How German health workers’ views on vaccine safety can be swayed by the AstraZeneca controversy

Several COVID-19 vaccines are now licensed, and the success of a rollout often depends on people’s willingness to accept any of them. Health workers are in a unique position to influence the public. Jan Priebe (German Institute for Global and Area Studies), Henning Silber, Christoph Beuthner, Steffen Pötzschke, Bernd Weiß, and Jessica Daikeler (GESIS – Leibniz Institute for the Social Sciences) show how their recommendations change when they are given different types of information about vaccines

Effect of L-carnitine on the hepatic transcript profile in piglets as animal model

<p>Abstract</p> <p>Background</p> <p>Carnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown.</p> <p>Methods</p> <p>To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver.</p> <p>Results</p> <p>Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid β-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation.</p> <p>Conclusion</p> <p>The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis.</p

Impaired Insulin/IGF1 Signaling Extends Life Span by Promoting Mitochondrial L-Proline Catabolism to Induce a Transient ROS Signal

SummaryImpaired insulin and IGF-1 signaling (iIIS) in C. elegans daf-2 mutants extends life span more than 2-fold. Constitutively, iIIS increases mitochondrial activity and reduces reactive oxygen species (ROS) levels. By contrast, acute impairment of daf-2 in adult C. elegans reduces glucose uptake and transiently increases ROS. Consistent with the concept of mitohormesis, this ROS signal causes an adaptive response by inducing ROS defense enzymes (SOD, catalase), culminating in ultimately reduced ROS levels despite increased mitochondrial activity. Inhibition of this ROS signal by antioxidants reduces iIIS-mediated longevity by up to 60%. Induction of the ROS signal requires AAK-2 (AMPK), while PMK-1 (p38) and SKN-1 (NRF-2) are needed for the retrograde response. IIIS upregulates mitochondrial L-proline catabolism, and impairment of the latter impairs the life span-extending capacity of iIIS while L-proline supplementation extends C. elegans life span. Taken together, iIIS promotes L-proline metabolism to generate a ROS signal for the adaptive induction of endogenous stress defense to extend life span

Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan.

Mutations and genetic variability affect gene expression and lifespan, but the impact of variations in gene expression within individuals on their aging-related mortality is poorly understood. We performed a longitudinal study in the short-lived killifish, Nothobranchius furzeri, and correlated quantitative variations in gene expression during early adult life with lifespan. Shorter- and longer-lived individuals differ in their gene expression before the onset of aging-related mortality; differences in gene expression are more pronounced early in life. We identified mitochondrial respiratory chain complex I as a hub in a module of genes whose expression is negatively correlated with lifespan. Accordingly, partial pharmacological inhibition of complex I by the small molecule rotenone reversed aging-related regulation of gene expression and extended lifespan in N. furzeri by 15%. These results support the use of N. furzeri as a vertebrate model for identifying the protein targets, pharmacological modulators, and individual-to-individual variability associated with aging.We thank Sabine Matz, Christin Hahn, Ivonne Heinze, and Ivonne Goerlich for technical assistance and Giorgio Bianchini for drawing. This work was partially supported by the German Ministry for Education and Research (JenAge; BMBF, support codes: 0315581A and 0315581C) and by intramural grant of Scuola Normale Superiore.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.cels.2016.01.01

Identifying resources used by young people to overcome mental distress in three Latin American cities: a qualitative study

OBJECTIVE: To explore which resources and activities help young people living in deprived urban environments in Latin America to recover from depression and/or anxiety. DESIGN: A multimethod, qualitative study with 18 online focus groups and 12 online structured group conversations embedded into arts workshops. SETTING: This study was conducted in Bogotá (Colombia), Buenos Aires (Argentina) and Lima (Peru). PARTICIPANTS: Adolescents (15–16 years old) and young adults (20–24 years old) with capacity to provide assent/consent and professionals (older than 18 years of age) that had experience of professionally working with young people were willing to share personal experience within a group, and had capacity to provide consent. RESULTS: A total of 185 participants took part in this study: 111 participants (36 adolescents, 35 young adults and 40 professionals) attended the 18 focus groups and 74 young people (29 adolescents and 45 young adults) took part in the 12 arts workshops. Eight categories captured the resources and activities that were reported by young people as helpful to overcome mental distress: (1) personal resources, (2) personal development, (3) spirituality and religion, (4) social resources, (5) social media, (6) community resources, (7) activities (subcategorised into artistic, leisure, sports and outdoor activities) and (8) mental health professionals. Personal and social resources as well as artistic activities and sports were the most common resources identified that help adolescents and young adults to overcome depression and anxiety. CONCLUSION: Despite the different contexts of the three cities, young people appear to use similar resources to overcome mental distress. Policies to improve the mental health of young people in deprived urban settings should address the need of community spaces, where young people can play sports, meet and engage in groups, and support community organisations that can enable and facilitate a range of social activities

Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi

ABSTRACT: BACKGROUND: Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans. RESULTS: 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. CONCLUSIONS: Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens

Whole Grain Wheat Consumption Affects Postprandial Inflammatory Response in a Randomized Controlled Trial in Overweight and Obese Adults with Mild Hypercholesterolemia in the Graandioos Study

BACKGROUND: Whole grain wheat (WGW) consumption is associated with health benefits in observational studies. However, WGW randomized controlled trial (RCT) studies show mixed effects. OBJECTIVES: The health impact of WGW consumption was investigated by quantification of the body's resilience, which was defined as the "ability to adapt to a standardized challenge." METHODS: A double-blind RCT was performed with overweight and obese (BMI: 25-35 kg/m2) men (n = 19) and postmenopausal women (n = 31) aged 45-70 y, with mildly elevated plasma total cholesterol (>5 mmol/L), who were randomly assigned to either 12-wk WGW (98 g/d) or refined wheat (RW). Before and after the intervention a standardized mixed-meal challenge was performed. Plasma samples were taken after overnight fasting and postprandially (30, 60, 120, and 240 min). Thirty-one biomarkers were quantified focusing on metabolism, liver, cardiovascular health, and inflammation. Linear mixed-models evaluated fasting compared with postprandial intervention effects. Health space models were used to evaluate intervention effects as composite markers representing resilience of inflammation, liver, and metabolism. RESULTS: Postprandial biomarker changes related to liver showed decreased alanine aminotransferase by WGW (P = 0.03) and increased β-hydroxybutyrate (P = 0.001) response in RW. Postprandial changes related to inflammation showed increased C-reactive protein (P = 0.001), IL-6 (P = 0.02), IL-8 (P = 0.007), and decreased IL-1B (P = 0.0002) in RW and decreased C-reactive protein (P < 0.0001), serum amyloid A (P < 0.0001), IL-8 (P = 0.02), and IL-10 (P < 0.0001) in WGW. Health space visualization demonstrated diminished inflammatory (P < 0.01) and liver resilience (P < 0.01) by RW, whereas liver resilience was rejuvenated by WGW (P < 0.05). CONCLUSIONS: Twelve-week 98 g/d WGW consumption can promote liver and inflammatory resilience in overweight and obese subjects with mildly elevated plasma cholesterol. The health space approach appeared appropriate to evaluate intervention effects as composite markers. This trial was registered at www.clinicaltrials.gov as NCT02385149.</p

Clinical Decision Making and Outcome in Routine Care for People with Severe Mental Illness (CEDAR): Study protocol

BACKGROUND: A considerable amount of research has been conducted on clinical decision making (CDM) in short-term physical conditions. However, there is a lack of knowledge on CDM and its outcome in long-term illnesses, especially in care for people with severe mental illness. METHODS/DESIGN: The study entitled "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR) is carried out in six European countries (Denmark, Germany, Hungary, Italy, Switzerland and UK). First, CEDAR establishes a methodology to assess CDM in people with severe mental illness. Specific instruments are developed (and psychometric properties established) to measure CDM style, key elements of CDM in routine care, as well as CDM involvement and satisfaction from patient and therapist perspectives. Second, these instruments are being put to use in a multi-national prospective observational study (bimonthly assessments during a one-year observation period; N = 560). This study investigates the immediate, short- and long-term effect of CDM on crucial dimensions of clinical outcome (symptom level, quality of life, needs) by taking into account significant variables moderating the relationship between CDM and outcome. DISCUSSION: The results of this study will make possible to delineate quality indicators of CDM, as well as to specify prime areas for further improvement. Ingredients of best practice in CDM in the routine care for people with severe mental illness will be extracted and recommendations formulated. With its explicit focus on the patient role in CDM, CEDAR will also contribute to strengthening the service user perspective. This project will substantially add to improving the practice of CDM in mental health care across Europe. TRIAL REGISTER: ISRCTN75841675

