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Background: Primary ovarian insufficiency (POI) is a disorder characterized by the premature decline in ovarian function, leading to significant fertility and health impacts on women under 40. The unclear etiology of POI hinders the development of effective treatments, highlighting the need for novel therapeutic targets. Methods: This study employed genome-wide association analysis (GWAS) integrated with expression quantitative trait loci (eQTL) data from the GTEx and eQTLGen databases. Mendelian randomization (MR) and colocalization analyses were conducted to investigate causal relationships between genetic variants and POI and to identify potential therapeutic targets. Results: We identified 431 genes with available index cis-eQTL signals, of which four (HM13, FANCE, RAB2A, and MLLT10) were significantly associated with POI. Colocalization analysis revealed strong evidence for FANCE and RAB2A, indicating their potential as therapeutic targets. Subsequent druggability assessments identified FANCE and RAB2A as promising candidates for POI treatment, supported by their involvement in DNA repair and autophagy regulation, respectively. Conclusions: Our study establishes a causal link between specific genes and POI, highlighting FANCE and RAB2A as potential drug targets. These findings provide a foundation for future research and therapeutic development, aiming to improve outcomes for women with POI. Validation in further trials is necessary to confirm these potential targets. [ABSTRACT FROM AUTHOR]

Background: Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid., Objective: The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids., Methodology: Liver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group)., Results: Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice., Conclusions: Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

Background: Ensuring that the scale and hierarchical structure of health human resources are rational, and that medical services are efficient and fair, is an important task of practical significance. On this basis, examining the impact of health human resources on the level of medical services presents a new and formidable challenge. This study aims to delve into how the scale and hierarchical structure of health human resources in China's four major economic regions affect the fairness and efficiency of medical services, and to identify optimization strategies. Methods: This study utilizes provincial panel data from China's four major economic regions spanning the years 2009 to 2021. Initially, it provides a statistical description of the current state of health human resources and the level of medical services. Subsequently, it employs a fixed-effects model to analyze the impact of the scale and hierarchical structure of health human resources, as well as their interactive effects, on the fairness and efficiency of medical services, and discusses the interactive mechanisms between medical service fairness and medical service efficiency. Furthermore, after conducting a comprehensive evaluation of the level of medical services using the entropy weight method, it explores the regional heterogeneity and temporal dynamics in the influence of the scale and hierarchical structure of health human resources on the level of medical services. Finally, the study examines the scientific validity and rationality of the research findings through various robustness checks, including the substitution of research variables and models. Results: The study found that the scale of health human resources has a promoting effect on the equity of medical services (β ≤ 0.643, p ≤ 0.01), but exhibits an inhibitory effect on the efficiency of medical services (β ≥ -0.079, p ≤ 0.1); the hierarchical structure of health human resources shows a positive impact on both the equity and efficiency of medical services (βequity ≤ 0.160, p ≤ 0.01; βefficiency ≤ 0.341, p ≤ 0.05); at the same time, the results indicate that the interactive effect of the scale and hierarchical structure of health human resources promotes equity in medical services (β = 0.067, p ≤ 0.01), but restricts the efficiency of medical services (β ≥ -0.039, p ≤ 0.01); the mechanism by which health human resources affect the level of medical services in China's western and northeastern regions is more pronounced than in the central and eastern regions; after the implementation of the "Healthy China 2030" Planning Outline, the role of health human resources in the level of medical services has been strengthened; in the robustness tests, the model remains robust after replacing the core explanatory variables, with R2 maintained between 0.869 and 0.972, and the dynamic GMM model test shows a significant second-order lag in the level of medical services (βequity ≤ 0.149, p ≤ 0.01; βefficiency ≤ 0.461, p ≤ 0.01); the channel test results prove that managerial personnel and other technical personnel are key pathways in regulating the impact of medical staff on the level of medical services. Conclusion: This study provides an in-depth analysis of the impact of health human resources on the level of medical services, revealing that both the scale and hierarchical structure of health human resources significantly affect the equity and efficiency of medical services. Furthermore, the influence of health human resources on the level of medical services exhibits regional heterogeneity and temporal characteristics. Robustness tests ensure the scientific validity and robustness of the research conclusions. This provides effective references for optimizing the allocation of health human resources and improving the level of medical services. [ABSTRACT FROM AUTHOR]

Background: With Primary Health Care (PHC) being a cornerstone of accessible, affordable, and effective healthcare worldwide, its efficiency, especially in developing countries like China, is crucial for achieving Universal Health Coverage (UHC). This study evaluates the efficiency of PHC systems in a southwest China municipality post-healthcare reform, identifying factors influencing efficiency and proposing strategies for improvement. Methods: Utilising a 10-year provincial panel dataset, this study employs an enhanced Data Envelopment Analysis (DEA) model integrating Slack-Based Measure (SBM) and Directional Distance Function (DDF) with the Global Malmquist-Luenberger (GML) index for efficiency evaluation. Tobit regression analysis identifies efficiency determinants within the context of China's healthcare reforms, focusing on horizontal integration, fiscal spending, urbanisation rates, and workforce optimisation. Results: The study reveals a slight decline in PHC system efficiency across the municipality from 2009 to 2018. However, the highest-performing county achieved a 2.36% increase in Total Factor Productivity (TFP), demonstrating the potential of horizontal integration reforms and strategic fiscal investments in enhancing PHC efficiency. However, an increase in nurse density per 1,000 population negatively correlated with efficiency, indicating the need for a balanced approach to workforce expansion. Conclusions: Horizontal integration reforms, along with targeted fiscal inputs and urbanisation, are key to improving PHC efficiency in underdeveloped regions. The study underscores the importance of optimising workforce allocation and skillsets over mere expansion, providing valuable insights for policymakers aiming to strengthen PHC systems toward achieving UHC in China and similar contexts. [ABSTRACT FROM AUTHOR]

