Eating disorders among international migrants: a systematic review and meta-analysis.

PURPOSE: Migrants may have elevated exposure to stressors, which can affect their physical and mental well-being. However, migrants often experience a healthy immigrant effect, the applicability of this phenomena to eating disorders is unknown. We aimed to synthesize the available literature and estimate a summary measure of prevalence odds ratio for eating disorders in migrant populations compared to local populations. METHODS: A literature search was conducted using MEDLINE, Embase, PsycINFO, and Web of Science with keywords on migration and eating disorders. Inclusion criteria involved using a validated eating disorder scale and having a comparator group. Two independent reviewers performed study screening and data extraction. The NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess risk of bias. Random-effects models of meta-analysis were applied to compare eating disorder prevalence between migrants and local populations. RESULTS: There were 10 studies included in our review (meta-analysis = 6, narrative synthesis = 4). Studies provided prevalence estimates for: any eating disorder, binge eating disorder, anorexia nervosa, and bulimia nervosa. Among studies with a diagnostic instrument, the pooled prevalence odds ratio (POR) between migrants and local populations for any eating disorder was 0.45 (95%CI: 0.35-0.59). However, a subgroup analysis of eating disorder instruments among studies using risk assessment tools demonstrated inconsistent findings, with both increases and decreases in prevalence. CONCLUSION: Migrants were found to have a lower prevalence of eating disorders compared to local populations, supporting the healthy immigrant hypothesis. However, this effect differs between diagnostic and risk assessment tools.

Validation of a youth suicide risk calculator in an adult sample with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) conveys the highest risk of suicide of all mental disorders. We sought to externally validate a risk calculator (RC) of suicide attempts developed in youth with BD from the Course and Outcome of Bipolar Youth (COBY) study in an adult sample. METHODS: A prospective cohort of adults with BD from the National Institute of Mental Health Collaborative Depression Study (CDS; N = 427; mean (+/- SD) age at intake (36 +/- 13 years)) was secondarily analyzed to validate the COBY RC for one-year risk of suicide attempts/deaths. Nine of the ten predictor variables from the COBY RC were available in the CDS and used: age, age of mood disorder onset, first and second (partial) degree family history of suicide, history of psychotic symptoms, substance use disorder, prior suicide attempt, socioeconomic status, and non-suicidal self-injury (prospectively, incompletely at baseline). RESULTS: Over a mean (SD) follow-up of 19 (10) years, 29 % of the CDS sample attempted suicide. The RC predicted suicide attempts/deaths over one-year follow-up with an area under the receiver operating characteristic curve (AUC) of 0.78 (95 % CI 0.75-0.80). The RC performed slightly better in those with a younger age of mood disorder onset. LIMITATIONS: Clinical samples may limit generalizability; the RC does not assess more acute suicide risk. CONCLUSIONS: One-year risk of suicide attempts/deaths can be predicted with acceptable accuracy in youth and adults with BD, comparable to commonly used RCs to predict cardiovascular risk. This RC may help identify higher-risk individuals with BD for personalized treatment and research. https://cobysuicideattemptsrc.shinyapps.io/Shiny.

Differential Effects of Short-term Environmental Enrichment in Juvenile and Adult Mice.

Environmental enrichment has been shown to increase cognitive abilities and accelerate recovery from a number of disease states. Typically, enrichment protocols last from four to eight weeks, however, it has previously been shown that two weeks of environmental enrichment is sufficient to increase cognitive abilities and the proliferation of the astroglial stem cell pool in juvenile mice. The current study examines whether a short-term enrichment protocol can induce similar effects in adults as compared to juveniles. Using juvenile and adult wild-type mice, we examined the effects of short-term environmental enrichment (including a running wheel) on cognitive abilities, anxiety-like behaviour, and the stem cell potential of sub-ventricular neural stem cells (NSC's) in vitro using neurosphere assays. We found that short-term environmental enrichment decreased anxiety behaviour and increased overall memory abilities similarly in juveniles and adults. However, the rate of acquisition on the Morris water maze, hippocampal Sox2 and Ki67 expression, and neurosphere potential increased in response to enrichment only in juveniles, suggesting that the effects of enrichment on these measures are age dependant. Together, these data suggest that the potential beneficial effects of environmental manipulations decrease with age.

Hiwi mediated tumorigenesis is associated with DNA hypermethylation.

