317 research outputs found

    Autophagy contributes to BMP type 2 receptor degradation and development of pulmonary arterial hypertension

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    Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure which almost invariably leads to right heart failure and premature death. More than 70% of familial PAH and 20% of idiopathic PAH patients carry heterozygous mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2). However, the incomplete penetrance of BMPR2 mutations suggests that other genetic and environmental factors contribute to the disease. In the current study, we investigate the contribution of autophagy in the degradation of BMPR2 in pulmonary vascular cells. We demonstrate that endogenous BMPR2 is degraded through the lysosome in primary human pulmonary artery endothelial (PAECs) and smooth muscle cells (PASMCs): two cell types that play a key role in the pathology of the disease. By means of an elegant HaloTag system, we show that a block in lysosomal degradation leads to increased levels of BMPR2 at the plasma membrane. In addition, pharmacological or genetic manipulations of autophagy allow us to conclude that autophagy activation contributes to BMPR2 degradation. It has to be further investigated whether the role of autophagy in the degradation of BMPR2 is direct or through the modulation of the endocytic pathway. Interestingly, using an iPSC‐derived endothelial cell model, our findings indicate that BMPR2 heterozygosity alone is sufficient to cause an increased autophagic flux. Besides BMPR2 heterozygosity, pro‐inflammatory cytokines also contribute to an augmented autophagy in lung vascular cells. Furthermore, we demonstrate an increase in microtubule‐associated protein 1 light chain 3 beta (MAP1LC3B) levels in lung sections from PAH induced in rats. Accordingly, pulmonary microvascular endothelial cells (MVECs) from end‐stage idiopathic PAH patients present an elevated autophagic flux. Our findings support a model in which an increased autophagic flux in PAH patients contributes to a greater decrease in BMPR2 levels. Altogether, this study sheds light on the basic mechanisms of BMPR2 degradation and highlights a crucial role for autophagy in PAH. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

    A new estimate of carbon for Bangladesh forest ecosystems with their spatial distribution and REDD+ implications

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    In tropical developing countries, reducing emissions from deforestation and forest degradation (REDD+) is becoming an important mechanism for conserving forests and protecting biodiversity. A key prerequisite for any successful REDD+ project, however, is obtaining baseline estimates of carbon in forest ecosystems. Using available published data, we provide here a new and more reliable estimate of carbon in Bangladesh forest ecosystems, along with their geo-spatial distribution. Our study reveals great variability in carbon density in different forests and higher carbon stock in the mangrove ecosystems, followed by in hill forests and in inland Sal (Shorea robusta) forests in the country. Due to its coverage, degraded nature, and diverse stakeholder engagement, the hill forests of Bangladesh can be used to obtain maximum REDD+ benefits. Further research on carbon and biodiversity in under-represented forest ecosystems using a commonly accepted protocol is essential for the establishment of successful REDD+ projects and for the protection of the country’s degraded forests and for addressing declining levels of biodiversity

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Assessing vulnerability for inhabitants of Dhaka City considering flood-hazard exposure

