Impacts of Upstream Drought and Water Withdrawals on the Health and Survival of Downstream Estuarine Oyster Populations

Increases in the frequency, duration, and severity of regional drought pose major threats to the health and integrity of downstream ecosystems. During 2007-2008, the U.S. southeast experienced one of the most severe droughts on record. Drought and water withdrawals in the upstream watershed led to decreased freshwater input to Apalachicola Bay, Florida, an estuary that is home to a diversity of commercially and ecologically important organisms. This study applied a combination of laboratory experiments and field observations to investigate the effects of reduced freshwater input on Apalachicola oysters. Oysters suffered significant disease-related mortality under high-salinity, drought conditions, particularly during the warm summer months. Mortality was size-specific, with large oysters of commercially harvestable size being more susceptible than small oysters. A potential salinity threshold was revealed between 17 and 25 ppt, where small oysters began to suffer mortality, and large oysters exhibited an increase in mortality. These findings have important implications for watershed management, because upstream freshwater releases could be carefully timed and allocated during stressful periods of the summer to reduce disease-related oyster mortality. Integrated, forward-looking water management is needed, particularly under future scenarios of climate change and human population growth, to sustain the valuable ecosystem services on which humans depend

The Epigenetic Clock at Birth : Associations With Maternal Antenatal Depression and Child Psychiatric Problems

Objective: Maternal antenatal depression may compromise the fetal developmental milieu and contribute to individual differences in aging and disease trajectories in later life. We evaluated the association between maternal antenatal depression and a novel biomarker of aging at birth, namely epigenetic gestational age (GA) based on fetal cord blood methylation data. We also examined whether this biomarker prospectively predicts and mediates maternal effects on early childhood psychiatric problems. Method: A total of 694 mothers from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) Study provided information on history of depression diagnosed before pregnancy; 581 completed the Center for Epidemiological Studies Depression Scale throughout pregnancy, and 407 completed the Child Behavior Checklist at child's age 3.7 years (SD = 0.75 year). DNA methylation (DNAm) GA of fetal cord blood DNA was based on the methylation profile of 148 selected cytosine linked to guanine by phosphate (CpG) sites. Epigenetic GA was calculated as the arithmetic difference between DNAm GA and chronological GA and adjusted for chronological GA. Results: Maternal history of depression diagnosed before pregnancy (mean difference = -0.25 SD units, 95% CI = -0.46 to -0.03) and greater antenatal depressive symptoms (-0.08 SD unit per I-SD unit increase, 95% CI = -0.16 to -0.004) were associated with child's lower epigenetic GA. Child's lower epigenetic GA, in turn, prospectively predicted total and internalizing problems and partially mediated the effects of maternal antenatal depression on internalizing problems in boys. Conclusion: Maternal antenatal depression is associated with lower epigenetic GA in offspring. This lower epigenetic GA seems to be associated with a developmental disadvantage for boys, who, in early childhood, show greater psychiatric problems.Peer reviewe

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.

BACKGROUND: COVID-19 outbreaks still occur in English care homes despite the interventions in place. METHODS: We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics. RESULTS: The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing. CONCLUSIONS: Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks

Tracing shadows: How gendered power relations shape the impacts of maternal death on living children in Sub-Saharan Africa

Driven by the need to better understand the full and intergenerational toll of maternal mortality (MM), a mixed-methods study was conducted in four countries in sub-Saharan Africa to investigate the impacts of maternal death on families and children. The present analysis identifies gender as a fundamental driver not only of maternal, but also child health, through manifestations of gender inequity in house- hold decision making, labor and caregiving, and social norms dictating the status of women. Focus group discussions were conducted with community members, and in depth qualitative interviews with key- informants and stakeholders, in Tanzania, Ethiopia, Malawi, and South Africa between April 2012 and October 2013. Findings highlight that socially constructed gender roles, which define mothers as care- givers and fathers as wage earners, and which limit women's agency regarding childcare decisions, among other things, create considerable gaps when it comes to meeting child nutrition, education, and health care needs following a maternal death. Additionally, our findings show that maternal deaths have differential effects on boy and girl children, and exacerbate specific risks for girl children, including early marriage, early pregnancy, and school drop-out. To combat both MM, and to mitigate impacts on children, investment in health services interventions should be complemented by broader interventions regarding social protection, as well as aimed at shifting social norms and opportunity structures regarding gendered divisions of labor and power at household, community, and society levels.Web of Scienc

Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: the effect of socioeconomic status and antibiotic exposure

Objective A growing body of research has investigated the human microbiota and pregnancy outcomes, especially preterm birth. Most studies of the prenatal microbiota have focused on the vagina, with fewer investigating other body sites during pregnancy. Although pregnancy involves profound hormonal, immunological and metabolic changes, few studies have investigated either shifts in microbiota composition across pregnancy at different body sites or variation in composition at any site that may be explained by maternal characteristics. The purpose of this study was to investigate: (1) the stability of the vaginal, oral, and gut microbiota from early (8–14 weeks) through later (24–30 weeks) pregnancy among African American women according to measures of socioeconomic status, accounting for prenatal antibiotic use; (2) whether measures of socioeconomic status are associated with changes in microbiota composition over pregnancy; and (3) whether exposure to prenatal antibiotics mediate any observed associations between measures of socioeconomic status and stability of the vaginal, oral, and gut microbiota across pregnancy. Methods We used paired vaginal, oral, or gut samples available for 16S rRNA gene sequencing from two time points in pregnancy (8–14 and 24–30 weeks) to compare within-woman changes in measures of alpha diversity (Shannon and Chao1) and beta-diversity (Bray–Curtis dissimilarity) among pregnant African American women (n = 110). Multivariable linear regression was used to examine the effect of level of education and prenatal health insurance as explanatory variables for changes in diversity, considering antibiotic exposure as a mediator, adjusting for age, obstetrical history, and weeks between sampling. Results For the oral and gut microbiota, there were no significant associations between measures of socioeconomic status or prenatal antibiotic use and change in Shannon or Chao1 diversity. For the vaginal microbiota, low level of education (high school or less) was associated with an increase in Shannon and Chao1 diversity over pregnancy, with minimal attenuation when controlling for prenatal antibiotic use. Conversely, for within-woman Bray–Curtis dissimilarity for early compared to later pregnancy, low level of education and prenatal antibiotics were associated with greater dissimilarity for the oral and gut sites, with minimal attenuation when controlling for prenatal antibiotics, and no difference in dissimilarity for the vaginal site. Conclusions Measures of maternal socioeconomic status are variably associated with changes in diversity across pregnancy for the vaginal, oral, and gut microbiota, with minimal attenuation by prenatal antibiotic exposure. Studies that evaluate stability of the microbiota across pregnancy in association with health outcomes themselves associated with socioeconomic status (such as preterm birth) should incorporate measures of socioeconomic status to avoid finding spurious relationships

Zim17/Tim15 links mitochondrial iron–sulfur cluster biosynthesis to nuclear genome stability

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron–sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron–sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron–sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants

“Without a mother”: caregivers and community members’ views about the impacts of maternal mortality on families in KwaZulu-Natal, South Africa.

BACKGROUND: Maternal mortality in South Africa is high and a cause for concern especially because the bulk of deaths from maternal causes are preventable. One of the proposed reasons for persistently high maternal mortality is HIV which causes death both indirectly and directly. While there is some evidence for the impact of maternal death on children and families in South Africa, few studies have explored the impacts of maternal mortality on the well-being of the surviving infants, older children and family. This study provides qualitative insight into the consequences of maternal mortality for child and family well-being throughout the life-course. METHODS: This qualitative study was conducted in rural and peri-urban communities in Vulindlela, KwaZulu-Natal. The sample included 22 families directly affected by maternal mortality, 15 community stakeholders and 7 community focus group discussions. These provided unique and diverse perspectives about the causes, experiences and impacts of maternal mortality. RESULTS AND DISCUSSION: Children left behind were primarily cared for by female family members, even where a father was alive and involved. The financial burden for care and children’s basic needs were largely met through government grants (direct and indirectly targeted at children) and/or through an obligation for the father or his family to assist. The repercussions of losing a mother were felt more by older children for whom it was harder for caregivers to provide educational supervision and emotional or psychological support. Respondents expressed concerns about adolescent’s educational attainment, general behaviour and particularly girl’s sexual risk. CONCLUSION: These results illuminate the high costs to surviving children and their families of failing to reduce maternal mortality in South Africa. Ensuring social protection and community support is important for remaining children and families. Additional qualitative evidence is needed to explore differential effects for children by gender and to guide future research and inform policies and programs aimed at supporting maternal orphans and other vulnerable children throughout their development.Web of Scienc