A host-gut microbial amino acid co-metabolite, p-cresol glucuronide, promotes blood-brain barrier integrity in vivo.

The sequential activity of gut microbial and host processes can exert a powerful modulatory influence on dietary components, as exemplified by the metabolism of the amino acids tyrosine and phenylalanine to p-cresol by gut microbes, and then to p-cresol glucuronide (pCG) by host enzymes. Although such glucuronide conjugates are classically thought to be biologically inert, there is accumulating evidence that this may not always be the case. We investigated the activity of pCG, studying its interactions with the cerebral vasculature and the brain in vitro and in vivo. Male C57Bl/6 J mice were used to assess blood-brain barrier (BBB) permeability and whole-brain transcriptomic changes in response to pCG treatment. Effects were then further explored using the human cerebromicrovascular endothelial cell line hCMEC/D3, assessing paracellular permeability, transendothelial electrical resistance and barrier protein expression. Mice exposed to pCG showed reduced BBB permeability and significant changes in whole-brain transcriptome expression. Surprisingly, treatment of hCMEC/D3 cells with pCG had no notable effects until co-administered with bacterial lipopolysaccharide, at which point it was able to prevent the permeabilizing effects of endotoxin. Further analysis suggested that pCG acts as an antagonist at the principal lipopolysaccharide receptor TLR4. The amino acid phase II metabolic product pCG is biologically active at the BBB, antagonizing the effects of constitutively circulating lipopolysaccharide. These data add to the growing literature showing glucuronide conjugates to be more than merely metabolic waste products and highlight the complexity of gut microbe to host communication pathways underlying the gut-brain axis

Outcome of early cardiopulmonary resuscitation in out-of-hospital cardiac arrest managed in Universiti Kebangsaan Malaysia Medical Centre

Out-of-hospital cardiac arrest (OHCA) patients require immediate cardiopulmonary resuscitation (CPR). Early initiation of CPR and defibrillation before arrival at Emergency Department (ED) increases the chance of survival from sudden cardiac arrest. The main objective of this study was to identify the factors that influenced the outcome of early cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA) patients managed at the ED of Universiti Kebangsaan Malaysia Medical Centre (UKMMC). The second objective was to determine the incidence of CPR initiated by the public prior to ambulance arrival. The present study was a one-year cross-sectional study. The OHCA patients were identified from the ED resuscitation logbook. Patients’ medical records were used to obtain details of the resuscitation. Factors recorded included: aetiology of arrest, initiation of on-scene CPR, use of automated external defibrillators (AEDs), mode of transportation and the incidence of return of spontaneous circulation (ROSC) in the ED. Categorical data was analysed using chi-square and Fisher exact tests. Nine patients out of 98 had early CPR. Three patients achieved ROSC. Gender was significantly associated with ROSC (p-value=0.015). More patients who received early CPR achieved ROSC compared to those who received late CPR. The provision of early CPR and usage of AEDs by the public is still low. Female gender had a positive influence on ROSC. Efforts are required to increase the awareness and involvement of the public in initiating early CPR prior to the arrival of ambulance service

Oral health behind the bars: oral health seeking behavior among jail prisoners at central jail of Peshawar, Pakistan: a cross-sectional study

Background: The oral health care-seeking behavior among prison inmates is an overlooked area, often leading to deteriorating general health due to the prisoners’ limited awareness of oral hygiene practices. It is crucial to address this issue and understand the factors associated with oral healthcare-seeking behavior in prisons. Objective: To assess the oral healthcare-seeking behavior of prison inmates at Central Prisoner Jail, Peshawar Pakistan and to look the factors associated with their dental care utilization. Material and Methods: This cross-sectional study was conducted at Central Prisoner Jail, Peshawar Khyber Pakhtunkhwa, Pakistan from November 2021 to April 2022. A consecutive sampling technique was used to collect data from both convicted and under-trial prisoners by using a pre-tested WHO Basic Oral Health Survey 2013 tool. Our outcome variable was “Visit to a dentist in the last 12 months (Never/Once or more than one visit). Chi-square test was used to determine univariate association with other explanatory variables while multivariable logistic regression was performed to adjust for potential confounders. Result: A total of 225 participants were recruited to the study with a mean (SD) age of 32.9(11.4). More than two-thirds of 200(88.9%) of the participants were males. One-third of the sample never visited the dentist75(33.3). Participants who completed college/university education and never visited the dentist in the last 12 months constituted a smaller proportion (17.6%) compared to those who visited the dentist once or more than once n = 28(82.4%, p-value = 0.003). Individuals who were using toothbrushes were most frequently visiting the dentist n = 130(72.6%=p value = 0.001) as compared to never visitors. Multivariate logistic regression analysis revealed that Participants who experienced teeth pain or discomfort had 0.42 times lower odds of visiting the dentist compared to those who did not experience any pain or discomfort [AOR 0.42 (95% CI 0.17–0.80), p = 0.04]. Similarly, Participants who do not use any denture have 4.06 times higher odds[AOR 4.06(95% CI 1.76–9.36), p = 0.001] of visiting the dentist compared to those who use a denture. Conclusion: Our result demonstrates that those prisoners who were experiencing tooth pain or discomfort and not using dentures were the strong predictors with lower dental visit frequency to seek oral health care

