Different definition of sarcopenia and mortality in cancer: A meta-analysis

Objectives: Sarcopenia has been an emerging theme in clinical oncology. Various definitions of sarcopenia have been proposed, but their prognostic performance have yet to be evaluated and compared. The aim of this meta-analysis is to comprehensively evaluate the performance of different cutoff definitions of sarcopenia in cancer mortality prognostication. / Methods: This is a meta-analysis. Cohort studies on lean mass and mortality published before December 20, 2017 were obtained by systematic search on PubMed, Cochrane Library, and Embase. Inclusion criteria were cohort studies reporting binary lean mass categorized according to clearly defined cutoffs, and with all-cause mortality as study outcome. Studies were stratified according to the cutoff(s) used in defining low lean mass. The cutoff-specific hazard ratios (HRs) and 95% confidence intervals (CIs) of low lean mass on cancer mortality were pooled with a random-effects model and compared. / Results: Altogether 81 studies that studied binary lean mass were included. The pooled HRs on cancer mortality using the 3 most used definitions were: 1.74 (95% CI, 1.46–2.07) using the definition proposed by International Consensus of Cancer Cachexia, 1.45 (95% CI, 1.21–1.75) using that by Martin, and 1.58 (95% CI, 1.35–1.84) using that by Prado. The associations between sarcopenia and cancer mortality using other definitions were all statistically significant, despite different estimates were observed. / Conclusions: The association of low lean mass with increased mortality was consistent across different definitions; this provides further evidence on the poorer survival in cancer patients with sarcopenia. However, further studies evaluating the performance of each definition are warranted

A Potent Lead Induces Apoptosis in Pancreatic Cancer Cells

Pancreatic cancer is considered a lethal and treatment-refractory disease. To obtain a potent anticancer drug, the cytotoxic effect of 2-(benzo[d]oxazol-3(2H)-ylmethyl)- 5-((cyclohexylamino)methyl)benzene-1,4-diol, dihydrochloride (NSC48693) on human pancreatic cancer cells CFPAC-1, MiaPaCa-2, and BxPC-3 was assessed in vitro. The proliferation of CFPAC-1, MiaPaCa-2, and BxPC-3 is inhibited with IC50 value of 12.9±0.2, 20.6±0.3, and 6.2±0.6 µM at 48 h, respectively. This discovery is followed with additional analysis to demonstrate that NSC48693 inhibition is due to induction of apoptosis, including Annexin V staining, chromatins staining, and colony forming assays. It is further revealed that NSC48693 induces the release of cytochrome c, reduces mitochondrial membrane potential, generates reactive oxygen species, and activates caspase. These results collectively indicate that NSC48693 mainly induces apoptosis of CFPAC-1, MiaPaCa-2, and BxPC-3 cells by the mitochondrial-mediated apoptotic pathway. Excitingly, the study highlights an encouraging inhibition effect that human embryonic kidney (HEK-293) and liver (HL-7702) cells are more resistant to the antigrowth effect of NSC48693 compared to the three cancer cell lines. From this perspective, NSC48693 should help to open up a new opportunity for the treatment of patients with pancreatic cancer

Association between Interpersonal Trust, Reciprocity, and Depression in South Korea: A Prospective Analysis

