ABSTRACT
Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non-directed homogeneous Pd-catalysis. Aromatic C-H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D2O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non-directed homogeneous Pd catalysis for H/T exchange on three different pharmaceuticals by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers.
ABSTRACT
The recently reported electrochemical, organo-mediator enabled deuteration of styrenes, a reaction referred to as "electrochemical deuterium atom transfer", differs mechanistically from reported direct electrochemical hydrogenations/deuterations only by a mediated, homogeneous SET to the substrates. By comparing direct vs. mediated processes in general and for styrene reduction, we display that Qiu's work does not change the concept of this chemistry. Experiments with mediators and the direct reduction of examples from the reported scope show that even electron-rich substrates can be reduced when our direct protocol, published six months before Qiu's work, is applied.
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We describe an operationally simple and user-friendly protocol that allows the site-selective hydrogenation and deuteration of di-, tri- and tetrasubstituted benzylic olefins by electroreduction while other groups prone to hydrogenation are present. The radical anionic intermediates react with the most inexpensive hydrogen/deuterium source H2 O/D2 O. Our method overcomes many limitations that arise from previously reported electroreductive hydrogenations. The applicability of this reaction is demonstrated by a broad substrate scope (>50 examples) that focuses on functional group tolerance and sites that are affected by metal-catalyzed hydrogenation (alkenes, alkynes, protecting groups).
Subject(s)
Alkenes , Water , Hydrogenation , Catalysis , HydrogenABSTRACT
Oesophageal atresia (EA) is associated with life-long gastrointestinal and respiratory morbidity and other associated malformations. The aim of this study is to compare physical activity (PA) levels of children and adolescents with and without EA. A validated questionnaire (MoMo-PAQ) was used to evaluate PA in EA patients EA (4-17 years), who were randomly matched for gender and age (1:5) with a representative sample of the Motorik-Modul Longitudinal Study (n = 6233). Sports activity per week (sports index) and minutes of moderate to vigorous physical activity per week (MVPA minutes) were calculated. Correlations between PA and medical factors were analysed. In total, 104 patients and 520 controls were included. Children with EA were significantly less active at higher intensities (mean MPVA minutes 462; 95% confidence interval (CI): 370-554) compared to controls (626; 95% CI: 576-676), although there was no statistically significant difference in the sports index (187; 95% CI: 156-220 versus 220; 95% CI: 203-237). A lower mean weight-for-age and height-for-age, additional urogenital (r = - 0.20, p = 0.04) or anorectal malformation (r = - 0.24, p = 0.01) were associated with fewer MVPA minutes. For other medical factors (prematurity, type of repair, congenital heart disease, skeletal malformation or symptom load), no statistically significant association with PA was found. Conclusion: EA patients participated in PA at a similar level but lower intensities compared to the reference cohort. PA in EA patients was largely independent of medical factors. TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00025276) on September 6, 2021. WHAT IS KNOWN: ⢠Oesophageal atresia is associated with a low body weight and height, delayed development of motor skills and impaired lung function and exercise capacity. WHAT IS NEW: ⢠Patients with oesophageal atresia have a similar amount of sports activity per week but engage significantly less in moderate to vigorous physical activities compared to peers. ⢠Physical activity was associated with weight-for-age and height-for-age, but largely independent of symptom load and other medical factors.
Subject(s)
Esophageal Atresia , Sports , Child , Adolescent , Humans , Cross-Sectional Studies , Longitudinal Studies , ExerciseABSTRACT
BACKGROUND: Incomplete data due to nonparticipation and noncompliance with the study protocol can bias the results of studies. We investigated how a nationwide accelerometer sample of adolescents and young adults is affected by such incomplete data. METHODS: We analyzed cross-sectional data from 6465 participants (11-31 y old) who participated in a national health survey in Germany (KiGGS Wave 2; 2014-2017). The data included information about the participation in the measurement of physical activity using accelerometers, compliance with the wear-time protocol, and sociodemographic and health-related variables. Multivariable regression analyses were conducted to detect factors associated with incomplete data. RESULTS: Of the total sample, 78.0% participated in the accelerometer part of the study, and 83.5% of the participants with data available complied with the wear-time protocol. In 11- to 17-year-olds, the likelihood of having incomplete accelerometer data was higher in boys, older adolescents, adolescents with a lower sociodemographic status, adolescents with overweight, adolescents not participating in organized sport, adolescents not speaking only German at home, current smokers, and adolescents having a higher soft drink consumption. In 18- to 31-year-olds, the likelihood of having incomplete accelerometer data was higher in men, adults with a lower educational level, adults not speaking only German at home, and adults who smoke. CONCLUSIONS: Our results suggest that accelerometer samples are biased such that participants with more beneficial health behaviors provide complete accelerometer data more often. This knowledge should be used to design effective recruitment strategies and should be considered when interpreting results of accelerometer studies.
Subject(s)
Exercise , Overweight , Male , Humans , Adolescent , Young Adult , Cross-Sectional Studies , Health Surveys , Accelerometry , GermanyABSTRACT
INTRODUCTION: Sufficient physical activity (PA) has the potential to mitigate late effects of cancer, but objective data of PA levels in adolescents are scarce. The aim of this study was to investigate differences in PA behavior between childhood cancer survivors (CCS) and healthy peers. METHODS: PA levels of n = 74 CCS and n = 1304 healthy peers from the MoMo study aged 9-15 years were assessed with validated objective accelerometry and group means were compared. A binary multiple logistic regression was performed to investigate the potential predictors of PA. RESULTS: CCS spent significantly more time sedentary (p < 0.001) and less time in moderate-to-vigorous physical activity (p = 0.002) compared to the healthy cohort. Subgroup analysis revealed the largest deviations of PA levels for CCS aged 9-11 years who fulfilled international PA recommendations on significantly fewer days than MoMo (p < 0.01). Health conditions seem to be a predictor concerning the fulfillment of international PA recommendations by the WHO (p = 0.015). CONCLUSIONS: Our study identified vulnerable groups which seem to require targeted exercise and health behavior change programs to increase physical activity and reduce sedentary time. The presence of treatment sequelae as a significant predictor of insufficient physical activity underlines the need of multidisciplinary supportive care approaches.
Subject(s)
Cancer Survivors , Neoplasms , Adolescent , Humans , Child , Exercise , Health Behavior , Sedentary Behavior , Survivors , Neoplasms/therapyABSTRACT
Recurrent pain can be a significant disruption in the activities of daily life, and is not only a health problem in adults but also in children and adolescents. This study analyzed the prevalence of recurrent pain in the current sample (n = 1516; 11-17 years (meanage = 14.4 ± 2.0 years); 50.8% female) of a nationwide study in Germany, evaluated the association of participants' device-based physical activity (PA) with the prevalence of recurrent pain, and assessed whether children and adolescents who reported pain for the last three months accumulated less PA than those who did not. A higher prevalence was found in girls for recurrent headaches (42.2% vs. 28.7%), abdominal pain (28.2% vs. 20.1%), and back pain (26.9% vs. 19.5%). We found higher odds for recurrent headaches in girls (OR = 1.54) and in participants that did not reach at least 60 min of moderate to vigorous PA (MVPA) per day (OR = 2.06). Girls who reported recurrent headaches accumulated 4.7 min less MVPA per day than those without. The prevalence of pain remains at a high level in the German youth and underscores the need for interventions to improve the health situations of children and adolescents.
