Non-synonymous single nucleotide polymorphisms in the P2X receptor genes: Association with diseases, impact on receptor functions and potential use as diagnosis biomarkers

P2X receptors are Ca2+-permeable cationic channels in the cell membranes, where they play an important role in mediating a diversity of physiological and pathophysiological functions of extracellular ATP. Mammalian cells express seven P2X receptor genes. Single nucleotide polymorphisms (SNPs) are widespread in the P2RX genes encoding the human P2X receptors, particularly the human P2X7 receptor. This article will provide anoverview of the non-synonymous SNPs (NS-SNPs) that have been associated with or implicated in altering the susceptibility to pathologies or disease conditions, and discuss the consequences of the mutations resulting from such NS-SNPs on the receptor functions. Disease-associated NS-SNPs in the P2RXgenes have been valuable in understanding the disease etiology and the receptor function, and are promising as biomarkers to be used for the diagnosis and development of stratified therapeutics. © 2014 by the authors; licensee MDPI, Basel, Switzerland

Sexual dimorphism in prostacyclin-mimetic responses within rat mesenteric arteries: A novel role for KV7.1 in shaping IP receptor-mediated relaxation

Background and Purpose Prostacyclin mimetics express potent vasoactive effects via prostanoid receptors that are not unequivocally defined, as to date no study has considered sex as a factor. The aim of this study was to determine the contribution of IP and EP3 prostanoid receptors to prostacyclin mimetic iloprost-mediated responses, whether KV7.1–5 channels represent downstream targets of selective prostacyclin-IP-receptor agonist MRE-269 and the impact of the oestrus cycle on vascular reactivity. Experimental Approach Within second-order mesenteric arteries from male and female Wistar rats, we determined (1) relative mRNA transcripts for EP1–4 (Ptger1–4), IP (Ptgi) and TXA2 (Tbxa) prostanoid receptors via RT-qPCR; (2) the effect of iloprost, MRE-269, isoprenaline and ML277 on precontracted arterial tone in the presence of inhibitors of prostanoid receptors, potassium channels and the molecular interference of KV7.1 via wire-myograph; (3) oestrus cycle stage via histological changes in cervical cell preparations. Key Results Iloprost evoked a biphasic response in male mesenteric arteries, at concentrations ≤100 nmol·L−1 relaxing, then contracting the vessel at concentration ≥300 nmol·L−1, a process attributed to IP and EP3 receptors respectively. Secondary contraction was absent in the females, which was associated with a reduction in Ptger3. Pharmacological inhibition and molecular interference of KV7.1 significantly attenuated relaxations produced by the selective IP receptor agonist MRE-269 in male and female Wistar in dioestrus/metoestrus, but not pro-oestrus/oestrus. Conclusions and Implications Stark sexual dimorphisms in iloprost-mediated vasoactive responses are present within mesenteric arteries. KV7.1 is implicated in IP receptor-mediated vasorelaxation and is impaired by the oestrus cycle

Care home manager attitudes to balancing risk and autonomy for residents with dementia

Objective: To determine how care home managers negotiate the conflict between maintaining a safe environment while enabling the autonomy of residents with dementia. This is important because there is limited research with care home managers; yet, they are key agents in the implementation of national policies. Method: Semi-structured interviews were conducted with 18 managers from care homes offering dementia care in the Northwest of England. Data were analysed using a thematic analysis approach. Results: There were three areas in which care home staff reported balancing safety and risk against the individual needs of residents. First, the physical environment created a tension between safety and accessibility to the outside world, which meant that care homes provided highly structured or limited access to outdoor space. Second, care home managers reflected a balancing act between an individual's autonomy and the need to protect their residents’ dignity. Finally, care home managers highlighted the ways in which an individual's needs were framed by the needs of other residents to the extent that on some occasions an individual's needs were subjugated to the needs of the general population of a home. Conclusion: There was a strong, even dominant, ethos of risk management and keeping people safe. Managing individual needs while maintaining a safe care home environment clearly is a constant dynamic interpersonal process of negotiating and balancing competing interests for care home managers

The Emerging Scholarly Brain

It is now a commonplace observation that human society is becoming a coherent super-organism, and that the information infrastructure forms its emerging brain. Perhaps, as the underlying technologies are likely to become billions of times more powerful than those we have today, we could say that we are now building the lizard brain for the future organism.Comment: to appear in Future Professional Communication in Astronomy-II (FPCA-II) editors A. Heck and A. Accomazz

Long-term postharvest aroma evolution of tomatoes with the alcobaça (alc) mutation

The postharvest evolution of Penjar tomatoes has been studied in four accessions representative of the variability of the varietal type. The long-term shelf life of these materials, which carry the alc allele, was confirmed with 31.2-59.1% of commercial fruits after 6 months of effective conservation at room temperature and a limited loss of weight (21.1-27.9%). Aroma in Penjar tomatoes is differentiated from other tomato varieties by a characteristic 'sharp-floral' aroma descriptor. The evolution of the 'sharp-floral' aroma during postharvest showed a peak of intensity at 2 months of postharvest, though in one accession a delay of 2 months in this response was detected. Out of 25 volatiles analysed, including main and background notes, a reverse iPLS variable selection revealed that the main candidates behind this aromatic behaviour are ¿-terpineol, trans-2-hexenal, 6-methyl-5-hepten-2-one, trans-2-octenal, ¿-pinene, ß-ionone, 2 + 3-methylbutanol and phenylacetaldehyde. Between harvest and 2 months postharvest, most compounds reduced considerably their concentration, while the intensity of the 'sharp-floral' descriptor increased, which means that probably there is a rearrangement of the relative concentrations among volatiles that may lead to masking/unmasking processes. © 2011 Springer-Verlag.This work was supported by grants from the Conselleria de Agricultura, Pesca y Alimentacio de la Comunidad Valenciana, the Fundacion de la Comunidad Valenciana para la Investigacion Agroalimentaria (AGROALIMED) and from the Departament d'Agricultura, Alimentacio i Accio Rural (DAR) de la Generalitat de Catalunya.Casals Missio, J.; Cebolla Cornejo, J.; Rosello Ripolles, S.; Beltran Arandes, J.; Casanas, F.; Nuez Viñals, F. (2011). Long-term postharvest aroma evolution of tomatoes with the alcobaça (alc) mutation. 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Is Incarceration a Contributor to Health Disparities? Access to Care of Formerly Incarcerated Adults

Despite the disproportionate prevalence of incarceration in communities of color, few studies have examined its contribution to health disparities. We examined whether a lifetime history of incarceration is associated with recent access to medical and dental care. We performed a secondary data analysis of the 2007 Los Angeles County Health Survey, a population-based random-digit-dialing telephone survey of county households. Any history of incarceration in a prison/jail/detention center as an adult was assessed for a random subsample. Bivariate and multivariate logistic regression analyses examined whether incarceration history was associated with access to care, controlling for other characteristics. Ten percent of our study population reported a history of incarceration. While persons with an incarceration history were similar to their peers with regard to health and insurance status, their access to medical and dental care was worse. Incarceration history was independently associated with disparities in access to care. Interventions to improve the health of communities affected by high rates of incarceration could include efforts that enable access to care for formerly incarcerated adults

Police Strategies and Suspect Responses in Real-Life Serious Crime Interviews

This research focuses exclusively on real-life taped interviews with serious crime suspects and examines the strategies used and types of questions asked by police, and suspects’ responses to these. The information source was audio-tape-recorded interviews with 56 suspects. These recordings were obtained from 11 police services across England and Wales and were analysed using a specially designed coding frame. It was found that interviewers employed a range of strategies with presentation of evidence and challenge the most frequently observed. Closed questions were by far the most frequently used, and open questions, although less frequent, were found to occur more during the opening phases of the interviews. The frequency of ineffective question types (e.g. negative, repetitive, multiple) was low. A number of significant associations were observed between interviewer strategies and suspect responses. Rapport/empathy and open-type questions were associated with an increased likelihood of suspects admitting the offence whilst describing trauma, and negative questions were associated with a decreased likelihood

Bursaries, writing grants and fellowships: a strategy to develop research capacity in primary health care

BACKGROUND: General practitioners and other primary health care professionals are often the first point of contact for patients requiring health care. Identifying, understanding and linking current evidence to best practice can be challenging and requires at least a basic understanding of research principles and methodologies. However, not all primary health care professionals are trained in research or have research experience. With the aim of enhancing research skills and developing a research culture in primary health care, University Departments of General Practice and Rural Health have been supported since 2000 by the Australian Government funded 'Primary Health Care Research Evaluation and Development (PHCRED) Strategy'. A small grant funding scheme to support primary health care practitioners was implemented through the PHCRED program at Flinders University in South Australia between 2002 and 2005. The scheme incorporated academic mentors and three types of funding support: bursaries, writing grants and research fellowships. This article describes outcomes of the funding scheme and contributes to the debate surrounding the effectiveness of funding schemes as a means of building research capacity. METHODS: Funding recipients who had completed their research were invited to participate in a semi-structured 40-minute telephone interview. Feedback was sought on acquisition of research skills, publication outcomes, development of research capacity, confidence and interest in research, and perception of research. Data were also collected on demographics, research topics, and time needed to complete planned activities. RESULTS: The funding scheme supported 24 bursaries, 11 writing grants, and three research fellows. Nearly half (47%) of all grant recipients were allied health professionals, followed by general practitioners (21%). The majority (70%) were novice and early career researchers. Eighty-nine percent of the grant recipients were interviewed. Capacity, confidence, and level of research skills in ten core areas were generally considered to have improved as a result of the award. More than half (53%) had presented their research and 32% had published or submitted an article in a peer-reviewed journal. CONCLUSION: A small grant and mentoring scheme through a University Department can effectively enhance research skills, confidence, output, and interest in research of primary health care practitioners

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives