La introducción de especies exóticas constituye una de las principales amenazas para la biodiversidad a nivel mundial. Spathodea campanulata es una especie arbórea cultivada como ornamental, cuyo ...néctar tóxico presenta propiedades con actividad insecticida, en especial contra abejas. En la Argentina se desconocen sus efectos sobre la entomofauna. Por lo tanto, este estudio explora los efectos de mortalidad causados por S. campanulata sobre la entomofauna nativa en un área verde de la ciudad de Corrientes. A partir del estudio de tres árboles se analizó el porcentaje de flores con especímenes de entomofauna muertos en su interior y se determinó la abundancia de los taxones representados. Se calcularon índices de diversidad, riqueza de especies, completitud del inventario y curva de rango abundancia. Los resultados indican que la abeja nativa Scaptotrigona jujuyensis presentó la mayor mortalidad, con un total de 46 ejemplares de un total de 151, entre los que se hallaron representantes de los órdenes Himenoptera, Diptera, Coleoptera, Hemiptera y Araneae. Este estudio exploratorio advierte que S. campanulata es una amenaza potencial para la entomofauna nativa en áreas urbanas.
El artículo consta de dos partes. En la primera se hace un rápido repaso de la actitud de la Iglesia ante el tema de la violencia, analizando de manera muy breve las distintas fases por las que ...atraviesa la institución en relación al tema, desde sus inicios al siglo XII, momento en que el fenómeno, debidamente integrado, alcanza plena justificación. En la segunda parte, centrada cronológicamente en esa misma centuria, se aborda el tema de los últimos vestigios de «pacifismo eclesiástico, analizados desde la perspectiva de la crítica a las Órdenes militares.
El presente artículo profundiza el estudio de los factores que influyen en el acceso a la justicia de las mujeres víctimas de violencia doméstica y las herramientas de programación de políticas ...públicas para garantizar el acceso a la justicia desarrolladas por la ONU-Mujeres. El objetivo es analizar las circunstancias situacionales y su relación con el derecho de acceso a la justicia en las mujeres víctimas de violencia doméstica. La metodología que se empleará será cualitativa, de lógica inductiva analítica. Las circunstancias situacionales presentes limitan la oportunidad de ejercer el derecho de acceso a la justicia en las mujeres en condiciones de igualdad en contraposición al principio de universalidad, para colocar en crisis la vigencia de este derecho fundamental.
Objectives We investigated whether reduced cardiovascular risk is more related to the progressive decrease of asleep or awake blood pressure. Background Independent studies have concluded that ...elevated sleep-time blood pressure is a better predictor of cardiovascular risk than awake or 24-h blood pressure means. However, the impact on cardiovascular risk of changes in these ambulatory blood pressure characteristics has not been properly investigated. Methods We prospectively studied 3,344 subjects (1,718 men and 1,626 women), 52.6 ± 14.5 years of age, during a median follow-up of 5.6 years. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. Blood pressure was measured for 48 h at baseline and again annually or more frequently (quarterly) if treatment adjustment was required. Results With data collected at baseline, when asleep blood pressure was adjusted by awake mean, only the former was a significant predictor of outcome in a Cox proportional hazards model also adjusted for sex, age, and diabetes. Analyses of changes in ambulatory blood pressure during follow-up revealed a 17% reduction in cardiovascular risk for each 5-mm Hg decrease in asleep systolic blood pressure mean (p < 0.001), independently of changes in any other ambulatory blood pressure parameter. Conclusions The sleep-time blood pressure mean is the most significant prognostic marker of cardiovascular morbidity and mortality. Most importantly, the progressive decrease in asleep blood pressure, a novel therapeutic target that requires proper patient evaluation by ambulatory monitoring, was the most significant predictor of event-free survival. (Prognostic Value of Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to Risk the MAPEC Study; NCT00295542 )
The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better ...cardiovascular disease (CVD) risk reduction.