Background: Globally, breast cancer in women is the fifth leading cause of cancer death. There is an urgent need to explore the molecular mechanism of breast cancer proliferation and metastasis. Method: TCGA database analysis was used to analyze genes expression in breast cancer and normal samples and the association between gene expression and prognosis. Immunohistochemical staining, qPCR and western blotting was sued to detected gene expression. The cell function tests were conducted to investigate the effects of TEX19 and CDK4 with abnormal expression on cell proliferation, migration, apoptosis, cell cycle, and colony formation. Bioinformatics analysis methods combined with CHX tracking experiment and Co-IP experiment were performed to screen and verify the downstream molecule and regulatory mechanism of TEX19. Besides, subcutaneous tumorigenesis model in nude mice was constructed. Results: TEX19 was significantly upregulated in breast cancer, and the TEX19 level was related to tumor invasion and prognosis. TEX19 knockdown inhibited the proliferation and migration of breast cancer cells, increased cell apoptosis, and blocked the cell cycle in the G2 phase. Besides, TEX19 suppressed the growth of tumors in the body. Mechanically, TEX19 upregulated the level of CDK4 protein, which depended on the E3 ubiquitin ligase SKP2. Specifically, TEX19 knockdown and SKP2 protein overexpression destroyed the stability of CDK4 protein and enhanced the ubiquitination of CDK4 protein. Additionally, CDK4 knockdown inhibited the proliferation, migration, and colony formation of breast cancer cells, and alleviated the promotion of TEX19 overexpression on the proliferation and migration of breast cancer cell. Conclusion: TEX19 and CDK4 were upregulated in breast cancer, and TEX19 increased the level of CDK4 protein by influencing SKP2-mediated ubiquitination of CDK4, thereby promoting the progression of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Patient satisfaction is a crucial humanistic outcome metric in pharmacy services. There was a lack of evidence on patients' satisfaction with pharmacy services in Gamo zone among users and nonusers of the CBHI scheme. Therefore, the aim this study is to compare the level of patient satisfaction with pharmacy services among users and nonusers of community based health insurance scheme at public health facilities in Gamo zone, South Ethiopia. Method: A facility based comparative cross sectional study design with mixed approach was conducted from June 1 to 30, 2023. A total of 522 study participants and 16 key informants were included as the sample size for quantitative and qualitative study, respectively. The quantitative data was gathered from the study participants who visited the outpatient pharmacy department during the study period by using a simple random sampling technique, while the purposive sampling technique was used to select clients and key informants for the qualitative study. The adjusted odds ratio (AOR) was used to measure the association between independent variables and patient satisfaction toward outpatient pharmacy services at the P values < 0.05 and 95% confidence interval (CI). Results: From the total of study participants, 195 (73.9%) of insured and 175 (67.8%) of noninsured clients were satisfied with pharmacy services offered at public health facilities. The gender of insured (95% CI = 2.00-12.36, (p 0.01)), and noninsured (95% CI = 0.658–2.881, (p 0.02)), waiting time of insured (95% CI = 0.057–0.766, (p 0.0027)), and noninsured (95% CI = 0.084–0.925, (p 0. 0021)) and premium affordability of insured (95% CI = 0.0605-4.860, (p 0.00)) were significantly associated factors with client satisfaction at p < 0.05 and 95% CI. Based on qualitative finding, as member of the CBHI scheme, the members had a greater opportunity to receive a good pharmacy services, because they were more familiar with the physicians and the institutions. Conclusion: The clients with insurance perceived high level of satisfaction with pharmacy services in public health facilities than noninsured. The gender and waiting times at outpatient pharmacy department for both groups of study participants and the premium affordability for the insured groups of clients were factors affecting client satisfactions with pharmacy services. [ABSTRACT FROM AUTHOR]

Background: Hospitals are the biggest consumers of health system budgets and hence measuring hospital performance by quantitative or qualitative accessible and reliable indicators is crucial. This review aimed to categorize and present a set of indicators for evaluating overall hospital performance. Methods: We conducted a literature search across three databases, i.e., PubMed, Scopus, and Web of Science, using possible keyword combinations. We included studies that explored hospital performance evaluation indicators from different dimensions. Results: We included 91 English language studies published in the past 10 years. In total, 1161 indicators were extracted from the included studies. We classified the extracted indicators into 3 categories, 14 subcategories, 21 performance dimensions, and 110 main indicators. Finally, we presented a comprehensive set of indicators with regard to different performance dimensions and classified them based on what they indicate in the production process, i.e., input, process, output, outcome and impact. Conclusion: The findings provide a comprehensive set of indicators at different levels that can be used for hospital performance evaluation. Future studies can be conducted to validate and apply these indicators in different contexts. It seems that, depending on the specific conditions of each country, an appropriate set of indicators can be selected from this comprehensive list of indicators for use in the performance evaluation of hospitals in different settings. [ABSTRACT FROM AUTHOR]

Background: In China, enhancing the pooling levels of basic health insurance has consistently been regarded as a pivotal measure to promote the refinement of the healthcare insurance system. From 2020 to 2022, the widespread outbreak of COVID-19 posed new challenges to China's basic health insurance. Methods: The research utilizes Data Envelopment Analysis (DEA), Malmquist index assessment, and fixed-effects panel Tobit models to analyze panel data from 2020 to 2022, assessing the efficiency of basic health insurance in Gansu Province. Results: From 2020 to 2022, the average overall efficiency of the municipal pooling of Basic Medical Insurance for Urban and Rural Residents was 0.941, demonstrating a stable trend with a modest increase. The efficiency frontier regions have expanded from 5 (35.71%) to 7 (50%). Operational efficiency exhibited a negative correlation with per capita hospitalization expenses and per capita fund balance but a positive correlation with per capita accumulated fund balance and reimbursement rates for hospitalized patients. In 2021, compared to 2020, the county-pooling Basic Medical Insurance for Urban Employees saw a decline of 0.126 in overall efficiency, reducing the efficiency frontier regions from 8 to 3. However, from 2021 to 2022, the municipal-coordinated Basic Medical Insurance for Urban Employees experienced a 0.069 increase in overall efficiency, with the efficiency frontier regions expanding from 3 to 5. Throughout 2020 to 2022, the operational efficiency of the Urban Employee Basic Medical Insurance showed a consistent negative correlation with per capita fund balance. Conclusion: From 2020 to 2022, the overall operational performance of basic health insurance in Gansu Province was satisfactory, and enhancing the pooling level is beneficial in addressing the impact of unforeseen events on the health insurance system. [ABSTRACT FROM AUTHOR]

Background: Accidental hypothermia with severe frostbite is a rare combination of injuries with a high risk for long-term sequelae. There are widely accepted recommendations for the management of avalanche victims and for frostbite treatment, but no recommendation exists for the treatment of frostbite in severe hypothermic patients, specifically for the management of hypothermic avalanche victims presenting with frostbite. Case presentation: We present a case of a previously healthy, 53-year-old male skier who was critically buried by an avalanche at 2300 m of altitude at an ambient temperature of − 8 °C for nearly 23 h. The victim was found with the right hand out of the snow and an air connection to outside. He was somnolent with Glasgow Coma Scale 11 (Eye 4, Verbal 2, Motor 5) and spontaneously breathing, in a severely hypothermic state with an initial core temperature of 23.1 °C and signs of cold injuries in all four extremities. After rescue and active external forced air rewarming in the intensive care unit, the clinical signs of first-degree frostbite on both feet and the left hand vanished, while third- to fourth-degree frostbite injuries became apparent on all fingers of the right hand. After reaching a core body temperature of approximately 36 °C, aggressive frostbite treatment was started with peripheral arterial catheter-directed thrombolysis with alteplase, intravenous iloprost, ibuprofen, dexamethasone and regional sympathicolysis with a right-sided continuous axillary block. After ten months, the patient had no tissue loss but needed neuropathic pain treatment with pregabalin. Conclusion: The combination of severe accidental hypothermia and severe frostbite is rare and challenging, as drug metabolism is unpredictable in a hypothermic patient and no recommendations for combined treatment exist. There is general agreement to give hypothermia treatment the priority and to begin frostbite treatment as early as possible after full rewarming of the patient. More evidence is needed to identify the optimal dosage and time point to initiate treatment of frostbite in severely hypothermic patients. This should be taken into consideration by future treatment recommendations. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to perform a systematic review of the outcomes of various frostbite treatments to determine which treatments are effective. We also planned to perform meta-analyses of the outcomes of individual treatments for which suitable data were available. Main Body: We performed a systematic review and meta-analyses in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched PubMed, Cochrane Trials, and EMBase to identify primary references from January 1, 1900, to June 18, 2022. After eliminating duplicates, we screened abstracts to identify eligible studies containing information on treatment and outcomes of Grade 2 to 4 frostbite. We performed meta-analyses of groups of articles that provided sufficient data. We registered our review in the prospective registry of systematic reviews PROSPERO (Nr. 293,693). We identified 4,835 potentially relevant studies. We excluded 4,610 studies after abstract screening. We evaluated the full text of the remaining 225 studies, excluding 154. Ultimately, we included 71 articles with 978 cases of frostbite originating from 1 randomized controlled trial, 20 cohort studies and 51 case reports. We found wide variations in classifications of treatments and outcomes. The two meta-analyses we performed both found that patients treated with thrombolytics within 24 h had better outcomes than patients treated with other modalities. The one randomized controlled trial found that the prostacyclin analog iloprost was beneficial in severe frostbite if administered within 48 h. Conclusions: Iloprost and thrombolysis may be beneficial for treating frostbite. The effectiveness of other commonly used treatments has not been validated. More prospective data from clinical trials or an international registry may help to inform optimal treatment. [ABSTRACT FROM AUTHOR]

Background: Abnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA. Methods: A retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age. Results: In our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group. Conclusion: The findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion. [ABSTRACT FROM AUTHOR]

Background: The primary differentially methylated regions (DMRs) which are maternally hypermethylated serve as imprinting control regions (ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting. Results: Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter CpG island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter CpG islands were methylated in oocytes and/or allelically methylated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these CpG islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting. Conclusions: In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting. [ABSTRACT FROM AUTHOR]

Background: The distribution of healthcare services should be based on the needs of the population, regardless of their ability to pay. Achieving universal health coverage implies first ensuring that people of all income levels have access to quality healthcare, and then allocating resources reasonably considering individual need. Hence, this study aims to understand how public benefits in Bangladesh are currently distributed among wealth quintiles considering different layers of healthcare facilities and to assess the distributional impact of public benefits. Methods: To conduct this study, data were extracted from the recent Bangladesh Demographic and Health Survey 2017–18. We performed benefit incidence analysis to determine the distribution of maternal and child healthcare utilization in relation to wealth quintiles. Disaggregated and national-level public benefit incidence analysis was conducted by the types of healthcare services, levels of healthcare facilities, and overall utilization. Concentration curves and concentration indices were estimated to measure the equity in benefits distribution. Results: An unequal utilization of public benefits observed among the wealth quintiles for maternal and child healthcare services across the different levels of healthcare facilities in Bangladesh. Overall, upper two quintiles (richest 19.8% and richer 21.7%) utilized more benefits from public facilities compared to the lower two quintiles (poorest 18.9% and poorer 20.1%). Benefits utilization from secondary level of health facilities was highly pro-rich, while benefit utilization found pro-poor at primary levels. The public benefits in Bangladesh were also not distributed according to the needs of the population; nevertheless, poorest 20% household cannot access 20% share of public benefits in most of the maternal and child healthcare services even if we ignore their needs. Conclusions: Benefit incidence analysis in public health spending demonstrates the efficacy with which the government allocates constrained health resources to satisfy the needs of the poor. Public health spending in Bangladesh on maternal and child healthcare services were not equally distributed among wealth quintiles. Overall health benefits were more utilized by the rich relative to the poor. Hence, policymakers should prioritize redistribution of resources by targeting the socioeconomically vulnerable segments of the population to increase their access to health services to meet their health needs. [ABSTRACT FROM AUTHOR]

Background: China's primary health care system has undergone major changes since the new round of medical reform in 2009, but the current status of primary health care institution service efficiency is still unsatisfactory. The purpose of this study is to compare and evaluate the China's primary health care institution service efficiency and provide a reference for improving the efficiency and promoting the development of primary health care institution. Methods: Based on panel data of 31 provinces (municipalities directly under the central government and autonomous regions) in mainland China from 2011 to 2020, using the super efficiency slack-based measure-data envelopment analysis model, to analyze the data from a static perspective, and the changes in the efficiency of primary health care services were analyzed from a dynamic perspective by using the Malmquist index method. Spatial autocorrelation analysis method was used to verify the spatial correlation of primary health care service efficiency among various regions. Results: The number of Primary health care institutions increased from 918,000 in 2011 to 970,000 in 2020. The average primary health care institution service efficiency in the northeastern region including Jilin (0.324), Heilongjiang (0.460), Liaoning (0.453) and northern regions such as Shaanxi (0.344) and Neimenggu (0.403) was at a low level, while the eastern coastal regions such as Guangdong (1.116), Zhejiang (1.211), Shanghai (1.402) have higher average service efficiency levels. The global Moran's I showed the existence of spatial autocorrelation, and the local Moran's I index suggested that the problem of uneven regional development was prominent, showing a contiguous regional distribution pattern. Among them, H–H (high-efficiency regions) were mainly concentrated in Jiangsu, Anhui and Shanghai, and L-L regions (low-efficiency regions) were mostly in northern and northeastern China. Conclusion: The service efficiency of primary health care institution in China showed a rising trend in general, but the overall average efficiency was still at a low level, and there were significant geographical differences, which showed a spatial distribution of "high in the east and low in the west, high in the south and low in the north". The northwestern region, after receiving relevant support, has seen a rapid development of primary health care, and its efficiency was steadily improving and gradually reaching a high level. The average primary health care institution service efficiency in the northeastern region including the northern region of China was at a low level, while the average efficiency in the eastern coastal region and some economically developed regions was high, which also verifies the dependence and high symbiosis of primary health care institution service efficiency on regional economy. [ABSTRACT FROM AUTHOR]

