P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

Community views on active case finding for tuberculosis in low- and middle-income countries: a qualitative evidence synthesis

Objectives: This is a protocol for a Cochrane Review (qualitative). The objectives are as follows:. To synthesize community views on tuberculosis active case finding programmes in low- and middle-income countries. Review question In areas of the world where tuberculosis is common, what views do communities and high-risk populations hold about tuberculosis active case finding programmes?. Target audience Policy groups at global, national and local levels considering, recommending, designing, or implementing active case finding programmes. Feasibility of programmes, as assessed by health staff, will not be part of this review

Fringe or background: Characterizing deep-water mudstones beyond the basin-floor fan sandstone pinchout

Mud dominates volumetrically the fraction of sediment delivered and deposited in deep-water environments, and mudstone is a major component of basin-floor successions. However, studies of basin-floor deposits have mainly focused on their proximal sandstone-prone part. A consequent bias therefore remains in the understanding of depositional processes and stratigraphic architecture in mudstone-prone distal settings beyond the sandstone pinchouts of basin-floor fans. This study uses macroscopic and microscopic descriptions of over 500 m of continuous cores from research boreholes from the Permian Skoorsteenberg Formation of the Karoo Basin, South Africa, to document the sedimentology, stratigraphy, and ichnology of a distal mudstone-prone basin-floor succession. Very thin- to thin-bedded mudstones, deposited by low-density turbidity currents, stack to form bedsets bounded by thin packages ( 0.7 m thick) background mudstones. Stratigraphic correlation between cores suggests that bedsets represent the distal fringes of submarine fan lobe elements and/or lobes, and bedset packages represent the distal fringes of lobe complexes and/or lobe complex sets. The internal stacking pattern of bedsets and bedset packages is highly variable vertically and laterally, which records dominantly autogenic processes (e.g., compensational stacking, avulsion of feeder channels). The background mudstones are characterized by remnant tractional structures and outsize particles, and are interpreted as deposited from low-density turbidity currents and debris flows before intense biogenic reworking. These observations challenge the idea that mud accumulates only from hemipelagic suspension fallout in distal basin-floor environments. Thin background mudstones separating bedsets ( 0.7 m thick) are interpreted to dominantly mark allogenically driven regional decrease of sand supply to the basin floor. The recognition of sandstone-prone basin-floor fans passing into genetically linked distal fringe mudstones suggests that submarine lobes are at least ∼ 20 km longer than previously estimated. This study provides sedimentological, stratigraphic, and ichnological criteria to differentiate mudstones deposited in different sub-environments in distal deep-water basin-floor settings, with implications for the accurate characterization of basin-floor fan architecture, and their use as archives of paleoenvironmental change

Transport and deposition of mud in deep‐water environments: Processes and stratigraphic implications

Deep-water mudstones are often considered as background sediments, deposited by vertical suspension fallout, and the range of transport and depositional processes are poorly understood compared to their shallow-marine counterparts. Here, we present a dataset from a 538.50 m-thick cored succession through the Permian muddy lower Ecca Group of the Tanqua depocentre (southwest Karoo Basin, South Africa). This study aims to characterize the range of mudstone facies, transport and depositional processes, and stacking patterns recorded in deep-water environments prior to deposition of the Tanqua Karoo sandy basin-floor fans. A combination of macroscopic and microscopic description techniques and ichnological analysis has defined nine sedimentary facies that stack in a repeated pattern to produce 2–26-m-thick depositional units. The lower part of each unit is characterized by bedded mudstone deposited by dilute, low-density turbidity currents with evidence for hyperpycnal-flow processes and sediment remobilization. The upper part of each unit is dominated by more organic-rich 27 bedded mudstone with common mudstone intraclasts, deposited by debris flows and transitional flows, with scarce indicators of suspension fallout. The intensity of bioturbation and burrow size increases upward through each depositional unit, consistent with a decrease in physicochemically stressed conditions, linked to a lower sediment accumulation rate. This vertical facies transition in the single well dataset can be interpreted to represent relative sea level variations, where the hyperpycnal stressed conditions in the lower part of the units were driven by sea level fall and the more bioturbated upper part of the unit represents backstepping, related to sea level rise. Alternatively, this facies transition may represent autogenic compensational stacking. The prevalence of sediment density flow deposits, even in positions distal or lateral to the sediment entry point, challenges the idea that deep-water mudstones are primarily the deposits of passive rainout along continental margins