In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome 0.55 (95% CI 0.50-0.61), P < 0.001 and each of its single components (P < 0.001 in all cases), i.e. CVD death 0.44 (0.34-0.56), myocardial infarction 0.66 (0.52-0.84), coronary revascularization 0.60 (0.47-0.75), heart failure 0.58 (0.49-0.70), and stroke 0.51 (0.41-0.63).
Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.
ClinicalTrials.gov, number NCT00741585.
Pharmacological activation of the hypothalamic glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is ...sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKD
). We also generated mice lacking Glp1r expression specifically in two GLP-1RA-responsive hypothalamic feeding nuclei/cell types, the paraventricular nucleus (GLP-1RKD
) and proopiomelanocortin neurons (GLP-1RKD
). Chow-fed GLP-1RKD
mice exhibited increased food intake and energy expenditure with no net effect on body weight. When fed a high-fat diet, these mice exhibited normal food intake but elevated energy expenditure, yielding reduced weight gain. None of these phenotypes were observed in GLP-1RKD
and GLP-1RKD
mice. The acute anorectic and glucose tolerance effects of peripherally dosed GLP-1RA exendin-4 and liraglutide were preserved in all mouse lines. Chronic liraglutide treatment reduced body weight in chow-fed GLP-1RKD
mice, but this effect was attenuated with high-fat diet feeding. In sum, classic homeostatic control regions are sufficient but not individually necessary for the effects of GLP-1RA on nutrient homeostasis.
Development of viral vectors capable of transducing photoreceptors by less invasive methods than subretinal injection would provide a major advancement in retinal gene therapy. We sought to develop ...novel AAV vectors optimized for photoreceptor transduction following intravitreal delivery and to develop methodology for quantifying this transduction in vivo. Surface exposed tyrosine (Y) and threonine (T) residues on the capsids of AAV2, AAV5 and AAV8 were changed to phenylalanine (F) and valine (V), respectively. Transduction efficiencies of self-complimentary, capsid-mutant and unmodified AAV vectors containing the smCBA promoter and mCherry cDNA were initially scored in vitro using a cone photoreceptor cell line. Capsid mutants exhibiting the highest transduction efficiencies relative to unmodified vectors were then injected intravitreally into transgenic mice constitutively expressing a Rhodopsin-GFP fusion protein in rod photoreceptors (Rho-GFP mice). Photoreceptor transduction was quantified by fluorescent activated cell sorting (FACS) by counting cells positive for both GFP and mCherry. To explore the utility of the capsid mutants, standard, (non-self-complementary) AAV vectors containing the human rhodopsin kinase promoter (hGRK1) were made. Vectors were intravitreally injected in wildtype mice to assess whether efficient expression exclusive to photoreceptors was achievable. To restrict off-target expression in cells of the inner and middle retina, subsequent vectors incorporated multiple target sequences for miR181, an miRNA endogenously expressed in the inner and middle retina. Results showed that AAV2 containing four Y to F mutations combined with a single T to V mutation (quadY-F+T-V) transduced photoreceptors most efficiently. Robust photoreceptor expression was mediated by AAV2(quadY-F+T-V) -hGRK1-GFP. Observed off-target expression was reduced by incorporating target sequence for a miRNA highly expressed in inner/middle retina, miR181c. Thus we have identified a novel AAV vector capable of transducing photoreceptors following intravitreal delivery to mouse. Furthermore, we describe a robust methodology for quantifying photoreceptor transduction from intravitreally delivered AAV vectors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pulmonary embolism response teams (PERTs) have emerged as a multidisciplinary, multispecialty team of experts in the care of highly complex symptomatic acute pulmonary embolism (PE), with a ...centralized unique activation process, providing rapid multimodality assessment and risk stratification, formulating the best individualized diagnostic and therapeutic approach, streamlining the care in challenging clinical case scenarios (e.g., intermediate–high risk and high‐risk PE), and facilitating the implementation of the recommended therapeutic strategies on time. PERTs are currently changing how complex acute PE cases are approached. The structure, organization, and function of a given PERT may vary from hospital to hospital, depending on local expertise, specific resources, and infrastructure for a given academic hospital center. Current emerging data demonstrate the value of PERTs in improving time to PE diagnosis; shorter time to initiation of anticoagulation reducing hospital length of stay; increasing use of advanced therapies without an increase in bleeding; and in some reports, decreasing mortality. Importantly, PERTs are positively impacting outcomes by changing the paradigm of care for acute PE through global adoption by the health‐care community.
