The role of basic health insurance on depression: an epidemiological cohort study of a randomized community sample in Northwest China

BACKGROUND: Little research has focused on the relationship between health insurance and mental health in the community. The objective of this study is to determine how the basic health insurance system influences depression in Northwest China. METHODS: Participants were selected from 32 communities in two northwestern Chinese cities through a three-stage random sampling. Three waves of interviews were completed in April 2006, December 2006, and January 2008. The baseline survey was completed by 4,079 participants. Subsequently, 2,220 participants completed the first follow-up, and 1,888 completed the second follow-up. Depression symptoms were measured by the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: A total of 40.0% of participants had at least one form of health insurance. The percentages of participants with severe depressive symptoms in the three waves were 21.7%, 22.0%, and 17.6%. Depressive symptoms were found to be more severe among participants without health insurance in the follow-up surveys. After adjusting for confounders, participants without health insurance were found to experience a higher risk of developing severe depressive symptoms than participants with health insurance (7 months: OR, 1.40; 95% CI, 1.09-1.82; p = 0.01; 20 months: OR, 1.89; 95% CI, 1.37-2.61; p < 0.001). CONCLUSION: A lack of basic health insurance can dramatically increase the risk of depression based on northwestern Chinese community samples

TAp63 Is a Master Transcriptional Regulator of Lipid and Glucose Metabolism

SummaryTAp63 prevents premature aging, suggesting a link to genes that regulate longevity. Further characterization of TAp63−/− mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulating energy metabolism by accumulating in response to metabolic stress and transcriptionally activating Sirt1, AMPKα2, and LKB1, resulting in increased fatty acid synthesis and decreased fatty acid oxidation. Moreover, we found that TAp63 lowers blood glucose levels in response to metformin. Restoration of Sirt1, AMPKα2, and LKB1 in TAp63−/− mice rescued some of the metabolic defects of the TAp63−/− mice. Our study defines a role for TAp63 in metabolism and weight control

Adenovirus-delivered CIAPIN1 small interfering RNA inhibits HCC growth in vitro and in vivo

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The specific cellular gene alterations responsible for hepatocarcinogenesis are not well known. Cytokine-induced antiapoptotic molecule (CIAPIN1), a recently reported antiapoptotic molecule which plays an essential role in mouse definitive hematopoiesis, is considered a downstream effecter of the receptor tyrosine kinase–Ras signaling pathway. However, the exact function of this gene in tumors is not clear. In this study, we reported that CIAPIN1 is highly expressed in HCC as compared with non-tumor hepatic tissue (P < 0.05). We employed adenovirus-mediated RNA interference technique to knock down CIAPIN1 expression in HCC cells and observed its effects on HCC cell growth in vitro and in vivo. Among the four HCC and one normal human liver cell lines we analyzed, CIAPIN1 was highly expressed in HCC cells. Knock down of CIAPIN1 could inhibit HCC cell proliferation by inhibiting the cell cycle S-phase entry. Soft agar colony formation assay indicated that the colony-forming ability of SMMC-7721 cells decreased by ∼70% after adenovirus AdH1-small interfering RNA (siRNA)/CIAPIN1 infection. In vivo experiments showed that adenovirus AdH1-siRNA/CIAPIN1 inhibited the tumorigenicity of SMMC-7721 cells and significantly suppressed tumor growth when injected directly into tumors. These results suggest that knock down of CIAPIN1 by adenovirus-delivered siRNA may be a potential therapeutic strategy for treatment of HCC in which CIAPIN1 is overexpressed

The p.V37I Exclusive Genotype Of GJB2: A Genetic Risk-Indicator of Postnatal Permanent Childhood Hearing Impairment

