Alternative Molecular Methods for Improved Detection of Meningococcal Carriage and Measurement of Bacterial Density.

Conventional methods for detecting pharyngeal carriage of Neisseria meningitidis are complex. There is a need for simpler methods with improved performance. We have investigated two alternative approaches. Three pharyngeal swabs were collected from 999 pupils aged 10 to 18 years in The Gambia. Carriage of N. meningitidis was investigated by using three different methods: (i) plating on Thayer-Martin selective medium and testing by conventional microbiological methods followed by PCR testing; (ii) seeding in Todd-Hewitt broth (THB) and, after culture overnight, testing by PCR; and (iii) compression of the swab on filter paper and, after DNA concentration, testing by PCR. PCR after culture in THB was more than twice as sensitive as conventional methods in detecting N. meningitidis (13.2% versus 5.7%; P < 0.0001). PCR after DNA extraction from filter paper had a sensitivity similar to that of conventional methods (4.9% versus 5.7%; P = 0.33). Capsular genogroups detected by broth culture were genogroups W (21 isolates), B (12 isolates), Y (8 isolates), E (3 isolates), and X (2 isolates), and 68 meningococci had the capsule-null intergenic region. The distributions of genogroups and of capsule-null organisms were similar with each of the three methods. The carriage density in samples extracted from filter paper ranged from 1 to 25,000 DNA copies. PCR of broth cultures grown overnight doubled the yield of N. meningitidis carriage isolates compared with conventional methods. This approach could improve the efficiency of carriage studies. Collection on filter paper followed by quantitative PCR could be useful for density measurement and for carriage studies in areas with limited resources.The study was funded by grants from the Bill and Melinda Gates Foundation, the Wellcome Trust and the Meningitis Research Foundation to the MenAfriCar Consortium.This is the final version of the article. It first appeared from the American Society for Microbiology via https://doi.org/10.1128/JCM.01428-1

MIGHTEE-Hi: Evolution of Hi Scaling Relations of Star-forming Galaxies at z &lt; 0.5*

We present the first measurements of H I galaxy scaling relations from a blind survey at z > 0.15. We perform spectral stacking of 9023 spectra of star-forming galaxies undetected in H I at 0.23 < z < 0.49, extracted from MIGHTEE-H I Early Science data cubes, acquired with the MeerKAT radio telescope. We stack galaxies in bins of galaxy properties (stellar mass M *, star formation rateSFR, and specific star formation rate sSFR, with sSFR ≡ M */SFR), obtaining ≳5σ detections in most cases, the strongest H I-stacking detections to date in this redshift range. With these detections, we are able to measure scaling relations in the probed redshift interval, finding evidence for a moderate evolution from the median redshift of our sample z med ~ 0.37 to z ~ 0. In particular, low-M * galaxies ( {\mathrm{log}}_{10}({M}_{* }/{M}_{\odot })\sim 9 )experienceastrongHIdepletion( 0.5dexinlog10(MHI/M⊙) ), while massive galaxies ( {\mathrm{log}}_{10}({M}_{* }/{M}_{\odot })\sim 11$ ) keep their H I mass nearly unchanged. When looking at the star formation activity, highly star-forming galaxies evolve significantly in M H I (f H I, where f H I ≡ M H I/M *) at fixed SFR (sSFR), while at the lowest probed SFR (sSFR) the scaling relations show no evolution. These findings suggest a scenario in which low-M * galaxies have experienced a strong H I depletion during the last ~5 Gyr, while massive galaxies have undergone a significant H I replenishment through some accretion mechanism, possibly minor mergers. Interestingly, our results are in good agreement with the predictions of the SIMBA simulation. We conclude that this work sets novel important observational constraints on galaxy scaling relations

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Can neighborhood green space mitigate health inequalities? A study of socio-economic status and mental health

This study examined whether the association of psychological distress with area-level socio-economic status (SES) was moderated by the area and attractiveness of local green space. As expected, the odds of higher psychological distress was higher in residents in lower SES areas than those in higher SES areas. However, our results were inconclusive with regard to the moderating role of green space in the relationship between psychological distress and SES. Further investigations incorporating safety and maintenance features of green space and street-level greenery are warranted

Living liveable? RESIDE's evaluation of the “Liveable Neighborhoods” planning policy on the health supportive behaviors and wellbeing of residents in Perth, Western Australia

Background The RESIDential Environments (RESIDE) project is a unique longitudinal natural experiment designed to evaluate the health impacts of the “Liveable Neighbourhoods” planning policy, which was introduced by the Western Australian government to create more walkable suburbs. Objectives To summarize the RESIDE evidence of the impact of the planning policy on a range of health-supportive behaviours and wellbeing outcomes and to assess the consistency and direction of the estimates of associations. Methods An audit of 26 RESIDE research papers (from 2003 to 2012) identified the number of positive associations (statistically significant and consistent with policy expectations), negative associations (statistically significant and inconsistent with policy expectations), and null findings from multiple-exposure models between objective and perceived measures of 20 policy design requirements and 13 health-supportive behaviors and wellbeing outcomes. Results In total 332 eligible estimates of associations (n = 257 objective measures and n = 75 perceived measures) were identified. Positively significant findings were detected for: 57% of walking estimates with objectively measured policy design features (negative = 3%; null = 40%) (n = 115) and 54% perceived measures (negative = 0%; null = 33%) (n = 27); 42% of sense of community estimates with objectively measured of policy design features (negative = 8%; null = 50%) (n = 12) and 61% perceived measures (negative = 8%; null = 31%) (n = 13); 39% of safety or crime-related estimates with objectively measured of policy design features (negative = 22%; null = 39%) (n = 28) and 100% perceived measures (n = 7). All (n = 4) estimates for mental health outcomes with objectively measured policy-related design features were positively significant. Conclusions The synthesis of findings suggests that new suburban communities built in accordance with the “Liveable Neighbourhoods” policy have the potential to encourage health supportive behaviors and wellbeing outcomes including transport and recreation walking, and to create neighborhoods with a stronger sense of community where residents may feel safer