Effects of Long-Term Hypoxia on Enzymes of Carbohydrate Metabolism in the Gulf killifish, Fundulus grandis

The goal of the current study was to generate a comprehensive, multi-tissue perspective of the effects of chronic hypoxic exposure on carbohydrate metabolism in the Gulf killifish Fundulus grandis. Fish were held at approximately 1.3·mg·l–1 dissolved oxygen (~3.6·kPa) for 4·weeks, after which maximal activities were measured for all glycolytic enzymes in four tissues (white skeletal muscle, liver, heart and brain), as well as for enzymes of glycogen metabolism (in muscle and liver) and gluconeogenesis (in liver). The specific activities of enzymes of glycolysis and glycogen metabolism were strongly suppressed by hypoxia in white skeletal muscle, which may reflect decreased energy demand in this tissue during chronic hypoxia. In contrast, several enzyme specific activities were higher in liver tissue after hypoxic exposure, suggesting increased capacity for carbohydrate metabolism. Hypoxic exposure affected fewer enzymes in heart and brain than in skeletal muscle and liver, and the changes were smaller in magnitude, perhaps due to preferential perfusion of heart and brain during hypoxia. The specific activities of some gluconeogenic enzymes increased in liver during long-term hypoxic exposure, which may be coupled to increased protein catabolism in skeletal muscle. These results demonstrate that when intact fish are subjected to prolonged hypoxia, enzyme activities respond in a tissue-specific fashion reflecting the balance of energetic demands, metabolic role and oxygen supply of particular tissues. Furthermore, within glycolysis, the effects of hypoxia varied among enzymes, rather than being uniformly distributed among pathway enzymes

Radiation‐Induced Oral Mucositis Hamster Model Using a Linear Accelerator Enhances Clinical Relevance of Preclinical Studies for Treatment Strategy Investigation

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory‐initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation‐induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro‐inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies

Translating and validating a Training Needs Assessment tool into Greek

<p>Abstract</p> <p>Background</p> <p>The translation and cultural adaptation of widely accepted, psychometrically tested tools is regarded as an essential component of effective human resource management in the primary care arena. The Training Needs Assessment (TNA) is a widely used, valid instrument, designed to measure professional development needs of health care professionals, especially in primary health care. This study aims to describe the translation, adaptation and validation of the TNA questionnaire into Greek language and discuss possibilities of its use in primary care settings.</p> <p>Methods</p> <p>A modified version of the English self-administered questionnaire consisting of 30 items was used. Internationally recommended methodology, mandating forward translation, backward translation, reconciliation and pretesting steps, was followed. Tool validation included assessing item internal consistency, using the alpha coefficient of Cronbach. Reproducibility (test – retest reliability) was measured by the kappa correlation coefficient. Criterion validity was calculated for selected parts of the questionnaire by correlating respondents' research experience with relevant research item scores. An exploratory factor analysis highlighted how the items group together, using a Varimax (oblique) rotation and subsequent Cronbach's alpha assessment.</p> <p>Results</p> <p>The psychometric properties of the Greek version of the TNA questionnaire for nursing staff employed in primary care were good. Internal consistency of the instrument was very good, Cronbach's alpha was found to be 0.985 (p < 0.001) and Kappa coefficient for reproducibility was found to be 0.928 (p < 0.0001). Significant positive correlations were found between respondents' current performance levels on each of the research items and amount of research involvement, indicating good criterion validity in the areas tested. Factor analysis revealed seven factors with eigenvalues of > 1.0, KMO (Kaiser-Meyer-Olkin) measure of sampling adequacy = 0.680 and Bartlett's test of sphericity, p < 0.001.</p> <p>Conclusion</p> <p>The translated and adapted Greek version is comparable with the original English instrument in terms of validity and reliability and it is suitable to assess professional development needs of nursing staff in Greek primary care settings.</p

In-reach specialist nursing teams for residential care homes : uptake of services, impact on care provision and cost-effectiveness