Background: Zambia has invested in several healthcare financing reforms aimed at achieving universal access to health services. Several evaluations have investigated the effects of these reforms on the utilization of health services. However, only one study has assessed the distributional incidence of health spending across different socioeconomic groups, but without differentiating between public and overall health spending and between curative and maternal health services. Our study aims to fill this gap by undertaking a quasi-longitudinal benefit incidence analysis of public and overall health spending between 2006 and 2014.Methods: We conducted a Benefit Incidence Analysis (BIA) to measure the socioeconomic inequality of public and overall health spending on curative services and institutional delivery across different health facility typologies at three time points. We combined data from household surveys and National Health Accounts.Results: Results showed that public (concentration index of - 0.003; SE 0.027 in 2006 and - 0.207; SE 0.011 in 2014) and overall (0.050; SE 0.033 in 2006 and - 0.169; SE 0.011 in 2014) health spending on curative services tended to benefit the poorer segments of the population while public (0.241; SE 0.018 in 2007 and 0.120; SE 0.007 in 2014) and overall health spending (0.051; SE 0.022 in 2007 and 0.116; SE 0.007 in 2014) on institutional delivery tended to benefit the least-poor. Higher inequalities were observed at higher care levels for both curative and institutional delivery services.Conclusion: Our findings suggest that the implementation of UHC policies in Zambia led to a reduction in socioeconomic inequality in health spending, particularly at health centres and for curative care. Further action is needed to address existing barriers for the poor to benefit from health spending on curative services and at higher levels of care. [ABSTRACT FROM AUTHOR]

Background: Developing essential health services through non-governmental organisations (NGOs) is an important strategy for progressing towards Universal Health Coverage (UHC), especially in low- and middle-income countries. It is crucial to understand NGOs' role in reaching UHC and the best way to engage them.Objective: This study reviewed the role of NGOs and their engagement strategies in progress toward UHC.Method: We systematically reviewed studies from five databases (PubMed, Web of Science (ISI), ProQuest, EMBASE and Scopus) that investigated NGOs interventions in public health-related activities. The quality of the selected studies was assessed using the mixed methods appraisal tool. PRISMA reporting guidelines were followed.Findings: Seventy-eight studies met the eligibility criteria. NGOs main activities related to service and population coverage and used different strategies to progress towards UHC. To ensure services coverage, NGOs provided adequate and competent human resources, necessary health equipment and facilities, and provided public health and health care services strategies. To achieve population coverage, they provided services to vulnerable groups through community participation. Most studies were conducted in middle-income countries. Overall, the quality of the reported evidence was good. The main funding sources of NGOs were self-financing and grants from the government, international organisations, and donors.Conclusion: NGOs can play a significant role in the country's progress towards UHC along with the government and other key health players. The government should use strategies and interventions in supporting NGOs, accelerating their movement toward UHC. [ABSTRACT FROM AUTHOR]

Background: A significant shortage of healthcare workforce exists globally. To achieve Universal Healthcare coverage, governments need to enhance their community-based health programmes. Community health volunteers (CHVs) are essential personnel in achieving this objective. However, their ability to earn a livelihood is compromised by the voluntary nature of their work; hence, the high attrition rates from community-based health programmes. There is an urgent need to support CHVs become economically self-reliant. We report here on the application of the Ultra-Poverty Graduation (UPG) Model to map CHVs' preferences for socio-economic empowerment strategies that could enhance their retention in a rural area in Kenya.Methods: This study adopted an exploratory qualitative approach. Using a semi-structured questionnaire, we conducted 10 Focus Group Discussions with the CHVs and 10 Key Informant Interviews with County and Sub-county Ministry of Health and Ministry of Agriculture officials including multi-lateral stakeholders' representatives from two sub-counties in the area. Data were audio-recorded and transcribed verbatim and transcripts analysed in NVivo. Researcher triangulation supported the first round of analysis. Findings were mapped and interpreted using a theory-driven analysis based on the six-step Ultra-Poverty Graduation Model.Results: We mapped the UPG Model's six steps onto the results of our analyses as follows: (1) initial asset transfer of in-kind goods like poultry or livestock, mentioned by the CHVs as a necessary step; (2) weekly stipends with consumption support to stabilise consumption; (3) hands-on training on how to care for assets, start and run a business based on the assets transferred; (4) training on and facilitation for savings and financial support to build assets and instil financial discipline; (5) healthcare provision and access and finally (6) social integration. These strategies were proposed by the CHVs to enhance economic empowerment and aligned with the UPG Model.Conclusion: These results provide a user-defined approach to identify and assess strategic needs of and approaches to CHVs' socio-economic empowerment using the UPG model. This model was useful in mapping the findings of our qualitative study and in enhancing our understanding on how these needs can be addressed in order to economically empower CHVs and enhance their retention in our setting. [ABSTRACT FROM AUTHOR]

Background: A simple indicator of technical efficiency, such as productivity of health workers, measured using routine health facility data, can be a practical approach that can inform initiatives to improve efficiency in low- and middle-income countries. This paper presents a proof of concept of using routine information from primary healthcare (PHC) facilities to measure health workers' productivity and its application in three regions of Ethiopia.Methods: In four steps, we constructed a productivity measure of the health workforce of Health Centers (HCs) and demonstrated its practical application: (1) developing an analytical dataset using secondary data from health management information systems (HMIS) and human resource information system (HRIS); (2) principal component analysis and factor analysis to estimate a summary measure of output from five indicators (annual service volume of outpatient visits, family planning, first antenatal care visits, facility-based deliveries by skilled birth attendants, and children [< 1 year] with three pentavalent vaccines); (3) calculating a productivity score by combining the summary measure of outputs and the total number of health workers (input), and (4) implementing regression models to identify the determinant of productivity and ranking HCs based on their adjusted productivity score.Results: We developed an analytical dataset of 1128 HCs; however, significant missing values and outliers were reported in the data. The principal component and factor scores developed from the five output measures were highly consistent (correlation coefficient = 0.98). We considered the factor score as the summary measure of outputs for estimating productivity. A very weak association was observed between the summary measure of output and the total number of staff. The result also highlighted a large variability in productivity across similar health facilities in Ethiopia, represented by the significant dispersion in summary measure of output occurring at similar levels of the health workers.Conclusions: We successfully demonstrated the analytical steps to estimate health worker productivity and its practical application using HMIS and HRIS. The methodology presented in this study can be readily applied in low- and middle-income countries using widely available data-such as DHIS2-that will allow further explorations to understand the causes of technical inefficiencies in the health system. [ABSTRACT FROM AUTHOR]