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The Fujiwara-Moritani reaction is a powerful tool for the olefination of arenes by Pd-catalysed C-H activation. However, the need for superstoichiometric amounts of toxic chemical oxidants makes the reaction unattractive from an environmental and atom-economical view. Herein, we report the first non-directed and regioselective olefination of simple arenes via an electrooxidative Fujiwara-Moritani reaction. The versatility of this operator-friendly approach was demonstrated by a broad substrate scope which includes arenes, heteroarenes and a variety of olefins. Electroanalytical studies suggest the involvement of a Pd(ii)/Pd(iv) catalytic cycle via a Pd(iii) intermediate.
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A useful protocol for achieving decarboxylative cross-coupling (DCC) of redox-active esters (RAE, isolated or generated in situ) and halo(hetero)arenes is reported. This pragmatically focused study employs a unique Ag-Ni electrocatalytic platform to overcome numerous limitations that have plagued this strategically powerful transformation. In its optimized form, coupling partners can be combined in a surprisingly simple way: open to the air, using technical-grade solvents, an inexpensive ligand and Ni source, and substoichiometric AgNO3, proceeding at room temperature with a simple commercial potentiostat. Most importantly, all of the results are placed into context by benchmarking with state-of-the-art methods. Applications are presented that simplify synthesis and rapidly enable access to challenging chemical space. Finally, adaptation to multiple scale regimes, ranging from parallel milligram-based synthesis to decagram recirculating flow is presented.
Subject(s)
Esters , Catalysis , Ligands , Oxidation-Reduction , SolventsABSTRACT
Objectives: Studies that assess all three dimensions of the integrative 24-hour physical behaviour (PB) construct, namely, intensity, posture/activity type and biological state, are on the rise. However, reviews on validation studies that cover intensity, posture/activity type and biological state assessed via wearables are missing. Design: Systematic review. The risk of bias was evaluated by using the QUADAS-2 tool with nine signalling questions separated into four domains (ie, patient selection/study design, index measure, criterion measure, flow and time). Data sources: Peer-reviewed validation studies from electronic databases as well as backward and forward citation searches (1970-July 2021). Eligibility criteria for selecting studies: Wearable validation studies with children and adolescents (age <18 years). Required indicators: (1) study protocol must include real-life conditions; (2) validated device outcome must belong to one dimension of the 24-hour PB construct; (3) the study protocol must include a criterion measure; (4) study results must be published in peer-reviewed English language journals. Results: Out of 13 285 unique search results, 76 articles with 51 different wearables were included and reviewed. Most studies (68.4%) validated an intensity measure outcome such as energy expenditure, but only 15.9% of studies validated biological state outcomes, while 15.8% of studies validated posture/activity type outcomes. We identified six wearables that had been used to validate outcomes from two different dimensions and only two wearables (ie, ActiGraph GT1M and ActiGraph GT3X+) that validated outcomes from all three dimensions. The percentage of studies meeting a given quality criterion ranged from 44.7% to 92.1%. Only 18 studies were classified as 'low risk' or 'some concerns'. Summary: Validation studies on biological state and posture/activity outcomes are rare in children and adolescents. Most studies did not meet published quality principles. Standardised protocols embedded in a validation framework are needed. PROSPERO registration number: CRD42021230894.
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Childhood and adolescence are important life periods for the development of health status and physical activity (PA) behaviours. This study analyses the stability and potential changes of self-rated health status, overweight and PA behaviour over time, specifically focusing on the age and the socioeconomic status of children and adolescents. We employ representative longitudinal data for German children and adolescents from the Motorik-Modul Study and the German Health Interview and Examination Survey. Using four different dichotomous health status and PA indicators (self-rated health status [SRHS]; overweight; moderate-to-vigorous PA; and leisure sports engagement), we report within-person transition rates across the panel waves when the survey was taken (2003-2006, 2009-2012, and 2014-2017). Additionally, we report results of logistic regressions estimating the impact of children's age, gender, migration background, and their parents' socioeconomic status on these transition rates. The transition rates show mixed results. While children and adolescents from highly problematic states reporting bad SRHS and no leisure sports engagement at an early stage tend to improve later on, overweight children mostly stay overweight. Age and social inequality indicators correlate with some of the chances of improving or worsening the health and PA states. Most clearly, high parental status prevents the health status and PA from worsening over all transitions, particularly becoming overweight, representing a ratchet effect. The results of the present study underline that health policy needs to target specific groups to reduce social inequality in the health status and PA of children and adolescents.
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Sufficient physical activity can help promote and maintain health, while its lack can jeopardize it. Since health and physical activity lay their foundation for later life in childhood and adolescence, it is important to examine this relationship from the beginning. Therefore, this scoping review aims to provide an overview of physical health indicators in children and adolescents in research on the effects of physical activity and sedentary behavior. We identified the indicators used to quantify or assess physical health and summarized the methods used to measure these indicators. We systematically searched Scopus, Pubmed, and Web of Science databases for systematic reviews. The search yielded 4595 records from which 32 records were included in the review. The measurements for physical health reported in the reviews contained measures of body composition, cardiometabolic biomarkers, physical fitness, harm/injury, or bone health. Body composition was the most used indicator to assess and evaluate physical health in children, whereas information on harm and injury was barely available. In future research longitudinal studies are mandatory to focus on the prospective relationships between physical activity or sedentary behavior, and physical health.
Subject(s)
Exercise , Sedentary Behavior , Adolescent , Child , Humans , Physical Fitness , Prospective Studies , Systematic Reviews as TopicABSTRACT
Accurate navigation to a desired goal requires consecutive estimates of spatial relationships between the current position and future destination throughout the journey. Although neurons in the hippocampal formation can represent the position of an animal as well as its nearby trajectories1-7, their role in determining the destination of the animal has been questioned8,9. It is, thus, unclear whether the brain can possess a precise estimate of target location during active environmental exploration. Here we describe neurons in the rat orbitofrontal cortex (OFC) that form spatial representations persistently pointing to the subsequent goal destination of an animal throughout navigation. This destination coding emerges before the onset of navigation, without direct sensory access to a distal goal, and even predicts the incorrect destination of an animal at the beginning of an error trial. Goal representations in the OFC are maintained by destination-specific neural ensemble dynamics, and their brief perturbation at the onset of a journey led to a navigational error. These findings suggest that the OFC is part of the internal goal map of the brain, enabling animals to navigate precisely to a chosen destination that is beyond the range of sensory perception.
Subject(s)
Goals , Neurons/physiology , Prefrontal Cortex/cytology , Prefrontal Cortex/physiology , Spatial Navigation/physiology , Action Potentials , Animals , Hippocampus/cytology , Hippocampus/physiology , Male , Rats , Rats, Long-Evans , Space PerceptionABSTRACT
In reply to the comment of Kersting et al [...].
ABSTRACT
We describe a general electrochemical method to functionalize donor-acceptor (D-A) cyclopropanes and -butanes with arenes utilizing Friedel-Crafts-type reactivity. The catalyst-free strategy relies on the direct anodic oxidation of the strained carbocycles, which leads after C(sp3)-C(sp3) cleavage to radical cations that act as electrophiles for the arylation reaction. Broad reaction scopes in regard to cyclopropanes, cyclobutanes, and aromatic reaction partners are presented. Additionally, a plausible electrolysis mechanism is proposed.
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Children in Germany showed positive physical activity changes during the first Covid-19 lockdown in April 2020, but it is unclear how the changes relate to population density, which we investigated in a longitudinal sample of 1711 youth (4-17 years). For each ten citizens more per km2, less positive physical activity changes were observed. For example, a child living in an area with 100 citizens/km2 increased daily life physical activity by 44.50 min/day, whereas a child living in an area with 3000 citizens/km2 only engaged in an additional 9.70 min/day. Policymakers should ensure that youth in densely populated areas have access to physical activity opportunities during the pandemic.
Subject(s)
Built Environment , COVID-19 , Exercise/physiology , Population Density , Child , Female , Germany , Humans , Male , QuarantineABSTRACT
BACKGROUND: As children show a more complex but less structured movement behavior than adults, assessment of their many spontaneous and impulsive movements is a challenge for physical activity (PA) assessment. Since neither questionnaires nor accelerometers enable optimal detection of all facets of PA, a multimodal, combined approach of self-reported and device-based methods is recommended. Based on the number of days on which the participants reached the physical activity (PA) values given in the WHO guideline, this study examines 1) the difference between self-reported and device-based, measured PA and 2) whether PA differences between age and gender groups obtained by two methods are comparable. METHODS: Participants aged 6-17 years were randomly chosen and data were collected representatively at 167 sample points throughout Germany within the Motorik-Modul Study. PA of n = 2694 participants (52.3% female) was measured using the ActiGraph accelerometer (ACC) and a physical activity questionnaire (PAQ). The sample was divided into three age groups (6-10 yrs. n = 788, 11-13 yrs. n = 823, 14-17 yrs. n = 1083). Numbers of days per week with at least 60 min moderate to vigorous PA (MVPA) were analyzed for both methods. RESULTS: Only every 25th respondent (4%) reaches the WHO standard of 60 min MVPA every day if measured with ACC. Self-reported PA was slightly higher (9%) (meanPAQ = 3.82 days; meanACC = 2.34 days; Fmethod = 915.85; p = <.001; fCohen = .64). The differences between the methods are significantly smaller in younger children than in the older age groups (Fage = 264.2, p < .001; fCohen = .48). The older the subjects are, the lower is the proportion of those who meet the WHO guideline on each day, with girls meeting the guideline less frequently than boys in all age groups. CONCLUSION: Children and adolescents living in Germany show a very low adherence to the WHO guideline on PA. While younger children are much more active with their free play, especially children over 10 years of age and especially girls should be the target of programs to increase PA.
Subject(s)
Ethnicity , Exercise , Accelerometry , Adolescent , Adult , Aged , Child , Female , Germany , Humans , Male , Self Report , Surveys and QuestionnairesABSTRACT
We describe the first electrochemical activation of D-A cyclopropanes and D-A cyclobutanes leading after C(sp3 )-C(sp3 ) cleavage to the formation of highly reactive radical cations. This concept is utilized to formally insert molecular oxygen after direct or DDQ-assisted anodic oxidation of the strained carbocycles, delivering ß- and γ-hydroxy ketones and 1,2-dioxanes electrocatalytically. Furthermore, insights into the mechanism of the oxidative process, obtained experimentally and by additional quantum-chemical calculations are presented. The synthetic potential of the reaction products is demonstrated by diverse derivatizations.
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Reduced physical activity (PA) and prolonged screen time (ST) negatively influence health-related quality of life (HRQoL), a protective factor against illness and mortality. Studies addressing the relationship between PA, ST, and mental health in youth are scarce, especially in times with high mental health burdens like the COVID-19 pandemic. The purpose of this examination was to investigate whether PA, ST, and HRQoL before COVID-19 predict PA, ST, and HRQoL during the COVID-19 pandemic. Participants from the Motorik-Modul Study (MoMo; N = 1711; Mage = 10.36 (SD = 4.04) years, female = 49.8%; healthy weight = 76.8%) self-reported their PA and ST as well as HRQoL both before and during COVID-19. Relationships of all variables, from before to during COVID-19, were investigated through a path prediction model. Results showed all variables during COVID-19 were predicted by the respective levels before COVID-19, independent of gender and age. Cross-lags revealed a negative influence of before COVID-19 ST on during COVID-19 PA. HRQoL before COVID-19 was positively associated with during COVID-19 PA in children younger than 10 years and females, but not in adolescents and boys. As age- and gender-independent negative influence of before COVID-19 ST on during COVID-19 PA has been detected, health policy may be advised to focus on a general reduction in ST instead of PA enhancement to ensure high PA levels.