Impact of metabolic perturbation on ovarian function

Metabolic perturbations including hyperinsulinemia that are induced during obesity and heat stress in humans and production animals are allied with several health hallmarks and impaired fertility. This dissertation research focused on charactering the impact of changes to central metabolism on ovarian function. We hypothesized that hyperinsulinemia induced during central metabolic perturbations, alters ovarian insulin-mediated PI3K signaling, negatively impacting ovarian folliculogenesis, steroidogenesis and xenobiotic biotransformation. To test this hypothesis, mRNA and protein expression profiles of insulin, PI3K, steroidogenic, inflammatory and chemical metabolism members were quantified using qRT-PCR, Western blotting or immunohistochemistry techniques using three models of hyperinsulinemia: 1) high fat diet (HFD)-induced obesity, 2) a transgenic mouse model of progressive obesity and 3) a porcine model of hyperinsulinemia. Overall, our data demonstrates that the ovarian insulin-KITLG-KIT-AKT signaling pathway is active and upregulated during central metabolic alterations. Perturbations to ovarian insulin-KITLG-KIT-AKT signaling pathway are likely to impact 1) follicle activation, oocyte viability and recruitment, 2) steroid hormone biosynthesis, and 3) xenobiotic biotransformation, potentially accelerating susceptibility to chemical exposure. All of these scenarios could lead to impairment of ovarian function, and may at least partially explain why female fecundity is compromised during altered metabolic states

Eficacia del procedimiento especial de desalojo con intervención notarial en los contratos de arrendamiento, Arequipa - 2020

La investigación sobre la Eficacia del procedimiento especial de desalojo con intervención notarial en los contratos de arrendamiento, Arequipa - 2020, es un reto desafiante porque aborda una realidad importante de la sociedad peruana: desde el punto de vista procesal, esto es la celeridad de los trámites de desalojo, ¿qué eficacia tiene para el arrendador y el arrendatario el proceso notarial de desalojo en los casos de arrendamiento? La presente investigación jurídica-procesal, aborda esta problemática desde un análisis del desalojo en su vertiente procesal y sobre los contratos de arrendamiento. Debe tenerse en cuenta que, para dicho objetivo investigador, se ha tenido en cuenta la doctrina jurídica que se desprende o infiere de la legislación vigente, la jurisprudencia vinculante y la doctrina de autores. Todo ello, reforzado por los instrumentos de investigación como son la encuesta y entrevista realizado a las principales Notarías Públicas del cercado de la ciudad de Arequipa y el análisis del expediente notarial sobre desalojo Nº 0328-2020-PNC. En este sentido, las principales conclusiones a las que ha llegado la presente investigación consiste en que la ley materia de investigación tiene como objetivo la celeridad y su eficacia se evidencia en el expediente notarial que se analiza en la investigación. La eficacia deficiente se evidencia en que los ciudadanos no acuden a desalojo notarial, además de los gastos económicos que supone. Todo ello, nos lleva a proponer una serie de recomendaciones como la necesidad de conceder facultades a los Notarios Públicos para el lanzamiento luego del Acta que ordena el desalojo y revisión a los costos económicos que supone el trámite de desalojo notarial.Campus Arequip

Effect of intermittent pneumatic compression on disability, living circumstances, quality of life, and hospital costs after stroke: secondary analyses from CLOTS 3, a randomised trial

Background The results of the CLOTS 3 trial showed that intermittent pneumatic compression (IPC) reduced the risk of deep vein thrombosis and improved survival in immobile patients with stroke. IPC is now being widely used in stroke units. Here we describe the disability, living circumstances, quality of life, and hospital costs of patients in CLOTS 3. Methods In CLOTS 3, a parallel group trial in 94 UK hospitals, immobile patients with stroke from days 0 to 3 of admission were assigned with a computer-generated allocation sequence in a 1:1 ratio to IPC or no IPC through a central randomisation system. We followed up patients at about 6 months with postal or telephone questionnaire to assess the secondary endpoints: disability (Oxford Handicap Scale [OHS]), living circumstances, health-related quality of life (EQ5D-3L), and hospital costs (based on use of IPC and length of hospital stay). Patients and carers who completed the postal questionnaires were not masked to treatment allocation, but telephone follow-up in non-responders was masked. All analyses were by intention to treat. This trial is registered, number ISRCTN93529999. Findings Between Dec 8, 2008, and Sept 6, 2012, we enrolled 2876 patients, with 1438 in each group. Despite the previously reported reduction in the risk of proximal deep vein thrombosis at 30 days (primary endpoint), there were no significant differences in disability (OHS 0–2 vs 3–6, adjusted odds ratio [OR] 0·98, 95% CI 0·80 to 1·19, p=0·83; adjusted ordinal analysis common OR 0·97, 95% CI 0·86 to 1·11), living circumstances (institutional care vs not; adjusted OR 1·11, 95% CI 0·89 to 1·37; p=0·358), or health-related quality of life (median utility value 0·26, IQR −0·07 to 0·66 with IPC, and 0·27, −0·06 to 0·64, with no IPC; p=0·952). The estimated cost of IPC was £64·10 per patient (SD 28·3). The direct costs of preventing a deep vein thrombosis and death were £1282 (95% CI 785 to 3077) and £2756 (1346 to not estimable), respectively, with IPC. Hospital costs increased by £451 with IPC compared with no IPC because of a longer stay in hospital (mean 44·5 days [SD 37·6] vs 42·8 days [37·2]; mean difference 1·8 days, 95% CI −1·0 to 4·5). By 6 months, despite an increase in survival (IPC 152·5 days [SD 60·6] vs no IPC 148·1 days [64·3]; mean difference 4·5 days, 95% CI −0·2 to 9·1), there was a non-significant increase in quality-adjusted survival associated with IPC (IPC 27·6 days [SD 40·6] vs no IPC 26·7 days [39·6]; mean difference 0·9 days, 95% CI −2·1 to 3·9). Interpretation IPC is inexpensive, prevents deep vein thrombosis, improves survival but not functional outcomes, and does not lead to a significant gain in quality-adjusted survival. When deciding whether to treat patients with IPC, clinicians need to take into account all these potential effects. Funding National Institute of Health Research Health Technology Assessment Programme, Chief Scientist Office of Scottish Government, and Covidien

Venous thromboembolism prevention in intracerebral hemorrhage: A systematic review and network meta-analysis

IntroductionTo summarize and compare the effectiveness of pharmacological thromboprophylaxis to pneumatic compression devices (PCD) for the prevention of venous thromboembolism in patients with acute intracerebral hemorrhage.MethodsMEDLINE, PUBMED, EMBASE, and CENTRAL were systematically searched to identify randomized and non-randomized studies that compared each intervention directly to each other or against a common control (hydration, anti-platelet agents, stockings) in adults with acute spontaneous intracerebral hemorrhage. Two investigators independently screened the studies, extracted data, and appraised risk of bias. Studies with a high risk of bias were excluded from our final analysis. The primary outcome was the occurrence of venous thromboembolism (proximal deep vein thrombosis or pulmonary embolism) in the first 30 days.Results8,739 articles were screened; four articles, all randomized control trials, met eligibility criteria. Bayesian network meta-analysis was performed to calculate risk estimates using both fixed and random effects analyses. 607 patients were included in the network analysis. PCD were associated with a significant decrease in venous thromboembolism compared to control (OR: 0.43, 95% Credible Limits [CrI]: 0.23-0.80). We did not find evidence of statistically significant differences between pharmacological thromboprophylaxis and control (OR: 0.93, 95% CrI: 0.19-4.37) or between PCD and pharmacological thromboprophylaxis (OR: 0.47, 95% CrI: 0.09-2.54).ConclusionPCDs are superior to control interventions, but meaningful comparisons with pharmacotherapy are not possible due to a lack of data. This requires further exploration via large pragmatic clinical trials.Trial registrationPROSPERO: CRD42018090960