Distinctive Left-Sided Distribution of Adrenergic-Derived Cells in the Adult Mouse Heart

Adrenaline and noradrenaline are produced within the heart from neuronal and non-neuronal sources. These adrenergic hormones have profound effects on cardiovascular development and function, yet relatively little information is available about the specific tissue distribution of adrenergic cells within the adult heart. The purpose of the present study was to define the anatomical localization of cells derived from an adrenergic lineage within the adult heart. To accomplish this, we performed genetic fate-mapping experiments where mice with the cre-recombinase (Cre) gene inserted into the phenylethanolamine-n-methyltransferase (Pnmt) locus were cross-mated with homozygous Rosa26 reporter (R26R) mice. Because Pnmt serves as a marker gene for adrenergic cells, offspring from these matings express the β-galactosidase (βGAL) reporter gene in cells of an adrenergic lineage. βGAL expression was found throughout the adult mouse heart, but was predominantly (89%) located in the left atrium (LA) and ventricle (LV) (p<0.001 compared to RA and RV), where many of these cells appeared to have cardiomyocyte-like morphological and structural characteristics. The staining pattern in the LA was diffuse, but the LV free wall displayed intermittent non-random staining that extended from the apex to the base of the heart, including heavy staining of the anterior papillary muscle along its perimeter. Three-dimensional computer-aided reconstruction of XGAL+ staining revealed distribution throughout the LA and LV, with specific finger-like projections apparent near the mid and apical regions of the LV free wall. These data indicate that adrenergic-derived cells display distinctive left-sided distribution patterns in the adult mouse heart

Maternal deaths in Pakistan : intersection of gender, class and social exclusion.

Background: A key aim of countries with high maternal mortality rates is to increase availability of competent maternal health care during pregnancy and childbirth. Yet, despite significant investment, countries with the highest burdens have not reduced their rates to the expected levels. We argue, taking Pakistan as a case study, that improving physical availability of services is necessary but not sufficient for reducing maternal mortality because gender inequities interact with caste and poverty to socially exclude certain groups of women from health services that are otherwise physically available. Methods: Using a critical ethnographic approach, two case studies of women who died during childbirth were pieced together from information gathered during the first six months of fieldwork in a village in Northern Punjab, Pakistan. Findings: Shida did not receive the necessary medical care because her heavily indebted family could not afford it. Zainab, a victim of domestic violence, did not receive any medical care because her martial family could not afford it, nor did they think she deserved it. Both women belonged to lower caste households, which are materially poor households and socially constructed as inferior. Conclusions: The stories of Shida and Zainab illustrate how a rigidly structured caste hierarchy, the gendered devaluing of females, and the reinforced lack of control that many impoverished women experience conspire to keep women from lifesaving health services that are physically available and should be at their disposal

ExoMol molecular line lists – XXVI: spectra of SH and NS

Line lists for the sulphur-containing molecules SH (the mercapto radical) and NS are computed as part of the ExoMol project. These line lists consider transitions within the X2Π ground state for 32SH, 33SH, 34SH,36SH and, 32SD, and 14N32S, 14N33S, 14N34S, 14N36S, and 15N32S. Ab initio potential energy (PEC) and spin-orbit coupling (SOC) curves are computed and then improved by fitting to experimentally observed transitions. Fully ab initio dipole moment curves (DMCs) computed at high level of theory are used to produce the final line lists. For SH, our fit gives a root-mean-square (rms) error of 0.03 cm−1 between the observed (⁠vmax = 4, Jmax = 34.5) and calculated transitions wavenumbers; this is extrapolated such that all X2Π rotational-vibrational-electronic (rovibronic) bound states are considered. For 32SH the resulting line list contains about 81 000 transitions and 2300 rovibronic states, considering levels up to vmax = 14 and Jmax = 60.5. For NS the refinement used a combination of experimentally determined frequencies and energy levels and led to an rms-fitting error of 0.002 cm−1. Each NS-calculated line list includes around 2.8 million transitions and 31 000 rovibronic states with a vibrational range up to v = 53 and rotational range up to J = 235.5, which covers up to 23 000 cm−1. Both line lists should be complete for temperatures up to 5000 K. Example spectra simulated using this line list are shown and comparisons made to the existing data in the CDMS data base. The line lists are available from the CDS (http://cdsarc.u-strasbg.fr) and ExoMol (www.exomol.com) data bases

Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review

International audienc

Identification of pathologically insignificant prostate cancer is not accurate in unscreened men.

BACKGROUND: Identification of men harbouring insignificant prostate cancer (PC) is important in selecting patients for active surveillance. Tools have been developed in PSA-screened populations to identify such men based on clinical and biopsy parameters. METHODS: Prospectively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre. Tumour volume was assessed by pathological examination. For each tool, receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared. Comparison of accuracy in screened and unscreened populations was performed. RESULTS: Of 848 patients, 415 had Gleason 3+3 disease on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded. One had positive lymph nodes. Two hundred and six (24% of cohort) were D'Amico low risk. Of these, 143 had more than two biopsy cores involved. None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden. Accuracy is low in PSA-screened and -unscreened populations. CONCLUSIONS: In our unscreened population, tools designed to identify insignificant PC are inaccurate. Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy