DE-PASS Best Evidence Statement (BESt): modifiable determinants of physical activity and sedentary behaviour in children and adolescents aged 5–19 years–a protocol for systematic review and meta-analysis

Introduction Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policymakers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5–19 years) and to quantify their effect on, or association with, PAB/SB. Methods and analysis A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane’s RoB V.2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health’s tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used. Ethics and dissemination No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance

DE-PASS Best Evidence Statement (BESt):modifiable determinants of physical activity and sedentary behaviour in children and adolescents aged 5–19 years–a protocol for systematic review and meta-analysis

Introduction: Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews (SLRs) and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policy makers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5-19 years) and to quantify their effect on, or association with, PAB/SB. Methods and analysis: A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane’s RoB 2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health’s tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used. Ethics and dissemination: No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance. Systematic review registration: CRD4202128287

DE-PASS Best Evidence Statement (BESt): modifiable determinants of physical activity and sedentary behaviour in children and adolescents aged 5-19 years-a protocol for systematic review and meta-analysis

Introduction Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policymakers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5-19 years) and to quantify their effect on, or association with, PAB/SB. Methods and analysis A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane's RoB V.2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health's tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used. Ethics and dissemination No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance. Systematic review registration CRD42021282874

Differential regulation and prognostic significance of cell cycle-associated regulators of the G1- and G2-phase subject to the anatomical localisation in gastrointestinal stromal tumors (GIST)

ZIEL: Gastrointestinale Stromatumore (GIST) zählen zu den häufigsten mesenchymalen Tumoren des Gastrointestinaltraktes (70%). GIST aus dem Magen weisen grundsätzlich einen besseren klinischen Verlauf auf als GIST aus dem Dünn- oder Dickdarm gleicher Größe und gleicher mitotischer Aktivität. Ziel dieser Arbeit war es herauszufinden, ob der unterschiedliche klinische Verlauf von verschieden lokalisierten GIST aus einer differenziellen anatomischen Regulation von zellzyklusassoziierten Proteinen resultiert. Des Weiteren sollte untersucht werden, ob von der Höhe der Proteinexpression im Vergleich zum Follow-up eine mögliche prognostische Bedeutung für GIST abgeleitet werden könnte. MATERIAL & METHODEN: Es wurden 148 primär operativ versorgte GIST mittels Tissue-Microarray-Technologie und immnhistochemischer Untersuchungsverfahren analysiert. Die quantitativen Proteinexpressionen von den G1-Phase-Proteinen E2F1 und Cyclin D1, sowie von den G2-Phase-Proteinen Cyclin A2 und Cyclin B1 und dem Transkriptionsfaktor Myc wurden in Abhängigkeit von den klinisch-pathologischen Parametern Lokalisation, Morphologie, Tumorgröße, Mitosenanzahl und Mutationsstatus untersucht. ERGEBNISSE: Lokalisationsabhängig zeigten sich zwei verschiedene Expressionsmuster unter den fünf Proteinen: Die frühen Proliferationsproteine E2F1 und tendenziell auch Cyclin D1 wiesen jeweils eine höhere Expression in KIT-mutierten GIST aus dem Magen und aus dem Dickdarm auf als in KIT-mutierten GIST aus dem Dünndarm. Die Expressionen von den späten Proliferationsproteinen Cyclin A2 und Cyclin B1, sowie von Myc verhielten sich genau gegensätzlich und zeigten eine deutlich höhere Expression in KIT-mutierten GIST aus dem Dünndarm als die GIST aus dem Magen. Die E2F1-Expression hatte im Gesamtkollektiv einen signifikanten Einfluss auf das progressionsfreie Überleben nach der Operation. Unter Berücksichtigung der anatomischen Lokalisation der GIST zeigte sich jedoch, dass die E2F1-Expression lediglich in KIT-mutierten GIST aus dem Dünn- und Dickdarm als signifikanter Prognosemarker fungieren könnte; eine ungleiche E2F1-Expression in KIT-mutierten GIST aus dem Magen führte nicht zu einem Unterschied hinsichtlich des klinischen Verlaufs. Cyclin D1 und Myc ließen keinen signifikanten Zusammenhang zwischen der Höhe ihrer Expression und der Länge des progressionsfreien Überlebens im Gesamtkollektiv erkennen. Hingegen hatte sowohl die Expression von Cyclin A2, als auch die von Cyclin B1 einen signifikanten Einfluss auf den klinischen Verlauf. SCHLUSSFOLGERUNG: Die lokalisationsabhängig unterschiedlichen Expressionsmuster lassen vermuten, dass es sich um zwei unterschiedliche Aktivierungswege in KIT-mutierten GIST aus dem Magen und Dünndarm handeln könnte: die Aktivierung im Magen könnte vorrangig durch die G1-Phase-Proteine Cyclin D1 und E2F1 geschehen, während im Dünndarm maßgeblich Myc und die S-/G2-Phase-Proteine Cyclin A2 und Cyclin B1 für die Zellzyklusprogression von Bedeutung sind. Andererseits führen die Ergebnisse zusammen mit dem Follow-up auch zu der Hypothese, dass E2F1 mit seiner deutlich höheren Expression in KIT-mutierten GIST im Magen dort vornehmlich Apoptose statt Proliferation auslösen und dies zum klinisch besseren Verlauf der GIST aus dem Magen beitragen könnte. Als Prognosemarker scheinen E2F1, Cyclin A2 und Cyclin B1 nützliche Parameter darzustellen um das klinische Verhalten der GIST einzuschätzen, wenngleich die Rolle von E2F1 in KIT-mutierten GIST aus dem Magen näherer Untersuchungen bedarf. Cyclin D1 und Myc scheinen weniger günstige Prognosemarker zu sein. Dennoch ist zu vermuten, dass Myc im Zellzyklus der GIST aus dem Dünndarm eine bedeutende Stellung einnimmt