The Empirical Landscape of Trade Policy

This chapter surveys empirically the broad features of trade policy in goods for 31 major economies that collectively represented 83 percent of the world's population and 91 percent of the world's GDP in 2013. We address five questions: Do some countries have more liberal trading regimes than others? Within countries, which industries receive the most import protection? How do trade policies change over time? Do countries discriminate among their trading partners when setting trade policy? Finally, how liberalized is world trade? Our analysis documents the extent of cross-sectional heterogeneity in applied commercial policy across countries, their economic sectors, and their trading partners, over time. We conclude that substantial trade policy barriers remain as an important feature of the world economy.antidumpin

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p> <p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p> <p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p> <p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p&gt

Construction of chromosome segment substitution lines in peanut (Arachis hypogaea L.) using a wild synthetic and QTL mapping for plant morphology

Chromosome segment substitution lines (CSSLs) are powerful QTL mapping populations that have been used to elucidate the molecular basis of interesting traits of wild species. Cultivated peanut is an allotetraploid with limited genetic diversity. Capturing the genetic diversity from peanut wild relatives is an important objective in many peanut breeding programs. In this study, we used a marker-assisted backcrossing strategy to produce a population of 122 CSSLs from the cross between the wild synthetic allotetraploid (A. ipae¨nsis6A. duranensis)4x and the cultivated Fleur11 variety. The 122 CSSLs offered a broad coverage of the peanut genome, with target wild chromosome segments averaging 39.2 cM in length. As a demonstration of the utility of these lines, four traits were evaluated in a subset of 80 CSSLs. A total of 28 lines showed significant differences from Fleur11. The line6trait significant associations were assigned to 42 QTLs: 14 for plant growth habit, 15 for height of the main stem, 12 for plant spread and one for flower color. Among the 42 QTLs, 37 were assigned to genomic regions and three QTL positions were considered putative. One important finding arising from this QTL analysis is that peanut growth habit is a complex trait that is governed by several QTLs with different effects. The CSSL population developed in this study has proved efficient for deciphering the molecular basis of trait variations and will be useful to the peanut scientific community for future QTL mapping studies. (Résumé d'auteur

Construction of chromosome segmen substitution lines in peanut (Arachis hypogaea L.) using a wild synthetic and QTL mapping for plant morphology.

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Plasma homocysteine and the risk of venous thromboembolism: insights from the FIELD study

Background The lipid-lowering effect of fenofibrate is accompanied by a rise in plasma homocysteine, a potential risk factor for venous thromboembolism (VTE). This study investigated the relationship between homocysteine and the risk of VTE in patients treated with fenofibrate. Methods and results The relationship between homocysteine and deep-vein thrombosis or pulmonary embolism was investigated in 9522 participants of the 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. All subjects received fenofibrate during a 6-week active run-in phase before randomization. A Cox proportional-hazards model was used to assess the effect of homocysteine on risk of venous thromboembolic events. During active-drug run-in, homocysteine rose on average by 6.5 μmol/L, accompanied by a substantial rise in plasma creatinine (+12%). Fenofibrate-induced changes in homocysteine and creatinine were fully reversible in the placebo group but persisted in the treatment group until reversing at the end of therapy. During follow-up, 1.8% had at least one episode of deep-vein thrombosis or pulmonary embolism: 103 on fenofibrate and 68 on placebo (log-rank P=0.006). In multivariate analysis, every 5 µmol/L higher baseline homocysteine was associated with 19% higher risk of VTE. Fenofibrate treatment was associated with 52% higher risk, but the change in homocysteine with fenofibrate was not significantly associated with VTE after adjustment for baseline homocysteine. Conclusions Hyperhomocysteinemia is prospectively associated with VTE. Fenofibrate may predispose individuals with high pretreatment homocysteine towards VTE. The fenofibrate-induced increase in homocysteine did not, however, explain the risk associated with fenofibrate therapy