Background: A growing body of empirical evidence indicates that low-level social capital is related to poor mental health outcomes. However, the prospective association between social capital and depression remains unclear, and no published studies have investigated the association with longitudinal data in East-Asian countries. Methods: We analyzed data from the ongoing Korean Welfare Panel Study to prospectively investigate association between social capital and depression. Social capital was measured at the individual level by two items specific to interpersonal trust and reciprocity. Depression was annually assessed as a dichotomous variable using the Center for Epidemiologic Studies Depression Scale. After excluding participants who had depression in 2006, logistic regression models were applied to estimate the association between each social capital indicator and new-onset depression developed in 2007 or long-term depression in both 2007 and 2008. We also examined the association in a subpopulation restricted to healthy participants after excluding individuals with any pre-existing disability, chronic disease, or poor self-rated health condition. Results: Compared to the high interpersonal trust group, the odds ratios of developing new-onset and long-term depression among the low interpersonal trust group were 1.22 (95% CI: 1.08∼1.38) and 1.23 (95% CI: 1.03∼1.50), respectively, and increased to 1.32 (95% CI: 1.10∼1.57) and 1.47 (95% CI: 1.05∼2.08) in the subpopulation analyses restricted to healthy individuals. Although the low and intermediate reciprocity group also had significantly higher odds of developing new-onset depression compared to the high reciprocity group, the effects were attenuated and statistically non-significant in the subpopulation analyses. Conclusion: Low interpersonal trust appears to be an independent risk factor for new-onset and long-term depression in South Korea

Long-term care cost drivers and expenditure projection to 2036 in Hong Kong

<p>Abstract</p> <p>Background</p> <p>Hong Kong's rapidly ageing population, characterised by one of the longest life expectancies and the lowest fertility rate in the world, is likely to drive long-term care (LTC) expenditure higher. This study aims to identify key cost drivers and derive quantitative estimates of Hong Kong's LTC expenditure to 2036.</p> <p>Methods</p> <p>We parameterised a macro actuarial simulation with data from official demographic projections, Thematic Household Survey 2004, Hong Kong's Domestic Health Accounts and other routine data from relevant government departments, Hospital Authority and other LTC service providers. Base case results were tested against a wide range of sensitivity assumptions.</p> <p>Results</p> <p>Total projected LTC expenditure as a proportion of GDP reflected secular trends in the elderly dependency ratio, showing a shallow dip between 2004 and 2011, but thereafter yielding a monotonic rise to reach 3.0% by 2036. Demographic changes would have a larger impact than changes in unit costs on overall spending. Different sensitivity scenarios resulted in a wide range of spending estimates from 2.2% to 4.9% of GDP. The availability of informal care and the setting of formal care as well as associated unit costs were important drivers of expenditure.</p> <p>Conclusion</p> <p>The "demographic window" between the present and 2011 is critical in developing policies to cope with the anticipated burgeoning LTC burden, in concert with the related issues of health care financing and retirement planning.</p

Hippocampal Gene Expression Analysis Highlights Ly6a/Sca-1 as Candidate Gene for Previously Mapped Novelty Induced Behaviors in Mice

In this study, we show that the covariance between behavior and gene expression in the brain can help further unravel the determinants of neurobehavioral traits. Previously, a QTL for novelty induced motor activity levels was identified on murine chromosome 15 using consomic strains. With the goal of narrowing down the linked region and possibly identifying the gene underlying the quantitative trait, gene expression data from this F2-population was collected and used for expression QTL analysis. While genetic variation in these mice was limited to chromosome 15, eQTL analysis of gene expression showed strong cis-effects as well as trans-effects elsewhere in the genome. Using weighted gene co-expression network analysis, we were able to identify modules of co-expressed genes related to novelty induced motor activity levels. In eQTL analyses, the expression of Ly6a (a.k.a. Sca-1) was found to be cis-regulated by chromosome 15. Ly6a also surfaced in a group of genes resulting from the network analysis that was correlated with behavior. Behavioral analysis of Ly6a knock-out mice revealed reduced novelty induced motor activity levels when compared to wild type controls, confirming functional importance of Ly6a in this behavior, possibly through regulating other genes in a pathway. This study shows that gene expression profiling can be used to narrow down a previously identified behavioral QTL in mice, providing support for Ly6a as a candidate gene for functional involvement in novelty responsiveness

Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of Infection and Cystic Fibrosis Lung Disease Severity

The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF. infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type. infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the ΔF508 mutation

An update on vitamin B12-related gene polymorphisms and B12 status.

Vitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified. The objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12. Relevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a  < 0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data. From 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA. Overall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations