Triclosan Disrupts SKN-1/Nrf2- Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells

Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment

The Human Oocyte Preservation Experience (HOPE) a phase IV, prospective, multicenter, observational oocyte cryopreservation registry

<p>Abstract</p> <p>Background</p> <p>It has been recommended by the American Society of Clinical Oncology and the American Society of Reproductive Medicine that options to preserve fertility be presented at the outset of treatment for cancer. This recommendation may have arisen, in part, to the increasing survival of patients with cancer and the realization that certain forms of cancer treatment can lead to infertility. One option for these patients, particularly those with ethical or religious objections to freezing embryos is oocyte cryopreservation. However universal acceptance of these procedures has yet to be established, most likely due to a poor history of success and concerns that there has yet to be a comprehensive approach to evaluating these techniques. In light of this, a registry of patients undergoing oocyte cryopreservation, called the HOPE registry, is being implemented.</p> <p>Discussion</p> <p>The intent of the HOPE Registry is to enroll approximately 400 women of reproductive age who will undergo thawing/warming of oocytes and subsequent transfer. Data from the patients enrolled will be collected via a uniform, standardized form and will document important parameters such as demographics, laboratory procedures and outcomes, including following the outcomes of babies born for one year after birth. The results of the registry will be published on a yearly basis.</p> <p>Summary</p> <p>A patient registry has been established in order to systematically document the techniques and outcomes of oocyte cryopreservation procedures. The results will be published in order to provide a widely accessible resource that will allow patients who are considering these procedures validated information in order to make informed decisions as to how their treatment will proceed.</p

AT2018cow: A Luminous Millimeter Transient

We present detailed submillimeter- through centimeter-wave observations of the extraordinary extragalactic transient AT2018cow. The apparent characteristics—the high radio luminosity, the rise and long-lived emission plateau at millimeter bands, and the sub-relativistic velocity—have no precedent. A basic interpretation of the data suggests ${E}_{k}\gtrsim 4\,\times \,{10}^{48}\,\mathrm{erg}$ coupled to a fast but sub-relativistic ($v\approx 0.13c$) shock in a dense (${n}_{e}\approx 3\,\times \,{10}^{5}\,{\mathrm{cm}}^{-3}$) medium. We find that the X-ray emission is not naturally explained by an extension of the radio-submm synchrotron spectrum, nor by inverse Compton scattering of the dominant blackbody UV/optical/IR photons by energetic electrons within the forward shock. By ${\rm{\Delta }}t\approx 20\,\mathrm{days}$, the X-ray emission shows spectral softening and erratic inter-day variability. Taken together, we are led to invoke an additional source of X-ray emission: the central engine of the event. Regardless of the nature of this central engine, this source heralds a new class of energetic transients shocking a dense medium, which at early times are most readily observed at millimeter wavelengths

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Maturation of GABAergic Inhibition Promotes Strengthening of Temporally Coherent Inputs among Convergent Pathways

Spike-timing-dependent plasticity (STDP), a form of Hebbian plasticity, is inherently stabilizing. Whether and how GABAergic inhibition influences STDP is not well understood. Using a model neuron driven by converging inputs modifiable by STDP, we determined that a sufficient level of inhibition was critical to ensure that temporal coherence (correlation among presynaptic spike times) of synaptic inputs, rather than initial strength or number of inputs within a pathway, controlled postsynaptic spike timing. Inhibition exerted this effect by preferentially reducing synaptic efficacy, the ability of inputs to evoke postsynaptic action potentials, of the less coherent inputs. In visual cortical slices, inhibition potently reduced synaptic efficacy at ages during but not before the critical period of ocular dominance (OD) plasticity. Whole-cell recordings revealed that the amplitude of unitary IPSCs from parvalbumin positive (Pv+) interneurons to pyramidal neurons increased during the critical period, while the synaptic decay time-constant decreased. In addition, intrinsic properties of Pv+ interneurons matured, resulting in an increase in instantaneous firing rate. Our results suggest that maturation of inhibition in visual cortex ensures that the temporally coherent inputs (e.g. those from the open eye during monocular deprivation) control postsynaptic spike times of binocular neurons, a prerequisite for Hebbian mechanisms to induce OD plasticity

Health Indicators of Native Hawaiian and Pacific Islanders in the United States

This study aimed to describe health indicators and behaviors of Native Hawaiian and Pacific Islander (NHPI) adults and to compare findings to previous reports on US NHPI and the US population. A sample of N = 100 (56 M, 44 F) NHPI adults aged 40–59 years completed an anonymous questionnaire addressing education and household income, tobacco use, physical activity, fruit and vegetable (F&V) consumption, cancer screening and health status. Objective measures of height and weight were taken to calculate body mass index (BMI). The study sample consisted of 49% current smokers and the majority was not meeting guidelines for physical activity (80%) or F&V consumption (99%). Cancer screening rates ranged from 0 to 57% and were higher among females. Mean BMI was 33.9 ± 7.5 kg/m2 and 95% were overweight or obese. While 36.7% were hypertensive, only 11.1% were taking prescribed medication. Compared to both the general US population and available data for US NHPI, study participants reported higher prevalence of obesity and chronic conditions (hypertension, high cholesterol, diabetes, and angina/CHD) and lower levels of physical activity, F&V consumption and cancer screening rates. Study findings contribute to the limited knowledge regarding health behaviors of US NHPI. Comparisons to US data increase evidence of NHPI health disparities, while comparisons to previous NHPI studies emphasize the magnitude of unhealthy lifestyle behaviors and subsequent adverse health conditions for this particular sample. Further improvements to community outreach and recruitment strategies could successfully encourage high-risk individuals to participate in health promotion and behavior intervention studies to improve NHPI health behaviors

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Reduced risk of Barrett’s esophagus in statin users: case–control study and meta-analysis

Background: Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett’s esophagus. Aim: The purpose of this study was to examine the association between statin use and the presence of Barrett’s esophagus in patients having their first gastroscopy. Methods: We have performed a case–control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett’s esophagus. Male Barrett’s cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case–control studies. Results: Regular statin use was associated with a significantly lower incidence of Barrett’s esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37–0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21–0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett’s was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett’s, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett’s esophagus [pooled adjusted OR 0.63 (95 % CI 0.51–0.77)]. Conclusions: Statin use is associated with a reduced incidence of a new diagnosis of Barrett’s esophagus