Background: Health policy interventions were expected to improve access to health care delivery, provide financial risk protection, besides reducing inequities that underlie geographic and socio-economic variation in population access to health care. This article examines whether health policy interventions and accelerated health investments in India during 2004–2018 could close the gap in inequity in health care utilization and access to public subsidy by different population groups. Did the poor and socio-economically vulnerable population gain from such government initiatives, compared to the rich and affluent sections of society? And whether the intended objective of improving equity between different regions of the country been achieved during the policy initiatives? This article attempts to assess and provide robust evidence in the Indian context. Methods: Employing Benefit-Incidence Analysis (BIA) framework, this paper advances earlier evidence by highlighting estimates of health care utilization, concentration and government subsidy by broader provider categories (public versus private) and across service levels (outpatient, inpatient, maternal, pre-and post-natal services). We used 2 waves of household surveys conducted by the National Sample Survey Organisation (NSSO) on health and morbidity. The period of analysis was chosen to represent policy interventions spanning 2004 (pre-policy) and 2018 (post-policy era). We present this evidence across three categories of Indian states, namely, high-focus states, high-focus north eastern states and non-focus states. Such categorization facilitates quantification of reform impact of policy level interventions across the three groups. Results: Utilisation of healthcare services, except outpatient care visits, accelerated significantly in 2018 from 2004. The difference in utilisation rates between poor and rich (between poorest 20% and richest 20%) had significantly declined during the same period. As far as concentration of healthcare is concerned, the Concentrate Index (CI) underlying inpatient care in public sector fell from 0.07 in 2004 to 0.05 in 2018, implying less pro-rich distribution. The CI in relation to pre-natal, institutional delivery and postnatal services in government facilities were pro-poor both in 2004 and 2018 in all 3 groups of states. The distribution of public subsidy underscoring curative services (inpatient and outpatient) remained pro-rich in 2004 but turned less pro-rich in 2018, measured by CIs which declined sharply across all groups of states for both outpatient (from 0.21 in 2004 to 0.16 in 2018) and inpatient (from 0.24 in 2004 to 0.14 in 2018) respectively. The CI for subsidy on prenatal services declined from approximately 0.01 in 2004 to 0.12 in 2018. In respect to post-natal care, similar results were observed, implying the subsidy on prenatal and post-natal services was overwhelmingly received by poor. The CI underscoring subsidy for institutional delivery although remained positive both in 2018 and 2004, but slightly increased from 0.17 in 2004 to 0.28 in 2018. Conclusions: Improvement in infrastructure and service provisioning through NHM route in the public facilities appears to have relatively benefited the poor. Yet they received a relatively smaller health subsidy than the rich when utilising inpatient and outpatient health services. Inequality continues to persist across all healthcare services in private health sector. Although the NHM remained committed to broader expansion of health care services, a singular focus on maternal and child health conditions especially in backward regions of the country has yielded desired results. [ABSTRACT FROM AUTHOR]

Background: For patients with early breast cancer considered at very-low risk of local relapse, risks of radiotherapy may outweigh the benefits. Decisions regarding treatment omission can lead to patient uncertainty (decisional conflict), which may be lessened with patient decision aids (PDA). PRIMETIME (ISRCTN 41579286) is a UK-led biomarker-directed study evaluating omission of adjuvant radiotherapy in breast cancer; an embedded Study Within A Trial (SWAT) investigated whether PDA reduces decisional conflict using a cluster stepped-wedge trial design.Methods: PDA diagrams and a video explaining risks and benefits of radiotherapy were developed in close collaboration between patient advocates and PRIMETIME trialists. The SWAT used a cluster stepped-wedge trial design, where each cluster represented the radiotherapy centre and referring peripheral centres. All clusters began in the standard information group (patient information and diagrams) and were randomised to cross-over to the enhanced information group (standard information plus video) at 2, 4 or 6 months. Primary endpoint was the decisional conflict scale (0-100, higher scores indicating greater conflict) which was assessed on an individual participant level. Multilevel mixed effects models used a random effect for cluster and a fixed effect for each step to adjust for calendar time and clustering. Robust standard errors were also adjusted for the clustering effect.Results: Five hundred twenty-one evaluable questionnaires were returned from 809 eligible patients (64%) in 24 clusters between April 2018 and October 2019. Mean decisional conflict scores in the standard group (N = 184) were 10.88 (SD 11.82) and 8.99 (SD 11.82) in the enhanced group (N = 337), with no statistically significant difference [mean difference - 1.78, 95%CI - 3.82-0.25, p = 0.09]. Compliance with patient information and diagrams was high in both groups although in the enhanced group only 121/337 (36%) reported watching the video.Conclusion: The low levels of decisional conflict in PRIMETIME are reassuring and may reflect the high-quality information provision, such that not everyone required the video. This reinforces the importance of working with patients as partners in clinical trials especially in the development of patient-centred information and decision aids. [ABSTRACT FROM AUTHOR]

Background: Sex-related genes play a crucial role in gonadal differentiation into testes or ovaries. However, the genetic control of gonadal differentiation in Muscovy ducks remains unknown. Therefore, the objective of our study was to screen new candidate genes associated with ovarian and testicular development. Results: In this study, 24 males before gonadal differentiation (MB), 24 females before gonadal differentiation (FB), 24 males after gonadal differentiation (MA) and 24 females after gonadal differentiation (FA) were selected from Putian Muscovy ducks, forming 4 groups. RNA-Seq revealed 101.76 Gb of clean reads and 2800 differentially expressed genes (DEGs), including 46 in MB vs FB, 609 in MA vs FA, 1027 in FA vs FB, and 1118 in MA vs MB. A total of 146 signalling pathways were enriched by KEGG analysis, among which 20, 108, 108 and 116 signalling pathways were obtained in MB vs FB, MA vs MB, MA vs FA and FA vs FB, respectively. In further GO and KEGG analyses, a total of 21 candidate genes related to gonad differentiation and development in Muscovy ducks were screened. Among these, 9 genes were involved in the differentiation and development of the testes, and 12 genes were involved in the differentiation and development of the ovaries. In addition, RNA-Seq data revealed 2744 novel genes. Conclusions: RNA-Seq data revealed 21 genes related to gonadal differentiation and development in Muscovy ducks. We further identified 12 genes, namely, WNT5B, HTRA3, RSPO3, BMP3, HNRNPK, NIPBL, CREB3L4, DKK3, UBE2R2, UBPL3KCMF1, ANXA2, and OSR1, involved in the differentiation and development of ovaries. Moreover, 9 genes, namely, TTN, ATP5A1, DMRT1, DMRT3, AMH, MAP3K1, PIK3R1, AGT and ADAMTSL1, were related to the differentiation and development of testes. Moreover, after gonadal differentiation, DMRT3, AMH, PIK3R1, ADAMTSL1, AGT and TTN were specifically highly expressed in males. WNT5B, ANXA2 and OSR1 were specifically highly expressed in females. These results provide valuable information for studies on the sex control of Muscovy ducks and reveal novel candidate genes for the differentiation and development of testes and ovaries. [ABSTRACT FROM AUTHOR]

