as Nab-El-Jama, sawda and Senf 870 were moderately susceptible. On leaf-pieces, Anbar and Kamatat were the least susceptible cultivars, whereas Debiya beda and Nab-El-Jamal were the most susceptible cultivars. The other tested cultivars such as Debiya swada, Senf 870 and Hetiya safra were moderately susceptible. Significant reductions were obtained for the size of unredial postules formed on leaf-pieces when inoculated in an unwounded state compared to the wounded indicating the importance of wounds during inoculation. The global results indicated the possibility of using above method of disease inoculating, scaling and rating for evaluation of wheat cultivars susceptibility for the eventual use in breeding program for resistant varieties in Palestine. (author)

Prevalence of and susceptibility to cigarette smoking among female students aged 13 to 15 years in Vietnam, 2007.

Science.gov (United States)

Minh, Hoang Van; Hai, Phan Thi; Giang, Kim Bao; Kinh, Ly Ngoc

2010-01-01

Recent reports show a sharp increase in smoking rates among girls. We describe prevalence of cigarette smoking and susceptibility to cigarette smoking among female students aged 13 to 15 years in Vietnam and examine the associated factors. We used data from female secondary school students aged 13 to 15 years (grades 8-10) from the 2007 Global Youth Tobacco Survey that was conducted in 9 provinces in Vietnam. We used multivariate logistic regression analysis to determine associations between independent variables with smoking status and susceptibility to smoking. Prevalence of cigarette smoking among girls was 1.2% (95% confidence interval [CI], 0.9-1.5), and 1.5% (95% CI, 1.2-1.9) of girls were susceptible to smoking. Having friends who smoke was the strongest predictor of both smoking status and susceptibility to smoking. Attendance at school classes that described the harmful effects of smoking had significant effects in reducing cigarette smoking. Girls who were exposed to billboard cigarette advertising were more likely to be susceptible to smoking than were those who had not seen advertisements. Our findings highlight the need for pursuing school-based intervention programs in Vietnam and for countering tobacco advertising and marketing practices that target young women.

Host Phenology and Leaf Effects on Susceptibility of California Bay Laurel to Phytophthora ramorum.

Science.gov (United States)

Johnston, Steven F; Cohen, Michael F; Torok, Tamas; Meentemeyer, Ross K; Rank, Nathan E

2016-01-01

Spread of the plant pathogen Phytophthora ramorum, causal agent of the forest disease sudden oak death, is driven by a few competent hosts that support spore production from foliar lesions. The relationship between traits of a principal foliar host, California bay laurel (Umbellularia californica), and susceptibility to P. ramorum infection were investigated with multiple P. ramorum isolates and leaves collected from multiple trees in leaf-droplet assays. We examined whether susceptibility varies with season, leaf age, or inoculum position. Bay laurel susceptibility was highest during spring and summer and lowest in winter. Older leaves (>1 year) were more susceptible than younger ones (8 to 11 months). Susceptibility was greater at leaf tips and edges than the middle of the leaf. Leaf surfaces wiped with 70% ethanol were more susceptible to P. ramorum infection than untreated leaf surfaces. Our results indicate that seasonal changes in susceptibility of U. californica significantly influence P. ramorum infection levels. Thus, in addition to environmental variables such as temperature and moisture, variability in host plant susceptibility contributes to disease establishment of P. ramorum.

Quantitative susceptibility mapping of human brain at 3T: a multisite reproducibility study.

Science.gov (United States)

Lin, P-Y; Chao, T-C; Wu, M-L

2015-03-01

Quantitative susceptibility mapping of the human brain has demonstrated strong potential in examining iron deposition, which may help in investigating possible brain pathology. This study assesses the reproducibility of quantitative susceptibility mapping across different imaging sites. In this study, the susceptibility values of 5 regions of interest in the human brain were measured on 9 healthy subjects following calibration by using phantom experiments. Each of the subjects was imaged 5 times on 1 scanner with the same procedure repeated on 3 different 3T systems so that both within-site and cross-site quantitative susceptibility mapping precision levels could be assessed. Two quantitative susceptibility mapping algorithms, similar in principle, one by using iterative regularization (iterative quantitative susceptibility mapping) and the other with analytic optimal solutions (deterministic quantitative susceptibility mapping), were implemented, and their performances were compared. Results show that while deterministic quantitative susceptibility mapping had nearly 700 times faster computation speed, residual streaking artifacts seem to be more prominent compared with iterative quantitative susceptibility mapping. With quantitative susceptibility mapping, the putamen, globus pallidus, and caudate nucleus showed smaller imprecision on the order of 0.005 ppm, whereas the red nucleus and substantia nigra, closer to the skull base, had a somewhat larger imprecision of approximately 0.01 ppm. Cross-site errors were not significantly larger than within-site errors. Possible sources of estimation errors are discussed. The reproducibility of quantitative susceptibility mapping in the human brain in vivo is regionally dependent, and the precision levels achieved with quantitative susceptibility mapping should allow longitudinal and multisite studies such as aging-related changes in brain tissue magnetic susceptibility. © 2015 by American Journal of Neuroradiology.

Use of Satellite Remote Sensing Data in the Mapping of Global Landslide Susceptibility

Science.gov (United States)

Hong, Yang; Adler, Robert F.; Huffman, George J.

2007-01-01

Satellite remote sensing data has significant potential use in analysis of natural hazards such as landslides. Relying on the recent advances in satellite remote sensing and geographic information system (GIS) techniques, this paper aims to map landslide susceptibility over most of the globe using a GIs-based weighted linear combination method. First , six relevant landslide-controlling factors are derived from geospatial remote sensing data and coded into a GIS system. Next, continuous susceptibility values from low to high are assigned to each of the six factors. Second, a continuous scale of a global landslide susceptibility index is derived using GIS weighted linear combination based on each factor's relative significance to the process of landslide occurrence (e.g., slope is the most important factor, soil types and soil texture are also primary-level parameters, while elevation, land cover types, and drainage density are secondary in importance). Finally, the continuous index map is further classified into six susceptibility categories. Results show the hot spots of landslide-prone regions include the Pacific Rim, the Himalayas and South Asia, Rocky Mountains, Appalachian Mountains, Alps, and parts of the Middle East and Africa. India, China, Nepal, Japan, the USA, and Peru are shown to have landslide-prone areas. This first-cut global landslide susceptibility map forms a starting point to provide a global view of landslide risks and may be used in conjunction with satellite-based precipitation information to potentially detect areas with significant landslide potential due to heavy rainfall. 1

ABA suppresses Botrytis cinerea elicited NO production in tomato to influence H2O2 generation and increase host susceptibility

Directory of Open Access Journals (Sweden)

Anushen eSivakumaran

2016-05-01

Full Text Available Abscisic acid (ABA production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with NO in tomato following challenge with the ABA-synthesising pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defence against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA (abscisic acid, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS generation but this was reduced in both L-NAME and ABA treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production.

Effects of mineral nutrients on ozone susceptibility of Lemna minor

Energy Technology Data Exchange (ETDEWEB)

Craker, L E

1971-01-01

Susceptibility of Lemna minor L. to ozone injury was influenced by the mineral nutrients available to the Lemna plants. Additional nitrogen or additional iron in the nutrient media respectively enhanced or reduced chlorophyll loss of Lemna plants fumigated with ozone. Lemna plants growing on a nutrient medium lacking copper had significantly less injury from ozone fumigation than Lemna plants growing on a complete nutrient medium. There were apparent interactions among phosphorus and potassium nutrient levels in determing the Lemna plant's susceptibility to ozone.

Hydrogen embrittlement susceptibility of laser-hardened 4140 steel

Energy Technology Data Exchange (ETDEWEB)

Tsay, L.W.; Lin, Z.W. [Nat. Taiwan Ocean Univ., Keelung (Taiwan). Inst. of Mater. Eng.; Shiue, R.K. [Institute of Materials Sciences and Engineering, National Dong Hwa University, Hualien, Taiwan (Taiwan); Chen, C. [Institute of Materials Sciences and Engineering, National Taiwan University, Taipei, Taiwan (Taiwan)

2000-10-15

Slow strain rate tensile (SSRT) tests were performed to investigate the susceptibility to hydrogen embrittlement of laser-hardened AISI 4140 specimens in air, gaseous hydrogen and saturated H{sub 2}S solution. Experimental results indicated that round bar specimens with two parallel hardened bands on opposite sides along the loading axis (i.e. the PH specimens), exhibited a huge reduction in tensile ductility for all test environments. While circular-hardened (CH) specimens with 1 mm hardened depth and 6 mm wide within the gauge length were resistant to gaseous hydrogen embrittlement. However, fully hardened CH specimens became susceptible to hydrogen embrittlement for testing in air at a lower strain rate. The strength of CH specimens increased with decreasing the depth of hardened zones in a saturated H{sub 2}S solution. The premature failure of hardened zones in a susceptible environment caused the formation of brittle intergranular fracture and the decrease in tensile ductility. (orig.)

Mechanical massage and mental training programmes affect employees' anxiety, stress susceptibility and detachment-a randomised explorative pilot study.

Science.gov (United States)

Muller, Jasmin; Handlin, Linda; Harlén, Mikael; Lindmark, Ulrika; Ekström, Anette

2015-09-02

Working people's reduced ability to recover has been proposed as a key factor behind the increase in stress-related health problems. One not yet evidence-based preventive method designed to help employees keep healthy and be less stressed is an armchair with built-in mechanical massage and mental training programmes, This study aimed to evaluate possible effects on employees' experience of levels of "Anxiety", "Stress Susceptibility", "Detachment" and "Social Desirability" when using mechanical massage and mental training programmes, both separately and in combination, during working hours. Employees from four different workplaces were randomly assigned to one of the following groups: i) Massage and mental training (sitting in the armchair and receiving mechanical massage while listening to the mental training programmes, n=19), ii) Massage (sitting in the armchair and receiving mechanical massage only, n=19), iii) Mental training (sitting in the armchair and listening to the mental training programmes only, n=19), iv) Pause (sitting in the armchair but not receiving mechanical massage or listening to the mental training programmes, n=19), v) Control (not sitting in the armchair at all, n=17). In order to discover how the employees felt about their own health they were asked to respond to statements from the "Swedish Scale of Personality" (SSP), immediately before the randomisation, after four weeks and after eight weeks (end-of-study). There were no significant differences between the five study groups for any of the traits studied ("Somatic Trait Anxiety", "Psychic Trait Anxiety", "Stress Susceptibility", "Detachment" and "Social Desirability") at any of the occasions. However, the massage group showed a significant decrease in the subscale "Somatic Trait Anxiety" (p=0.032), during the entire study period. Significant decreases in the same subscale were also observed in the pause group between start and week eight (p=0.040) as well as between week four and week

Increasing Incidence of Severe Epstein-Barr Virus-Related Infectious Mononucleosis: Surveillance Study

Science.gov (United States)

Tattevin, Pierre; Le Tulzo, Yves; Minjolle, Sophie; Person, Arnaud; Chapplain, Jean Marc; Arvieux, Cedric; Thomas, Remi; Michelet, Christian

2006-01-01

Older patients are more susceptible to severe Epstein-Barr virus (EBV)-related infectious mononucleosis (IM). This condition may increase in industrialized countries where primary EBV infection occurs later in life. Between 1990 and 2004, 38 patients were admitted to our department with EBV-related IM. Two patients died. The annual incidence increased significantly (r = 0.623; P = 0.013). PMID:16672427

How heterogeneous susceptibility and recovery rates affect the spread of epidemics on networks

Directory of Open Access Journals (Sweden)

Wei Gou

2017-08-01

Full Text Available In this paper, an extended heterogeneous SIR model is proposed, which generalizes the heterogeneous mean-field theory. Different from the traditional heterogeneous mean-field model only taking into account the heterogeneity of degree, our model considers not only the heterogeneity of degree but also the heterogeneity of susceptibility and recovery rates. Then, we analytically study the basic reproductive number and the final epidemic size. Combining with numerical simulations, it is found that the basic reproductive number depends on the mean of distributions of susceptibility and disease course when both of them are independent. If the mean of these two distributions is identical, increasing the variance of susceptibility may block the spread of epidemics, while the corresponding increase in the variance of disease course has little effect on the final epidemic size. It is also shown that positive correlations between individual susceptibility, course of disease and the square of degree make the population more vulnerable to epidemic and avail to the epidemic prevalence, whereas the negative correlations make the population less vulnerable and impede the epidemic prevalence. Keywords: Networks, Heterogeneity, Susceptibility, Recovery rates, Correlation, The basic reproductive number, The final epidemic size

FXR-deficiency confers increased susceptibility to torpor

NARCIS (Netherlands)

Cariou, Bertrand; Bouchaert, Emmanuel; Abdelkarim, Mouaadh; Dumont, Julie; Caron, Sandrine; Fruchart, Jean-Charles; Burcelin, Remy; Kuipers, Folkert; Staels, Bart

2007-01-01

The role of the nuclear receptor FXR in adaptive thermogenesis was investigated using FXR-deficient mice. Despite elevated serum bile acid concentrations and increased mRNA expression profiles of thermogenic genes in brown adipose tissue, FXR-deficiency did not alter energy expenditure under basal

Interspecies Variation in the Susceptibility of a Wild-Derived Colony of Mice to Pinworms (Aspiculuris tetraptera).

Science.gov (United States)

Curtis, Ryan C; Murray, Jill K; Campbell, Polly; Nagamori, Yoko; Molnar, Adam; Jackson, Todd A

2017-01-01

Pinworms are common parasites in wild and laboratory rodents. Despite their relative nonpathogenicity in immunocompetent models, pinworm infections add an unwanted variable and may confound some types of research. For this reason, health monitoring programs and biosecurity measures aim to minimize the spread of pinworm infections into colonies free from the organisms. Wild-derived and laboratory strains of mice have shown varied susceptibility to infection with Aspiculuris tetraptera, the most commonly found murine pinworm. In particular, susceptibility is increased in wild-derived mice, young animals, and males. Routine surveillance at our institution revealed pinworm infection (A. tetraptera only) within a colony of multiple, wild-derived species of Mus, although only specific species showed positive results during initial sampling. To assess whether species-associated differences in susceptibility were present, we analyzed fecal egg counts of A. tetraptera in every cage of the colony. Our results revealed significant differences in susceptibility between various species and subspecies of Mus. Egg counts were significantly higher in Mus spicilegus than Mus m. domesticus (WSB/EiJ) and Mus macedonicus. Mus spretus had higher egg counts than M. m. domesticus (WSB/EiJ), M. m. musculus (PWK/PhJ), and M. macedonicus. Egg counts did not differ in regard to age, sex, or number of mice per cage. As wild-derived mouse models continue to compliment research largely based on laboratory strains, it will be important to understand host-parasite interactions and their effects on research, particularly studies evaluating immune responses, behavior, growth, and other physiologic parameters.

Susceptibility tensor imaging (STI) of the brain.

Science.gov (United States)

Li, Wei; Liu, Chunlei; Duong, Timothy Q; van Zijl, Peter C M; Li, Xu

2017-04-01

Susceptibility tensor imaging (STI) is a recently developed MRI technique that allows quantitative determination of orientation-independent magnetic susceptibility parameters from the dependence of gradient echo signal phase on the orientation of biological tissues with respect to the main magnetic field. By modeling the magnetic susceptibility of each voxel as a symmetric rank-2 tensor, individual magnetic susceptibility tensor elements as well as the mean magnetic susceptibility and magnetic susceptibility anisotropy can be determined for brain tissues that would still show orientation dependence after conventional scalar-based quantitative susceptibility mapping to remove such dependence. Similar to diffusion tensor imaging, STI allows mapping of brain white matter fiber orientations and reconstruction of 3D white matter pathways using the principal eigenvectors of the susceptibility tensor. In contrast to diffusion anisotropy, the main determinant factor of the susceptibility anisotropy in brain white matter is myelin. Another unique feature of the susceptibility anisotropy of white matter is its sensitivity to gadolinium-based contrast agents. Mechanistically, MRI-observed susceptibility anisotropy is mainly attributed to the highly ordered lipid molecules in the myelin sheath. STI provides a consistent interpretation of the dependence of phase and susceptibility on orientation at multiple scales. This article reviews the key experimental findings and physical theories that led to the development of STI, its practical implementations, and its applications for brain research. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Possible origins of the susceptibility contrast in the brain. Presidential award proceedings

International Nuclear Information System (INIS)

Fukunaga, Masaki; Li, T.Q.; Lee, J.; Matsuura, Eiji; Gelderen, P.V.; Zwart, J.A. de; Merkle, H.; Duyn, J.H.

2011-01-01

The magnetic susceptibility contrast derived from high resolution T 2 *-weighted magnetic resonance (MR) imaging at ultra high field strength has been used to reveal laminar contrast in the gray matter (GM) and fiber bundle-like structure in the white matter (WM) of the human brain. This contrast has been attributed to subtle variations in the magnetic properties of brain tissue, which possibly reflect varying iron and myelin content and haemoglobin in the microvasculature. To investigate the origin of this contrast, MRI data from postmortem brain samples were compared with histological staining for iron and myelin. The laminar susceptibility variations in GM strongly correlate with local iron content, which generally co-localized with myelin. On the other hand, fiber bundles in white matter, shows strong susceptibility contrast in the absence of iron while myelin is high. The results suggest that iron contributes significantly to susceptibility contrast across the cortical GM, but myelin is the dominant source of susceptibility in WM bundles. (author)

Short post-weaning social isolation induces long-term changes in the dopaminergic system and increases susceptibility to psychostimulants in female rats.

Science.gov (United States)

Lampert, Carine; Arcego, Danusa Mar; de Sá Couto-Pereira, Natividade; Dos Santos Vieira, Aline; Toniazzo, Ana Paula; Krolow, Rachel; Garcia, Emily; Vendite, Deusa Aparecida; Calcagnotto, Maria Elisa; Dalmaz, Carla

2017-10-01

Childhood and adolescence are sensitive periods of development, marked by high brain maturation and plasticity. Exposure to early life stress, such as social isolation, is able to prompt changes in sensitive brain circuitries, essentially in the mesolimbic dopaminergic system and increase the risk for addictive behaviors later in life. Post-weaning social isolation can stimulate the consumption of rewarding substances, like drugs of abuse and palatable foods. However, most studies analyze long periods of social isolation and very little is known about the effects of a brief social isolation in a sensitive period of development and its association with palatable food on the reward system sensitization. Furthermore, females are more susceptible to the reinforcing effect of drugs than males. Therefore, the aim of this study was to analyze the effects of a short post-weaning social isolation combined with a free access to a chronic high sugar diet (HSD) on the dopaminergic system, oxidative status and behavioral response to an amphetamine-like drug in adulthood. We used female Wistar rats that were socially isolated from post-natal days (PD) 21 to 35 and received free access to a HSD until PD 60. On PD 65, animals were submitted to a challenge with diethylpropion (DEP), an amphetamine-like drug and different responses were analyzed: locomotor activity, immmunocontent of dopamine related proteins, and the oxidative status in the striatum, before and after the DEP challenge. We showed that a short post-weaning social isolation (SI) increased the locomotor response to DEP, when compared with previous saline administration. Social isolation also increased dopamine transporter, tyrosine hydroxylase, and decreased dopamine D2 receptor immunocontent. Additionally, SI increased the overall oxidative status parameters after the challenge with DEP. Interestingly, the exposure to a HSD prevented the SI effects on locomotor response, but did not interfere in the dopaminergic

Increased brain iron deposition is a risk factor for brain atrophy in patients with haemodialysis: a combined study of quantitative susceptibility mapping and whole brain volume analysis.