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    Globalna opasnost od poplave postupno se povećava. Iako ih je nemoguće izbjeći, gubici i šteta od opasnosti (npr. poplave, cikloni i potresi) mogu se učinkovito smanjiti smanjenjem ranjivosti kućanstava odgovarajućim mjerama. Cilj ove studije je kvantitativno mjerenje ranjivosti kućanstava obzirom na opasnosti od poplave kao alata za njihovo ublažavanje. Također je predložen jedinstveni pristup za kvantificiranje ugroženosti kućanstava obzirom na opasnosti od poplave, a kao primjer predstavljena je primjena u gradu Dhaki sklonom poplavama. Podaci su prikupljeni i sa siromašnih i bogatih područja kako bi bilo pokriveno cijelo urbano područje te kako bi se usporedila razina ugroženosti od poplava. Ukupno 300 kućanstava anketirano je strukturiranim upitnikom na temelju pet čimbenika (ekonomskih, socijalnih, okolišnih, strukturnih i institucionalnih) ugroženosti od poplava. Analitički hijerarhijski postupak (AHP) primijenjen je za mjerenje pojedinačnih rezultata ranjivosti kućanstva korištenjem relativne težine varijabli i pokazatelja uz pravilnu standardizaciju. Analitički rezultati pokazali su da je 63,06% siromašnih kućanstava i 20,02% bogatih kućanstava vrlo osjetljivo na poplave. Uz to, ovaj je rad utvrdio i procijenio čimbenike odgovorne za ranjivost kućanstava u Dhaki. Što se tiče strukturne ranjivosti, rezultati su pokazali da je 82% kućanstava u siromašnim krajevima bilo visoko ranjivo, a 95,3% kućanstava koja nisu iz siromašnih četvrti bilo je umjereno ranjivo. Društveno, 67,3% siromašnih i 78,7% kućanstava koja nisu iz siromašnih naselja bila su umjereno i slabo ranjiva. Većina kućanstava u siromašnoj i nesiromašnoj četvrti (84%, odnosno 59,3%) pokazala je visoku i umjerenu ekonomsku ranjivost. Štoviše, za 69,3% siromašnih i 65,3% nesiromašnih kućanstava institucionalna ranjivost je bila visoka. Od stanovnika siromašnih naselja, 63,3% je bilo izloženo ekološkom riziku, a 78% staništa koja nisu u siromašnim područjima bilo je u kategoriji niske ranjivosti. Uz odgovarajuću prilagodbu ovdje predložen učinkoviti alat za mjerenje ranjivosti koji je ovdje prilagođen specifičnoj lokaciji, primjenjiv je i za mjerenje ranjivosti drugih gradova u svijetu. Na temelju ove studije moglo bi se provesti buduće istraživanje s više čimbenika, varijabli i pokazatelja ljudske ranjivosti na prirodne ili umjetne opasnosti / katastrofe. Budući rad mogao bi pružiti bolju sliku stanja ranjivosti od pojedinačne / višestruke opasnosti / katastrofe.Global flood hazard is gradually increasing. Though it is impossible to avoid them, losses and damage of hazards (e.g., floods, cyclones, and earthquakes) could be efficiently reduced by reducing household vulnerability with appropriate measures. This study aims to quantitatively measure the household vulnerability of flood hazards as a mitigation tool. It also proposed a unique approach to quantify flood-hazard household vulnerability, and shows its application in the flood prone city of Dhaka as an example case. Data were collected from both slum and non-slum areas to cover the entire urban habitat, and to compare their level of flood vulnerability. A total of 300 households were surveyed by structured questionnaire on the basis of five factors (economic, social, environmental, structural, and institutional) of flood vulnerability. The analytical hierarchy process (AHP) was applied to measure individual household vulnerability scores by using the relative weightage of variables and indicators with proper standardisation. Analytical results demonstrated that 63.06% slum and 20.02% non-slum households were highly vulnerable to floods. In addition, this paper determined and assessed responsible factors for household flood vulnerability in Dhaka. For structural vulnerability, results exhibited that 82% of slum households were highly vulnerable, and 95.3% of non-slum households were moderately vulnerable. Socially, 67.3% of slum and 78.7% of non-slum households were moderately and low-vulnerable. The majority of slum and non-slum households (84% and 59.3%, respectively) showed high and moderate vulnerability with respect to economic vulnerability. Moreover, 69.3% of slum and 65.3% of nonslum household institutional vulnerability levels were high. Of slum inhabitants, 63.3% were environmentally at high risk, and 78% of non-slum habitats were in the low-vulnerability category. However, as an effective tool to measure location-specific vulnerability, it is applicable for the measuring vulnerability of other cities in the world with proper customisation. On the basis of this study, future research could be conducted with more factors, variables, and indicators of human vulnerability to natural or artificial hazards/disasters. Future work may provide a better reflection of the vulnerability status of single/multiple hazard(s)/disaster(s)

    The prevalence of adaptive immunity to COVID-19 and reinfection after recovery - a comprehensive systematic review and meta-analysis.

