Patterning and folding of intestinal villi by active mesenchymal dewetting.

Tissue folding generates structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, the numerous finger-like protrusions that are essential for nutrient absorption. However, the molecular and mechanical mechanisms driving the initiation and morphogenesis of villi remain a matter of debate. Here, we identify an active mechanical mechanism that simultaneously patterns and folds intestinal villi. We find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. At the cell-level, this occurs through a process dependent upon matrix metalloproteinase-mediated tissue fluidization and altered cell-ECM adhesion. By combining computational models with in vivo experiments, we reveal these cellular features manifest at the tissue-level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active de-wetting of a thin liquid film.

Health service delivery models for elderly people: A systematic review.

Background: Current Health care delivery systems are not effective for the elderly. Countries with high elderly populations are expected to design special models to serve their elderly population. The aim of this study is to investigate the models of health care delivery to the elderly in different countries. Methods: The present study is a systematic review based on PRISMA standard guidelines. The search for related studies was conducted in electronic databases (Cochran Library, Scopus, PubMed, Embase, Web of Science) and the Google Scholar search engine without time limits until May 2019. Keywords were extracted based on MeSH strategies. At first, 16243 articles were found. After the screening phase (elimination of duplicated articles, title screening, abstract screening, and full-text screening) 19 articles remained. Two articles deleted after text appraisal using the CASP checklist. In the next stage, after reviewing the gray literature and reviewing the references of remaining articles, three new articles were added (Included studies = 20). Results: Twenty articles (models) corresponding to the study objectives were finally extracted. These models are limited to nine countries and most have local scopes. These models mainly use a case manager, an intra- or inter-disciplinary team, and an elderly assessment tool in their structure. In addition to the use of an information system, these models provide a wide range of services to the elderly. Conclusion: Most of the models mentioned are local models. Smaller models to become applicable at the national level, they need to be reviewed and evaluated by policymakers and experts. Given the inefficiency of current systems in providing services to the elderly, it is recommended that countries use an integrated model of health care provision for the elderly.

Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men.

SARS-CoV-2 infection has led to a global health crisis, and yet our understanding of the disease and potential treatment options remains limited. The infection occurs through binding of the virus with angiotensin converting enzyme 2 (ACE2) on the cell membrane. Here, we established a screening strategy to identify drugs that reduce ACE2 levels in human embryonic stem cell (hESC)-derived cardiac cells and lung organoids. Target analysis of hit compounds revealed androgen signaling as a key modulator of ACE2 levels. Treatment with antiandrogenic drugs reduced ACE2 expression and protected hESC-derived lung organoids against SARS-CoV-2 infection. Finally, clinical data on COVID-19 patients demonstrated that prostate diseases, which are linked to elevated androgen, are significant risk factors and that genetic variants that increase androgen levels are associated with higher disease severity. These findings offer insights on the mechanism of disproportionate disease susceptibility in men and identify antiandrogenic drugs as candidate therapeutics for COVID-19.

Androgen Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a global health crisis, and yet our understanding of the disease pathophysiology and potential treatment options remains limited. SARS-CoV-2 infection occurs through binding and internalization of the viral spike protein to angiotensin converting enzyme 2 (ACE2) on the host cell membrane. Lethal complications are caused by damage and failure of vital organs that express high levels of ACE2, including the lungs, the heart and the kidneys. Here, we established a high-throughput drug screening strategy to identify therapeutic candidates that reduce ACE2 levels in human embryonic stem cell (hESC) derived cardiac cells. Drug target analysis of validated hit compounds, including 5 alpha reductase inhibitors, revealed androgen signaling as a key modulator of ACE2 levels. Treatment with the 5 alpha reductase inhibitor dutasteride reduced ACE2 levels and internalization of recombinant spike receptor binding domain (Spike-RBD) in hESC-derived cardiac cells and human alveolar epithelial cells. Finally, clinical data on coronavirus disease 2019 (COVID-19) patients demonstrated that abnormal androgen states are significantly associated with severe disease complications and cardiac injury as measured by blood troponin T levels. These findings provide important insights on the mechanism of increased disease susceptibility in male COVID-19 patients and identify androgen receptor inhibition as a potential therapeutic strategy.

Challenges of implementation: Strategic purchasing in Iran Health Insurance Organization.

BACKGROUND: Strategic purchasing has been introduced as a key strategy for solving the problems faced by insurance companies. In Iran, the government has mandated the Iran Health Insurance Organization (IHIO) to implement this strategy. However, there are serious challenges to achieving that. The present study aims to identify these challenges. METHODS: In this qualitative study, a semi-structured interview was conducted on 27 health managers and experts at the national level. The dimensions of the A. Preker model were used to analyze the data. RESULTS: Challenges of strategic purchasing in the IHIO were categorized into five concepts-political economy, policy design, organizational structure, organizational environment, and management capacity; within these concepts, 22 challenges were identified. CONCLUSIONS: Improving strategic purchasing in Iran requires adopting a coherent approach and taking into account all the affecting factors. By revising some policies, and modifying and defining the rules needed to solve the infrastructural problems, the success of strategic purchasing can be obtained.

Evaluation of plasma MMP-8, MMP-9 and TIMP-1 identifies candidate cardiometabolic risk marker in metabolic syndrome: results from double-blinded nested case-control study.

AIMS: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are dysregulated in metabolic syndrome (MetS) and associated with atherosclerosis and cardiovascular disease (CVD). Previous studies on the association between MMPs/TIMPs and MetS are controversial. We aimed to evaluate circulating MMP-8, MMP-9 and TIMP-1 in a group of MetS individuals and healthy controls to find the potential marker associated with MetS and its components. METHODS: 243 MetS individuals participated in a nested case-control design, of whom 63 were excluded (study subjects for analysis n=180; 87 MetS cases, 93 controls). We employed the International Diabetes Federation criteria using national waist circumference cutoffs for case definition. Anthropometric and biochemical measurements were done using standard methods. RESULTS: Plasma MMP-8, TIMP-1, tumor necrosis factor-alpha (TNF-α), highly sensitive C-reactive protein (hs-CRP) and MMP-8/TIMP-1 ratio were significantly higher in MetS cases (P for all < 0.05). Each component of MetS except raised fasting plasma glucose positively correlated with MMP-8 and numbers of MetS components increased with higher MMP-8. In all regression models, MMP-8 was a significant predictor of MetS and in the final model the relationship persisted even after adjusting for pro-inflammatory cytokines hs-CRP and TNF-α (odds ratio=6.008, 95% confidence interval: 1.612-22.389, P=0.008). CONCLUSION: Strong associations of MMP-8 with components of MetS in univariate, bivariate and multivariate models suggest plasma MMP-8 as a potential cardiometabolic risk marker for MetS. Higher MMP-8 in MetS is possibly mediated through mechanisms both dependent and independent of chronic low grade inflammation.

Urban family physician plan in Iran: challenges of implementation in Kerman.

BACKGROUND: The Family Physician Plan has recently been implemented in three provinces of Iran on a pilot basis and is going to be implemented throughout Iran in the future. Through a qualitative design, this study aims to determine probable implementation challenges of Family Physician Plan in Kerman. METHODS: This study was conducted in Kerman in 2013. Data were collected through interviews with 21 experts in the field. Sampling continued until data saturation level was achieved. All interviews were recorded and then analyzed, and main themes and subgroups were extracted from them based on a framework analysis model. RESULTS: most prevalent establishment challenges of Family Physician Plan were classified into policy-making, financial supply, laws and resources. CONCLUSION: The urban Family Physician Plan can be carried out more effectively by implementing this plan step by step, highlighting the relationships between the related organizations, using new payment mechanisms e.g Per Capita, DRG, make national commitment and proper educational programs for providers, development the health electronic Record, justifying providers and community about advantages of this plan, clarifying regulatory status about providers' Duties and most importantly considering a specific funding source.