Understanding the role of P2X7 in affective disorders—are glial cells the major players?

Pathophysiology associated with several psychiatric disorders has been linked to inflammatory biomarkers. This has generated a theory of major depressive disorders as an inflammatory disease. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia. Numerous candidate genes have been identified for psychiatric disorders in the last decade. Single nucleotide polymorphisms (SNPs) in the human P2X7 gene have been linked to bipolar disorder, depression, and to the severity of depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia with lower levels found on astrocytes and on some neuronal populations. In microglia P2X7 is a major regulator of pro-inflammatory cytokines of the interleukin-1 family. Genetic deletion of P2X7 in mice is protective for depressive behavior in addition to inflammatory responses. P2X7−/− mice have been shown to demonstrate anti-depressive-like behavior in forced swim and tail suspension behavioral tests and stressor-induced behavioral responses were blunted. Both neurochemical (norepinephrine, serotonin, and dopamine) and inflammatory changes have been observed in the brains of P2X7−/− mice. This review will discuss the recent evidence for involvement of P2X7 in the pathophysiology of depressive disorders and propose mechanisms by which altered signaling through this ion channel may affect the inflammatory state of the brain

Preserving the New England Mill Town: Encouraging Adaptive Re-Use by Identifying Community Factors that Contribute to Success in Mill Revitalization Districts

Mill Revitalization Districts have the ability to generate new vitality in some of the nation\u27s oldest communities. When efficacious, these districts promote economic development, community beautification, and environmental health. However, when attempts at redevelopment fail they leave ugly scars in the form of decaying buildings and underutilized resources. Monetary investment and intent to improve a community are two factors that by themselves, will not preserve a mill complex or benefit a city. The first Environmental Protection Agency (EPA) recognized districts in the early 2000s showed signs of varying success; there was a missing catalyst besides monetary investment. In fact, it seems that it is not the developer, but something within the community itself that produces a successful revitalization. This project was founded on the idea that the human elements of a community promote the realization of a Mill Revitalization District (MRD)

Protective actions of des-acylated ghrelin on brain injury and blood-brain barrier disruption after stroke in mice

The major ghrelin forms, acylated ghrelin and des-acylated ghrelin, are novel gastrointestinal hormones. Moreover, emerging evidence indicates that these peptides may have other functions including neuro- and vaso-protection. Here, we investigated whether post-stroke treatment with acylated ghrelin or des-acylated ghrelin could improve functional and histological endpoints of stroke outcome in mice after transient middle cerebral artery occlusion (tMCAo). We found that des-acylated ghrelin (1 mg/kg) improved neurological and functional performance, reduced infarct and swelling, and decreased apoptosis. In addition, it reduced blood-brain barrier (BBB) disruption in vivo and attenuated the hyper-permeability of mouse cerebral microvascular endothelial cells after oxygen glucose deprivation and reoxygenation (OGD + RO). By contrast, acylated ghrelin (1 mg/kg or 5 mg/kg) had no significant effect on these endpoints of stroke outcome. Next we found that des-acylated ghrelin's vasoprotective actions were associated with increased expression of tight junction proteins (occludin and claudin-5), and decreased cell death. Moreover, it attenuated superoxide production, Nox activity and expression of 3-nitrotyrosine. Collectively, these results demonstrate that post-stroke treatment with des-acylated ghrelin, but not acylated ghrelin, protects against ischaemia/reperfusion-induced brain injury and swelling, and BBB disruption, by reducing oxidative and/or nitrosative damage

The impact of the COVID-19 lockdowns on wildlife-vehicle collisions in the UK

Wildlife–vehicle collisions (WVCs) cause millions of vertebrate mortalities globally, threatening population viability and influencing wildlife behaviour and survival. Traffic volume and speed can influence wildlife mortality on roads, but roadkill risk is species specific and depends on ecological traits. The COVID-19 pandemic, and associated UK-wide lockdowns, offered a unique opportunity to investigate how reducing traffic volume alters WVC. These periods of reduced human mobility have been coined the ‘anthropause’. We used the anthropause to identify which ecological traits may render species vulnerable to WVC. We did this by comparing the relative change in WVC of species with differing traits before and during the anthropause. We used Generalised Additive Model predictions to assess which of the 19 species most frequently observed as WVC in the UK exhibited changes in road mortality during two lockdown periods, March–May 2020 and December 2020–March 2021, relative to the same time periods in previous years (2014–2019). Compositional data analysis was used to identify ecological traits associated with changes in the relative number of observations during lockdown periods compared to previous years. WVC were, across all species, 80% lower during the anthropause than predicted. Compositional data analysis revealed proportionally fewer reports of nocturnal mammals, urban visitors, mammals with greater brain mass and birds with a longer flight initiation distance. Species that have several of these traits, and correspondingly significantly lower than predicted WVC during lockdowns, included badgers Meles meles, foxes Vulpes vulpes, and pheasants, Phasianus colchicus; we posit they stand to benefit most from reduced traffic, and, of the species studied here, have highest mortality under ‘normal’ traffic levels. This study identifies traits and species that may have experienced a temporary reprieve during the anthropause, and highlights the impacts of traffic-induced mortality on species numbers and ultimately on trait frequency in a road-dominated landscape. By taking advantage of reductions in traffic offered by the anthropause, we can understand how vehicles influence wildlife survival and behaviour and may be exerting a selective force for certain species and traits

Overview of systematic reviews assessing the evidence for shorter versus longer duration antibiotic treatment for bacterial infections in secondary care

<div><p>Our objective was to assess the clinical effectiveness of shorter versus longer duration antibiotics for treatment of bacterial infections in adults and children in secondary care settings, using the evidence from published systematic reviews. We conducted electronic searches in MEDLINE, Embase, Cochrane, and Cinahl. Our primary outcome was clinical resolution. The quality of included reviews was assessed using the AMSTAR criteria, and the quality of the evidence was rated using the GRADE criteria. We included 6 systematic reviews (n = 3,162). Four reviews were rated high quality, and two of moderate quality. In adults, there was no difference between shorter versus longer duration in clinical resolution rates for peritonitis (RR 1.03, 95% CI 0.98 to 1.09, I² = 0%), ventilator-associated pneumonia (RR 0.93; 95% CI 0.81 to 1.08, I² = 24%), or acute pyelonephritis and septic UTI (clinical failure: RR 1.00, 95% CI 0.46 to 2.18). The quality of the evidence was very low to moderate. In children, there was no difference in clinical resolution rates for pneumonia (RR 0.98, 95% CI 0.91 to 1.04, I² = 48%), pyelonephritis (RR 0.95, 95% CI 0.88 to 1.04) and confirmed bacterial meningitis (RR 1.02, 95% CI 0.93 to 1.11, I² = 0%). The quality of the evidence was low to moderate. In conclusion, there is currently a limited body of evidence to clearly assess the clinical benefits of shorter versus longer duration antibiotics in secondary care. High quality trials assessing strategies to shorten antibiotic treatment duration for bacterial infections in secondary care settings should now be a priority.</p></div

“I’ve got somebody there, someone cares”: what support is most valued following a stroke?

Purpose: There is often a need for increased support following a stroke. This study explored what types of support are provided by different network members, and what support functions are most valued. Methods: Adults with first stroke were recruited from a stroke unit, and participated in in-depth interviews 8-15 months post stroke. Framework Analysis was used to build thematic and explanatory accounts of the data. Results: Twenty-nine participants took part. Main themes to emerge were: the spouse was the most important provider of support; children were a relatively stable source of support, although many participants expressed reservations about worrying a child; relatives and friends typically provided social companionship and emotional support rather than on-going practical support. The only universally valued support function was the sense that someone was concerned and cared. Other valued functions were: social companionship including everyday social ‘chit chat’; practical support provided sensitively; and, for many, sharing worries and sensitive encouragement. The manner and context in which support was provided was important: support was easiest to receive when it communicated concern, and was part of a reciprocal, caring relationship. Conclusions: As well as measuring supportive acts, researchers and clinicians should consider the manner and context of support

The impact of funding models on the integration of registered nurses in primary health care teams: protocol for a multi-phase mixed-methods study in Canada.