Expression of Piwi proteins is confined to early development and stem cells during which they suppress transposon migration via DNA methylation to ensure genomic stability. Piwi's genomic protective function conflicts with reports that its human ortholog, Hiwi, is expressed in numerous cancers and prognosticates shorter survival. However, the role of Hiwi in tumorigenesis has not been examined. Here we demonstrate that (1) over-expressing Hiwi in sarcoma precursors inhibits their differentiation in vitro and generates sarcomas in vivo; (2) transgenic mice expressing Hiwi (mesodermally restricted) develop sarcomas; and (3) inducible down-regulation of Hiwi in human sarcomas inhibits growth and re-establishes differentiation. Our data indicates that Hiwi is directly tumorigenic and Hiwi-expressing cancers may be addicted to Hiwi expression. We further show that Hiwi associated DNA methylation and cyclin-dependent kinase inhibitor (CDKI) silencing is reversible along with Hiwi-induced tumorigenesis, via DNA-methyltransferase inhibitors. Our studies reveal for the first time not only a novel oncogenic role for Hiwi as a driver of tumorigenesis, but also suggest that the use of epigenetic agents may be clinically beneficial for treatment of tumors that express Hiwi. Additionally, our data showing that Hiwi-associated DNA hyper-methylation with subsequent genetic and epigenetic changes favoring a tumorigenic state reconciles the conundrum of how Hiwi may act appropriately to promote genomic integrity during early development (via transposon silencing) and inappropriately in adult tissues with subsequent tumorigenesis.

Piwis and piwi-interacting RNAs in the epigenetics of cancer.

An increasing body of evidence suggests that cancer cells acquire "stem-like" epigenetic and signaling characteristics during the tumorigenic process, including global DNA hypo-methylation, gene-specific DNA hyper-methylation, and small RNA deregulation. RNAs have been known to be epigenetic regulators, both in stem cells and in differentiated cells. A novel class of small RNAs, called piwi-interacting RNAs (piRNAs), maintains genome integrity by epigenetically silencing transposons via DNA methylation, especially in germline stem cells. piRNAs interact exclusively with the Piwi family of proteins. The human Piwi ortholog, Hiwi, has been found to be aberrantly expressed in a variety of human cancers and in some, its expression correlates with poor clinical prognosis. However, there has been little investigation into the potential role that Piwi and piRNAs might play in contributing to the "stem-like" epigenetic state of a cancer. This review will highlight the current evidence supporting the importance of Piwi and piRNAs in the epigenetics of cancer and provide a potential model for the role of Piwi and piRNAs in tumorigenesis.

Chromatin structure predicts epigenetic therapy responsiveness in sarcoma.

To formally explore the potential therapeutic effect of histone deacetylase inhibitors (HDACI) and DNA-methyltransferase inhibitors (DNA-MI) on sarcomas, we treated a large sarcoma cell line panel with five different HDACIs in the absence and presence of the DNA-MI decitabine. We observed that the IC(50) value of each HDACI was consistent for all cell lines whereas decitabine as a single agent showed no growth inhibition at standard doses. Combination HDACI/DNA-MI therapy showed a preferential synergism for specific sarcoma cell lines. Subsequently, we identified and validated (in vitro and in vivo) a two-gene set signature (high CUGBP2; low RHOJ) that associated with the synergistic phenotype. We further uncover that the epigenetic synergism leading to specific upregulation of CDKI p21 in specific cell lines is a function of the differences in the degree of baseline chromatin modification. Finally, we show that these chromatin and gene expression patterns are similarly present in the majority of high-grade primary sarcomas. Our results provide the first demonstration of a gene set that can predict responsiveness to HDACI/DNA-MI and links this responsiveness mechanistically to the baseline chromatin structure.

Epigenetic remodeling of chromatin architecture: exploring tumor differentiation therapies in mesenchymal stem cells and sarcomas.

Sarcomas are the mesenchymal-derived malignant tumors of connective tissues (e.g., fat, bone, and cartilage) presumed to arise from aberrant development or differentiation of mesenchymal stem cells (MSCs). Appropriate control of stem cell maintenance versus differentiation allows for normal connective tissue development. Current theories suggest that loss of this control--through accumulation of genetic lesions in MSCs at various points in the differentiation process--leads to development of sarcomas, including undifferentiated, high grade sarcoma tumors. The initiation of stem cell differentiation is highly associated with alteration of gene expression, which depends on chromatin remodeling. Epigenetic chromatin modifying agents have been shown to induce cancer cell differentiation and are currently being used clinically to treat cancer. This review will focus on the importance of epigenetic chromatin remodeling in the context of mesenchymal stem cells, sarcoma tumorigenesis and differentiation therapy.

MFH classification: differentiating undifferentiated pleomorphic sarcoma in the 21st Century.

The essence and origin of malignant fibrous histiocytoma (MFH) have been debated for now close to five decades. Originally characterized as a morphologically unique soft-tissue sarcoma subtype of unclear etiology in 1963, with a following 15 years of research only to conclude that "the issue of histogenesis [of MFH] is largely unresolvable"; it is "now regarded as synonymous with [high grade] undifferentiated pleomorphic sarcoma and essentially represents a diagnosis of exclusion". Yet despite this apparent lack of progress, the first decade of the 21st century has seen some significant progress in terms of defining the origins of MFH. Perhaps more importantly these origins might also pave the way for novel therapies. This manuscript will highlight MFH's troubled history, discuss recent advances, and comment as to what the coming years may promise and what further needs to be done to make sure that progress continues.