Postnatal permanent childhood hearing impairment (PCHI) is frequent (0.25%–0.99%) and difficult to detect in the early stage, which may impede the speech, language and cognitive development of affected children. Genetic tests of common variants associated with postnatal PCHI in newborns may provide an efficient way to identify those at risk. In this study, we detected a strong association of the p.V37I exclusive genotype of GJB2 with postnatal PCHI in Chinese Hans (P = 1.4×10−10; OR 62.92, 95% CI 21.27–186.12). This common genotype in Eastern Asians was present in a substantial percentage (20%) of postnatal PCHI subjects, and its prevalence was significantly increased in normal-hearing newborns who failed at least one newborn hearing screen. Our results indicated that the p.V37I exclusive genotype of GJB2 may cause subclinical hearing impairment at birth and increases risk for postnatal PCHI. Genetic testing of GJB2 in East Asian newborns will facilitate prompt detection and intervention of postnatal PCHI

NDH Expression Marks Major Transitions in Plant Evolution and Reveals Coordinate Intracellular Gene Loss

Key innovations have facilitated novel niche utilization, such as the movement of the algal predecessors of land plants into terrestrial habitats where drastic fluctuations in light intensity, ultraviolet radiation and water limitation required a number of adaptations. The NDH (NADH dehydrogenase-like) complex of Viridiplantae plastids participates in adapting the photosynthetic response to environmental stress, suggesting its involvement in the transition to terrestrial habitats. Although relatively rare, the loss or pseudogenization of plastid NDH genes is widely distributed across diverse lineages of photoautotrophic seed plants and mutants/transgenics lacking NDH function demonstrate little difference from wild type under non-stressed conditions. This study analyzes large transcriptomic and genomic datasets to evaluate the persistence and loss of NDH expression across plants. Results: Nuclear expression profiles showed accretion of the NDH gene complement at key transitions in land plant evolution, such as the transition to land and at the base of the angiosperm lineage. While detection of transcripts for a selection of non-NDH, photosynthesis related proteins was independent of the state of NDH, coordinate, lineage-specific loss of plastid NDH genes and expression of nuclear-encoded NDH subunits was documented in Pinaceae, gnetophytes, Orchidaceae and Geraniales confirming the independent and complete loss of NDH in these diverse seed plant taxa. Conclusion: The broad phylogenetic distribution of NDH loss and the subtle phenotypes of mutants suggest that the NDH complex is of limited biological significance in contemporary plants. While NDH activity appears dispensable under favorable conditions, there were likely sufficiently frequent episodes of abiotic stress affecting terrestrial habitats to allow the retention of NDH activity. These findings reveal genetic factors influencing plant/environment interactions in a changing climate through 450 million years of land plant evolution.National Science Foundation IOS-1027259Innovative Translational Agricultural Research Administrative OfficeIntegrative Biolog

Genome Analysis of Multi- and Extensively-Drug-Resistant Tuberculosis from KwaZulu-Natal, South Africa

The KZN strain family of Mycobacterium tuberculosis is a highly virulent strain endemic to the KwaZulu-Natal region of South Africa, which has recently experienced an outbreak of extensively-drug resistant tuberculosis. To investigate the causes and evolution of drug-resistance, we determined the DNA sequences of several clinical isolates - one drug-susceptible, one multi-drug resistant, and nine extensively drug-resistant - using whole-genome sequencing. Analysis of polymorphisms among the strains is consistent with the drug-susceptibility profiles, in that well-known mutations are observed that are correlated with resistance to isoniazid, rifampicin, kanamycin, ofloxacin, ethambutol, and pyrazinamide. However, the mutations responsible for rifampicin resistance in rpoB and pyrazinamide in pncA are in different nucleotide positions in the multi-drug-resistant and extensively drug-resistant strains, clearly showing that they acquired these mutations independently, and that the XDR strain could not have evolved directly from the MDR strain (though it could have arisen from another similar MDR strain). Sequencing of eight additional XDR strains from other areas of KwaZulu-Natal shows that they have identical drug resistant mutations to the first one sequenced, including the same polymorphisms at sites associated with drug resistance, supporting the theory that this represents a case of clonal expansion

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead