Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates

Background: Sexual differentiation in female mammals can be altered by the proximity of male littermates in utero, a phenomenon known as the intrauterine position effect (IUP). Among simian primates, callitrichines (marmosets and tamarins) are likely candidates for IUP, since they exhibit obligate dizygotic twinning and fetuses share extensive vascularization in utero. In this paper, we determined whether female reproductive parameters are altered by gestating with a male twin and evaluated changes in genes associated with anti-Müllerian and steroid hormones in twinning callitrichine primates. Methods: We assessed the impact of gestation with male cotwins on reproductive performance and survivorship in female marmosets (Callithrix) and lion tamarins (Leontopithecus), contrasting measures for females gestated with one or more littermates (M+) or no male littermates (0M). We compared targeted coding regions for genes involved in steroidal and anti-Müllerian hormone mediation of sexual differentiation for representatives of twinning callitrichines (Callithrix, Saguinus, and Leontopithecus) with closely related New World primates that produce single births (Saimiri and Callimico). Results: IUP effects in females were absent in female callitrichine primates: age at first ovulation, average litter size, and the proportion of stillborn infants, and lifetime survivorship did not differ between M+ and 0M females. We documented multiple nonsynonymous substitutions in genes associated with steroid synthesis, transport, and cellular action (SRD5A2, CYP19A1, SHBG, and AR) and with anti-Müllerian hormone (AMH and AMHR2) in callitrichines. In the only callitrichine to produce single infants (Callimico), two genes contained nonsynonymous substitutions relative to twinning callitrichines (CYP19A1 and AMRHR2); these substitutions were identical with nontwinning Saimiri and humans, suggesting a reversion to an ancestral sequence.Conclusions: In spite of a shared placental vasculature with opposite-sex twins throughout embryonic and fetal development, female callitrichine primates gestated with a male cotwin exhibit no decrement in reproductive performance relative to females gestated with female cotwins. Hence, IUP effects on female reproduction in callitrichines are modest. We have identified mutations in candidate genes relevant for steroid hormone signaling and metabolism, and especially in AMH-related genes, that are likely to alter protein structure and function in the callitrichines. These mutations may confer protection for females from the masculinizing and defeminizing influences of gestating with a male cotwin

Petrology, Palynology, and Geochemistry of Gray Hawk Coal (Early Pennsylvanian, Langsettian) in Eastern Kentucky, USA

This study presents recently collected data examining the organic petrology, palynology, mineralogy and geochemistry of the Gray Hawk coal bed. From the Early Pennsylvanian, Langsettian substage, Gray Hawk coal has been mined near the western edge of the eastern Kentucky portion of the Central Appalachian coalfield. While the coal is thin, rarely more than 0.5-m thick, it has a low-ash yield and a low-S content, making it an important local resource. The Gray Hawk coal palynology is dominated by Lycospora spp., and contains a diverse spectrum of small lycopods, tree ferns, small ferns, calamites, and gymnosperms. The maceral assemblages show an abundance of collotelinite, telinite, vitrodetrinite, fusinite, and semifusinite. Fecal pellet-derived macrinite, albeit with more compaction than is typically seen in younger coals, was observed in the Gray Hawk coal. The minerals in the coal are dominated by clay minerals (e.g., kaolinite, mixed-layer illite/smectite, illite), and to a lesser extent, pyrite, quartz, and iron III hydroxyl-sulfate, along with traces of chlorite, and in some cases, jarosite, szomolnokite, anatase, and calcite. The clay minerals are of authigenic and detrital origins. The occurrence of anatase as cell-fillings also indicates an authigenic origin. With the exception of Ge and As, which are slightly enriched in the coals, the concentrations of other trace elements are either close to or much lower than the averages for world hard coals. Arsenic and Hg are also enriched in the top bench of the coal and probably occur in pyrite. The elemental associations (e.g., Al2O3/TiO2, Cr/Th-Sc/Th) indicate a sediment-source region with intermediate and felsic compositions. Rare metals, including Ga, rare earth elements and Ge, are highly enriched in the coal ashes, and the Gray Hawk coals have a great potential for industrial use of these metals. The rare earth elements in the samples are weakly fractionated or are characterized by heavy-REE enrichment, indicating an input of natural waters or probably epithermal solutions

Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women\u27s interagency HIV study.

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear. In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI). We found liver fibrosis (APRI) was 50% lower in Elites and ARTc compared to ARTuc. Higher liver fibrosis was associated with significantly low CD4+ T cell counts (P \u3c 0.001, coefficient r = −0.463). Immune activation varied by HIV phenotype but was not modified by HCV viremia. HCV viremia was associated with elevated CD8 T-cell Caspase-3 in Elites, ARTuc, and HIV− except ARTc. CD8 T-cell Caspase-3 levels were significantly higher in HCV RNA+ Elites (P = 0.04) and ARTuc (P = 0.001) and HIV− groups (P = 0.02) than ARTc. Importantly, ARTuc HCV RNA+ had significantly higher CD4 T-cell interleukin-17 levels than ARTuc HCV RNA− (P = 0.005). HIV control was associated with lower liver fibrosis in HCV/HIV co-infected women. HCV viremia is associated with an inflammatory CD4 TH-17 phenotype in absence of HIV control and higher frequency of pro-apoptosis CD8 T-cells critical to avert progression of HIV and HCV disease that is attenuated in ART controllers. Elite controllers with HCV viremia are more prone to CD8 T-cell apoptosis than ART controllers, which could have negative consequences over time, highlighting the importance of ART control in HCV/HIV coinfected individuals

The effect of HIV infection and HCV viremia on Inflammatory Mediators and Hepatic Injury-The Women\u27s Interagency HIV Study.

Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18), ART-treated HIV-controlled (ARTc, n = 20), uncontrolled on anti-retroviral therapy (ARTuc, n = 21) and elite HIV controllers (Elite, n = 20). All were HCV seroreactive and had either resolved (HCV RNA-; \u3c50IU/mL) or had chronic HCV infection (HCV RNA+). In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI) was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection

Effectiveness and cost-effectiveness of a physical activity loyalty scheme for behaviour change maintenance: a cluster randomised controlled trial

Abstract Background Increasing physical activity in the workplace can provide employee physical and mental health benefits, and employer economic benefits through reduced absenteeism and increased productivity. The workplace is an opportune setting to encourage habitual activity. However, there is limited evidence on effective behaviour change interventions that lead to maintained physical activity. This study aims to address this gap and help build the necessary evidence base for effective, and cost-effective, workplace interventions. Methods/design This cluster randomised control trial will recruit 776 office-based employees from public sector organisations in Belfast and Lisburn city centres, Northern Ireland. Participants will be randomly allocated by cluster to either the Intervention Group or Control Group (waiting list control). The 6-month intervention consists of rewards (retail vouchers, based on similar principles to high street loyalty cards), feedback and other evidence-based behaviour change techniques. Sensors situated in the vicinity of participating workplaces will promote and monitor minutes of physical activity undertaken by participants. Both groups will complete all outcome measures. The primary outcome is steps per day recorded using a pedometer (Yamax Digiwalker CW-701) for 7 consecutive days at baseline, 6, 12 and 18 months. Secondary outcomes include health, mental wellbeing, quality of life, work absenteeism and presenteeism, and use of healthcare resources. Process measures will assess intervention “dose”, website usage, and intervention fidelity. An economic evaluation will be conducted from the National Health Service, employer and retailer perspective using both a cost-utility and cost-effectiveness framework. The inclusion of a discrete choice experiment will further generate values for a cost-benefit analysis. Participant focus groups will explore who the intervention worked for and why, and interviews with retailers will elucidate their views on the sustainability of a public health focused loyalty card scheme. Discussion The study is designed to maximise the potential for roll-out in similar settings, by engaging the public sector and business community in designing and delivering the intervention. We have developed a sustainable business model using a ‘points’ based loyalty platform, whereby local businesses ‘sponsor’ the incentive (retail vouchers) in return for increased footfall to their business. Trial registration ISRCTN17975376 (Registered 19/09/2014)

Report on the 2022 excavations at Wogan Cavern (Pembroke, Pembrokeshire, UK)

Publisher Copyright: © 2023 British Cave Research Association. All rights reserved.Peer reviewe

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

<p>Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.</p> <p>Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.</p> <p>Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.</p> <p>Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.</p&gt

Measuring the costs of outreach motivational interviewing for smoking cessation and relapse prevention among low-income pregnant women

<p>Abstract</p> <p>Background</p> <p>Economic theory provides the philosophical foundation for valuing costs in judging medical and public health interventions. When evaluating smoking cessation interventions, accurate data on costs are essential for understanding resource consumption. Smoking cessation interventions, for which prior data on resource costs are typically not available, present special challenges. We develop a micro-costing methodology for estimating the real resource costs of outreach motivational interviewing (MI) for smoking cessation and relapse prevention among low-income pregnant women and report results from a randomized controlled trial (RCT) employing the methodology. Methodological standards in cost analysis are necessary for comparison and uniformity in analysis across interventions. Estimating the costs of outreach programs is critical for understanding the economics of reaching underserved and hard-to-reach populations.</p> <p>Methods</p> <p>Randomized controlled trial (1997-2000) collecting primary cost data for intervention. A sample of 302 low-income pregnant women was recruited from multiple obstetrical sites in the Boston metropolitan area. MI delivered by outreach health nurses vs. usual care (UC), with economic costs as the main outcome measures.</p> <p>Results</p> <p>The total cost of the MI intervention for 156 participants was $48,672 or$312 per participant. The total cost of $311.8 per participant for the MI intervention compared with a cost of$4.82 per participant for usual care, a difference of $307 ([CI],$289.2 to $322.8). The total fixed costs of the MI were$3,930 and the total variable costs of the MI were $44,710. The total expected program costs for delivering MI to 500 participants would be 147,430, assuming no economies of scale in program delivery. The main cost components of outreach MI were intervention delivery, travel time, scheduling, and training.</p> <p>Conclusion</p> <p>Grounded in economic theory, this methodology systematically identifies and measures resource utilization, using a process tracking system and calculates both component-specific and total costs of outreach MI. The methodology could help improve collection of accurate data on costs and estimates of the real resource costs of interventions alongside clinical trials and improve the validity and reliability of estimates of resource costs for interventions targeted at underserved and hard-to-reach populations.</p