Maternal depression in rural Pakistan: the protective associations with cultural postpartum practices

Background Traditional postpartum practices are intended to provide care to mothers, but there is mixed evidence concerning their impact on postpartum depression (PPD). It remains unknown if there is a unique impact of postpartum practices on PPD separately from other types of social support, or if practices differentially affect those with existing prenatal depression. In Pakistan, chilla (چله) is a traditional postpartum practice in which women receive relief from household work, additional familial support, and supplemental food for up to 40 days postpartum. This study aims to understand if chilla protects against PPD independent of other support and whether this relationship varies by prenatal depression status. Methods Data come from the Bachpan cohort study in rural Pakistan. Chilla participation and social support (Multidimensional Scale of Perceived Social Support) were assessed at 3 months postpartum. Women were assessed for major depressive episodes (MDE) with the Structured Clinical Interview, DSM-IV and for depression symptom severity with the Patient Health Questionnaire (PHQ-9) in their third trimester and at 6 months postpartum. Adjusted linear mixed models were used to assess the relationship between chilla participation and PPD. Results Eighty-nine percent of women (N = 786) participated in chilla and almost 70% of those that participated took part in all of chilla’s aspects. In adjusted models, chilla participation was inversely related to MDE (OR = 0.56;95%CI = 0.31,1.03) and symptom severity (Mean Difference (MD) = − 1.54;95%CI: − 2.94,-0.14). Chilla participation was associated with lower odds of MDE (OR = 0.44;95%CI = 0.20,0.97) among those not prenatally depressed and with lower symptom severity among those prenatally depressed (MD = -2.05;95%CI:-3.81,-0.49). Conclusions Chilla is inversely associated with both MDE and symptom severity at 6 months postpartum above and beyond social support. Specifically, chilla is inversely associated with MDE among those not prenatally depressed and with lower symptom severity among those prenatally depressed. This relationship signals an opportunity for interventions aimed at preventing and treating PPD in this region to draw upon chilla and similar traditional postpartum practices in creating community-based, low-cost, sustainable interventions for maternal mental health

Maternal adverse childhood experiences on child growth and development in rural Pakistan: An observational cohort study

Maternal adverse childhood experiences (ACEs) have significant impacts on the next generation with links to negative birth outcomes, impaired cognitive development, and increased socioemotional problems in children. However, not all types or levels of adversity are similarly deleterious and research from diverse contexts is needed to better understand why and how intergenerational transmission of adversity occurs. We examined the role of maternal ACEs on children’s growth, cognitive, and socioemotional development at 36 months postpartum in rural Pakistan. We used data from 877 mother-child dyads in the Bachpan Cohort, a birth cohort study. Maternal ACEs were captured using an adapted version of the ACE-International Questionnaire. Outcomes at 36 months of age included child growth using the WHO growth z-scores, fine motor and receptive language development assessed with the Bayley Scales of Infant and Toddler Development, and socioemotional and behavioral development measured with the Ages and Stages Questionnaire: Socioemotional and Strengths and Difficulties Questionnaire. To estimate the associations between maternal ACEs and child outcomes, we used multivariable generalized linear models with inverse probability weights to account for sampling and loss to follow-up. Over half of mothers in our sample (58%) experienced at least one ACE. Emotional abuse, physical abuse, and emotional neglect were the most commonly reported ACEs. We found null relationships between the number of maternal ACEs and child growth. Maternal ACEs were associated with higher fine motor and receptive language development and worse socioemotional and behavioral outcomes. Maternal ACE domains had similarly varying relationships with child outcomes. Our findings highlight the complexity of intergenerational associations between maternal ACEs and children’s growth and development. Further work is necessary to examine these relationships across cultural contexts and identify moderating factors to mitigate potential negative intergenerational effects

The contribution of grandmother involvement to child growth and development: an observational study in rural Pakistan

INTRODUCTION: Early childhood interventions primarily focus on the mother-child relationship, but grandmothers are often critical in childcare in low-resource settings. Prior research is mixed on how grandmother involvement influences child outcomes and there is a paucity of research on grandmother caregiving in low-income and middle-income countries. We examined the role of grandmother involvement on child growth and development in the first 2 years of life cross sectionally and longitudinally in rural Pakistan. METHODS: We used data from the Bachpan Cohort, a longitudinal birth cohort in rural Pakistan. Maternally reported grandmother involvement in daily instrumental and non-instrumental caregiving was collected at 3 and 12 months. A summed score was created and categorised into non-involved, low and high. Outcomes included 12-month and 24-month child growth, 12-month Bayley Scales of Infant and Toddler Development and 24-month Ages and Stages Questionnaire-Socioemotional. We used multivariable generalised linear models to estimate mean differences (MD) at 12 months (n=727) and 24 months (n=712). Inverse probability weighting was used to account for missingness and sampling. RESULTS: In our sample, 68% of children lived with a grandmother, and most grandmothers were involved in caregiving. Greater 3-month grandmother involvement was positively associated with 12-month weight z-scores; however, greater involvement was associated with lower 24-month weight z-scores. High 12-month grandmother involvement was associated with improved 12-month cognitive (MD=0.38, 95% CI -0.01 to 0.76), fine motor skills (MD=0.45, 95% CI 0.08 to 0.83) and 24-month socioemotional development (MD=-17.83, 95% CI -31.47 to -4.19). No meaningful associations were found for length z-scores or language development. CONCLUSION: In rural Pakistan, grandmothers provide caregiving that influences early child development. Our findings highlight the complex relationship between grandmother involvement and child weight, and suggest that grandmothers may positively promote early child cognitive, fine motor and socioemotional development. Understanding how grandmother involvement affects child outcomes in early life is necessary to inform caregiving interventions

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Funding Source and Research Report Quality in Nutrition Practice-Related Research

BACKGROUND: The source of funding is one of many possible causes of bias in scientific research. One method of detecting potential for bias is to evaluate the quality of research reports. Research exploring the relationship between funding source and nutrition-related research report quality is limited and in other disciplines the findings are mixed. OBJECTIVE: The purpose of this study is to determine whether types of funding sources of nutrition research are associated with differences in research report quality. DESIGN: A retrospective study of research reporting quality, research design and funding source was conducted on 2539 peer reviewed research articles from the American Dietetic Association's Evidence Analysis Library® database. RESULTS: Quality rating frequency distributions indicate 43.3% of research reports were rated as positive, 50.1% neutral, and 6.6% as negative. Multinomial logistic regression results showed that while both funding source and type of research design are significant predictors of quality ratings (χ2 = 118.99, p≤0.001), the model's usefulness in predicting overall research report quality is little better than chance. Compared to research reports with government funding, those not acknowledging any funding sources, followed by studies with University/hospital funding were more likely to receive neutral vs positive quality ratings, OR = 1.85, P <0.001 and OR = 1.54, P<0.001, respectively and those that did not report funding were more likely to receive negative quality ratings (OR = 4.97, P<0.001). After controlling for research design, industry funded research reports were no more likely to receive a neutral or negative quality rating than those funded by government sources. CONCLUSION: Research report quality cannot be accurately predicted from the funding source after controlling for research design. Continued vigilance to evaluate the quality of all research regardless of the funding source and to further understand other factors that affect quality ratings are warranted