LINE1 retrotransposons are mobile DNA elements that copy and paste themselves into new sites in the genome. To ensure their evolutionary success, heritable new LINE-1 insertions accumulate in cells that can transmit genetic information to the next generation (i.e., germ cells and embryonic stem cells). It is our hypothesis that LINE1 retrotransposons, insertional mutagens that affect expression of genes, may be causal agents of early miscarriage in humans. The cell has evolved various defenses restricting retrotransposition-caused mutation, but these are occasionally relaxed in certain somatic cell types, including those of the early embryo. We predict that reduced suppression of L1s in germ cells or early-stage embryos may lead to excessive genome mutation by retrotransposon insertion, or to the induction of an inflammatory response or apoptosis due to increased expression of L1-derived nucleic acids and proteins, and so disrupt gene function important for embryogenesis. If correct, a novel threat to normal human development is revealed, and reverse transcriptase therapy could be one future strategy for controlling this cause of embryonic damage in patients with recurrent miscarriages. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the anti-cancer effects of Tadalafil (potent PDE-5 inhibitor) in female albino wistar rats against n-methyl n-nitrosourea induced mammary gland carcinogenesis.Methods: The animals were selected and randomly divided among four groups and each group contains six animals per group. The animal tissue and serum samples were evaluated for the presence of antioxidant parameters and the cellular morphology was studied using carminic staining, haematoxylin staining and scanning electron microscopy followed by immunoblotting analysis.Results: On the grounds of hemodynamic recordings and morphology, n-methyl n-nitrosourea treated group showed distorted changes along with distorted morphological parameters. For morphological analysis, the mammary gland tissues were evaluated using scanning electron microscopy, whole mount carmine staining, haematoxylin and eosin staining. The serum samples were evaluated for the evaluation of oxidative stress markers and inflammatory markers. The level of caspase 3 and 8 were also evaluated for the estimation of apoptosis. The fatty acid profiling of mammary gland tissue was evaluated using fatty acid methyl esters formation. The mitochondrial mediated apoptosis and inflammatory markers were evaluated using immunoblotting assay.Conclusion: The results confirm that Tadalafil treatment restored all the biological markers to the normal and its involvement in mitochondrial mediated death apoptosis pathway along with inhibition of inflammatory markers. [ABSTRACT FROM AUTHOR]

Retrotransposons have generated about 40 % of the human genome. This review examines the strategies the cell has evolved to coexist with these genomic "parasites", focussing on the non-long terminal repeat retrotransposons of humans and mice. Some of the restriction factors for retrotransposition, including the APOBECs, MOV10, RNASEL, SAMHD1, TREX1, and ZAP, also limit replication of retroviruses, including HIV, and are part of the intrinsic immune system of the cell. Many of these proteins act in the cytoplasm to degrade retroelement RNA or inhibit its translation. Some factors act in the nucleus and involve DNA repair enzymes or epigenetic processes of DNA methylation and histone modification. RISC and piRNA pathway proteins protect the germline. Retrotransposon control is relaxed in some cell types, such as neurons in the brain, stem cells, and in certain types of disease and cancer, with implications for human health and disease. This review also considers potential pitfalls in interpreting retrotransposon-related data, as well as issues to consider for future research. [ABSTRACT FROM AUTHOR]

Background Breast cancer is attributable to modifiable risk factors including the intake of dietary n-3 polyunsaturated fatty acids (PUFA). A key piece of evidence, yet to be addressed, that would demonstrate a causal relationship between n-3 PUFA and breast cancer, is a dose-dependent effect of n-3 PUFA on tumour outcomes. Thus, the objective of the present study was to determine whether n-3 PUFA reduces mammary gland tumor outcomes in a dose-dependent manner in female MMTV-neu(ndl)-YD5 transgenic mice, an aggressive model of human breast cancer. Methods Harems were provided one of three experimental diets comprised of 0, 3 or 9% (w/w) menhaden fish oil containing n-3 PUFA. Female offspring were weaned onto the same parental diet and maintained on their respective diet for 20 weeks. Tumour onset, size and multiplicity were measured throughout the study. Fatty acid composition of mammary gland and tumours were determined by gas-liquid chromatography. Results Tumour size was significantly (p < 0.05) reduced in a dose-dependent manner. n-3 PUFA were also incorporated in a dose-dependent manner; differential incorporation was observed for eicosapentaenoic and docosapentaenoic acids into mammary gland tissue, while docosahexaenoic acid was preferentially incorporated into tumours. Conclusion Overall, the present study provides fundamental knowledge about the dose-dependent effect of n-3 PUFA on tumour outcomes in a pre-clinical model and also sheds light on the differential role of individual n-3 PUFA on tumour outcomes. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have shown that consumption of a high-fat diet (HFD) increases the risk of developing breast cancer (BC). Studies in rodents have shown HFD causes changes in the genetic programming of the maturing mammary gland (MG) increasing the susceptibility of developing the disease. Less is known about how HFD induced genes impact BC development. HFD exposure two weeks before conception to six weeks of age was previously shown to dramatically change MG gene expression in 10 week old mice. Therefore, we investigated these differentially expressed HFD-induced genes for their expression in BC using the NKI 295 breast tumor dataset. Results: To examine the potential role of HFD induced genes in BC, we first investigated whether these HFD-induced genes in mouse MGs were differentially expressed in different types of human BC. Of the 28 HFD induced genes that were differentially expressed between BC subtypes in the NKI set, 79% were significantly higher in basal-like BC. Next, we analyzed whether HFD induced genes were associated with BC prognosis utilizing gene expression and survival data for each HFD induced gene from the NKI data and constructed Kaplan Meier survival plots. Significantly, 93% of the prognosis associated genes (13/14) were associated with poor prognosis (P = 0.002). Kaplan Meier analysis with 249 non-basal-like BC found that all but one of the genes examined were still significantly associated with poor prognosis. Furthermore, gene set enrichment analysis (GSEA) with HFD microarray data revealed that invasive BC genes where enriched in HFD samples that also had lost expression of luminal genes. Conclusions: HFD exposed mouse MGs maintain differential expression of genes that are found highly expressed in basal-like breast cancer. These HFD-induced genes associate with poor survival in numerous BC subtypes, making them more likely to directly impact prognosis. Furthermore, HFD exposure leads to a loss in the expression of luminal genes and a gain in expression of mesenchymal and BC invasion genes in MGs. Collectively, our study suggests that HFD exposure during development induces genes associated with poor prognosis, thus identifying how HFD diet may regulate BC development. [ABSTRACT FROM AUTHOR]