Science.gov (United States)

Chai, Chao; Zhang, Mengjie; Long, Miaomiao; Chu, Zhiqiang; Wang, Tong; Wang, Lijun; Guo, Yu; Yan, Shuo; Haacke, E Mark; Shen, Wen; Xia, Shuang

2015-08-01

To explore the correlation between increased brain iron deposition and brain atrophy in patients with haemodialysis and their correlation with clinical biomarkers and neuropsychological test. Forty two patients with haemodialysis and forty one age- and gender-matched healthy controls were recruited in this prospective study. 3D whole brain high resolution T1WI and susceptibility weighted imaging were scanned on a 3 T MRI system. The brain volume was analyzed using voxel-based morphometry (VBM) in patients and to compare with that of healthy controls. Quantitative susceptibility mapping was used to measure and compare the susceptibility of different structures between patients and healthy controls. Correlation analysis was used to investigate the relationship between the brain volume, iron deposition and neuropsychological scores. Stepwise multiple regression analysis was used to explore the effect of clinical biomarkers on the brain volumes in patients. Compared with healthy controls, patients with haemodialysis showed decreased volume of bilateral putamen and left insular lobe (All P brain iron deposition is negatively correlated with the decreased volume of bilateral putamen (P brain iron deposition and dialysis duration was risk factors for brain atrophy in patients with haemodialysis. The decreased gray matter volume of the left insular lobe was correlated with neurocognitive impairment.

Confined Brownian motion of individual magnetic nanoparticles on a chip: Characterization of magnetic susceptibility.

NARCIS (Netherlands)

van Ommering, K.; Nieuwenhuis, J.H.; IJzendoorn, van L.J.; Koopmans, B.; Prins, M.W.J.

2006-01-01

An increasing number of biomedical applications requires detailed knowledge of the magnetic susceptibility of individual particles. With conventional techniques it is very difficult to analyze individual particles smaller than 1 µm. The authors demonstrate how the susceptibility of individual

Prediction Equations Overestimate the Energy Requirements More for Obesity-Susceptible Individuals.

Science.gov (United States)

McLay-Cooke, Rebecca T; Gray, Andrew R; Jones, Lynnette M; Taylor, Rachael W; Skidmore, Paula M L; Brown, Rachel C

2017-09-13

Predictive equations to estimate resting metabolic rate (RMR) are often used in dietary counseling and by online apps to set energy intake goals for weight loss. It is critical to know whether such equations are appropriate for those susceptible to obesity. We measured RMR by indirect calorimetry after an overnight fast in 26 obesity susceptible (OSI) and 30 obesity resistant (ORI) individuals, identified using a simple 6-item screening tool. Predicted RMR was calculated using the FAO/WHO/UNU (Food and Agricultural Organisation/World Health Organisation/United Nations University), Oxford and Miflin-St Jeor equations. Absolute measured RMR did not differ significantly between OSI versus ORI (6339 vs. 5893 kJ·d -1 , p = 0.313). All three prediction equations over-estimated RMR for both OSI and ORI when measured RMR was ≤5000 kJ·d -1 . For measured RMR ≤7000 kJ·d -1 there was statistically significant evidence that the equations overestimate RMR to a greater extent for those classified as obesity susceptible with biases ranging between around 10% to nearly 30% depending on the equation. The use of prediction equations may overestimate RMR and energy requirements particularly in those who self-identify as being susceptible to obesity, which has implications for effective weight management.

Physiological and pathological adaptations in dairy cows that may increase susceptibility to periparturient diseases and disorders

Directory of Open Access Journals (Sweden)

Juan J. Loor

2010-01-01

Full Text Available Dairy cows undergo tremendous metabolic and physiological adaptations around parturition to support lactation. The liver  is central to many of these processes, including gluconeogenesis and metabolism of fatty acids mobilized from adipose tis-  sue. Fat accumulation may impair normal functions of the liver and increase ketogenesis, which in turn may predispose cows  to other metabolic abnormalities. Several aspects of dietary management and body condition may alter these adaptations,  affect dry matter intake, and increase or decrease susceptibility to periparturient health problems. Overfeeding energy dur-  ing the dry period is a prominent risk factor. Considerable progress has been made in recent years in describing the adap-  tive changes in the liver and other organs in normal and abnormal states, but this knowledge has not yet identified unequiv-  ocally the key steps that might be compromised during development of metabolic disorders. The potential role of signaling  compounds, such as the inflammatory cytokines released in response to environmental stressors, infectious challenge, and  oxidative stress, in the pathogenesis of periparturient disease is under investigation. New techniques such as functional  genomics, using cDNA or oligonucleotide microarrays, as well as proteomics and metabolomics, provide additional high-  throughput tools to determine the effects of nutrition, management, or stressors on tissue function in development of dis-  ease. Integrative approaches should be fruitful in unraveling the complex interactions of metabolism, immune activation,  stress physiology, and endocrinology that likely underlie development of periparturient disease. 

Droughts may increase susceptibility of prairie dogs to fleas: Incongruity with hypothesized mechanisms of plague cycles in rodents

Science.gov (United States)

Eads, David A.; Biggins, Dean E.; Long, Dustin H.; Gage, Kenneth L.; Antolin, Michael F.

2016-01-01

Plague is a reemerging, rodent-associated zoonosis caused by the flea-borne bacterium Yersinia pestis. As a vector-borne disease, rates of plague transmission may increase when fleas are abundant. Fleas are highly susceptible to desiccation under hot-dry conditions; we posited that their densities decline during droughts. We evaluated this hypothesis with black-tailed prairie dogs (Cynomys ludovicianus) in New Mexico, June–August 2010–2012. Precipitation was relatively plentiful during 2010 and 2012 but scarce during 2011, the driest spring–summer on record for the northeastern grasslands of New Mexico. Unexpectedly, fleas were 200% more abundant in 2011 than in 2010 and 2012. Prairie dogs were in 27% better condition during 2010 and 2012, and they devoted 287% more time to grooming in 2012 than in 2011. During 2012, prairie dogs provided with supplemental food and water were in 23% better condition and carried 40% fewer fleas. Collectively, these results suggest that during dry years, prairie dogs are limited by food and water, and they exhibit weakened defenses against fleas. Long-term data are needed to evaluate the generality of whether droughts increase flea densities and how changes in flea abundance during sequences of dry and wet years might affect plague cycles in mammalian hosts.

Susceptibility testing of fish cell lines for virus isolation

DEFF Research Database (Denmark)

Ariel, Ellen; Skall, Helle Frank; Olesen, Niels Jørgen

2009-01-01

and laboratories, but also between lineages of the same cell line. To minimise the occurrence of false negatives in a cell culture based surveillance system, we have investigated methods, to select cell lineages that are relatively superior in their susceptibility to a panel of virus isolates. The procedures...... cell lineages, we increased the number of isolates of each virus, propagated stocks in a given cell line and tested all lineages of that line in use in the laboratory. Testing of relative cell line susceptibility between laboratories is carried out annually via the Inter-laboratory Proficiency Test...... sensitivity for surveillance purposes within a cell line and between laboratories.In terms of economic and practical considerations as well as attempting to approach a realistic test system, we suggest the optimal procedure for susceptibility testing of fish cell lines for virus isolation to be a combination...

An in-depth characterization of the major psoriasis susceptibility locus identifies candidate susceptibility alleles within an HLA-C enhancer element.

Directory of Open Access Journals (Sweden)

Alex Clop

Full Text Available Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC.

Relationship between antimicrobial susceptibility of clinical mastitis pathogens and treatment outcome in cows.

Science.gov (United States)

Hoe, Fernanda G H; Ruegg, Pamela L

2005-11-01

To determine whether there was any association between results of in vitro antimicrobial susceptibility testing of pathogens isolated from cows with mild or moderate clinical mastitis and outcome of treatment. Observational study. 133 cows with mild or moderate mastitis in a single quarter. Cows were treated by means of intramammary infusion of pirlimycin (50 mg) in the affected quarter once daily for 2 days; additional intramammary treatments with the same product were administered if the milk continued to appear abnormal. Duration of treatment and days until clinical cure were recorded. Bacterial isolates were tested for antimicrobial susceptibility by means of a broth micro-dilution technique. Environmental streptococci, coliforms, and coagulase-negative Staphylococcus spp were the most commonly isolated pathogens. Duration of treatment and days until clinical cure were not significantly different for cows from which pathogens that were susceptible or resistant to pirlimycin were isolated. Bacteriologic cure rates 14 and 21 days after treatment were not significantly different for cows with mastitis caused by susceptible or resistant bacteria. Similar results were found when data only from cows with mastitis caused by gram-positive isolates were analyzed. In the present study, differences in clinical outcome for cows with mild or moderate mastitis that could be attributed to differences in results of in vitro susceptibility testing were not identified. The use of in vitro susceptibility testing to guide intramammary mastitis treatment cannot be recommended on the basis of results of this study.