Active immunization with myelin-derived altered peptide ligand reduces mechanical pain hypersensitivity following peripheral nerve injury

BACKGROUND: T cells have been implicated in neuropathic pain that is caused by peripheral nerve injury. Immunogenic myelin basic protein (MBP) peptides have been shown to initiate mechanical allodynia in a T cell-dependent manner. Antagonistic altered peptide ligands (APLs) are peptides with substitutions in amino acid residues at T cell receptor contact sites and can inhibit T cell function and modulate inflammatory responses. In the present study, we studied the effects of immunization with MBP-derived APL on pain behavior and neuroinflammation in an animal model of peripheral nerve injury. METHODS: Lewis rats were immunized subcutaneously at the base of the tail with either a weakly encephalitogenic peptide of MBP (cyclo-MBP(87-99)) or APL (cyclo-(87-99)[A(91),A(96)]MBP(87-99)) in complete Freund’s adjuvant (CFA) or CFA only (control), following chronic constriction injury (CCI) of the left sciatic nerve. Pain hypersensitivity was tested by measurements of paw withdrawal threshold to mechanical stimuli, regulatory T cells in spleen and lymph nodes were analyzed by flow cytometry, and immune cell infiltration into the nervous system was assessed by immunohistochemistry (days 10 and 30 post-CCI). Cytokines were measured in serum and nervous tissue of nerve-injured rats (day 10 post-CCI). RESULTS: Rats immunized with the APL cyclo-(87-99)[A(91),A(96)]MBP(87-99) had significantly reduced mechanical pain hypersensitivity in the ipsilateral hindpaw compared to cyclo-MBP(87-99)-treated and control rats. This was associated with significantly decreased infiltration of T cells and ED1+ macrophages in the injured nerve of APL-treated animals. The percentage of anti-inflammatory (M2) macrophages was significantly upregulated in the APL-treated rats on day 30 post-CCI. Compared to the control rats, microglial activation in the ipsilateral lumbar spinal cord was significantly increased in the MBP-treated rats, but was not altered in the rats immunized with the MBP-derived APL. In addition, immunization with the APL significantly increased splenic regulatory T cells. Several cytokines were significantly altered after CCI, but no significant difference was observed between the APL-treated and control rats. CONCLUSIONS: These results suggest that immune deviation by active immunization with a non-encephalitogenic MBP-derived APL mediates an analgesic effect in animals with peripheral nerve injury. Thus, T cell immunomodulation warrants further investigation as a possible therapeutic strategy for the treatment of peripheral neuropathic pain

Exercise-based cardiac rehabilitation improves exercise capacity and health-related quality of life in people with atrial fibrillation: A systematic review and meta-analysis of randomised and non-randomised trials

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjective The aim of this study was to undertake a contemporary review of the impact of exercise-based cardiac rehabilitation (CR) targeted at patients with atrial fibrillation (AF). Methods We conducted searches of PubMED, EMBASE and the Cochrane Library of Controlled Trials (up until 30 November 2017) using key terms related to exercise-based CR and AF. Randomised and non-randomised controlled trials were included if they compared the effects of an exercise-based CR intervention to a no exercise or usual care control group. Meta-analyses of outcomes were conducted where appropriate. Results The nine randomised trials included 959 (483 exercise-based CR vs 476 controls) patients with various types of AF. Compared with control, pooled analysis showed no difference in all-cause mortality (risk ratio (RR) 1.08, 95% CI 0.77 to 1.53, p=0.64) following exercise-based CR. However, there were improvements in health-related quality of life (mean SF-36 mental component score (MCS): 4.00, 95% CI 0.26 to 7.74; p=0.04 and mean SF-36 physical component score: 1.82, 95% CI 0.06 to 3.59; p=0.04) and exercise capacity (mean peak VO2: 1.59 ml/kg/min, 95% CI 0.11 to 3.08; p=0.04; mean 6 min walk test: 46.9 m, 95% CI 26.4 to 67.4; p<0.001) with exercise-based CR. Improvements were also seen in AF symptom burden and markers of cardiac function. Conclusions Exercise capacity, cardiac function, symptom burden and health-related quality of life were improved with exercise-based CR in the short term (up to 6 months) targeted at patients with AF. However, high-quality multicentre randomised trials are needed to clarify the impact of exercise-based CR on key patient and health system outcomes (including health-related quality of life, mortality, hospitalisation and costs) and how these effects may vary across AF subtypes.National Institute for Health Research (NIHR