BACKGROUND: Family practice registered nurses co-managing patient care as healthcare professionals in interdisciplinary primary care teams have been shown to improve access, continuity of care, patient satisfaction, and clinical outcomes for patients with chronic diseases while being cost-effective. Currently, however, it is unclear how different funding models support or hinder the integration of family practice nurses into existing primary health care systems and interdisciplinary practices. This has resulted in the underutilisation of family practice nurses in contributing to high-quality patient care. METHODS: This mixed-methods project is comprised of three studies: (1) a funding model analysis; (2) case studies; and (3) an online survey with family practice nurses. The funding model analysis will employ policy scans to identify, describe, and compare the various funding models used in Canada to integrate family practice nurses in primary care. Case studies involving qualitative interviews with clinic teams (family practice nurses, physicians, and administrators) and family practice nurse activity logs will explore the variation of nursing professional practice, training, skill set, and team functioning in British Columbia, Nova Scotia, Ontario, and Quebec. Interview transcripts will be analysed thematically and comparisons will be made across funding models. Activity log responses will be analysed to represent nurses\u27 time spent on independent, dependent, interdependent, or non-nursing work in each funding model. Finally, a cross-sectional online survey of family practice nurses in Canada will examine the relationships between funding models, nursing professional practice, training, skill set, team functioning, and patient care co-management in primary care. We will employ bivariate tests and multivariable regression to examine these relationships in the survey results. DISCUSSION: This project aims to address a gap in the literature on funding models for family practice nurses. In particular, findings will support provincial and territorial governments in structuring funding models that optimise the roles of family practice nurses while establishing evidence about the benefits of interdisciplinary team-based care. Overall, the findings may contribute to the integration and optimisation of family practice nursing within primary health care, to the benefit of patients, primary healthcare providers, and health care systems nationally

Tectonic Transport Directions, Shear Senses and Deformation Temperatures Indicated by Quartz c‐Axis Fabrics and Microstructures in a NW‐SE Transect across the Moine and Sgurr Beag Thrust Sheets, Caledonian Orogen of Northern Scotland

Moine metasedimentary rocks of northern Scotland are characterized by arcuate map patterns of mineral lineations that swing progressively clockwise from orogen‐perpendicular E‐trend-ing lineations in greenschist facies mylonites above the Moine thrust on the foreland edge of the Caledonian Orogen, to S‐trending lineations at higher structural levels and metamorphic grades in the hinterland. Quartz c‐axis fabrics measured on a west to east coast transect demonstrate that the lineations developed parallel to the maximum principal extension direction and therefore track the local tectonic transport direction. Microstructures and c‐axis fabrics document a progressive change from top to the N shearing in the hinterland to top to the W shearing on the foreland edge. Field relationships indicate that the domain of top to the N shearing was at least 55 km wide before later horizontal shortening on km‐scale W‐vergent folds that detach on the underlying Moine thrust. Previously published data from the Moine thrust mylonites demonstrate that top to the W shearing had largely ceased by 430 Ma, while preliminary isotopic age data suggest top to the N shearing occurred at ~470–450 Ma. In addition, data from the east coast end of our transect indicate normal-sense top down‐SE shearing at close to peak temperatures at ~420 Ma that may be related to the closing stages of Scandian deformation, metamorphism and cooling/exhumation

Small and mighty: adaptation of superphylum Patescibacteria to groundwater environment drives their genome simplicity.

BackgroundThe newly defined superphylum Patescibacteria such as Parcubacteria (OD1) and Microgenomates (OP11) has been found to be prevalent in groundwater, sediment, lake, and other aquifer environments. Recently increasing attention has been paid to this diverse&nbsp;superphylum including &gt;&nbsp;20 candidate phyla&nbsp;(a large part of the candidate phylum radiation, CPR) because it refreshed our view of the tree of life. However, adaptive traits contributing to its prevalence are still not well known.ResultsHere, we investigated the genomic features and metabolic pathways of Patescibacteria in groundwater through genome-resolved metagenomics analysis of &gt; 600 Gbp sequence data. We observed that, while the members of Patescibacteria have reduced genomes (~ 1 Mbp) exclusively, functions essential to growth and reproduction such as genetic information processing were retained. Surprisingly, they have sharply reduced redundant and nonessential functions, including specific metabolic activities and stress response systems. The Patescibacteria have ultra-small cells and simplified membrane structures, including flagellar assembly, transporters, and two-component systems. Despite the lack of CRISPR viral defense, the bacteria may evade predation through deletion of common membrane phage receptors and other alternative strategies, which may explain the low representation of prophage proteins in their genomes and lack of CRISPR. By establishing the linkages between bacterial features and the groundwater environmental conditions, our results provide important insights into the functions and evolution of this CPR group.ConclusionsWe found that Patescibacteria has streamlined many functions while acquiring advantages such as avoiding phage invasion, to adapt to the groundwater environment. The unique features of small genome size, ultra-small cell size, and lacking CRISPR of this large lineage are bringing new understandings on life of Bacteria. Our results provide important insights into the mechanisms for adaptation of the superphylum in the groundwater environments, and demonstrate a case where less is more, and small is mighty