Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine

The 492 GHz emission of Sgr A* constrained by ALMA

We report linearly polarized continuum emission properties of Sgr A* at $\sim$492 GHz, based on the Atacama Large Millimeter Array (ALMA) observations. We used the observations of the likely unpolarized continuum emission of Titan, and the observations of C\textsc{i} line emission, to gauge the degree of spurious polarization. The Stokes I flux of 3.6$\pm$0.72 Jy during our run is consistent with extrapolations from the previous, lower frequency observations. We found that the continuum emission of Sgr A* at $\sim$492 GHz shows large amplitude differences between the XX and the YY correlations. The observed intensity ratio between the XX and YY correlations as a function of parallactic angle may be explained by a constant polarization position angle of $\sim$158$^{\circ}$$\pm$3$^{\circ}$. The fitted polarization percentage of Sgr A* during our observational period is 14\%$\pm$1.2\%. The calibrator quasar J1744-3116 we observed at the same night can be fitted to Stokes I = 252 mJy, with 7.9\%$\pm$0.9\% polarization in position angle P.A. = 4.1$^{\circ}$$\pm$4.2$^{\circ}$. The observed polarization percentage and polarization position angle in the present work appear consistent with those expected from longer wavelength observations in the period of 1999-2005. In particular, the polarization position angle at 492 GHz, expected from the previously fitted 167$^{\circ}$$\pm$7$^{\circ}$ intrinsic polarization position angle and (-5.6$\pm$0.7)$\times$10$^{5}$ rotation measure, is 155$^{+9}_{-8}$, which is consistent with our new measurement of polarization position angle within 1$\sigma$. The polarization percentage and the polarization position angle may be varying over the period of our ALMA 12m Array observations, which demands further investigation with future polarization observations.Comment: 10 pages, 6 figures, 1st referee report received and revise

Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants.

Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function

Online suicidal thoughts and/or behaviours talk: A scoping review protocol

The anonymity that the internet and social media affords users means that suicidal thoughts and/or behaviours can be talked about with a sense of freedom and disinhibition that is often not possible in face-to-face contexts. Better understanding online suicidal thoughts and/or behaviour talk is critical as more people turn to online spaces for support. Without this the potentiality of such spaces as sites for suicide prevention and intervention is likely to remain unrealised. Currently there are no scoping or systematic review syntheses focusing on internet and/or on social media suicidal thoughts and/or behaviour talk. This lack of synthesis is problematic as it makes it more difficult for online suicide prevention and intervention practices, policies, and our understanding of suicide to advance in a coherent and evidence-based manner. A scoping review protocol following Arksey and O’Malley’s six-step modified framework has been developed to address this synthesis gap. It aims to systematically map the empirical literature that has investigated online suicidal thoughts and/or behaviours talk. It is anticipated that review outcomes could inform the training of health practitioners and peer/professional online moderators in how to best talk with people experiencing suicidal thoughts and/or behaviours. Outcomes could also form an evidence-base for developing policies and practices that focus on online places as safe spaces to talk about suicidal thoughts and/or behaviours. Developers of safe language guidelines could also use the outcomes to audit how well current guidelines reflect empirical evidence. Outcomes could enable researchers to design future online suicidal thoughts and/behaviours talk studies that extend our understandings of suicide leading to potential refinements of contemporary suicide theories/models

Primary Sources of Polycyclic Aromatic Hydrocarbons to Streambed Sediment in Great Lakes Tributaries Using Multiple Lines of Evidence

Polycyclic aromatic hydrocarbons (PAHs) are among the most widespread and potentially toxic contaminants in Great Lakes (USA/Canada) tributaries. The sources of PAHs are numerous and diverse, and identifying the primary source(s) can be difficult. The present study used multiple lines of evidence to determine the likely sources of PAHs to surficial streambed sediments at 71 locations across 26 Great Lakes Basin watersheds. Profile correlations, principal component analysis, positive matrix factorization source-receptor modeling, and mass fractions analysis were used to identify potential PAH sources, and land-use analysis was used to relate streambed sediment PAH concentrations to different land uses. Based on the common conclusion of these analyses, coal-tar-sealed pavement was the most likely source of PAHs to the majority of the locations sampled. The potential PAH-related toxicity of streambed sediments to aquatic organisms was assessed by comparison of concentrations with sediment quality guidelines. The sum concentration of 16 US Environmental Protection Agency priority pollutant PAHs was 7.4-196 000 mu g/kg, and the median was 2600 mu g/kg. The threshold effect concentration was exceeded at 62% of sampling locations, and the probable effect concentration or the equilibrium partitioning sediment benchmark was exceeded at 41% of sampling locations. These results have important implications for watershed managers tasked with protecting and remediating aquatic habitats in the Great Lakes Basin.Environ Toxicol Chem2020;00:1-17. (c) 2020 The Authors.Environmental Toxicology and Chemistrypublished by Wiley Periodicals LLC on behalf of SETAC.Peer reviewe

Prearraignment forensic evaluations: Toward a new policy

Prearraignment forensic evaluations are forensic psychiatric evaluations performed on a suspect soon after his or her arrest. In the guise of ethics, the committee members who originated this code have imposed apparently personal and political views on all members of respective professional organizations in order to circumvent rulings of the judiciary, including the U.S. Supreme Court. The prohibition against prearraignment evaluations represents a misapplication of physician-as-healer-based medical ethics-in which the core principle is the physician's beneficence to the patient-to the forensic arena, where no physicianpatient relationship exists and healing is not the purpose. The ethical code prohibiting prearraignment evaluations reflects misguided paternalism and political bias, as well as being in direct conflict with current law. Whether or not prearraignment evaluations should be permitted is primarily a Fifth and Sixth Constitutional Amendment issue more than a traditional medical-ethical one. Ethics and the law, when both are examined carefully, suggest prearraignment evaluations are proper when performed responsibly