Maternal Docosahexaenoic Acid Exposure Needed to Achieve Maternal–Newborn EQ

Achieving maternal docosahexaenoic acid (DHA) status equal to or greater than the infant’s DHA status at delivery is known as maternal–newborn DHA equilibrium (EQ) and is thought to be important for optimizing newborn DHA status throughout infancy. The objective of this study was to determine the daily DHA intake during pregnancy most likely to result in EQ. The participants (n = 1145) were from two randomized control trials of DHA supplementation in pregnancy. DHA intake was estimated using an abbreviated food frequency questionnaire. Total DHA exposure during pregnancy was calculated as a weighted average of the estimated DHA intake throughout pregnancy and the randomized DHA dose (200, 800, 1000 mg). Red blood cell DHA was measured from maternal and cord blood plasma at delivery and EQ status was calculated. The DHA intake required to achieve EQ was estimated by regression. In terms of DHA exposure, the point estimate and 95% confidence interval to achieve EQ was 643 (583, 735) mg of DHA/day. The results of our trial suggest an intake of 650 mg of DHA/day is necessary to increase the potential for EQ at delivery. The clinical benefits of achieving EQ deserves continued study

Relationship of Sedentary Behavior and Physical Activity to Incident Cardiovascular Disease Results From the Women's Health Initiative

ObjectivesThe aim of this study was to examine the independent and joint associations of sitting time and physical activity with risk of incident cardiovascular disease (CVD).BackgroundSedentary behavior is recognized as a distinct construct beyond lack of leisure-time physical activity, but limited data exist on the interrelationship between these 2 components of energy balance.MethodsParticipants in the prospective Women’s Health Initiative Observational Study (n = 71,018), 50 to 79 years of age and free of CVD at baseline (1993 to 1998), provided information on sedentary behavior, defined as hours of sitting/day, and usual physical activity at baseline and during follow-up through September 2010. First CVD (coronary heart disease or stroke) events were centrally adjudicated.ResultsSitting ≥10 h/day compared with ≤5 h/day was associated with increased CVD risk (hazard ratio: 1.18, 95% confidence interval: 1.09 to 1.29) in multivariable models including physical activity. Low physical activity was also associated with higher CVD risk (p for trend < 0.001). When women were cross-classified by sitting time and physical activity (p for interaction = 0.94), CVD risk was highest in inactive women (≤1.7 metabolic equivalent task-h/week) who also reported ≥10 h/day of sitting. Results were similar for coronary heart disease and stroke when examined separately. Associations between prolonged sitting and risk of CVD were stronger in overweight versus normal weight women and women 70 years of age and older compared with younger women.ConclusionsProlonged sitting time was associated with increased CVD risk, independent of leisure-time physical activity, in postmenopausal women without a history of CVD. A combination of low physical activity and prolonged sitting augments CVD risk

Comparative Genomic Characterization of the Multimammate Mouse Mastomys coucha.

Mastomys are the most widespread African rodent and carriers of various diseases such as the plague or Lassa virus. In addition, mastomys have rapidly gained a large number of mammary glands. Here, we generated a genome, variome, and transcriptomes for Mastomys coucha. As mastomys diverged at similar times from mouse and rat, we demonstrate their utility as a comparative genomic tool for these commonly used animal models. Furthermore, we identified over 500 mastomys accelerated regions, often residing near important mammary developmental genes or within their exons leading to protein sequence changes. Functional characterization of a noncoding mastomys accelerated region, located in the HoxD locus, showed enhancer activity in mouse developing mammary glands. Combined, our results provide genomic resources for mastomys and highlight their potential both as a comparative genomic tool and for the identification of mammary gland number determining factors

The relationship between partial upper-airway obstruction and inter-breath transition period during sleep

Short pauses or “transition-periods” at the end of expiration and prior to subsequent inspiration are commonly observed during sleep in humans. However, the role of transition periods in regulating ventilation during physiological challenges such as partial airway obstruction (PAO) has not been investigated. Twenty-nine obstructive sleep apnea patients and eight controls underwent overnight polysomnography with an epiglottic catheter. Sustained-PAO segments (increased epiglottic pressure over ≥5 breaths without increased peak inspiratory flow) and unobstructed reference segments were manually scored during apnea-free non-REM sleep. Nasal pressure data was computationally segmented into inspiratory (T, shortest period achieving 95% inspiratory volume), expiratory (T, shortest period achieving 95% expiratory volume), and inter-breath transition period (T, period between T and subsequent T). Compared with reference segments, sustained-PAO segments had a mean relative reduction in T (−24.7\ua0±\ua017.6%, P\ua