Breast, cervical, and colorectal cancer screening rates amongst female Cambodian, Somali, and Vietnamese immigrants in the USA

<p>Abstract</p> <p>Introduction</p> <p>Minority women, particularly immigrants, have lower cancer screening rates than Caucasian women, but little else is known about cancer screening among immigrant women. Our objective was to assess breast, cervical, and colorectal cancer screening rates among immigrant women from Cambodia, Somalia, and Vietnam and explore screening barriers.</p> <p>Methods</p> <p>We measured screening rates by systematic chart review (N = 100) and qualitatively explored screening barriers via face-to-face questionnaire (N = 15) of women aged 50–75 from Cambodia, Somalia, and Vietnam attending a general medicine clinic (Portland, Maine, USA).</p> <p>Results</p> <p><it>Chart Review </it>– Somali women were at higher risk of being unscreened for breast, cervical, and colorectal cancer compared with Cambodian and Vietnamese women. A longer period of US residency was associated with being screened for colorectal cancer. We observed a 7% (OR 1.07, 95% CI 1.01–1.13, p = 0.01) increase in the odds that a woman would undergo a fecal occult blood test for each additional year in the US, and a 39% increase in the odds of a woman being screened by colonoscopy or flexible sigmoidoscopy for every five years of additional US residence (OR 1.39, 95% CI 1.21–1.61, p = 0.02). We did not observe statistically significant relationships between odds of being screened by mammography, clinical breast exam or papanicolaou test according to years in the US. <it>Questionnaire </it>– We identified several barriers to breast, cervical, and colorectal cancer screening, including discomfort with exams conducted by male physicians.</p> <p>Discussion</p> <p>Somali women were less likely to be screened for breast, cervical, and colorectal cancer than Cambodian and Vietnamese women in this population, and uptake of colorectal cancer screening is associated with years of residency in this country. Future efforts to improve equity in cancer screening among immigrants may require both provider and community education.</p

Cardiovascular disease risk prediction in older people: a qualitative study.

BACKGROUND: Despite cardiovascular disease (CVD) risk prediction equations becoming more widely available for people aged ≥75 years, views of older people on CVD risk assessment are unknown. AIM: To explore older people's views on CVD risk prediction and its assessment. DESIGN AND SETTING: Qualitative study of community-dwelling older people in New Zealand. METHOD: A diverse group of older people was purposively recruited. Semi-structured interviews and focus groups were conducted, transcribed verbatim, and thematically analysed. RESULTS: Thirty-nine participants (mean age 74 years) of Māori, Pacific, South Asian, and European ethnicities participated in one of 26 interviews or one of three focus groups. Three key themes emerged: poor knowledge and understanding of CVD and its risk assessment; acceptability and perceived benefit of knowing and receiving advice on managing personal CVD risk; and distinguishing between CVD outcomes - stroke and heart attack are not the same. Most participants did not understand CVD terms, but were familiar with the terms 'heart attack' and 'stroke', and understood lifestyle risk factors for these events. Participants valued CVD outcomes differently, fearing stroke and disability - which might adversely affect independence and quality of life - but were less concerned about a heart attack, which was perceived as causing less disability or swifter death. These findings and preferences were similar across ethnic groups. All but two participants wanted to know their CVD risk, how to manage it, and distinguish between CVD outcomes. Those who did not wish to know perceived this as something only their God could decide. CONCLUSION: To inform clinical decision making for older people, consideration of an individual's wish to know their risk is important, and risk prediction tools should provide separate event types rather than just composite outcomes