Magnetic susceptibility of scandium-hydrogen and lutetium-hydrogen solid-solution alloys from 2 to 3000K

International Nuclear Information System (INIS)

Stierman, R.J.

1982-12-01

Results for pure Sc show that the maximum and minimum in the susceptibility discovered earlier are enhanced as the impurity level of iron in scandium decreases. The Stoner enhancement factor, calculated from low-temperature heat capacity data, susceptibility data, and band-structure calculations show Sc to be a strongly enhanced paramagnet. Below 2 0 K, the magnetic anisotropy between the hard and easy directions of scandium decreases linearly with decreasing temperature, tending toward zero at 0 K. The large increase in the susceptibility of Sc at lower temperatures indicates magnetic ordering. Pure Lu and Lu-H alloys showed an anisotropy in susceptibility vs orientation; thus the samples were not random polycrystalline samples. Pure Lu shows the shallow maximum and minimum, but the increase in susceptibility at low temperatures is larger than previously observed. The susceptibility-composition dependence of the Lu-H alloys also did not match other data. The susceptibility-composition dependence does not match the composition dependence of the electronic specific heat constant below 150 K, showing the electronic specific heat is being affected by terms other than phonon-electron and pure electron-electron interactions

Frequency and antibiotic susceptibility patterns of urinary pathogens in male outpatients in Argentina.

Science.gov (United States)

Villar, Hugo E; Jugo, Mónica B; Macan, Alejandro; Visser, Matias; Hidalgo, Mariana; Maccallini, Gustavo Cesar

2014-06-11

Knowledge of the etiology and antimicrobial susceptibility patterns of uropathogens is important for determining the best treatment option. This study aimed to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from adult male outpatients. Between November 2012 and April 2013, 3,105 community urine samples were analyzed from adult male patients who attended the Laboratorio Hidalgo, Buenos Aires, Argentina. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method. Isolates resistant to third generation cephalosporin were tested for extended-spectrum beta-lactamase (ESBL) production using the double-disk synergy test. Of the 3,105 urine samples analyzed, 791 (25.5%) had significant bacteriuria. The frequency of positive urine cultures increased significantly with patient age. Escherichia coli was isolated most frequently (47.3%), followed by Enterococcus faecalis (13.6%), and Klebsiella pneumoniae (11.9%). Gram-negative organisms represented 78.8% of urinary pathogens. The highest activities against Gram-negative bacteria were found with imipenem (99.0%), amikacin (98.1%), ertapenem (94.2%), fosfomycin (90.7%), and piperacillin-tazobactam (90.1%). The frequencies of ESBLs among E. coli, K. pneumoniae, and P. mirabilis were 15.2 %, 22.3%, and 8%, respectively. Fosfomycin, piperacillin-tazobactam, and nitrofurantoin were most effective against Gram-positive organisms. Fosfomycin may be an excellent option for cystitis treatment in patients without risk factors, whereas piperacillin-tazobactam is preferred for the treatment of parenchymatous UTIs, complicated UTIs, and UTIs associated with risk factors. To ensure the optimal selection of antibiotics, physicians should have access to up-to-date information about the local prevalence of antimicrobial resistance.

Continuous background light significantly increases flashing-light enhancement of photosynthesis and growth of microalgae.

Science.gov (United States)

Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

2015-01-01

Under specific conditions, flashing light enhances the photosynthesis rate in comparison to continuous illumination. Here we show that a combination of flashing light and continuous background light with the same integrated photon dose as continuous or flashing light alone can be used to significantly enhance photosynthesis and increase microalgae growth. To test this hypothesis, the green microalga Dunaliella salina was exposed to three different light regimes: continuous light, flashing light, and concomitant application of both. Algal growth was compared under three different integrated light quantities; low, intermediate, and moderately high. Under the combined light regime, there was a substantial increase in all algal growth parameters, with an enhanced photosynthesis rate, within 3days. Our strategy demonstrates a hitherto undescribed significant increase in photosynthesis and algal growth rates, which is beyond the increase by flashing light alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

Science.gov (United States)

Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

Science.gov (United States)

Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

Dielectric susceptibility of classical Coulomb systems. II

International Nuclear Information System (INIS)

Choquard, Ph.; Piller, B.; Rentsch, R.

1987-01-01

This paper deals with the shape dependence of the dielectric susceptibility (equivalently defined, in a canonical ensemble, by the mean square fluctuation of the electric polarization or by the second moment of the charge-charge correlation function) of classical Coulomb systems. The concept of partial second moment is introduced with the aim of analyzing the contributions to the total susceptibility of pairs of particles of increasing separation. For a disk-shaped one-component plasma with coupling parameter γ=2 it is shown, numerically and algebraically for small and large systems, that (1) the correlation function of two particles close to the edge of the disk decays as the inverse of the square of their distance, and (2) the susceptibility is made up of a bulk contribution, which saturates rapidly toward the Stillinger-Lovett value, and of surface contribution, which varies on the scale of the disk diameter and is described by a new law called the arc sine law. It is also shown that electrostatics and statistical mechanics with shape-dependent thermodynamic limits are consistent for the same model in a strip geometry, whereas the Stillinger-Lovett sum rule is verified for a boundary-free geometry such as the surface of a sphere. Some results of extensive computer simulations of one- and two-component plasmas in circular and elliptic geometries are shown. Anisotropy effects on the susceptibilities are clearly demonstrated and the arc sine law for a circular plasma is well confirmed

Effects of mineral nutrients on ozone susceptibility of Lemna minor

Energy Technology Data Exchange (ETDEWEB)

Craker, L.E.

1971-01-01

Susceptibility of Lemna minor L. to ozone injury was influenced by the mineral nutrients available to the Lemna plants. Additional nitrogen or additional iron in the nutrient media respectively enhanced or reduced chlorophyll loss of Lemna plants fumigated with ozone. Lemna plants growing on a nutrient medium lacking copper had significantly less injury from ozone fumigation than Lemna plants growing on a complete nutrient medium. There were apparent interactions among phosphorus and potassium nutrient levels in determing the Lemna plant's susceptibility to ozone.

Transthyretin knockout mice display decreased susceptibility to AMPA-induced neurodegeneration

DEFF Research Database (Denmark)

Nunes, Ana Filipa; Montero, Maria; Franquinho, Filipa

2009-01-01

Transthyretin (TTR) has been regarded as a neuroprotective protein given that TTR knockout (KO) mice display increased susceptibility for amyloid beta deposition and memory deficits during aging. In parallel, TTR KO mice have increased levels of neuropeptide Y (NPY), which promotes neuroprotectio...

Magnetic susceptibilities of Ca/sub y/U/sub 1-y/O/sub 2+x/ solid solutions

International Nuclear Information System (INIS)

Hinatsu, Y.; Fujino, T.

1988-01-01

Magnetic susceptibilities of Ca/sub y/U/sub 1-y/O/sub 2+x/ solid solutions with fluorite structure were measured from 4.2 K to room temperature. An antiferromagnetic transition was observed for all the solid solutions examined in this study (y ≤ 0.33). The Neel temperature of the oxygen-hypostoichiometric solid solutions (x 2 solid solutions, but different from that of (U,Th)O 2 solid solutions. The effective magnetic moment decreased with increasing calcium concentration, which indicates the oxidation of uranium in the solid solutions. From the analysis of the magnetic susceptibility data, it was found that the oxidation state of uranium was either tetravalent or pentavalent. The Neel temperature of the hyperstoichiometric solid solutions (x > 0) did not change appreciably with calcium concentrations. From the comparison of the magnetic susceptibility data of the hypostoichiometric solid solutions with those of the hyperstoichiometric solid solutions, the effect of oxygen vacancies is more significant than that of interstitial oxygens on the decrease of magnetic interactions between uranium ions

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

International Nuclear Information System (INIS)

Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A.

2016-01-01

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. - Highlights: • To define susceptible populations is important for risk assessment and management; • Genetic susceptibility may influence the individual response to nanomaterial exposure; • Susceptibility factors in workplace settings have both scientific and ethical issues.

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

Energy Technology Data Exchange (ETDEWEB)

Iavicoli, Ivo, E-mail: ivo.iavicoli@unina.it [Department of Public Health, Division of Occupational Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples (Italy); Leso, Veruscka, E-mail: veruscka@email.it [Institute of Public Health, Section of Occupational Medicine, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome (Italy); Schulte, Paul A., E-mail: pas4@cdc.gov [National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 4676 Columbia Parkway, MS C-14, Cincinnati, OH 45226 (United States)

2016-05-15

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. - Highlights: • To define susceptible populations is important for risk assessment and management; • Genetic susceptibility may influence the individual response to nanomaterial exposure; • Susceptibility factors in workplace settings have both scientific and ethical issues.

Prevalence and Antimicrobial Susceptibility of Coagulase-Negative Staphylococci isolated from Bovine Mastitis

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Kaliwal B.B.