Needs-oriented discharge planning and monitoring for high utilisers of psychiatric services (NODPAM): Design and methods

<p>Abstract</p> <p>Background</p> <p>Attempts to reduce high utilisation of psychiatric inpatient care by targeting the critical time of hospital discharge have been rare.</p> <p>Methods</p> <p>This paper presents design and methods of the study "Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services" (NODPAM), a multicentre RCT conducted in five psychiatric hospitals in Germany. Inclusion criteria are receipt of inpatient psychiatric care, adult age, diagnosis of schizophrenia or affective disorder, defined high utilisation of psychiatric care during two years prior to the current admission, and given informed consent. Consecutive recruitment started in April 2006. Since then, during a period of 18 months, comprehensive outcome data of 490 participants is being collected at baseline and during three follow-up measurement points.</p> <p>The manualised intervention applies principles of needs-led care and focuses on the inpatient-outpatient transition. A trained intervention worker provides two intervention sessions: (a) Discharge planning: Just before discharge with the patient and responsible clinician at the inpatient service; (b) Monitoring: Three months after discharge with the patient and outpatient clinician. A written treatment plan is signed by all participants after each session.</p> <p>Primary endpoints are whether participants in the intervention group will show fewer hospital days and readmissions to hospital. Secondary endpoints are better compliance with aftercare, better clinical outcome and quality of life, as well as cost-effectiveness and cost-utility.</p> <p>Discussion</p> <p>If a needs-oriented discharge planning and monitoring proves to be successful in this RCT, a tool will be at hand to improve patient outcome and reduce costs via harmonising fragmented mental health service provision.</p> <p>Trial Registration</p> <p>ISRCTN59603527</p

Effects of cereal breakfasts on postprandial glucose, appetite regulation and voluntary energy intake at a subsequent standardized lunch; focusing on rye products

<p>Abstract</p> <p>Background</p> <p>Rye products have been demonstrated to lower the acute insulin demand, induce a low and prolonged blood glucose response (high Glycemic Profile, GP) and reduce subclinical inflammation. These products may therefore contribute to a lowered risk of obesity, type 2 diabetes and cardio vascular disease. The objective of the present paper was to evaluate the mechanism for a reduced postprandial insulin demand with rye products, and to explore possible appetite regulating properties.</p> <p>Methods</p> <p>10 healthy subjects were served breakfast meals (50 g of available starch) with endosperm- or whole grain rye breads, with and without lactic acid, boiled whole grain rye- (RK) or wheat (WK) kernels, or white wheat bread reference (WWB) in random order in a cross-over design. Plasma concentrations of glucose, ghrelin, serum insulin, free fatty acids, adiponectin, breath hydrogen excretion (H₂), and subjective satiety was evaluated during the postprandial phase. 270 min after the breakfast, an ad lib lunch buffet was served and the voluntary energy intake (EI) was registered.</p> <p>Results</p> <p>All rye products and WK induced lower insulinemic indices (II) than WWB. A lower incremental insulin peak following breakfast correlated with a lower EI at lunch (r = 0.38). A low II was related to improved satiety in the early postprandial phase (fullness AUC 0-60 min, r = -0.36). RK induced a higher GP compared to WWB and WK. A higher GP was related to a lowered <it>desire to eat </it>before lunch (AUC 210-270) and to a lower concentration of ghrelin in the late postprandial phase after breakfast (270 min), r = -0.29 and -0.29), which in turn was related to a lower voluntary EI (r = 0.43 and 0.33). The RK breakfast improved satiety in the early postprandial phase (0-60 min) compared to WWB, and induced a lower EI at lunch (-16%). A high content of indigestible carbohydrates in the breakfast products was related to improved satiety (0-60 min, r = 0.68 for fullness), and a higher breath H₂in the late postprandial phase (120-270 and 270-390 min, r = 0.46 and 0.70). High H₂(AUC 120-270 min) also correlated with lower EI (r = -0.34).</p> <p>Conclusions</p> <p>Rye products, rich in indigestible carbohydrates, induce colonic fermentation already post the breakfast meal, and lowers acute insulin responses. A high excretion of breath H2 also correlated with a higher GP. Especially, rye kernels induced a high GP which was associated with a 16% lowering of energy intake at a subsequent lunch meal. The bulking effect of rye fiber, colonically derived fermentation metabolites, a high GP and a low insulin response possibly all contributes to the benefits on glucose- and appetite regulation seen in an acute and semi-acute perspective.</p