Glucagon-like peptide-1 (GLP-1) receptor knockout (Glp1r(-/-)) mice exhibit impaired hepatic insulin action. High fat (HF)-fed Glp1r(-/-) mice exhibit improved, rather than the expected impaired, ...hepatic insulin action. This is due to decreased lipogenic gene expression and triglyceride accumulation. The present studies overcome these secondary adaptations by acutely modulating GLP-1R action in HF-fed wild-type mice. The central GLP-1R was targeted given its role as a regulator of hepatic insulin action. We hypothesized that acute inhibition of the central GLP-1R impairs hepatic insulin action beyond the effects of HF feeding. We further hypothesized that activation of the central GLP-1R improves hepatic insulin action in HF-fed mice. Insulin action was assessed in conscious, unrestrained mice using the hyperinsulinemic euglycemic clamp. Mice received intracerebroventricular (icv) infusions of artificial cerebrospinal fluid, GLP-1, or the GLP-1R antagonist exendin-9 (Ex-9) during the clamp. Intracerebroventricular Ex-9 impaired the suppression of hepatic glucose production by insulin, whereas icv GLP-1 improved it. Neither treatment affected tissue glucose uptake. Intracerebroventricular GLP-1 enhanced activation of hepatic Akt and suppressed hypothalamic AMP-activated protein kinase. Central GLP-1R activation resulted in lower hepatic triglyceride levels but did not affect muscle, white adipose tissue, or plasma triglyceride levels during hyperinsulinemia. In response to oral but not intravenous glucose challenges, activation of the central GLP-1R improved glucose tolerance. This was associated with higher insulin levels. Inhibition of the central GLP-1R had no effect on oral or intravenous glucose tolerance. These results show that inhibition of the central GLP-1R deteriorates hepatic insulin action in HF-fed mice but does not affect whole body glucose homeostasis. Contrasting this, activation of the central GLP-1R improves glucose homeostasis in HF-fed mice by increasing insulin levels and enhancing hepatic insulin action.
Pharmacological inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme potentiates incretin action and is widely used to treat type 2 diabetes. Nevertheless, the precise cells and tissues critical ...for incretin degradation and glucose homeostasis remain unknown. Here, we use mouse genetics and pharmacologic DPP4 inhibition to identify DPP4+ cell types essential for incretin action. Although enterocyte DPP4 accounted for substantial intestinal DPP4 activity, ablation of enterocyte DPP4 in Dpp4Gut−/− mice did not produce alterations in plasma DPP4 activity, incretin hormone levels, and glucose tolerance. In contrast, endothelial cell (EC)-derived DPP4 contributed substantially to levels of soluble plasma DPP4 activity, incretin degradation, and glucose control. Surprisingly, DPP4+ cells of bone marrow origin mediated the selective degradation of fasting GIP, but not GLP-1. Collectively, these findings identify distinct roles for DPP4 in the EC versus the bone marrow compartment for selective incretin degradation and DPP4i-mediated glucoregulation.
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•Endothelial-derived DPP4 controls the enteroinsular incretin axis•DPP4 expressed by hematopoietic cells selectively regulates cleavage of GIP•DPP4 in villin+ gut epithelium is dispensable for incretin-mediated glucoregulation
Mulvihill et al. show that, although a substantial amount of DPP4 is produced by enterocytes, it is the endothelial cell-derived DPP4 that contributes to plasma DPP4 activity and glucose metabolism. Unexpectedly, bone marrow-derived DPP4 selectively inactivates GIP but not GLP-1.
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