2011-08-01

Full Text Available The study was carried out to investigate the prevalence and antimicrobial susceptibility of Coagulase-Negative Staphylococci isolated from Bovine Mastitis in and around Dharwad region. A total of 310 samples were screened and 180 confirmed Coagulase-Negative Staphylococci were obtained. The antimicrobial susceptibility of Coagulase-Negative Staphylococci against 10 antimicrobial agents was tested using the disc diffusion method. The highest numbers of Coagulase-Negative Staphylococci were susceptible to ceftriaxone 83.88% followed by cefotaxime 79.41%, methicillin 76.47%, ciprofloxacin 73.52%, erythromycin 70.05%, amikacin 66.11%, gentamycin 42.94%, amoxicillin 36.76%, ampicillin 29.41%, and the lowest susceptibility was shown in penicillin 23.23% . The results indicated that the increase in prevalence and antibiotic resistance pattern of the Coagulase-Negative Staphylococci isolated from bovine mastitis exhibited the highest degree of susceptible to ceftriaxone of all the tested antimicrobial agents. [Vet. World 2011; 4(4.000: 158-161

Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

International Nuclear Information System (INIS)

Zhang, Huan; Su, Yu-liang; Yu, Herbert; Qian, Bi-yun

2012-01-01

MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs. TT, OR=1.15, 95%CI=1.05–1.27; CC vs. TT, OR=1.23, 95%CI=1.08–1.39; Dominant model, OR=1.17, 95%CI=1.06–1.30; Additive model, OR=1.08, 95%CI=1.01–1.14). In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations

Design and development of novel MRI compatible zirconium- ruthenium alloys with ultralow magnetic susceptibility.

Science.gov (United States)

Li, H F; Zhou, F Y; Li, L; Zheng, Y F

2016-04-19

In the present study, novel MRI compatible zirconium-ruthenium alloys with ultralow magnetic susceptibility were developed for biomedical and therapeutic devices under MRI diagnostics environments. The results demonstrated that alloying with ruthenium into pure zirconium would significantly increase the strength and hardness properties. The corrosion resistance of zirconium-ruthenium alloys increased significantly. High cell viability could be found and healthy cell morphology observed when culturing MG 63 osteoblast-like cells and L-929 fibroblast cells with zirconium-ruthenium alloys, whereas the hemolysis rates of zirconium-ruthenium alloys are zirconium-ruthenium alloys (1.25 × 10(-6) cm(3)·g(-1)-1.29 × 10(-6) cm(3)·g(-1) for zirconium-ruthenium alloys) are ultralow, about one-third that of Ti-based alloys (Ti-6Al-4V, ~3.5 × 10(-6) cm(3)·g(-1), CP Ti and Ti-6Al-7Nb, ~3.0 × 10(-6) cm(3)·g(-1)), and one-sixth that of Co-Cr alloys (Co-Cr-Mo, ~7.7 × 10(-6) cm(3)·g(-1)). Among the Zr-Ru alloy series, Zr-1Ru demonstrates enhanced mechanical properties, excellent corrosion resistance and cell viability with lowest magnetic susceptibility, and thus is the optimal Zr-Ru alloy system as therapeutic devices under MRI diagnostics environments.

Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility.

Science.gov (United States)

Han, Xia; Liu, Lili; Niu, Jiamin; Yang, Jun; Zhang, Zengtang; Zhang, Zhiqiang

2015-01-01

Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.

Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer

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Kevin Tong

2017-12-01

Full Text Available Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2, stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.

Behavioral and physiological responses of cabbage looper,Trichoplusia ni (Hübner), to steam distillates from resistant versus susceptible soybean plants.

Science.gov (United States)

Khan, Z R; Ciepiela, A; Norris, D M

1987-08-01

Soybean plant volatiles, extracted as steam distillates, significantly affected the behavior and biology of the cabbage looper,Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae). Distillates from the susceptible Davis variety attractedT. ni larvae and female adults, whereas those from resistant PI 227687 plants repelled them. When mixed in an artificial diet, steam distillates from PI 227687 plants caused mortality of first-instar larvae. Adults emerging from pupae topically treated with 5 μg of such PI 227687 extractable showed developmental abnormalities. Larval feeding was significantly less on Davis leaves treated with PI 227687 volatiles as compared to solvent (acetone) or such Davis extractables. However, Davis volatiles on PI 227687 leaves did not increase larval feeding. HPLC analyses of steam distillates from susceptible Davis versus resistant PI 227687 indicated differences.

Forkhead box C2 promoter variant c.-512C>T is associated with increased susceptibility to chronic venous diseases.

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Sumi Surendran

Full Text Available Chronic venous disease (CVD is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (FoxC2 gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 5' and 3' flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 5' flanking region and one in 3' flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 4±1.42 fold increased compared to saphenous veins from 20 normal subjects (pT (rs34221221: C>T variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C>T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C>T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers Dll4 and Hey2 and downregulation of venous marker COUP-TFII. Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in patients with varicose veins.

Antibiotic susceptibility of Salmonella spp.: a comparison of two surveys with a 5 years interval

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Gordana Mijović

2012-02-01

Full Text Available Salmonella infections are one of the major global public health problems. During the last decade, antibiotic resistance and multiresistance of Salmonella spp. have increased a great deal, especially in developing countries with an increased and indiscriminate use of antibiotics in the treatment of humans and animals. This study aims to investigate and compare antimicrobial susceptibility patterns of Salmonella during 2005 and 2010.A total of 186 Salmonella strain during 2005 and 140 Salmonella strain during 2010 were isolated from stool specimens using standard methods. The isolates were confirmed as Salmonella by using a battery of biochemical reactions. Specific antisera were used for serologic characterization of Salmonella strain. Antimicrobial susceptibility testing was performed by standard disk diffusion method using ampicillin, trimethoprim-sulfamethoxasole, ceftriaxon, chloramphenicol, nalidixic acid and ciprofloxacin.One hundred eighty (96.8% of 186 isolated Salmonella strains in 2005, and 133 (95% of 140 isolated Salmonella strain in 2010 are recognized as Salmonella Enteritidis. Sensitivity of Salmonella isolates during 2005 and 2010 were 91.9% and 92.9% to ampicillin, 95.7% and 97.1% to trimethoprim-sulfamethoxasole, 99.5% and 100% to chloramphenicol, 99.5% and 100% to ciprofloxacin, 98.9% and 97.1% to ceftriaxon, 73.1% and 95.7% to nalidixic acid, respectively.Sensitivity of Salmonella isolates to all tested antimicrobial agents except to ceftriaxon was been slightly improved over testing period. Resistance rate to ceftriaxon was higher in 2010 than in 2005, and this fact deserves attention. Significantly increase susceptibility rate to nalidixic acid was observed between the two surveys

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

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Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

2016-03-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Variation of the dynamic susceptibility along an isochrone

DEFF Research Database (Denmark)

Bailey, Nicholas; Schrøder, Thomas; Dyre, J. C.

2014-01-01

Koperwas et al. showed in a recent paper [Phys. Rev. Lett. 111, 125701 (2013)] that the dynamic susceptibility χ4 as estimated by dielectric measurements for certain glass-forming liquids decreases substantially with increasing pressure along a curve of constant relaxation time. This observation...

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults.

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Zhifang Wang

Full Text Available Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV. Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China, with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program.To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades.This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province.The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001. During the study period, the reported incidence rate in individuals aged ≤19 years declined to the historically lowest record in 2014. Compared with individuals aged ≤19 years, those aged ≥20 years showed the highest incidence rate (P< 0.001. Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases.Childhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.

Evaluation of semisolid agar method for antifungal susceptibility test of T. rubrum

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Sultana Razia

2016-08-01

Full Text Available Background: With increasing fungal disease many newer antifungal drugs are available with different spectrum of activ­ity. Antifungal susceptibility test will help clinicians for selection of effective drug and thereby treatment of patient. Objective: The study was undertaken to perform a simple screening drug susceptibility test of T. rnbrum by Semi Solid Agar Antifungal Susceptibility (SAAS Method: Perfonnance of susceptibility method was assessed by comparing the MICs of three commonly prescribed antifungal agents namely- tluconazole (FCZ, itraconazole (ITZ and terbinafine (TER to the CLSI (Clinical and Laboratory Standard Institute recommended M-38, a broth microdilution method. Results: In SAAS method, among twenty nine T. rubrum, twenty five (86.2% were susceptible (MIC range 0.5-64 µg/ml to Fluconazole (FCZ and four (13.7% were resistant (MIC value >64 µg/ml. In broth microdilution method, among twenty nine T. rubrum, twenty six (89.6% were susceptible (MIC range 0.3-64 µg/ml to FCZ and three (10.3% were resistant (MIC value >64 µg/ml. In case of both ITZ and TER, all were susceptible (MIC range 0.3-64 µg/ml to both methods. The SAAS method demonstrated the susceptibility pattern of T. rubrum against FCZ, ITZ and TER usually within 72 to 96 hours after organism isolation and results were concordance with the results of CLSI broth microdilution method. Conclusion: Though it is a newer method with proper standardization of the test method, SAAS method is simple and easily applicable screening method for susceptibility testing of antifungal agents against dermatophytes in any microbiology laboratories.

[Polymorphisms of TLR7 rs3853839 and rs179010 are associated with susceptibility to and severity of hand, foot and mouth disease caused by enterovirus 71 in male children].

Science.gov (United States)

Li, Yaping; Zhai, Song; Li, Mei; Wang, Yuan; Lu, Tong; Deng, Huiling; Zhang, Xin; Dang, Shuangsuo

2017-07-01

Objective To investigate whether the polymorphisms of TLR7/MyD88 signaling pathway is associated with the susceptibility to and severity of hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) in children. Methods We collected 180 EV71 HFMD cases and 201 healthy controls from both the Second Affiliated Hospital of Xi'an Jiaotong University and Xi'an Children's Hospital. The genotypes including rs3853839, rs179010 of TLR7, and rs7744 of MyD88 were detected in the 381 samples by SNPscan kit. Results The susceptibility risk (OR=2.343, 95%CI:1.516-3.621) and severity risk (OR=1.939, 95%CI: 1.064-3.521) of TLR7 rs3853839 allele C significantly increased in the male children with EV71 HFMD. Also, the susceptibility risk (OR=1.701, 95%CI: 1.142-2.535) and severity risk (OR=1.852, 95%CI: 1.038-3.305) of TLR7 rs179010 allele T significantly increased in the male children with EV71 HFMD. But there was no significant difference in the distribution of TLR7 rs179010 and rs3853839 genes between female children with EV71 HFMD and female controls. There was no correlation between the genetic polymorphisms of MyD88 rs7744 and the susceptibility to and severity of EV71 HFMD in the children. Conclusion Polymorphisms of TLR7 rs3853839 and rs179010 are correlated to the susceptibility to and severity of EV71 HFMD in male children.

Extended biofilm susceptibility assay for Staphylococcus aureus bovine mastitis isolates: evidence for association between genetic makeup and biofilm susceptibility.

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Melchior, M B; van Osch, M H J; Lam, T J G M; Vernooij, J C M; Gaastra, W; Fink-Gremmels, J

2011-12-01

Staphylococcus aureus is one of the most prevalent causes of bovine mastitis. The antimicrobial treatment of this disease is currently based on antimicrobial susceptibility tests according to Clinical and Laboratory Standards Institute standards. However, various authors have shown a discrepancy between the results of this standard susceptibility test and the actual cure rate of the applied antimicrobial treatment. Increasing evidence suggests that in vivo biofilm formation by Staph. aureus, which is not assessed in the antimicrobial susceptibility tests, is associated with this problem, resulting in disappointing cure rates, especially for infections of longer duration. Previous data obtained with a limited number of strains showed that the extended biofilm antimicrobial susceptibility (EBS) assay reveals differences between strains, which cannot be derived from a standard susceptibility test or from a 24-h biofilm susceptibility test. The objective of this study was to test a collection of Staph. aureus bovine mastitis strains in the EBS assay and to model the effect of antimicrobial exposure, duration of antimicrobial exposure, and genotype profile of the strains on antimicrobial susceptibility. With the results from a previous study with the same collection of strains, the effect of genotype represented by accessory gene regulator gene (agr-type), the presence of insertional sequence 257 (IS257), intercellular adhesion (ica), and the β-lactamase (blaZ) gene were entered as explanatory factors in a logistic regression model. The agr locus of Staph. aureus controls the expression of most of the virulence factors, represses the transcription of several cell wall-associated proteins, and activates several exoproteins during the post-exponential phase. The IS257 gene has been related to biofilm formation in vitro and was found earlier in 50% of the agr-type 2 strains. The ica gene cluster encodes for the production of an extracellular polysaccharide adhesin, termed

Low-field susceptibilities of rare-earth spin glass alloys

International Nuclear Information System (INIS)

Sarkissian, B.V.B.

1978-01-01

The low-field AC susceptibilities of the dilute rare-earth spin glass alloys Sc-Gd, Sc-Tb, Pr-Tb and Pr-Gd are reported and compared with low-field DC susceptibilities of the same samples. The similarities between their behaviour and that of Au-Fe spin glass alloys is also considered. When single-ion anisotropy is important, this can cause a dramatic broadening of the sharp peak. Broadening in the AC peak has also observed as the frequency of the deriving field is increased. These data can be qualitatively discussed in terms of a recent magnetic-cluster model for spin glasses. (author)

Drug susceptibility of fungi isolated from ICU patients

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Modrzewska, Barbara D; Kurnatowska,, Anna J; Khalid, Katarzyna

Candida species can be a reason of infections associated with high morbidity and mortality. The risk of invasive candidosis for patients admitted to intensive care units (ICUs) is increased due to immunosuppressive states, prolonged length of stay, broad-spectrum antibiotics and Candida colonization. The aim of the study was to determine selected properties of fungi isolated from patients treated in the ICUs of hospitals in Lodz. The materials were collected from the oral cavity, the tracheostomy or endotracheal tube and urine from 16 children and 35 adult. In total, 127 samples were examined to differentiate the fungal strains with used morphological and biochemical methods. Candida species were isolated from adult patients (82.9%), but were not isolated from any of the children; C. albicans was the predominant fungus (61.7%), much less frequent were C. glabrata (12.8%), C. tropicalis (6.4%) and C. kefyr, C. dubliniensis (4.3% each).The susceptibility of fungi to antimycotic drugs revealed that almost all of the strains were susceptible to nystatin (97.9%) and to amphotericin B (72.3%), and resistant to fluconazole (72.3%) and ketoconazole (57.5%). No isolation of fungi from children remaining in ICU may be an evidence of high sanitary regime at these wards; fungi from the genus Candida are the etiological factors for ICU infections; 3/5 of them are caused by C. albicans, mostly of the code 2 576 174, characteristic for strains isolated from hospitalized patients; it is necessary to determine the species of the fungus and its susceptibility to drugs, which allows to conduct effective therapy; prophylactic administration of fluconazole leads to an increase in the number of strains resistant to this chemotherapeutic agent; in the antifungal local treatment, nystatin should be a drug of choice as the drug to which most fungi are susceptible.

Source-water susceptibility assessment in Texas—Approach and methodology

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Ulery, Randy L.; Meyer, John E.; Andren, Robert W.; Newson, Jeremy K.

2011-01-01

and time; that increased levels of COC-producing activities within a source area may increase susceptibility to COC exposure; and that natural and manmade conditions within the source area may increase, decrease, or have no observable effect on susceptibility to COC exposure. Incorporating these assumptions, eight SWSA components were defined: identification, delineation, intrinsic susceptibility, point- and nonpoint-source susceptibility, contaminant occurrence, area-of-primary influence, and summary components. Spatial datasets were prepared to represent approximately 170 attributes or indicators used in the assessment process. These primarily were static datasets (approximately 46 gigabytes (GB) in size). Selected datasets such as PWS surface-water-intake or groundwater-well locations and potential source of contamination (PSOC) locations were updated weekly. Completed assessments were archived, and that database is approximately 10 GB in size. SWSA components currently (2011) are implemented in the Source Water Assessment Program-Decision Support System (SWAP-DSS) computer software, specifically developed to produce SWSAs. On execution of the software, the components work to identify the source of water for the well or intake, assess intrinsic susceptibility of the water- supply source, assess susceptibility to contamination with COCs from point and nonpoint sources, identify any previous detections of COCs from existing water-quality databases, and summarize the results. Each water-supply source's susceptibility is assessed, source results are weighted by source capacity (when a PWS has multiple sources), and results are combined into a single SWSA for the PWS.'SWSA reports are generated using the software; during 2003, more than 6,000 reports were provided to PWS operators and the public. The ability to produce detailed or summary reports for individual sources, and detailed or summary reports for a PWS, by COC or COC group was a unique capability of SWAP

Susceptibility of SCADA systems and the energy sector

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Goike, Lindsay

The research in this paper focused on analyzing SCADA systems in the energy sector for susceptibility to cyber attacks, in furtherance of providing suggestions to mitigate current and future cyber attacks. The research will be addressing the questions: how are SCADA systems susceptible to cyber attacks, and what are the suggested ways to mitigate both current and future cyber attacks. The five main categories of security vulnerabilities facing current SCADA systems were found to be: connectivity to the Internet, failure to plan, interdependency of sectors, numerous different types of threats, and outdated software. Some of the recommendations mentioned to mitigate current and future risks were: virtual private networks, risk assessments, increased physical security, updating of software, and firewalls.

Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species.

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Nagayoshi, Yohsuke; Miyazaki, Taiga; Shimamura, Shintaro; Nakayama, Hironobu; Minematsu, Asuka; Yamauchi, Shunsuke; Takazono, Takahiro; Nakamura, Shigeki; Yanagihara, Katsunori; Kohno, Shigeru; Mukae, Hiroshi; Izumikawa, Koichi

2017-01-01

The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions.

Effect of a 16% Carbamide Peroxide Bleaching Gel on Enamel Staining Susceptibility

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M. Ghavamnasiri

2005-03-01

Full Text Available Statement of Problem: Due to the growing popularity of vital bleaching by CarbamidePeroxide it is imperative to understand the effect of such agents on enamel and dentine.Purpose: The purpose of this study was to evaluate the effect of a 16% carbamide peroxide bleaching gel; Vivastyle on enamel staining susceptibility.Materials and Methods: Thirty bovine specimens were selected and randomly divided into two groups of fifteen. The experimental group was subjected to Vivastyle gel and then was immersed in coffee, for half an hour daily for three weeks. The control group was only immersed in coffee. The teeth were evaluated by colorimeter readings to measure L*, a*, b* of each tooth. Total color differences between two colors (ΔE were calculated using the following formula: ΔE= [(ΔL* 2 + (Δa* 2+ (Δb* 2].ΔE1 represent color difference after bleaching; ΔE2: bleached and immersed in coffee,and ΔE3 immersed in coffee.Results: Mean color difference were: 9.478, 13.808, and 7.230 for ΔE1, ΔE2, and ΔE3 respectively. Paired comparison by Duncan test showed that there was a significant difference between ΔE1 and ΔE2 (P0.000. t-test showed that there was no significant difference between ΔE3 and ΔE1. (P=0.08, however, ΔE3 had significant difference with ΔE2 (P0.000.Conclusion: After vital bleaching, the enamel staining susceptibility is significantly increased.

Undefined familial colorectal cancer and the role of pleiotropism in cancer susceptibility genes.