Background: A joint NHS-Local Authority initiative in England designed to provide a dedicated nursing and physiotherapy in-reach team (IRT) to four residential care homes has been evaluated.The IRT supported 131 residents and maintained 15 'virtual' beds for specialist nursing in these care homes. Methods: Data captured prospectively (July 2005 to June 2007) included: numbers of referrals; reason for referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of stay in IRT; prevented hospital admissions; early hospital discharges; avoided nursing home transfers; and detection of unrecognised illnesses. An economic analysis was undertaken. Results: 733 referrals were made during the 2 years (range 0.5 to 13.0 per resident per annum)resulting in a total of 6,528 visits. Two thirds of referrals aimed at maintaining the resident's independence in the care home. According to expert panel assessment, 197 hospital admissions were averted over the period; 20 early discharges facilitated; and 28 resident transfers to a nursing home prevented. Detection of previously unrecognised illnesses accounted for a high number of visits. Investment in IRT equalled £44.38 per resident per week. Savings through reduced hospital admissions, early discharges, delayed transfers to nursing homes, and identification of previously unrecognised illnesses are conservatively estimated to produce a final reduction in care cost of £6.33 per resident per week. A sensitivity analysis indicates this figure might range from a weekly overall saving of £36.90 per resident to a 'worst case' estimate of £2.70 extra expenditure per resident per week. Evaluation early in implementation may underestimate some cost-saving activities and greater savings may emerge over a longer time period. Similarly, IRT costs may reduce over time due to the potential for refinement of team without major loss in effectiveness. Conclusion: Introduction of a specialist nursing in-reach team for residential homes is at least cost neutral and, in all probability, cost saving. Further benefits include development of new skills in the care home workforce and enhanced quality of care. Residents are enabled to stay in familiar surroundings rather than unnecessarily spending time in hospital or being transferred to a higher dependency nursing home setting

Brain-based discourses and early intervention: a critical debate for health visiting

Neuroscientific discourses about early brain development and its plasticity have placed considerable importance upon parenting, emotional nurturing and attachment during the first 1001 ‘Critical Days’. This has informed a policy shift towards early intervention in the early years, and is shaping public health practice in this field particularly health visiting. This paper reviews these developments and outlines a critical debate that has been taking place amongst commentators concerned with how these brain based discourses are being applied in policy. Concerns include the policy readiness of the science, the focus upon parenting quality rather than contextual issues such as poverty, and that these developments are creating a new form of governance of families. In contrast these concerns have not been debated within health visiting raising questions about the profession’s engagement with evidence and policy

Dimethylthiourea protects against chlorine induced changes in airway function in a murine model of irritant induced asthma

<p>Abstract</p> <p>Background</p> <p>Exposure to chlorine (Cl₂) causes airway injury, characterized by oxidative damage, an influx of inflammatory cells and airway hyperresponsiveness. We hypothesized that Cl₂-induced airway injury may be attenuated by antioxidant treatment, even after the initial injury.</p> <p>Methods</p> <p>Balb/C mice were exposed to Cl₂gas (100 ppm) for 5 mins, an exposure that was established to alter airway function with minimal histological disruption of the epithelium. Twenty-four hours after exposure to Cl₂, airway responsiveness to aerosolized methacholine (MCh) was measured. Bronchoalveolar lavage (BAL) was performed to determine inflammatory cell profiles, total protein, and glutathione levels. Dimethylthiourea (DMTU;100 mg/kg) was administered one hour before or one hour following Cl₂exposure.</p> <p>Results</p> <p>Mice exposed to Cl₂had airway hyperresponsiveness to MCh compared to control animals pre-treated and post-treated with DMTU. Total cell counts in BAL fluid were elevated by Cl₂exposure and were not affected by DMTU treatment. However, DMTU-treated mice had lower protein levels in the BAL than the Cl₂-only treated animals. 4-Hydroxynonenal analysis showed that DMTU given pre- or post-Cl₂prevented lipid peroxidation in the lung. Following Cl₂exposure glutathione (GSH) was elevated immediately following exposure both in BAL cells and in fluid and this change was prevented by DMTU. GSSG was depleted in Cl₂exposed mice at later time points. However, the GSH/GSSG ratio remained high in chlorine exposed mice, an effect attenuated by DMTU.</p> <p>Conclusion</p> <p>Our data show that the anti-oxidant DMTU is effective in attenuating Cl₂induced increase in airway responsiveness, inflammation and biomarkers of oxidative stress.</p