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    This study aims to estimate the prevalence and longevity of detectable SARS-CoV-2 antibodies and T and B memory cells after recovery. In addition, the prevalence of COVID-19 reinfection and the preventive efficacy of previous infection with SARS-CoV-2 were investigated. A synthesis of existing research was conducted. The Cochrane Library, the China Academic Journals Full Text Database, PubMed, and Scopus, and preprint servers were searched for studies conducted between 1 January 2020 to 1 April 2021. Included studies were assessed for methodological quality and pooled estimates of relevant outcomes were obtained in a meta-analysis using a bias adjusted synthesis method. Proportions were synthesized with the Freeman-Tukey double arcsine transformation and binary outcomes using the odds ratio (OR). Heterogeneity was assessed using the I and Cochran's Q statistics and publication bias was assessed using Doi plots. Fifty-four studies from 18 countries, with around 12,000,000 individuals, followed up to 8 months after recovery, were included. At 6-8 months after recovery, the prevalence of SARS-CoV-2 specific immunological memory remained high; IgG - 90.4% (95%CI 72.2-99.9, I = 89.0%), CD4+ - 91.7% (95%CI 78.2-97.1y), and memory B cells 80.6% (95%CI 65.0-90.2) and the pooled prevalence of reinfection was 0.2% (95%CI 0.0-0.7, I = 98.8). Individuals previously infected with SARS-CoV-2 had an 81% reduction in odds of a reinfection (OR 0.19, 95% CI 0.1-0.3, I = 90.5%). Around 90% of recovered individuals had evidence of immunological memory to SARS-CoV-2, at 6-8 months after recovery and had a low risk of reinfection

    Effects of rapid urbanisation on the urban thermal environment between 1990 and 2011 in Dhaka Megacity, Bangladesh

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    This study investigates the influence of land-use/land-cover (LULC) change on land surface temperature (LST) in Dhaka Megacity, Bangladesh during a period of rapid urbanisation. LST was derived from Landsat 5 TM scenes captured in 1990, 2000 and 2011 and compared to contemporaneous LULC maps. We compared index-based and linear spectral mixture analysis (LSMA) techniques for modelling LST. LSMA derived biophysical parameters corresponded more strongly to LST than those produced using index-based parameters. Results indicated that vegetation and water surfaces had relatively stable LST but it increased by around 2 °C when these surfaces were converted to built-up areas with extensive impervious surfaces. Knowledge of the expected change in LST when one land-cover is converted to another can inform land planners of the potential impact of future changes and urges the development of better management strategies

    Burden of obesity in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study

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    Mokdad AH, El Bcheraoui C, Afshin A, et al. Burden of obesity in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study. INTERNATIONAL JOURNAL OF PUBLIC HEALTH. 2018;63(Suppl. 1):165-176.We used the Global Burden of Disease (GBD) 2015 study results to explore the burden of high body mass index (BMI) in the Eastern Mediterranean Region (EMR). We estimated the prevalence of overweight and obesity among children (2-19 years) and adults (20 years) in 1980 and 2015. The burden of disease related to high BMI was calculated using the GBD comparative risk assessment approach. The prevalence of obesity increased for adults from 15.1% (95% UI 13.4-16.9) in 1980 to 20.7% (95% UI 18.8-22.8) in 2015. It increased from 4.1% (95% UI 2.9-5.5) to 4.9% (95% UI 3.6-6.4) for the same period among children. In 2015, there were 417,115 deaths and 14,448,548 disability-adjusted life years (DALYs) attributable to high BMI in EMR, which constitute about 10 and 6.3% of total deaths and DALYs, respectively, for all ages. This is the first study to estimate trends in obesity burden for the EMR from 1980 to 2015. We call for EMR countries to invest more resources in prevention and health promotion efforts to reduce this burden
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