Background Increased ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs) in diet or serum may have a protective effect on the risk of breast cancer (BC); however, the conclusions from prospective studies are still controversial. The purpose of this study is to ascertain the relationship between intake ratio of n-3/n-6 PUFAs and the risk of BC, and estimate the potential summarized dose--response trend. Methods Relevant English-language studies were identified through Cochrane Library, PubMed and EMBASE database till April 2013. Eligible prospective studies reporting the multivariate adjusted risk ratios (RRs) for association of n-3/n-6 PUFAs ratio in diet or serum with BC risk. Data extraction was conducted independently by 2 investigators; disagreements were reconciled by consensus. Study quality was assessed using the Newcastle-Ottawa scale. Study-specific RRs were combined via a random-effects model. Results Six prospective nested case--control and 5 cohort studies, involving 8,331 BC events from 274,135 adult females across different countries, were included in present study. Subjects with higher dietary intake ratio of n-3/n-6 PUFAs have a significantly lower risk of BC among study populations (pooled RR = 0.90; 95% CI: 0.82, 0.99), and per 1/10 increment of ratio in diet was associated with a 6% reduction of BC risk (pooled RR = 0.94; 95% CI: 0.90, 0.99; P for linear trend = 0.012). USA subjects with higher ratio of n-3/n-6 in serum phospholipids (PL) have a significantly lower risk of BC (pooled RR = 0.62; 95% CI: 0.39, 2 0.97; I = 0.00%; P for metaregression = 0.103; P for a permutation test = 0.100), and per 1/10 increment of ratio in serum PL was associated with 27% reduction of BC risk (pooled RR = 0.73; 95% CI: 0.59, 0.91; P for linear trend = 0.004; P for metaregression = 0.082; P for a permutation test = 0.116). Conclusions Higher intake ratio of n-3/n-6 PUFAs is associated with lower risk of BC among females, which implies an important evidence for BC prevention and treatment is by increasing dietary intake ratio of n-3/n-6 PUFA. No firm conclusions from USA populations could be obtained, due to the limited numbers of USA studies. [ABSTRACT FROM AUTHOR]

Introduction: Research on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes. Methods: In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the coenrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients. Results: Among 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P < 0.001) were illness severity (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.19 to 1.53 for each 10-point Acute Physiology and Chronic Health Evaluation (APACHE) II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03 to 5.41), experience of persons inviting consent (OR 2.67, 1.74 to 4.11 for persons with > 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events. Conclusions: Co-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of coenrollment during critical illness. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most common cancer for women in the western world. From very few cases an extraordinary increase in BC was observed in the Inuit population of Greenland and Canada although still lower than in western populations. Previous data suggest that exposure to persistent organic pollutants (POPs) might contribute to the risk of BC. Rat studies showed that perfluorinated compounds (PFCs) cause significantly increase in mammary fibroadenomas. This study aimed at evaluating the association between serum levels of POPs/PFCs in Greenlandic Inuit BC cases and their controls, and whether the combined POP related effect on nuclear hormone receptors affect BC risk.Methods: Thirty-one BC cases and 115 controls were sampled during 2000-2003 from various Greenlandic districts. The serum levels of POPs, PFCs, some metals and the combined serum POP related effect on estrogen- (ER), androgen- (AR) and Ah-receptor (AhR) transactivity were determined. Independent student t-test was used to compare the differences and the odds ratios were estimated by unconditional logistic regression models.Results: We observed for the very first time a significant association between serum PFC levels and the risk of BC. The BC cases also showed a significantly higher concentration of polychlorinated biphenyls at the highest quartile. Also for the combined serum POP induced agonistic AR transactivity significant association to BC risk was found, and cases elicited a higher frequency of samples with significant POP related hormone-like agonistic ER transactivity. The AhR toxic equivalent was lowest in cases.Conclusions: The level of serum POPs, particularly PFCs, might be risk factors in the development of BC in Inuit. Hormone disruption by the combined serum POP related xenoestrogenic and xenoandrogenic activities may contribute to the risk of developing breast cancer in Inuit. Further investigations are needed to document these study conclusions. [ABSTRACT FROM AUTHOR]

Background: Jiangsu was one of the first four pilot provinces to engage in comprehensive health care reform in China, which has been on-going for the past 5 years. This study aims to evaluate the equity, efficiency and productivity of health care resource allocation in Jiangsu Province using the most recent data, analyse the causes of deficiencies, and discuss measures to solve these problems. Methods: Data were extracted from the Jiangsu Health/Family Planning Statistical Yearbook (2015–2019) and Jiangsu Statistical Yearbook (2015–2019). The Gini coefficient (G), Theil index (T) and health resource density index (HRDI) were chosen to study the fairness of health resource allocation in Jiangsu Province. Data envelopment analysis (DEA) and the Malmquist productivity index (MPI) were used to analyse the efficiency and productivity of this allocation. Results: From 2014 to 2018, the total amount of health resources in Jiangsu Province increased. The G of primary resource allocation by population remained below 0.15, and that by geographical area was between 0.14 and 0.28; additionally, the G of health financial resources was below 0.26, and that by geographical area was above 0.39. T was consistent with the results for G and Lorenz curves. The HRDI shows that the allocated amounts of health care resources were the highest in southern Jiangsu, except for the number of health institutions. The average value of TE was above 0.93, and the DEA results were invalid for only two cities. From 2014 to 2018, the mean TFPC in Jiangsu was less than 1, and the values exceeded 1 for only five cities. Conclusion: The equity of basic medical resources was better than that of financial resources, and the equity of geographical allocation was better than that of population allocation. The overall efficiency of health care resource allocation was high; however, the total factor productivity of the whole province has declined due to technological regression. Jiangsu Province needs to further optimize the allocation and increase the utilization efficiency of health care resources. [ABSTRACT FROM AUTHOR]

Background: District hospitals (DHs) provide secondary level of healthcare to a wide range of population in Bangladesh. Efficient utilization of resources in these secondary hospitals is essential for delivering health services at a lower cost. Therefore, we aimed to estimate the technical efficiency of the DHs in Bangladesh. Methods: We used input-oriented data envelopment analysis method to estimate the variable returns to scale (VRS) and constant returns to scale (CRS) technical efficiency of the DHs using data from Local Health Bulletin, 2015. In this model, we considered workforce as well as number of inpatient beds as input variables and number of inpatient, outpatient, and maternal services provided by the DHs as output variables. A Tobit regression model was applied for assessing the association of institutional and environmental characteristics with the technical efficiency scores. Results: The average scale, VRS, and CRS technical efficiency of the DHs were estimated to 85%, 92%, and 79% respectively. Population size, poverty headcount, bed occupancy ratio, administrative divisions were significantly associated with the technical efficiency of the DHs. The mean VRS and CRS technical efficiency demonstrated that the DHs, on an average, could reduce their input mix by 8% and 21% respectively while maintaining the same level of output. Conclusion: Since the average technical efficiency of the DHs was 79%, there is little scope for overall improvements in these facilities by adjusting inputs. Therefore, we recommend to invest further in the DHs for improvement of services. The Ministry of Health and Family Welfare (MoHFW) should improve the efficiency in resource allocation by setting an input-mix formula for DHs considering health and socio-economic indicators (e.g., population density, poverty, bed occupancy ratio). The formula can be designed by learning from the input mix in the more efficient DHs. The MoHFW should conduct this kind of benchmarking study regularly to assess the efficiency level of health facilities which may contribute to reduce the wastage of resources and consequently to provide more affordable and accessible public hospital care. [ABSTRACT FROM AUTHOR]

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapies. [ABSTRACT FROM AUTHOR]