The north west Adelaide health study: detailed methods and baseline segmentation of a cohort for selected chronic diseases

The North West Adelaide Health Study is a population-based biomedical cohort study investigating the prevalence of a number of chronic conditions and health-related risk factors along a continuum. This methodology may assist with evidence-based decisions for health policy makers and planners, and inform health professionals who are involved in chronic disease prevention and management, by providing a better description of people at risk of developing or already diagnosed with selected chronic conditions for more accurate targeting groups for health gain and improved health outcomes. Longitudinal data will provide information on progression of chronic conditions and allow description of those who move forward and back along the continuum over time. Detailed methods are provided regarding the random recruitment and examination of a representative sample of participants (n = 4060), including the rationale for various processes and valuable lessons learnt. Self-reported and biomedical data were obtained on risk factors (smoking, alcohol consumption, physical activity, family history, body mass index, blood pressure, cholesterol) and chronic conditions (asthma, chronic obstructive pulmonary disease, diabetes) to classify participants according to their status along a continuum. Segmenting this population sample along a continuum showed that 71.5% had at least one risk factor for developing asthma, chronic obstructive pulmonary disease or diabetes. Almost one-fifth (18.8%) had been previously diagnosed with at least one of these chronic conditions, and an additional 3.9% had at least one of these conditions but had not been diagnosed. This paper provides a novel opportunity to examine how a cohort study was born. It presents detailed methodology behind the selection, recruitment and examination of a cohort and how participants with selected chronic conditions can be segmented along a continuum that may assist with health promotion and health services planning.Janet F Grant, Catherine R Chittleborough, Anne W Taylor, Eleonora Dal Grande, David H Wilson, Patrick J Phillips, Robert J Adams, Julianne Cheek, Kay Price, Tiffany Gill and Richard E Ruffi

The Incidence of Molluscum contagiosum among American Indians and Alaska Natives

The epidemiology of Molluscum contagiosum (MC) in the United States is largely unknown, despite the fact that the virus is directly communicable and large outbreaks occur. This study provides population-based estimates to describe the epidemiology of MC in the United States among American Indian and Alaska Native (AI/AN) persons. This population was selected because of the comprehensiveness and quality of available data describing utilization of out-patient services.Outpatient visits listing MC as a diagnosis in the Indian Health Service National Patient Information Reporting System during 2001-2005 were analyzed to assess patient characteristics, visit frequency and concurrent skin conditions. Outpatient visit rates and incidence rates were calculated based on known population denominators (retrospective cohort). Overall outpatient visit rates were also calculated for the general US population using national data. The average annual rate of MC-associated outpatient visits was 20.15/10,000 AI/AN persons for 2001-2005 (13,711 total visits), which was similar to the rate for the general US population (22.0/10,000 [95% CI: 16.9-27.1]). The incidence of MC-associated visits was 15.34/10,000. AI/AN children 1-4 years old had the highest incidence (77.12), more than twice that for children 5-14 years old (30.79); the incidence for infants (<1 year) was higher than that for adults. AI/AN persons living in the West region had the highest incidence, followed by those in the East and Alaska regions (26.96, 22.88 and 21.38, respectively). There were age-specific associations between MC and concurrent skin conditions (e.g., atopic dermatitis, eczema).This study highlights the need for periodic population-based measurements to assess trends in incidence and healthcare utilization for MC in the United States. High rates of MC were found among AI/AN persons, especially among children <15 years old. The AI/AN population would benefit from greater availability of effective strategies for prevention and treatment of MCV infection