Human CardioChimeras: Creation of a Novel "Next-Generation" Cardiac Cell.

Background CardioChimeras produced by fusion of murine c-kit+ cardiac interstitial cells with mesenchymal stem cells promote superior structural and functional recovery in a mouse model of myocardial infarction compared with either precursor cell alone or in combination. Creation of human CardioChimeras (hCCs) represents the next step in translational development of this novel cell type, but new challenges arise when working with c-kit+ cardiac interstitial cells isolated and expanded from human heart tissue samples. The objective of the study was to establish a reliable cell fusion protocol for consistent optimized creation of hCCs and characterize fundamental hCC properties. Methods and Results Cell fusion was induced by incubating human c-kit+ cardiac interstitial cells and mesenchymal stem cells at a 2:1 ratio with inactivated Sendai virus. Hybrid cells were sorted into 96-well microplates for clonal expansion to derive unique cloned hCCs, which were then characterized for various cellular and molecular properties. hCCs exhibited enhanced survival relative to the parent cells and promoted cardiomyocyte survival in response to serum deprivation in vitro. Conclusions The generation of hCC is demonstrated and validated in this study, representing the next step toward implementation of a novel cell product for therapeutic development. Feasibility of creating human hybrid cells prompts consideration of multiple possibilities to create novel chimeric cells derived from cells with desirable traits to promote healing in pathologically damaged myocardium.

Does public health system provide adequate financial risk protection to its clients? Out of pocket expenditure on inpatient care at secondary level public health institutions: Causes and determinants in an eastern Indian state.

This study is undertaken to estimate the out of pocket expenditure (OOPE) for various diseases and its determinants at secondary level public health facilities in Odisha. METHODS: A cross-sectional survey was conducted among the inpatients utilising secondary level public health facilities in the 2 districts of Odisha. More than 80% of the inpatients were selected conveniently, and data on OOPE and socioeconomic status of patients were collected. The OOPE was estimated separately on surgery, nonsurgery, and child birth conditions. Ordinary least square regression models were developed to explain the factors determining OOPE. RESULTS: The mean OOPE for the secondary care facility was Indian National Rupee 3136.14, (95% CI: 2869.08-3403.19), of which, Indian National Rupee 1622.79 (95% CI: 1462.70-1782.89) was on medicine constituting 79% of total medical expenditure. The mean OOPE on surgery was highest followed by nonsurgery and child birth conditions. The OOPE is mainly influenced by caste and educational status of patients as revealed by the regression results. With increase in social status, the OOPE increases and the results are statistically significant. CONCLUSION: This evidence should be used to design financial strategies to reduce OOPE at secondary care public health facilities, which is largely due to medicine, diagnostic services, and transport expenditure. Efforts should be made to protect the interest of the poor, who utilise public health facility in a low resource setting in India.

Estimating financial resources for universal access to sexual reproductive health care: Evidence from two states in India.

UNLABELLED: India has made insignificant progress towards achieving universal access to sexual and reproductive health (SRH). One of the key inputs for achieving universal access to SRH is financial resources. Given this, many international agencies including the UN are emphasising on monitoring the financial progress towards achieving SRH. OBJECTIVE: To generate evidence on spending on SRH from various sources - (government, household, international donors and NGOs) to improve the accountability of the government towards SRH goal. METHODOLOGY: Adapting a sub account framework of the NHA, this paper investigated the SRH expenditure of the two divergent states of India. The data were collected from government, households (NSSO), and foreign donors and were classified as per the International Classification of Health Accounts (ICHA). RESULTS AND DISCUSSIONS: Total SRH expenditure is less than one percent of SGDP from all sources in each state. Among the sources, government's spending on SRH is more than household. A large part of household spending is on curative care which has implications for accessing services by the poor. In spite of data constraints, this paper presents a comprehensive analysis on SRH spending, which is critical for monitoring the commitment towards universal access to SRH. This evidence can be used for further improving data quality for RCH account in LMICs.

ELMO1 has an essential role in the internalization of Salmonella Typhimurium into enteric macrophages that impacts disease outcome.

BACKGROUNDS AND AIMS: 4-6 million people die of enteric infections each year. After invading intestinal epithelial cells, enteric bacteria encounter phagocytes. However, little is known about how phagocytes internalize the bacteria to generate host responses. Previously, we have shown that BAI1 (Brain Angiogenesis Inhibitor 1) binds and internalizes Gram-negative bacteria through an ELMO1 (Engulfment and cell Motility protein 1)/Rac1-dependent mechanism. Here we delineate the role of ELMO1 in host inflammatory responses following enteric infection. METHODS: ELMO1-depleted murine macrophage cell lines, intestinal macrophages and ELMO1 deficient mice (total or myeloid-cell specific) was infected with Salmonella enterica serovar Typhimurium. The bacterial load, inflammatory cytokines and histopathology was evaluated in the ileum, cecum and spleen. The ELMO1 dependent host cytokines were detected by a cytokine array. ELMO1 mediated Rac1 activity was measured by pulldown assay. RESULTS: The cytokine array showed reduced release of pro-inflammatory cytokines, including TNF-α and MCP-1, by ELMO1-depleted macrophages. Inhibition of ELMO1 expression in macrophages decreased Rac1 activation (~6 fold) and reduced internalization of Salmonella. ELMO1-dependent internalization was indispensable for TNF-α and MCP-1. Simultaneous inhibition of ELMO1 and Rac function virtually abrogated TNF-α responses to infection. Further, activation of NF-κB, ERK1/2 and p38 MAP kinases were impaired in ELMO1-depleted cells. Strikingly, bacterial internalization by intestinal macrophages was completely dependent on ELMO1. Salmonella infection of ELMO1-deficient mice resulted in a 90% reduction in bacterial burden and attenuated inflammatory responses in the ileum, spleen and cecum. CONCLUSION: These findings suggest a novel role for ELMO1 in facilitating intracellular bacterial sensing and the induction of inflammatory responses following infection with Salmonella.