Fundamentals of expert opinions on child pornographic images in forensic medicine

The extensive seizure of child pornographic material from suspects throughout Germany is leading to an increasing number of requests for analysis being received by forensic medical institutes and anthropological experts. Depending on the type of material and the circumstances of the case, different issues have to be considered. These range from the identification of the depicted perpetrator and/or victim to questions of age determination and the question of penetration into the body, which is important for the legal evaluation. It is easy to comprehend that the assessability of the material plays an essential role here, and limitations in the validity of the evidence must be clearly and communicated, whether in a written or oral expert opinion. The relevance of these expert opinions for criminal proceedings is high. Critical queries, e.g. in a main court hearing, are therefore unavoidable. The expert must be appropriately prepared for these situations

Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood

Objectives Sudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death. Design We performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-related genes. Multiple in silico analyses were conducted together with a thorough review of the literature in order to prioritise the putative pathogenic variants. Results A total of 63 variants in 35 cases were validated. The largest proportion of these variants is located within cardiomyopathy genes although this would have been more expected of channelopathy gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset cardiomyopathy as a predisposing condition to sudden unexpected death in some individuals. Conclusions Next-generation sequencing technologies reveal the existence of a wide spectrum of rare and novel genetic variants in sarcomere genes, compared with that of cardiac ion channels, in sudden unexplained death in infants and children. Our findings encourage further investigation of the role of early onset inherited cardiomyopathies and other diseases involving myocardial dysfunction in these deaths. Early detection of variants in these individuals could help to unmask subtle forms of disease within their relatives, who would eventually benefit from better counselling about their genetic history

Organ distribution of diclazepam, pyrazolam and 3-fluorophenmetrazine

The organ distribution of 3-fluorophenmetrazine (3-FPM), pyrazolam, diclazepam as well as its main metabolites delorazepam, lormetazepam and lorazepam, was investigated. A solid phase extraction (SPE) and a QuEChERS (acronym for quick, easy, cheap, effective, rugged and safe) - approach were used for the extraction of the analytes from human tissues, body fluids and stomach contents. The detection was performed on a liquid chromatography-tandem mass spectrometry system (LCMS/MS). The analytes of interest were detected in all body fluids and tissues. Results showed femoral blood concentrations of 10 mu g/L for 3-FPM, 28 mu g/L for pyrazolam, 1 mu g/L for diclazepam, 100 mu g/L for delorazepam, 6 mu g/L for lormetazepam, and 22 mu g/L for lorazepam. Tissues (muscle, kidney and liver) and bile exhibited higher concentrations of the mentioned analytes than in blood. Additional positive findings in femoral blood were for 2-fluoroamphetamine (2-FA, approx. 89 mu g/L), 2-flourometamphetamine (2-FMA, hint), methiopropamine (approx. 2.2 mu g/L), amphetamine (approx. 21 mu g/L) and caffeine (positive). Delorazepam showed the highest ratio of heart (C) and femoral blood (P) concentration (C/P ratio = 2.5), supported by the concentrations detected in psoas muscle (430 mu g/kg) and stomach content (approx. 210 mu g/L, absolute 84 mu g). The C/P ratio indicates that delorazepam displays susceptibility for postmortem redistribution (PMR), supported by the findings in muscle tissue. 3-FPM, pyrazolam, diclazepam, lorazepam and lormetazepam did apparently not exhibit any PMR. The cause of death, in conjunction with autopsy findings was concluded as a positional asphyxia promoted by poly-drug intoxication by arising from designer benzodiazepines and the presence of synthetic stimulants. (C) 2019 Elsevier B.V. All rights reserved

Applications of a sugar based surveillance system to track arboviruses in wild mosquito populations

Effective arbovirus surveillance is essential to ensure the implementation of control strategies, such as mosquito suppression, vaccination, or dissemination of public warnings. Traditional strategies employed for arbovirus surveillance, such as detection of virus or virus-specific antibodies in sentinel animals, or detection of virus in hematophagous arthropods, have limitations as an early-warning system. A system was recently developed that involves collecting mosquitoes in CO2-baited traps, where the insects expectorate virus on sugar-baited nucleic acid preservation cards. The cards are then submitted for virus detection using molecular assays. We report the application of this system for detecting flaviviruses and alphaviruses in wild mosquito populations in northern Australia. This study was the first to employ nonpowered passive box traps (PBTs) that were designed to house cards baited with honey as the sugar source. Overall, 20/144 (13.9%) of PBTs from different weeks contained at least one virus-positive card. West Nile virus Kunjin subtype (WNVKUN), Ross River virus (RRV), and Barmah Forest virus (BFV) were detected, being identified in 13/20, 5/20, and 2/20 of positive PBTs, respectively. Importantly, sentinel chickens deployed to detect flavivirus activity did not seroconvert at two Northern Territory sites where four PBTs yielded WNVKUN. Sufficient WNVKUN and RRV RNA was expectorated onto some of the honey-soaked cards to provide a template for gene sequencing, enhancing the utility of the sugar-bait surveillance system for investigating the ecology, emergence, and movement of arboviruses