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Dobbins, Sara E; Broderick, Peter; Chubb, Daniel; Kinnersley, Ben; Sherborne, Amy L; Houlston, Richard S

2016-10-01

Although family history is a major risk factor for colorectal cancer (CRC) a genetic diagnosis cannot be obtained in over 50 % of familial cases when screened for known CRC cancer susceptibility genes. The genetics of undefined-familial CRC is complex and recent studies have implied additional clinically actionable mutations for CRC in susceptibility genes for other cancers. To clarify the contribution of non-CRC susceptibility genes to undefined-familial CRC we conducted a mutational screen of 114 cancer susceptibility genes in 847 patients with early-onset undefined-familial CRC and 1609 controls by analysing high-coverage exome sequencing data. We implemented American College of Medical Genetics and Genomics standards and guidelines for assigning pathogenicity to variants. Globally across all 114 cancer susceptibility genes no statistically significant enrichment of likely pathogenic variants was shown (6.7 % cases 57/847, 5.3 % controls 85/1609; P = 0.15). Moreover there was no significant enrichment of mutations in genes such as TP53 or BRCA2 which have been proposed for clinical testing in CRC. In conclusion, while we identified genes that may be considered interesting candidates as determinants of CRC risk warranting further research, there is currently scant evidence to support a role for genes other than those responsible for established CRC syndromes in the clinical management of familial CRC.

Parental genetic diversity of brown trout (Salmo trutta m. fario) brood stock affects offspring susceptibility to whirling disease.

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Eszterbauer, Edit; Forró, Barbara; Tolnai, Zoltán; Guti, Csaba Ferenc; Zsigmond, Gergely; Hoitsy, György; Kallert, Dennis Marc

2015-03-03

Whirling disease, caused by the myxozoan parasite Myxobolus cerebralis, has high economical and ecological importance worldwide. Susceptibility to the disease varies considerably among salmonid species. In brown trout (Salmo trutta) the infection is usually subclinical with low mortality, which increases the risk of parasite dissemination, especially when farm fish are used for stocking natural habitats. The influence of intraspecific genetic differences (especially the level of homozygosity) on susceptibility is unknown. Therefore, we examined the possible correlations between parental genetic diversity and offspring susceptibility of brown trout stocks to whirling disease. Two brown trout brood stocks from a German and a Hungarian fish farm were genetically characterized using microsatellite and lineage-specific genetic markers. The individual inbreeding coefficient f and pairwise relatedness factor r were estimated based on eight microsatellite markers. Brood stock populations were divided into groups according to low and high f and r value estimates and subjected to selective fertilization. The offspring from these separate groups were exposed to M. cerebralis actinospores, and the infection prevalence and intensity was measured and statistically analysed. The analysis of phylogeographic lineage heritage revealed high heterogeneity in the Hungarian brood stock since > 50% of individuals were Atlantic-Danubian hybrids, while only pure Atlantic-descending specimens were detected in the German population. Based on f msat and r msat estimations, classified non-inbred (NIB), inbred (IB) and a group of closely related fish (REL) were created. The susceptibility of their offspring varied considerably. Although there was no significant difference in the prevalence of M. cerebralis infection, the mean intensity of infection differed significantly between NIB and IB groups. In REL and IB groups, a high variability was observed in infection intensity. No external

Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection.

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Zhu, Junping; Zhang, Tong; Cao, Lina; Li, Aixin; Zheng, Kai; Zhang, Nan; Su, Bin; Chen, Zhiyun; Chen, Ning; Wu, Hao; He, Qiushui

2017-09-29

Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men.

Susceptibility tensor imaging and tractography of collagen fibrils in the articular cartilage.

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Wei, Hongjiang; Gibbs, Eric; Zhao, Peida; Wang, Nian; Cofer, Gary P; Zhang, Yuyao; Johnson, G Allan; Liu, Chunlei

2017-11-01

To investigate the B 0 orientation-dependent magnetic susceptibility of collagen fibrils within the articular cartilage and to determine whether susceptibility tensor imaging (STI) can detect the 3D collagen network within cartilage. Multiecho gradient echo datasets (100-μm isotropic resolution) were acquired from fixed porcine articular cartilage specimens at 9.4 T. The susceptibility tensor was calculated using phase images acquired at 12 or 15 different orientations relative to B 0 . The susceptibility anisotropy of the collagen fibril was quantified and diffusion tensor imaging (DTI) was compared against STI. 3D tractography was performed to visualize and track the collagen fibrils with DTI and STI. STI experiments showed the distinct and significant anisotropic magnetic susceptibility of collagen fibrils within the articular cartilage. STI can be used to measure and quantify susceptibility anisotropy maps. Furthermore, STI provides orientation information of the underlying collagen network via 3D tractography. The findings of this study demonstrate that STI can characterize the orientation variation of collagen fibrils where diffusion anisotropy fails. We believe that STI could serve as a sensitive and noninvasive marker to study the collagen fibrils microstructure. Magn Reson Med 78:1683-1690, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Meta-analysis and genome-wide interpretation of genetic susceptibility to drug addiction

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2011-01-01

Background Classical genetic studies provide strong evidence for heritable contributions to susceptibility to developing dependence on addictive substances. Candidate gene and genome-wide association studies (GWAS) have sought genes, chromosomal regions and allelic variants likely to contribute to susceptibility to drug addiction. Results Here, we performed a meta-analysis of addiction candidate gene association studies and GWAS to investigate possible functional mechanisms associated with addiction susceptibility. From meta-data retrieved from 212 publications on candidate gene association studies and 5 GWAS reports, we linked a total of 843 haplotypes to addiction susceptibility. We mapped the SNPs in these haplotypes to functional and regulatory elements in the genome and estimated the magnitude of the contributions of different molecular mechanisms to their effects on addiction susceptibility. In addition to SNPs in coding regions, these data suggest that haplotypes in gene regulatory regions may also contribute to addiction susceptibility. When we compared the lists of genes identified by association studies and those identified by molecular biological studies of drug-regulated genes, we observed significantly higher participation in the same gene interaction networks than expected by chance, despite little overlap between the two gene lists. Conclusions These results appear to offer new insights into the genetic factors underlying drug addiction. PMID:21999673

Susceptibility Genes in Thyroid Autoimmunity

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Yoshiyuki Ban

2005-01-01

Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

Combined value of susceptibility weighted imaging and dynamic susceptibility-weighted contrast-enhanced MR perfusion-weighted imaging in brain astrocytoma grading

International Nuclear Information System (INIS)

Wang Xiaochun; Zhang Hui; Qin Jiangbo; Wang Le; Wu Xiaofeng

2012-01-01

Objective: To assess the value of combination of susceptibility weighted imaging (SWI) and dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion-weighted magnetic resonance imaging in astrocytoma grading. Methods: SWI and DSC scans were performed in 82 patients with pathologically confirmed astrocytoma. The patient group consisted of grade Ⅱ (15), grade Ⅲ (10), and grade Ⅳ (57). The intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max were used to determine the grade of astrocytomas by Kruskal Wallis test, Welch test, Spearman correlation coefficients, Pearson correlation coefficients, and receiver operating characteristic curve (ROC)statistic methods. Results: There were no ITSS in 14 cases of low-grade astrocytomas, the degree of ITSS were grade 1 to 3 in anaplastic astrocytomas, the degree of ITSS were grade 3 in all of the glioblastomas, the degree of ITSS were significant difference in all grades (H=71.96, P<0.01). rCBV max in grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were 1.26 ± 0.42, 3.59 ± 2.09 and 8.34 ± 1.16 respectively, rCBV max were significant difference in all grades (F'=681.72, P<0.01). ITSS showed significant correlation with rCBV max (r=0.72, P<0.01) and tumor grades (r=0.89, P<0.01), and rCBV and tumor grades showed significant correlation (r=0.78, P<0.01). Area under the ROC curve application SWI, DSC, SWI and DSC in differentiation of the grade Ⅱ and grade Ⅲ astrocytomas were 0.99, 0.93, 1.00, differentiate grade Ⅲ from grade Ⅳ were 0.70, 0.94, 0.94, and differentiate high-grade from low-grade astrocytomas were 1.00, 0.99, 1.00. Conclusions: ITSS is helpful to determine the grade of astrocytomas. The use of SWI in combination with DSC may improve the diagnostic accuracy of astrocytoma grading. (authors)

Real-time and quantitative isotropic spatial resolution susceptibility imaging for magnetic nanoparticles

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Pi, Shiqiang; Liu, Wenzhong; Jiang, Tao

2018-03-01

The magnetic transparency of biological tissue allows the magnetic nanoparticle (MNP) to be a promising functional sensor and contrast agent. The complex susceptibility of MNPs, strongly influenced by particle concentration, excitation magnetic field and their surrounding microenvironment, provides significant implications for biomedical applications. Therefore, magnetic susceptibility imaging of high spatial resolution will give more detailed information during the process of MNP-aided diagnosis and therapy. In this study, we present a novel spatial magnetic susceptibility extraction method for MNPs under a gradient magnetic field, a low-frequency drive magnetic field, and a weak strength high-frequency magnetic field. Based on this novel method, a magnetic particle susceptibility imaging (MPSI) of millimeter-level spatial resolution (<3 mm) was achieved using our homemade imaging system. Corroborated by the experimental results, the MPSI shows real-time (1 s per frame acquisition) and quantitative abilities, and isotropic high resolution.

Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective, propensity-score-adjusted case-control and cohort analysis.

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Nissen, Jette Lindbjerg; Skov, Robert; Knudsen, Jenny Dahl; Ostergaard, Christian; Schønheyder, Henrik Carl; Frimodt-Møller, Niels; Benfield, Thomas

2013-08-01

Penicillin-susceptible Staphylococcus aureus isolates account for a fifth of cases of S. aureus bacteraemia (SAB) in Denmark, but little is known about treatment outcomes with penicillins or other antimicrobials. Here we compare penicillin, dicloxacillin and cefuroxime as definitive treatments in relation to 30 day mortality. A retrospective chart review of 588 penicillin-susceptible S. aureus cases at five centres from January 1995 to December 2010. Data on demographics, antimicrobial treatment, clinical signs and symptoms, and mortality at day 30 were collected. Hazard ratios (HRs) with 95% CIs associated with mortality were modelled using propensity-score-adjusted Cox proportional hazards regression analysis. Propensity-score-matched case-control studies were carried out. Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49-4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case-control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P = 0.037; and cefuroxime treatment (38%) versus dicloxacillin treatment (10%), P = 0.004. Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or dicloxacillin.

Chilo suppressalis and Sesamia inferens display different susceptibility responses to Cry1A insecticidal proteins.

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Li, Bo; Xu, Yangyang; Han, Cao; Han, Lanzhi; Hou, Maolin; Peng, Yufa

2015-10-01

Chilo suppressalis and Sesamia inferens are important lepidopteran rice pests that occur concurrently in rice-growing areas of China. The development of transgenic rice expressing Cry1A insecticidal proteins has provided a useful strategy for controlling these pests. This study evaluated the baseline susceptibilities of C. suppressalis and S. inferens to Cry1A, as well as their responses to selection with Cry1A. Wide geographic variation in susceptibility was observed across all field populations. Within a given population, the LC50 of both Cry1Ab and Cry1Ac against S. inferens was drastically higher than that of C. suppressalis. Large LC50 differences (74.6-fold) were detected between the two species for Cry1Ab in the Poyang population, while small differences (3.6-fold) were detected for Cry1Ac in the Changsha population. The Cry1Ac LC50 of C. suppressalis and S. inferens increased 8.4- and 4.4-fold after 21 and eight selection generations respectively. Additionally, the estimated realised heritabilities (h(2) ) of Cry1Ac tolerance were 0.11 in C. suppressalis and 0.292 in S. inferens. S. inferens exhibited a significantly lower susceptibility and more rapidly evolved resistance to Cry1A compared with C. suppressalis. Therefore, S. inferens is more likely to evolve increased resistance, which threatens the sustainability of rice expressing Cry1A protein. © 2014 Society of Chemical Industry.

Susceptibility to Food Advertisements and Sugar-Sweetened Beverage Intake in Non-Hispanic Black and Non-Hispanic White Adolescents.

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Cervi, Meredith M; Agurs-Collins, Tanya; Dwyer, Laura A; Thai, Chan L; Moser, Richard P; Nebeling, Linda C

2017-08-01

Obesity among adolescents in the United States has risen by 16% in the past 30 years. One important contributing factor may be the increased consumption of sugar sweetened beverages (SSBs), which is encouraged by advertisements for unhealthy foods and drinks that are targeted to adolescents. The purpose of this analysis was to determine the association between susceptibility to food and drink advertisements and sugar-sweetened beverage (SSB) consumption in non-Hispanic black (NHB) and non-Hispanic white (NHW) adolescents and to examine if BMI is associated with SSB consumption. Data were obtained from 765 NHB and NHW of ages 14-17 who were surveyed in the Family Life, Activity, Sun, Health, and Eating study sponsored by the National Cancer Institute. Two weighted adjusted logistic regression models were conducted. The first examined the associations of advertisement susceptibility, race, and BMI with SSB consumption. The second examined the associations of race and BMI with advertisement susceptibility. Adolescents with high advertisement susceptibility were more likely to consume at least one SSB daily (OR 1.73, 95% CI 1.21, 2.47). Additionally, non-Hispanic blacks were more likely to consume at least one SSB daily (OR 1.75, 95% CI 1.08, 2.85) and more likely to be highly susceptible to advertisements (OR 1.72, 95% CI 1.19, 2.48) than non-Hispanic whites. No significant associations were found between BMI and advertising susceptibility or BMI and daily SSB consumption. One approach to addressing the consumption of SSBs may be to reduce advertising that markets unhealthy food and beverages to adolescents and minorities.

Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility.

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Lin, Hsiu-Ling; Ueng, Kwo-Chang; Hsieh, Yih-Shou; Chiang, Whei-Ling; Yang, Shun-Fa; Chu, Shu-Chen

2012-09-01

Coronary artery disease (CAD) was the second leading cause of death during the last 3 years in Taiwan. Smooth muscle cells, monocytes/macrophages, and endothelial cells produce monocyte chemoattractant protein-1 (MCP-1) within atherosclerotic plaques following binding to the chemokine receptor-2 (CCR-2). Previous studies have well-documented the association between MCP-1 expression and susceptibility to, or clinicopathological features, of CAD. This study investigated the relationships between MCP-1-2518A/G and CCR-2-V64I genetic polymorphisms and CAD in the Taiwanese population. A total of 608 subjects, including 392 non-CAD controls and 216 patients with CAD, were recruited and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to evaluate the effects of these two polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR = 1.629; 95 % CI = 1.003-2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006-2.270), had a higher risk of CAD as compared with AA genotypes. Results also revealed that subjects with at least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD. G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518G could be through effects on atrial fibrillation in CAD patients.

Macrophage Migration Inhibitory Factor (MIF) Gene Promotor Polymorphism Is Associated with Increased Fibrosis in Biliary Atresia Patients, but Not with Disease Susceptibility.

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Sadek, Khaled H; Ezzat, Sameera; Abdel-Aziz, Samira A; Alaraby, Hanaa; Mosbeh, Asmaa; Abdel-Rahman, Mohamed H

2017-09-01

Two polymorphisms, rs755622 and rs5844572, in the promoter region of the macrophage migration inhibitory factor (MIF) gene influence the basal and/or induced transcriptional activity and have been linked to several inflammatory and autoimmune diseases. The aim of this study was to investigate the association between these two polymorphisms and disease susceptibility in patients with biliary atresia (BA). Allele frequencies of rs755622 and rs5844572 were assessed in 60 Egyptian infants with a confirmed diagnosis of BA. DNA was extracted from archival material. For the rs755622, samples were tested using Taqman real-time PCR, and for the rs5844572, samples were tested using fluorescence-based genotyping. The allele frequency in the general population was assessed in 141 healthy adults from the same geographical location. No statistical differences were observed in the allele frequencies of either rs755622 or rs5844572 between BA patients and controls. The homozygous and heterozygous short repeats (5/5, or 5/X) of rs5844572 were observed more frequently (16/28, 57.1%) in BA patients with mild to moderate fibrosis compared with those with marked fibrosis (10/32, 31.3%). The difference was statistically significant (P  =  0.032). In conclusion, we observed no association between MIF rs755622 and rs5844572 polymorphisms and susceptibility to BA; however, the rs5844572 could be linked to the rate of progression of the disease and extent of fibrosis. © 2017 John Wiley & Sons Ltd/University College London.

Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21.

Science.gov (United States)

Lamb, N E; Feingold, E; Savage, A; Avramopoulos, D; Freeman, S; Gu, Y; Hallberg, A; Hersey, J; Karadima, G; Pettay, D; Saker, D; Shen, J; Taft, L; Mikkelsen, M; Petersen, M B; Hassold, T; Sherman, S L

1997-09-01

Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non-disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.

Perceived susceptibility and self-protective behavior: a field experiment to encourage home radon testing

International Nuclear Information System (INIS)

Weinstein, N.D.; Sandman, P.M.; Roberts, N.E.

1991-01-01

Tested in a field experiment (N = 647) the hypothesis that perceptions of personal susceptibility are important in decisions to test one's home for radioactive radon gas. Experimental group subjects received a personal telephone call to tell them they lived in a high-risk area and a personal letter to reinforce the telephone message. After the intervention, experimental subjects were significantly more likely than minimal-treatment subjects to acknowledge the possibility of high radon levels in their homes. Perceptions of susceptibility and illness severity were significantly correlated with orders of radon test kits and with testing intentions. Nevertheless, there were no differences between groups in test orders or intentions. Results are discussed in terms of the difficulty of getting people to acknowledge susceptibility and the factors other than risk perceptions that influence self-protective behavior

Sinkhole Susceptibility Analysis for Karapinar/konya via Multi Criteria Decision

Science.gov (United States)

Sarı, F.

2017-11-01

Sinkholes are being a natural hazard which threads economic and human life. Sudden occurrence characteristic of sinkholes make it unable to escape. There are a lot of factor that activate sinkholes such as geology, irrigation, land use and human related factors. In Karapınar, Konya, there are over 200 sinkholes and this count is getting increased in recent years. Especially active agricultural lands, decreasing ground water level, extreme irrigation by 55267 water wells increase the risk factor of Karapınar. Nowadays, considering the economic contribution of Karapınar to Turkey economy in the field of agriculture, solar energy fields and thermal reactor which will be planned in next few years, prediction of sinkholes and searching for preventation ways are being more important issue. In this study, sinkhole susceptibility map via AHP was carried out for Karapınar in Konya. Slope, land use, elevation, geology, water wells, distance to roads and settlements criteria are included to determine susceptibility. The weights are calculated with AHP for each criterion and generated susceptibility map is overlapped with existing sinkholes. Suggestions and results are shared for this study.