Dysfunction of the Intestinal Microbiome in Inflammatory Bowel Disease and Treatment

Background: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. Results: Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways. Conclusions: This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis

Quantitative effects of soil salinity on the symbiosis of wild lima bean (Phaseolus lunatus L.) and Bradyrhizobium in Costa Rica

Global climate change and local anthropogenic activities are increasing soil salinization with permanent negative effects on agricultural and ecosystem productivity. While salt stress is known to affect plant performance, its effects on the association with key microbial plant symbionts, such as legume-associated nitrogen-fixing rhizobia, are less understood. In this field study conducted in Costa Rica (Puntarenas), we used sympatrically-occurring wild lima bean (Phaseolus lunatus L.) and Bradyrhizobium to quantify biomass production of unfertilized rhizobial (R+) and fertilized rhizobia-free (R-) plants at different levels of experimentally manipulated salinity in native soil. In response to salt stress, nodulation was significantly reduced even at slightly increased salt levels. Plants growing at soil salinity levels of 2, 4, 6, and 8 mS/cm showed a mean reduction of nodules by 60.22, 76.52, 83.98, and 92.5% compared to the controls. Similarly, we also observed a significant decline in plant biomass at elevated salinity. However, biomass accumulation of R- plants was significantly less impacted compared to R+ plants, suggesting that the plant-microbe symbiosis is more salt-sensitive than the plant host itself. We suggest that the search for more salt-tolerant, crop plant-compatible rhizobial strains may provide a sustainable approach to maintain agricultural productivity on low to moderately saline soils

Effect of Dupilumab on Sleep Apnea Severity in Patients With Chronic Rhinosinusitis

Patients with chronic rhinosinusitis (CRS) report improved sleep quality after dupilumab, an anti IL4/13 therapy. Concurrent CRS and obstructive sleep apnea (OSA) cases are not rare, and CRS seemingly raises nasal resistance. Thus, we hypothesized that improved sleep quality by dupilumab therapy in CRS patients might be due to lowered nasal resistance and subsequent improvement of unrecognized comorbid OSA. Patients with concurrent CRS and OSA were recruited. Nasal resistance was measured invasively with transnasal pressure and flow data collected during normal respiration in the supine position. Results from the first five participants did not support our hypothesis. Subjective and objective measures for CRS and nasal resistance values were improved with dupilumab therapy in CRS patients with nasal polyps. However, apnea severity and sleep-related subjective parameters did not change. In the patients with CRS without nasal polyps, no significant changes in either CRS or OSA-related measures were observed

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

Making the cut: The production of 'self-harm' in post-1945 Anglo-Saxon psychiatry.

'Deliberate self-harm', 'self-mutilation' and 'self-injury' are just some of the terms used to describe one of the most prominent issues in British mental health policy in recent years. This article demonstrates that contemporary literature on 'self-harm' produces this phenomenon (to varying extents) around two key characteristics. First, this behaviour is predominantly performed by those identified as female. Second, this behaviour primarily involves cutting the skin. These constitutive characteristics are traced back to a corpus of literature produced in the 1960s and 1970s in North American psychiatric inpatient institutions; analysis shows how pre-1960 works were substantially different. Finally, these gendered and behavioural assertions are shown to be the result of historically specific processes of exclusion and emphasis

PIP2-Binding Site in Kir Channels: Definition by Multiscale Biomolecular Simulations†

Phosphatidylinositol bisphosphate (PIP(2)) is an activator of mammalian inwardly rectifying potassium (Kir) channels. Multiscale simulations, via a sequential combination of coarse-grained and atomistic molecular dynamics, enabled exploration of the interactions of PIP(2) molecules within the inner leaflet of a lipid bilayer membrane with possible binding sites on Kir channels. Three Kir channel structures were investigated: X-ray structures of KirBac1.1 and of a Kir3.1-KirBac1.3 chimera and a homology model of Kir6.2. Coarse-grained simulations of the Kir channels in PIP(2)-containing lipid bilayers identified the PIP(2)-binding site on each channel. These models of the PIP(2)-channel complexes were refined by conversion to an atomistic representation followed by molecular dynamics simulation in a lipid bilayer. All three channels were revealed to contain a conserved binding site at the N-terminal end of the slide (M0) helix, at the interface between adjacent subunits of the channel. This binding site agrees with mutagenesis data and is in the proximity of the site occupied by a detergent molecule in the Kir chimera channel crystal. Polar contacts in the coarse-grained simulations corresponded to long-lived electrostatic and H-bonding interactions between the channel and PIP(2) in the atomistic simulations, enabling identification of key side chains