309 research outputs found

    Liver Cirrhosis Patients Homozygous for MTHFR C677T Develop Portal Vein Thrombosis 8 Years Earlier Than Wild Type

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    Background and Aim Age at portal vein thrombosis (PVT) in liver cirrhosis (LC) carriers of the methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C -> T667 transition) polymorphism has never been addressed; we compared age at PVT in LC patients genotyped for the MTHFR and explored the interrelated clinical and laboratory factors predicting age at PVT. Approach and Results Retrospective cross-sectional cohort study. PVT participants: MTHFR CC n = 36, MTHFR CT n = 53, MTHFR TT n = 19; age, sex, age at PVT, Child-Pugh score, rs1799963 PT polymorphisms (G -> A 20,210 transition), plasma HC and natural anticoagulants available for all participants. Age at PVT was lower in MTHFR TT than CT and CC (56 +/- 13 vs. 57 +/- 13 vs. 64 +/- 9 years, p = 0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [(17 (9.4, 23.3) vs 13 (8,14.7) vs 11 (8.9, 12.7) mu mol/l, p = 0.03)]. MTHFR TT, male gender and protein C predicted age at PVT (p = 0.02, p = 0.04 and p = 0.08); MTHFR TT and Child-Pugh score predicted plasma HC (p = 0.005 and p = 0.01) as well as low plasma protein C (p < 0.0001 and p = 0.0002). Plasma HC inversely related to protein C in the MTHFR TT group (p < 0.0001). Compound MTHFR TT with PT GA had lower age at PVT compared to MTHFR TT alone (49 +/- 18 vs 58 +/- 12 years). Conclusions MTHFR TT anticipates PVT associated with LC by an average of 8 years; MTHFR TT associates with severity of liver disease and to high plasma HC; the latter may contribute to the prematurity of PVT by interfering with the anticoagulant activity of protein C

    Antiphospholipid antibodies and heart failure with preserved ejection fraction. The multicenter athero-aps study

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    Background. The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. Methods. A prospective multicenter cohort study including 125 patients was conducted: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP > 220 pg/mL, left atrial (LA) enlargement, increased left ventricular filling pressure. Results. Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE. Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG > 40 GPL (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.09–10.77, p = 0.035), anti β-2-glycoprotein-I IgG > 40 GPL (OR 5.28, 1.53– 18.27, p = 0.009), lupus anticoagulants DRVVT > 1.25 (OR 5.20, 95% CI 1.10–24.68, p = 0.038), and triple positivity (OR 3.56, 95% CI 1.11–11.47, p = 0.033) were associated with HFpEF after adjustment for age and sex. By multivariate analysis, hypertension (OR 19.49, 95% CI 2.21–171.94, p = 0.008), age (OR 1.07, 95% CI 1.00–1.14, p = 0.044), and aβ2GPI IgG > 40 GPL (OR 8.62, 95% CI 1.23–60.44, p = 0.030) were associated with HFpEF. Conclusion. HFpEF is detectable in a relevant proportion of APS patients. The role of aPL in the pathogenesis and prognosis of HFpEF needs further investigation.publishersversionpublishe

    Intimate Partner Violence and Abuse Against Men: Voices of Victimization Among Ex-Servicemen of the British Armed Forces

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    This study presents the personal testimonies of male British ex-Armed Forces personnel who have experienced violence and abuse victimization that was perpetrated by civilian female partners. In this research, we argue that to embark upon any understanding of the domestic lives of military personnel, an appreciation of the linkages to the cultural context of the military institution is necessary. Understanding the influence of the military institution beyond the military domain is crucial. We unveil the nature and character of the violence and abuse and how the servicemen negotiated their relationships. In doing so, we highlight the embodiment of military discipline, skills, and tactics in the home—not ones of violence which may be routinely linked to military masculinities; rather ones of restraint, tolerance, stoicism, and the reduction of a threat to inconsequential individual significance

    Neonicotinoid seed treatments of soybean provide negligible benefits to US farmers

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    Neonicotinoids are the most widely used insecticides worldwide and are typically deployed as seed treatments (hereafter NST) in many grain and oilseed crops, including soybeans. However, there is a surprising dearth of information regarding NST effectiveness in increasing soybean seed yield, and most published data suggest weak, or inconsistent yield benefit. The US is the key soybean-producing nation worldwide and this work includes soybean yield data from 194 randomized and replicated field studies conducted specifically to evaluate the effect of NSTs on soybean seed yield at sites within 14 states from 2006 through 2017. Here we show that across the principal soybean-growing region of the country, there are negligible and management-specific yield benefits attributed to NSTs. Across the entire region, the maximum observed yield benefits due to fungicide (FST = fungicide seed treatment) + neonicotinoid use (FST + NST) reached 0.13 Mg/ha. Across the entire region, combinations of management practices affected the effectiveness of FST + N ST to increase yield but benefits were minimal ranging between 0.01 to 0.22 Mg/ha. Despite widespread use, this practice appears to have little benefit for most of soybean producers; across the entire region, a partial economic analysis further showed inconsistent evidence of a break-even cost of FST or FST + N ST. These results demonstrate that the current widespread prophylactic use of NST in the key soybean-producing areas of the US should be re-evaluated by producers and regulators alike

    Neonicotinoid seed treatments of soybean provide negligible benefits to US farmers

    Get PDF
    Neonicotinoids are the most widely used insecticides worldwide and are typically deployed as seed treatments (hereafter NST) in many grain and oilseed crops, including soybeans. However, there is a surprising dearth of information regarding NST effectiveness in increasing soybean seed yield, and most published data suggest weak, or inconsistent yield benefit. The US is the key soybean-producing nation worldwide and this work includes soybean yield data from 194 randomized and replicated field studies conducted specifically to evaluate the effect of NSTs on soybean seed yield at sites within 14 states from 2006 through 2017. Here we show that across the principal soybean-growing region of the country, there are negligible and management-specific yield benefits attributed to NSTs. Across the entire region, the maximum observed yield benefits due to fungicide (FST = fungicide seed treatment) + neonicotinoid use (FST + NST) reached 0.13 Mg/ha. Across the entire region, combinations of management practices affected the effectiveness of FST + N ST to increase yield but benefits were minimal ranging between 0.01 to 0.22 Mg/ha. Despite widespread use, this practice appears to have little benefit for most of soybean producers; across the entire region, a partial economic analysis further showed inconsistent evidence of a break-even cost of FST or FST + N ST. These results demonstrate that the current widespread prophylactic use of NST in the key soybean-producing areas of the US should be re-evaluated by producers and regulators alike

    Rates of age- and amyloid β-associated cortical atrophy in older adults with superior memory performance

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    Introduction: Superior cognitive performance in older adults may reflect underlying resistance to age-associated neurodegeneration. While elevated amyloid b (Ab) deposition (Ab1) has been associated with increased cortical atrophy, it remains unknown whether “SuperAgers” may be protected from Ab-associated neurodegeneration. Methods: Neuropsychologically defined SuperAgers (n 5 172) and cognitively normal for age (n 5 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Ab status. Results: Of the case-matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Ab1. Rates of age- and Ab-associated atrophy did not differ between the groups on any measure. Ab2 individuals displayed the slowest rates of atrophy. Discussion: Maintenance of superior memory in late life does not reflect resistance to age- or Abassociated atrophy. However, those individuals who reached old age without cognitive impairment nor elevated Ab deposition (i.e. Ab2) displayed reduced rates of cortical atrophy

    A New Highly Conserved Antibiotic Sensing/Resistance Pathway in Firmicutes Involves an ABC Transporter Interplaying with a Signal Transduction System

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    Signal transduction systems and ABC transporters often contribute jointly to adaptive bacterial responses to environmental changes. In Bacillus subtilis, three such pairs are involved in responses to antibiotics: BceRSAB, YvcPQRS and YxdJKLM. They are characterized by a histidine kinase belonging to the intramembrane sensing kinase family and by a translocator possessing an unusually large extracytoplasmic loop. It was established here using a phylogenomic approach that systems of this kind are specific but widespread in Firmicutes, where they originated. The present phylogenetic analyses brought to light a highly dynamic evolutionary history involving numerous horizontal gene transfers, duplications and lost events, leading to a great variety of Bce-like repertories in members of this bacterial phylum. Based on these phylogenetic analyses, it was proposed to subdivide the Bce-like modules into six well-defined subfamilies. Functional studies were performed on members of subfamily IV comprising BceRSAB from B. subtilis, the expression of which was found to require the signal transduction system as well as the ABC transporter itself. The present results suggest, for the members of this subfamily, the occurrence of interactions between one component of each partner, the kinase and the corresponding translocator. At functional and/or structural levels, bacitracin dependent expression of bceAB and bacitracin resistance processes require the presence of the BceB translocator loop. Some other members of subfamily IV were also found to participate in bacitracin resistance processes. Taken together our study suggests that this regulatory mechanism might constitute an important common antibiotic resistance mechanism in Firmicutes. [Supplemental material is available online at http://www.genome.org.
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