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Increased afterload results in ‘pathological’ cardiac hypertrophy, the most important risk factor for the development of heart failure. Current in vitro models fall short in deciphering the mechanisms of hypertrophy induced by afterload enhancement. The aim of this study was to develop an experimental model that allows investigating the impact of afterload enhancement (AE) on work-performing heart muscles in vitro. Fibrin-based engineered heart tissue (EHT) was cast between two hollow elastic silicone posts in a 24-well cell culture format. After 2?weeks, the posts were reinforced with metal braces, which markedly increased afterload of the spontaneously beating EHTs. Serum-free, triiodothyronine-, and hydrocortisone-supplemented medium conditions were established to prevent undefined serum effects. Control EHTs were handled identically without reinforcement. Endothelin-1 (ET-1)- or phenylephrine (PE)-stimulated EHTs served as positive control for hypertrophy. Cardiomyocytes in EHTs enlarged by 28.4?% under AE and to a similar extent by ET-1- or PE-stimulation (40.6 or 23.6?%), as determined by dystrophin staining. Cardiomyocyte hypertrophy was accompanied by activation of the fetal gene program, increased glucose consumption, and increased mRNA levels and extracellular deposition of collagen-1. Importantly, afterload-enhanced EHTs exhibited reduced contractile force and impaired diastolic relaxation directly after release of the metal braces. These deleterious effects of afterload enhancement were preventable by endothelin-A, but not endothelin-B receptor blockade. Sustained afterload enhancement of EHTs alone is sufficient to induce pathological cardiac remodeling with reduced contractile function and increased glucose consumption. The model will be useful to investigate novel therapeutic approaches in a simple and fast manner.  相似文献   
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Background

Alcohol misuse is associated with increased human immunodeficiency virus sexual risk behaviors by women. Drug use, intimate partner violence (IPV), and depressive symptoms frequently co-occur, are well-recognized alcohol misuse comorbidities, and may interact to increase risk behaviors. Using a syndemic framework we examined associations between drug use, IPV, and depressive symptoms and sexual risk behaviors by 400 women with alcohol misuse attending an urban sexually transmitted infections clinic.

Methods

Participants completed computer-assisted interviews querying drug use, IPV, and depressive symptoms and sexual risk behavior outcomes—unprotected sex under the influence of alcohol, sex for drugs/money, and number of lifetime sexual partners. We used multivariable analysis to estimate prevalence ratios (PR) for independent and joint associations between drug use, IPV, and depressive symptoms and our outcomes. To investigate synergy between risk factors we calculated the relative excess prevalence owing to interaction for all variable combinations.

Results

In multivariable analysis, drug use, IPV, and depressive symptoms alone and in combination were associated with higher prevalence/count of risk behaviors compared with women with alcohol misuse alone. The greatest prevalence/count occurred when all three were present (unprotected sex under the influence of alcohol [PR, 2.6; 95% confidence interval, 1.3–4.9]), sex for money or drugs [PR, 2.6; 95% confidence interval, 1.7–4.2], and number of lifetime partners [PR, 3.2; 95% confidence interval, 1.9–5.2]). Drug use, IPV, and depressive symptoms did not interact synergistically to increase sexual risk behavior prevalence.

Conclusions

A higher prevalence of sexual risk behaviors by women with alcohol misuse combined with drug use, IPV, and depressive symptoms supports the need for alcohol interventions addressing these additional comorbidities.  相似文献   
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Background

In every anatomic lung resection operation, the pulmonary artery itself or its branches must be sealed. This involves either stapling or ligating the vessels. Based on the positive results with the bipolar vessel sealing ≤7 mm in abdominal surgery the present study aimed to evaluate burst pressures of the pulmonary artery after sealing with the sealing instrument SealSafe G3 (Gebrüder Martin & CoKG, Tuttlingen, Germany).

Material and methods

The whole pulmonary artery above the pulmonary valve was exposed up to the periphery of the left lung in freshly removed pig heart–lung blocks. A pressure-measuring cylinder was then implanted in the prepared vessel on the side at the main trunk of the pulmonary artery to determine the pressure in the vessel. After either ligation or bipolar sealing of the pulmonary artery, the pneumatic burst pressure (millimeters of mercury) was determined in a water bath. Three groups (n = 12 for each seal type) with different vessel diameters were examined: group 1: 0–6 mm, group 2: 7–12 mm, and group 3: >12 mm. In all cases, vessel sealing was performed with a MARSEAL 5 instrument (Gebrüder Martin & Co KG, Tuttlingen, Germany) and the SealSafe G3 current. The mean burst pressures of the individual groups (ligature and bipolar sealing) were compared using two-tailed, nonparametric Mann–Whitney U test. Significance was defined as P < 0.05.

Results

The mean burst pressures in group 1 were measured by 340 ± 13.4 mm Hg with ligature and 205 ± 44.4 mm Hg with bipolar sealing (P < 0.001). In group 2, the mean values obtained were 270 ± 28.2 mm Hg for ligature and 162 ± 36.0 mm Hg for bipolar sealing (P < 0.001). In group 3, the mean burst pressures for bipolar sealing were only 52.1 ± 15.1 mm Hg, whereas those for ligated vessels were 253 ± 46.9 mm Hg (P < 0.001). For this size of vessel the burst pressure was also determined after stapling. The mean value in this case was 230 ± 21.8 mm Hg.

Conclusions

In all groups, the mean burst pressures after bipolar sealing were significantly lower than those achieved with ligation, but they were sufficient for a save closure of the pulmonary artery with diameters up to 12 mm.  相似文献   
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Owing to the high activity and low-cost, copper-based catalysts are promising candidates for transforming aromatic halides to yield phenols. In this work, we report the selective hydroxylation of aromatic iodides to produce phenols using an atomically dispersed copper catalyst (Cu–ZnO–ZrO2) under mild reaction conditions. The reactions were conducted without the use of additional organic ligands, and the protection of an inert atmosphere environment is not required. The catalyst can be easily prepared, scalable, and is very efficient for a wide range of substrates. The catalytic reactions can be carried out with only 1.24 mol% Cu loading, which shows great potential in mass production.

Atomically dispersed Cu catalyst was designed for highly efficient hydroxylation of aryl iodides under mild conditions.  相似文献   
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In 2015, the United Nations adopted the Sustainable Development Goals, which include fostering gender equality and women's empowerment and ending hunger and malnutrition. To monitor progress and evaluate programmes that aim to achieve these goals, survey instruments are needed that can accurately assess related indicators. The project‐level Women's Empowerment in Agriculture Index (pro‐WEAI) is being developed to address the need for an instrument that is sensitive to changes in empowerment over the duration of an intervention. The pro‐WEAI includes new modules with previously untested survey questions, including a health and nutrition module (focused on women's agency in this area) and an intrahousehold relationships module. This study uses cognitive interviewing to identify how new survey questions might be misinterpreted and to understand what experiences women are referencing when they respond to these questions. This was undertaken with the goal of informing revision to the modules. The study was conducted in Bangladesh with women from nuclear, extended, and migrant‐sending households and from two regions of the country to identify difficulties with interpretation and response formulation across these groups. Findings revealed that questions were generally understood, but participants occasionally responded to the wrong part of the question, did not understand key phrases, or were uncomfortable with questions. The findings also suggested ways to revise the modules and strengthen the pro‐WEAI. The revised pro‐WEAI health and nutrition and intrahousehold relationships modules will advance the ability to measure changes in these domains and their relationship with the health and nutritional status of women and their children.  相似文献   
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