Background: In recent years, developing countries like Bangladesh are facing a higher burden of non-communicable diseases such as hypertension as a result of demographic transition. Prevalence of hypertension is often studied in this setting. However, evidence on undiagnosed hypertension is not widely available in the existing literature. Therefore, the current study focuses on inequalities in the prevalence of undiagnosed hypertension in Bangladesh. Methods: A total of 8835 participants aged 35+ years were included in this study using nationally representative Bangladesh Demographic and Health Survey 2011 (BDHS). In the survey, systolic blood pressure (SBP) and diastolic blood pressure (DBP) of these participants were measured three times with approximately 10 minutes of an interval between each measurement. Any respondent with either SBP ≥ 140 mmHg or DBP ≥ 90 mmHg was considered as patient with hypertension as per the guidelines from American Heart Association. Among the participants, undiagnosed hypertension was defined as having SBP > =140 mmHg or DBP > =90 mmHg and never taking prescribed medicine or being told by health professionals to lower/control blood pressure. Multiple logistic regression analysis was applied for identifying factors associated with undiagnosed hypertension. Further, socioeconomic inequalities in the prevalence of undiagnosed hypertension were estimated using Concentration Index (C). Results: We found 978 (59.9% of the total) were undiagnosed among 1685 hypertensive patients studied. Regression analysis showed individuals with being underweight, having poor socioeconomic conditions, and lower educational qualifications were more likely to have undiagnosed hypertension. A similar association between undiagnosed hypertension and socioeconomic quintiles was observed using concentration index (C = − 0.07). On the other hand, individuals from higher age group (50–64 or above), female sex, and Sylhet region were at lower risk of undiagnosed hypertension. Conclusions: This study showed that a large proportion of the cases with hypertension are remained undiagnosed in Bangladesh, especially among the poor and low educated population. Screening and awareness building initiatives on hypertension should be taken for this group of population to reduce the burden of undiagnosed hypertension. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving loss of motor neurons and having no known cure and uncertain etiology. Several studies have drawn connections between altered retrotransposon expression and ALS. Certain features of the LINE-1 (L1) retrotransposon-encoded ORF1 protein (ORF1p) are analogous to those of neurodegeneration-associated RNA-binding proteins, including formation of cytoplasmic aggregates. In this study we explore these features and consider possible links between L1 expression and ALS. Results: We first considered factors that modulate aggregation and subcellular distribution of LINE-1 ORF1p, including nuclear localization. Changes to some ORF1p amino acid residues alter both retrotransposition efficiency and protein aggregation dynamics, and we found that one such polymorphism is present in endogenous L1s abundant in the human genome. We failed, however, to identify CRM1-mediated nuclear export signals in ORF1p nor strict involvement of cell cycle in endogenous ORF1p nuclear localization in human 2102Ep germline teratocarcinoma cells. Some proteins linked with ALS bind and colocalize with L1 ORF1p ribonucleoprotein particles in cytoplasmic RNA granules. Increased expression of several ALS-associated proteins, including TAR DNA Binding Protein (TDP-43), strongly limits cell culture retrotransposition, while some disease-related mutations modify these effects. Using quantitative reverse transcription PCR (RT-qPCR) of ALS tissues and reanalysis of publicly available RNA-Seq datasets, we asked if changes in expression of retrotransposons are associated with ALS. We found minimal altered expression in sporadic ALS tissues but confirmed a previous report of differential expression of many repeat subfamilies in C9orf72 gene-mutated ALS patients. Conclusions: Here we extended understanding of the subcellular localization dynamics of the aggregation-prone LINE-1 ORF1p RNA-binding protein. However, we failed to find compelling evidence for misregulation of LINE-1 retrotransposons in sporadic ALS nor a clear effect of ALS-associated TDP-43 protein on L1 expression. In sum, our study reveals that the interplay of active retrotransposons and the molecular features of ALS are more complex than anticipated. Thus, the potential consequences of altered retrotransposon activity for ALS and other neurodegenerative disorders are worthy of continued investigation. [ABSTRACT FROM AUTHOR]

Retrotransposons are transposable elements (TEs) capable of "jumping" in germ, embryonic and tumor cells and, as is now clearly established, in the neuronal lineage. Mosaic TE insertions form part of a broader landscape of somatic genome variation and hold significant potential to generate phenotypic diversity, in the brain and elsewhere. At present, the LINE-1 (L1) retrotransposon family appears to be the most active autonomous TE in most mammals, based on experimental data obtained from disease-causing L1 mutations, engineered L1 reporter systems tested in cultured cells and transgenic rodents, and single-cell genomic analyses. However, the biological consequences of almost all somatic L1 insertions identified thus far remain unknown. In this review, we briefly summarize the current state-of-the-art in the field, including estimates of L1 retrotransposition rate in neurons. We bring forward the hypothesis that an extensive subset of retrotransposition-competent L1s may be de-repressed and mobile in the soma but largely inactive in the germline. We discuss recent reports of non-canonical L1-associated sequence variants in the brain and propose that the elevated L1 DNA content reported in several neurological disorders may predominantly comprise accumulated, unintegrated L1 nucleic acids, rather than somatic L1 insertions. Finally, we consider the main objectives and obstacles going forward in elucidating the biological impact of somatic retrotransposition. [ABSTRACT FROM AUTHOR]

Background: Government health subsidy (GHS) is an effective tool to improve population health in China. Ensuring an equitable allocation of GHS, particularly among the poorer socio-economic groups, is a major goal of China's healthcare reform. The paper aims to explore how GHS was allocated across different socioeconomic groups, and how well the overall health system was performing in terms of the allocation of subsidy for different types of health services. Methods: Data from China's National Health Services Survey (NHSS) in 2013 were used. Benefit incidence analysis (BIA) was applied to examine if GHS was equally distributed across income quintile. Benefit incidence was presented as each quintile's percentage share of total benefits, and the concentration index (CI) and Kakwani index (KI) were calculated. Health benefits from three types of healthcare services (primary health care, outpatient and inpatient services) were analyzed, separated into urban and rural populations. In addition, the distribution of benefits was compared to the distribution of healthcare need (measured by self-reported illness and chronic disease) across income quintiles. Results: In urban populations, the CI value of GHS for primary care was negative. (− 0.14), implying an allocation tendency toward poor region; the CI values of outpatient and inpatient services were both positive (0.174 and 0.194), indicating allocation tendencies toward rich region. Similar allocation pattern was observed in rural population, with pro-poor tendency of primary care service (CI = − 0.082), and pro-rich tendencies of outpatient (CI = 0.153) and inpatient services (CI = 0.203). All the KI values of three health services in urban and rural populations were negative (− 0.4991,-0.1851 and − 0.1651; − 0.482, − 0.247and − 0.197), indicating that government health subsidy was progressive and contributed to the narrowing of economic gap between the poor and rich. Conclusions: The inequitable distribution of GHS in China exited in different healthcare services; however, the GHS benefit is generally progressive. Future healthcare reforms in China should not only focus on expanding the coverage, but also on improving the equity of distribution of healthcare benefits. [ABSTRACT FROM AUTHOR]