The dipeptide Phe-Phe amide attenuates signs of hyperalgesia, allodynia and nociception in diabetic mice using a mechanism involving the sigma receptor system

<p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrated that intrathecal administration of the substance P amino-terminal metabolite substance P_1-7(SP_1-7) and its C-terminal amidated congener induced antihyperalgesic effects in diabetic mice. In this study, we studied a small synthetic dipeptide related to SP_1-7and endomorphin-2, i.e. Phe-Phe amide, using the tail-flick test and von Frey filament test in diabetic and non-diabetic mice.</p> <p>Results</p> <p>Intrathecal treatment with the dipeptide increased the tail-flick latency in both diabetic and non-diabetic mice. This effect of Phe-Phe amide was significantly greater in diabetic mice than non-diabetic mice. The Phe-Phe amide-induced antinociceptive effect in both diabetic and non-diabetic mice was reversed by the σ₁receptor agonist (+)-pentazocine. Moreover, Phe-Phe amide attenuated mechanical allodynia in diabetic mice, which was reversible by (+)-pentazocine. The expression of spinal σ1 receptor mRNA and protein did not differ between diabetic mice and non-diabetic mice. On the other hand, the expression of phosphorylated extracellular signal-regulated protein kinase 1 (ERK1) and ERK2 proteins was enhanced in diabetic mice. (+)-Pentazocine caused phosphorylation of ERK1 and ERK2 proteins in non-diabetic mice, but not in diabetic mice.</p> <p>Conclusions</p> <p>These results suggest that the spinal σ₁receptor system might contribute to diabetic mechanical allodynia and thermal hyperalgesia, which could be potently attenuated by Phe-Phe amide.</p

Food Web Responses to Artificial Mixing in a Small Boreal Lake

In order to simulate food web responses of small boreal lakes to changes in thermal stratification due to global warming, a 4 year whole-lake manipulation experiment was performed. Within that time, period lake mixing was intensified artificially during two successive summers. Complementary data from a nearby lake of similar size and basic water chemistry were used as a reference. Phytoplankton biomass and chlorophyll a did not respond to the greater mixing depth but an increase was observed in the proportional abundance of diatoms, and the proportional abundance of cryptophytes also increased immediately after the onset of mixing. Obligate anoxic green sulphur bacteria vanished at the onset of mixing but gradually recovered after re-establishment of hypolimnetic anoxic conditions. No major effect on crustacean zooplankton was found, but their diversity increased in the metalimnion. During the mixing, the density of rotifers declined but protozoan density increased in the hypolimnion. Littoral benthic invertebrate density increased during the mixing due to Ephemeroptera, Asellus aquaticus and Chironomidae, whereas the density of Chaoborus larvae declined during mixing and lower densities were still recorded one year after the treatment. No structural changes in fish community were found although gillnet catches increased after the onset of the study. The early growth of perch (Perca fluviatilis) increased compared to the years before the mixing and in comparison to the reference lake, suggesting improved food availability in the experimental lake. Although several food web responses to the greater mixing depth were found, their persistence and ecological significance were strongly dependent on the extent of the disturbance. To better understand the impacts of wind stress on small lakes, long term whole-lake experiments are needed.Peer reviewe

Evaluation of a health promotion program in children: Study protocol and design of the cluster-randomized Baden-Württemberg primary school study [DRKS-ID: DRKS00000494]

<p>Abstract</p> <p>Background</p> <p>Increasing prevalences of overweight and obesity in children are known problems in industrialized countries. Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school-based program to promote a healthier lifestyle. Main goals of the intervention are to increase physical activity, decrease the consumption of sugar-sweetened beverages, and to decrease time spent sedentary by promoting active choices for healthy lifestyle. The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools. The efficacy of this large scale intervention is examined via the Baden-Württemberg Study.</p> <p>Methods/Design</p> <p>The Baden-Württemberg Study is a prospective, stratified, cluster-randomized, and longitudinal study with two groups (intervention group and control group). Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the intervention is being assessed using three main outcomes: changes in waist circumference, skinfold thickness and 6 minutes run. Stratified cluster-randomization (according to class grade level) was performed for primary schools; pupils, teachers/principals, and parents were investigated. An approximately balanced number of classes in intervention group and control group could be reached by stratified randomization and was maintained at follow-up.</p> <p>Discussion</p> <p>At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school-based health promotion program in Germany. Comparative objective main outcomes are used for the evaluation of efficacy. Simulations showed sufficient power with the existing sample size. Therefore, the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children, teachers and parents. The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program.</p> <p>Trial registration</p> <p>German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494</p

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

An audit of dietitians' documentation : Comparing the level of agreement between the audit instruments Diet-NCP-Audit and NCP-QUEST

To explore the inter-rater reliability of the Swedish translation of NCP-QUEST in a Swedish context and investigate the level of agreement between Diet-NCP-Audit and NCP-QUEST in assessment of documentation quality. A retrospective audit was conducted of 40 electronic patient records written by dietitians at one University Hospital in Sweden. NCP-QUEST showed good inter-rater reliability for the quality category (ICC = 0.85) and excellent inter-rater reliability for total score (ICC = 0.97)

"We were all together"- families' experiences of the health-promoting programme - A Healthy Generation.

BACKGROUND: Healthy lifestyle habits, including physical activity (PA), are associated with a broad range of positive psychosocial and physical health benefits. However, there are challenges involved in reaching vulnerable groups in socioeconomically disadvantaged areas. There is a lack of research on family-based PA interventions, specifically considering psychosocial health. The purpose of this study was to explore how families experienced psychosocial aspects of health after participation in a family-based programme, A Healthy Generation. METHODS: A Healthy Generation is a health-promoting, family-based programme delivered in collaboration with local municipalities and sport associations in socioeconomically disadvantaged areas in Sweden. Families with children in grade 2 (8-9 years), including siblings, participate in health-promoting activities, including activity sessions, healthy meals, health information and parental support groups. Data was collected through interviews with parents and children (n = 23) from a controlled pilot trial of the programme. Interviews were audio recorded, transcribed and analysed using a phenomenological hermeneutical method. RESULTS: Three themes and seven sub-themes emerged. The themes were: "A sense of belonging", "Awareness of one's role as a parent" and "Inspiration towards new and healthier behaviours". In terms of A sense of belonging, participation in the programme was the families own free zone, where they also had the opportunity of being together with other families in the programme. For participants that were isolated and lacked a social network, their participation helped them towards social participation. During the programme, parents created an Awareness of one's role as a parent, with new insights on how to act as a parent and they also negotiated differences between each other. Participation in the programme contributed to Inspiration towards new and healthier behaviours such as experience-based insights and healthy lifestyle changes. CONCLUSIONS: This study highlights the importance of co-participation in family-based health-promoting programmes to enhance psychosocial health among families in socioeconomically disadvantaged areas. The results give new insights into participants' experiences of psychosocial aspects of health after participation in a family-based PA programme. This knowledge can contribute to the understanding of how to design health-promoting, family-based interventions to promote psychosocial health in socioeconomically disadvantaged areas. TRIAL REGISTRATION: ISRCTN ISRCTN11660938 . Retrospectively registered 23 September 2019

Heterogeneity in the associations between common mental disorders and labour outcomes - a population study from southern Sweden

BACKGROUND: Previous research has shown that Common Mental Disorders (CMD) are unequally distributed between population subgroups, but we know less about how labour outcomes following such disorders are distributed. Our aim is to investigate how the labour outcomes following a CMD diagnosis differ over sex, age, schooling and country of birth.METHODS: We use a population sample from southern Sweden of patients diagnosed with CMD during calendar years 2009-2011, and a matched general population control group, to study labour market outcomes three years following diagnosis. Logistic regression is used to study the associations between a CMD diagnosis and outcomes in employment, sick leave, and disability pension. Interaction analysis is used to study heterogeneity in these associations.RESULTS: CMD diagnosis is associated with reduced employment and increased odds of sick leave and disability pension. Following a CMD diagnosis, men and higher educated individuals have higher odds of non-employment and sick leave compared to women and the lower educated. Foreign-born individuals have higher odds of non-employment and lower odds of sick leave, compared to individuals born in Sweden. Heterogeneity appears to be present also based on age. Younger age is associated with higher odds of non-employment and disability pension and lower odds of sick leave, following a CMD diagnosis.CONCLUSIONS: Heterogeneity in labour outcomes following a CMD diagnosis sometimes contributes to and sometimes mitigates inequalities in employment, sick leave and disability pension between population subgroups. When developing new strategies to tackle mental ill-health in the population, it may therefore be motivated to consider not only inequalities in the prevalence of mental disorders but also heterogeneity in associated adverse labour outcomes

Effectiveness of a Family Intervention to Increase Physical Activity in Disadvantaged Areas-A Healthy Generation, a Controlled Pilot Study.

There are large social inequalities in health. The purpose of this study was to evaluate the effects of a family intervention on physical activity (PA) and sedentary time (ST) in children and their parents. In this controlled pilot study, all 8-9-year-old children from four schools from a socioeconomically disadvantaged area in Sweden were invited and 67 children and 94 parents were included. The intervention was run by a foundation in co-operation with the municipality. The 9-month program included: (1) activity sessions, (2) healthy meals, (3) health information and (4) parental support groups. PA was primary outcome and ST was secondary outcome, measured by accelerometry. In total, 40 of the children (60%) and 45 of the adults (50%) had at least one day of valid accelerometer data at both baseline and follow-up. Significant intervention effects for the whole group were found in total PA (p = 0.048, mean difference (MD) intervention/control 150 counts per minute) and in vigorous PA (p = 0.02, MD 8 min/day) during the weekends. There were no differences between groups in the other PA variables or ST. This pilot study shows that it is possible to influence PA in families from a disadvantaged area through a family program