The protective effects of social bonding on behavioral and pituitary-adrenal axis reactivity to chronic mild stress in prairie voles.

Positive social interactions may protect against stress. This study investigated the beneficial effects of pairing with a social partner on behaviors and neuroendocrine function in response to chronic mild stress (CMS) in 13 prairie vole pairs. Following 5 days of social bonding, male and female prairie voles were exposed to 10 days of CMS (mild, unpredictable stressors of varying durations, for instance, strobe light, white noise, and damp bedding), housed with either the social partner (paired group) or individually (isolated group). Active and passive behavioral responses to the forced swim test (FST) and tail-suspension test (TST), and plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, were measured in all prairie voles following the CMS period. Both female and male prairie voles housed with a social partner displayed lower durations of passive behavioral responses (immobility, a maladaptive behavioral response) in the FST (mean ± SEM; females: 17.3 ± 5.4 s; males: 9.3 ± 4.6 s) and TST (females: 56.8 ± 16.4 s; males: 40.2 ± 11.3 s), versus both sexes housed individually (females, FST: 98.6 ± 12.9 s; females, TST: 155.1 ± 19.3 s; males, FST: 92.4 ± 14.1 s; males, TST: 158.9 ± 22.0 s). Female (but not male) prairie voles displayed attenuated plasma stress hormones when housed with a male partner (ACTH: 945 ± 24.7 pg/ml; corticosterone: 624 ± 139.5 ng/ml), versus females housed individually (ACTH: 1100 ± 23.2 pg/ml; corticosterone: 1064 ± 121.7 ng/ml). These results may inform understanding of the benefits of social interactions on stress resilience. Lay Summary: Social stress can lead to depression. The study of social bonding and stress using an animal model will inform understanding of the protective effects of social bonds. This study showed that social bonding in a rodent model can protect against behavioral responses to stress, and may also be protective against the elevation of stress hormones. This study provides evidence that bonding and social support are valuable for protecting against stress in humans

Calculation of health expectancies with administrative data for North Rhine-Westphalia, a Federal State of Germany, 1999–2005

Pinheiro JP, Krämer A. Calculation of health expectancies with administrative data for North Rhine-Westphalia, a Federal State of Germany, 1999-2005. Population Health Metrics. 2009;7(1):4.OBJECTIVES: The main objectives of this study were to prove the feasibility of health expectancy analyses with regional administrative health statistics and to explore the utility of the calculated health expectancies in describing the health state of the population living in North Rhine-Westphalia, a Federal State of Germany. MATERIALS AND METHODS: Administrative population and mortality data as well as health data on disability and long-term care provided by public services were used to calculate: a) the life expectancy and b) the health expectancies Severe-Disability-Free Life Expectancy (SDFLE) and Long-Term-Care-Free Life Expectancy (LTCFLE) from 1999 to 2005. Calculations were done using the Sullivan method. RESULTS: SDFLE at birth was 69.9 years (males 66.2 and females 73.2 years) in 1999 and it increased to 71.7 years (males 68.6 and females 74.7 years) in 2005. The proportion of the SDFLE on the total life expectancy at birth was 89.8% (males 88.6 and females 90.8%) in 1999 and 90.7% (males 89.8 and females 91.4%) in 2005.LTCFLE at birth was 75.3 years (males 73.1 and females 77.5 years) in 1999 and it increased to 76.6 years (males 74.7 and females 78.6 years) in 2005. The proportion of the LTCFLE on the total life expectancy at birth was 96.8% (males 97.8 and females 96.1%) in 1999 and 96.8% (males 97.8 and females 96.2%) in 2005. DISCUSSION AND CONCLUSION: Both health expectancies indicate an improvement in the quantity as well as in the quality of healthy life for the population living in North Rhine Westphalia and therefore suggest a compression of morbidity from 1999 to 2005. The findings however have several limitations in their sensitivity, since we applied dichotomous valuations to the health states. In addition, the results are restricted to comparisons over time because the morbidity concepts do not allow for comparisons with populations other than the German one. Refined calculations with other summary measures of population health and with health data on other morbidity concepts are therefore reasonable

Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths

Trends and variation in mild disability and functional limitations among older adults in Norway, 1986–2008

An increase in the number of older adults may raise the demand for health and care services, whereas decreasing prevalence of disability and functional limitations among them might counteract this demographic effect. However, the trends in health are inconsistent between studies and countries. In this article, we estimated the trends in mild disability and functional limitations among older Norwegians and analyzed whether they differ between socio-demographic groups. Data were obtained from repeated cross-sectional surveys conducted in 1987, 1991, 1995, 2002, 2005, and 2008, in total 4,036 non-institutionalized persons aged 67 years or older. We analyzed trends using multivariate logistic regression. On average, the age-adjusted trend in functional limitations was −3.3% per year, and in disability 3.4% per year. The risk for functional limitations or disability was elevated for women compared to men, for married compared to non-married, and was inversely associated with educational level The trends were significantly weaker with increasing age for disabilities, whereas none of the trends differed significantly between subgroups of sexes, educational level or marital status. Both functional limitations free and disability-free life expectancy appeared to have increased more than total life expectancy at age 67 during this period. The analysis suggests downward trends in the prevalence of mild disability and functional limitations among older Norwegians between 1987 and 2008 and a compression of lifetime in such health states. The reduced numbers of older people with disability and functional limitations may have restrained the demand for health and care services caused by the increase in the number of older adults

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD.</p> <p>Methods</p> <p>Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA.</p> <p>Results</p> <p>Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.</p> <p>Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.</p> <p>In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A.</p> <p>Conclusions</p> <p>Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis.</p

Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics

We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10−9), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients’ fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: −2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: −1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients

Modelling the effects of glucagon during glucose tolerance testing.

From Europe PMC via Jisc Publications RouterHistory: ppub 2019-12-01, epub 2019-12-12Publication status: PublishedBACKGROUND:Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. RESULTS:Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). CONCLUSIONS:The models are used to investigate how different degrees of pax'tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted

Has the DOTS Strategy Improved Case Finding or Treatment Success? An Empirical Assessment

Background: Nearly fifteen years after the start of WHO's DOTS strategy, tuberculosis remains a major global health problem. Given the lack of empirical evidence that DOTS reduces tuberculosis burden, considerable debate has arisen about its place in the future of global tuberculosis control efforts. An independent evaluation of DOTS, one of the most widely-implemented and longest-running interventions in global health, is a prerequisite for meaningful improvements to tuberculosis control efforts, including WHO's new Stop TB Strategy. We investigate the impact of the expansion of the DOTS strategy on tuberculosis case finding and treatment success, using only empirical data. Methods and Findings: We study the effect of DOTS using time-series cross-sectional methods. We first estimate the impact of DOTS expansion on case detection, using reported case notification data and controlling for other determinants of change in notifications, including HIV prevalence, GDP, and country-specific effects. We then estimate the effect of DOTS expansion on treatment success. DOTS programme variables had no statistically significant impact on case detection in a wide range of models and specifications. DOTS population coverage had a significant effect on overall treatment success rates, such that countries with full DOTS coverage benefit from at least an 18% increase in treatment success (95% CI: 5–31%). Conclusions: The DOTS technical package improved overall treatment success. By contrast, DOTS expansion had no effect on case detection. This finding is less optimistic than previous analyses. Better epidemiological and programme data would facilitate future monitoring and evaluation efforts