The Paradoxical Effects of Chronic Intra-Amniotic Ureaplasma parvum Exposure on Ovine Fetal Brain Development

Chorioamnionitis is associated with adverse neurodevelopmental outcomes in preterm infants. Ureaplasma spp. are the microorganisms most frequently isolated from the amniotic fluid of women diagnosed with chorioamnionitis. However, controversy remains concerning the role of Ureaplasma spp. in the pathogenesis of neonatal brain injury. We hypothesize that re-exposure to an inflammatory trigger during the perinatal period might be responsible for the variation in brain outcome of preterms following Ureaplasma driven chorioamnionitis. To investigate these clinical scenarios, we performed a detailed multi-modal study in which ovine neurodevelopmental outcomes were assessed following chronic intra-amniotic Ureaplasma parvum (UP) infection, either alone or combined with subsequent lipopolysaccharide (LPS) exposure. We show that chronic intra-amniotic UP exposure during the second trimester provoked a decrease of astrocytes, increased oligodendrocyte numbers and elevated 5-methylcytosine levels. In contrast, short-term LPS exposure before preterm birth induced increased microglial activation, myelin loss, elevation of 5-hydroxymethylcytosine levels and lipid profile changes. These LPS-induced changes were prevented by chronic pre-exposure to UP (preconditioning). These data indicate that chronic UP exposure provokes dual effects on preterm brain development in utero. On one hand, prolonged UP exposure causes detrimental cerebral changes which may predispose to adverse postnatal clinical outcomes. On the other, chronic intra-amniotic UP exposure preconditions the brain against a second inflammatory hit. This study demonstrates that microbial interactions, timing and duration of inflammatory insults will determine the effects on the fetal brain. Therefore, this study helps to understand the complex and diverse postnatal neurological outcomes following UP driven chorioamnionitis

Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis

Identifying dietary tools that prevent disordered insulin secretion from pancreatic β‐cells is an attractive strategy to combat the increasing prevalence of type 2 diabetes. Dietary resistant starch has been linked to improvements in the function of β‐cells, possibly via increased colonic fermentation and production of short‐chain fatty acids (SCFAs). Increasing the resistant starch content of commonly consumed foods could therefore maintain glucose homeostasis at the population level. As part of Biotechnology and Biological Sciences Research Council (BBSRC) Diet and Health Research Industry Club (DRINC) initiative, variants of Pisum sativum L. (pea) are being investigated to identify the features of pea starch that make it resistant to digestion and available for colonic fermentation and SCFA production. Parallel in vitro and in vivo studies are being conducted using both whole pea seeds and pea flour to facilitate a better understanding of how cells in the pea cotyledons are affected by processing and, in turn, how this influences starch digestibility. Trials in human volunteers are being used to monitor a full spectrum of short‐ and long‐term physiological responses relevant to pancreatic β‐cell function and glucose homeostasis. This project is providing new insights into variants of crops that are associated with the specific types of resistant starch that provide the best protection against defects in insulin secretion and function

Physical activity but not sedentary activity is reduced in primary Sjögren’s syndrome

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren’s syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594–3158) versus 3708 (1732–8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135–375) versus 343 (223–433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0–480) versus 1560 (570–3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0–480) versus 480 (0–1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

GW190814: gravitational waves from the coalescence of a 23 solar mass black hole with a 2.6 solar mass compact object

We report the observation of a compact binary coalescence involving a 22.2–24.3 Me black hole and a compact object with a mass of 2.50–2.67 Me (all measurements quoted at the 90% credible level). The gravitational-wave signal, GW190814, was observed during LIGO’s and Virgo’s third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to 18.5 deg2 at a distance of - + 241 45 41 Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves, - + 0.112 0.009 0.008, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to �0.07. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries