Effectiveness of an Ecological Model-Based Active Transport Education Program on Physical and Mental Health in High School Students (MOV-ES Project): Study Protocol for a Randomized Controlled Trial.

The United Nations, through its 2030 Agenda and Sustainable Development Goals, advocates for the establishment of conducive environments for physical activity, following the ecological model. In line with this initiative, active transportation emerges as an accessible, cost-effective, and sustainable approach to augmenting daily physical activity levels. This study protocol endeavors to assess the impact of an active transportation education program rooted in the ecological model on the physical and mental well-being of high school students. Drawing upon scientific insights, we hypothesize that a 16-week active transportation intervention will lead to a 3% reduction in average body fat percentage and a noteworthy enhancement in executive function (including inhibition, cognitive flexibility, and working memory), physical fitness (comprising cardiorespiratory fitness and muscle strength), and mental health (encompassing mood disorders and cognitive functioning). If this intervention proves effective, it could offer a viable solution for the school community, especially in reducing congestion within the school environment. The study protocol aims to evaluate the impact of an active transportation educational program based on the ecological model on the physical and mental well-being of high school students. Three high schools located in the urban area of Talca, Chile, will be randomly selected (one public, one privately subsidized, and one private non-subsidized). Each high school will be randomly assigned an experimental group (n = 30) and a control group (n = 30; without intervention). The experimental groups will receive an active transportation educational intervention during their physical education classes for four months (60 to 90 min sessions, once a week), while the control group will receive no intervention. The primary outcome will provide information on body composition and executive function. Secondary outcomes will include objective physical activity level, physical fitness, mental well-being, academic achievement, health-related quality of life, perception of environmental urban features, physical activity barriers, and adherence to active transportation. It is expected that the results of the MOV-ES Project will transcend the physical health of schoolchildren and will have an impact on the school community, especially by decongesting the school environment.

Effect of abamectin on osmoregulation in red swamp crayfish (Procambarus clarkii).

As a widely used pesticide, abamectin could be a threat to nontarget organisms. In this study, the toxic mechanism of abamectin on osmoregulation in Procambarus clarkii was explored for the first time. The results of this study showed that with increasing abamectin concentration, the membrane structures of gill filaments were damaged, with changes in ATPase activities, transporter contents, biogenic amine contents, and gene expression levels. The results of this study indicated that at 0.2 mg/L abamectin, ion diffusion could maintain osmoregulation. At 0.4 mg/L abamectin, passive transport was inhibited due to damage to the membrane structures of gill filaments, and active transport needed to be enhanced for osmoregulation. At 0.6 mg/L abamectin, the membrane structures of gill filaments were seriously damaged, and the expression level of osmoregulation-related genes decreased, but the organisms were still mobilizing various transporters, ATPases, and biogenic amines to address abamectin stress. This study provided a theoretical basis for further study of the effects of contaminations in aquatic environment on the health of crustaceans.

My Way to School Through a Camera Lens: Involving Children to Inform a Policy Recommendation on Active School Travel.

Active school travel (AST) is an effective approach for increasing children's physical activity and independent mobility, but policy supporting AST is lacking. This study aims to explore children's experiences of AST to inform a policy recommendation. Photovoice methodology with a qualitative approach was applied, with children taking pictures on their way to school. This was followed by focus groups where the children explored their experiences of AST based on their photos. The data were analyzed using qualitative content analysis. The results show that the children valued independent mobility and wanted to be involved in decisions about their travels; they also expressed feelings of increased responsibility and personal growth as a consequence. Although the children recognized areas of improvement regarding infrastructure, especially regarding heavy traffic that jeopardized travel safety, they continued using AST. Finally, the children talked about the value of the health and environmental benefits of AST. Opportunities for friendship, play, and making decisions about their own time were highlighted as important incentives. The benefits from AST are many for children, as well as for society. The result has informed policy recommendations for AST, and the children's input will be used to communicate the recommendations. Listening to the voices of children could be a steppingstone toward forming future healthy mobility initiatives. In that process, it is key to include children's perspectives when formulating the AST policy for successful adoption and implementation.

Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier.

BACKGROUND: The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism. METHODS: A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included. RESULTS: During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects. CONCLUSIONS: Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects.

New insights in bacterial organophosphorus cycling: From human pathogens to environmental bacteria.

In terrestrial and aquatic ecosystems, phosphorus (P) availability controls primary production, with consequences for climate regulation and global food security. Understanding the microbial controls on the global P cycle is a prerequisite for minimising our reliance on non-renewable phosphate rock reserves and reducing pollution associated with excessive P fertiliser use. This recognised importance has reinvigorated research into microbial P cycling, which was pioneered over 75 years ago through the study of human pathogenic bacteria-host interactions. Immobilised organic P represents a significant fraction of the total P pool. Hence, microbes have evolved a plethora of mechanisms to transform this fraction into labile inorganic phosphate, the building block for numerous biological molecules. The 'genomics era' has revealed an extraordinary diversity of organic P cycling genes exist in the environment and studies going 'back to the lab' are determining how this diversity relates to function. Through this integrated approach, many hitherto unknown genes and proteins that are involved in microbial P cycling have been discovered. Not only do these fundamental discoveries push the frontier of our knowledge, but several examples also provide exciting opportunities for biotechnology and present possible solutions for improving the sustainability of how we grow our food, both locally and globally. In this review, we provide a comprehensive overview of bacterial organic P cycling, covering studies on human pathogens and how this knowledge is informing new discoveries in environmental microbiology.

Promoting children's health through community-led street interventions: analyzing sustained voluntarism in Canadian School Streets.

BACKGROUND: Active School Travel (AST) initiatives align with the Ottawa Charter for Health Promotion, which calls for 'creating supportive environments' and 'strengthening community action.' However, their reliance on volunteers poses sustainability challenges. The main objectives of this study were to document the motivations, satisfaction, and experiences of volunteers involved in sustaining two AST initiatives in Ontario for an entire school year. METHODS: Two volunteer-led School Street initiatives in Kingston, Ontario successfully operated during pick-up and drop-off times of each school day. The first initiative operated for the entire 2021-2022 school year, and the second operated for the entire 2022-2023 school year. These initiatives were the first of their kind in the province of Ontario, Canada. Volunteers from both sites (n = 56) participated in online surveys and their motivations, satisfaction, and experiences of their role were compared using the 2-sided Fisher's Exact Test. RESULTS: Over 80% of volunteers were highly motivated to promote safety and over 70% of volunteers were highly motivated to disrupt the status quo of unsupportive, car-centric urban environments by reimagining how streets can be used. By taking collective action to re-shape the environment around these public schools to support healthy, active living, our findings reveal that over 90% of volunteers were highly satisfied. Of the volunteers, 87% felt they contributed to child safety and 85% felt they had developed stronger community connections. They appreciated the short (i.e., 40 minute) time commitment of each shift, weekly email communications by the community organization leading the initiative, and the volunteer schedule. They also appreciated the positive social interactions during volunteer shifts, which they felt outweighed the minimal resistance they experienced. CONCLUSIONS: This research demonstrates the importance of logistical, motivational, and social factors in recruiting and retaining volunteers for community-led School Streets. Our findings support appealing to prospective volunteers' influence in achieving School Street objectives (e.g., improved safety) in recruitment efforts, as well as highlighting School Streets' innovative approach. Communicating with volunteers throughout School Street planning and implementation processes and limiting traffic in the closed street zone (i.e., by excluding the school staff parking lot and private driveways from the scope) are additional recommendations based on the findings of this study.

Associations between transport modes and site-specific cancers: a systematic review and meta-analysis.

BACKGROUND: Physical inactivity is a global public health problem. A practical solution would be to build physical activity into the daily routine by using active modes of transport. Choice of transport mode can influence cancer risk through their effects on levels of physical activity, sedentary time, and environmental pollution. This review synthesizes existing evidence on the associations of specific transport modes with risks of site-specific cancers. METHODS: Relevant literature was searched in PubMed, Embase, and Scopus from 1914 to 17th February 2023. For cancer sites with effect measures available for a specific transport mode from two or more studies, random effects meta-analyses were performed to pool relative risks (RR) comparing the highest vs. lowest activity group as well as per 10 Metabolic Equivalent of Task (MET) hour increment in transport-related physical activity per week (∼150 min of walking or 90 min of cycling). RESULTS: 27 eligible studies (11 cohort, 15 case-control, and 1 case-cohort) were identified, which reported the associations of transport modes with 10 site-specific cancers. In the meta-analysis, 10 MET hour increment in transport-related physical activity per week was associated with a reduction in risk for endometrial cancer (RR: 0.91, 95% CI: 0.83-0.997), colorectal cancer (RR: 0.95, 95% CI: 0.91-0.99) and breast cancer (RR: 0.99, 95% CI: 0.89-0.996). The highest level of walking only or walking and cycling combined modes, compared to the lowest level, were significantly associated with a 12% and 30% reduced risk of breast and endometrial cancers respectively. Cycling, compared to motorized modes, was associated with a lower risk of overall cancer incidence and mortality. CONCLUSION: Active transport appears to reduce cancer risk, but evidence for cancer sites other than colorectum, breast, and endometrium is currently limited.

Nose-to-brain delivery of nanotherapeutics: Transport mechanisms and applications.

The blood-brain barrier presents a key limitation to the administration of therapeutic molecules for the treatment of brain disease. While drugs administered orally or intravenously must cross this barrier to reach brain targets, the unique anatomical structure of the olfactory system provides a route to deliver drugs directly to the brain. Entering the brain via receptor, carrier, and adsorption-mediated transcytosis in the nasal olfactory and trigeminal regions has the potential to increase drug delivery. In this review, we introduce the physiological and anatomical structures of the nasal cavity, and summarize the possible modes of transport and the relevant receptors and carriers in the nose-to-brain pathway. Additionally, we provide examples of nanotherapeutics developed for intranasal drug delivery to the brain. Further development of nanoparticles that can be applied to intranasal delivery systems promises to improve drug efficacy and reduce drug resistance and adverse effects by increasing molecular access to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Experimental and Computational Methods to Assess Central Nervous System Penetration of Small Molecules.

In CNS drug discovery, the estimation of brain exposure to lead compounds is critical for their optimization. Compounds need to cross the blood-brain barrier (BBB) to reach the pharmacological targets in the CNS. The BBB is a complex system involving passive and active mechanisms of transport and efflux transporters such as P-glycoproteins (P-gp) and breast cancer resistance protein (BCRP), which play an essential role in CNS penetration of small molecules. Several in vivo, in vitro, and in silico methods are available to estimate human brain penetration. Preclinical species are used as in vivo models to understand unbound brain exposure by deriving the Kp,uu parameter and the brain/plasma ratio of exposure corrected with the plasma and brain free fraction. The MDCK-mdr1 (Madin Darby canine kidney cells transfected with the MDR1 gene encoding for the human P-gp) assay is the commonly used in vitro assay to estimate compound permeability and human efflux. The in silico methods to predict brain exposure, such as CNS MPO, CNS BBB scores, and various machine learning models, help save costs and speed up compound discovery and optimization at all stages. These methods enable the screening of virtual compounds, building of a CNS penetrable compounds library, and optimization of lead molecules for CNS penetration. Therefore, it is crucial to understand the reliability and ability of these methods to predict CNS penetration. We review the in silico, in vitro, and in vivo data and their correlation with each other, as well as assess published experimental and computational approaches to predict the BBB penetrability of compounds.

Are Spanish adolescents who actively commute to and from school more active in other domains? A spatiotemporal investigation.

We examined the association between mode of commuting to/from school (i.e., walking, multimodal, and motorized-vehicle) and movement behaviours in several space-time domains (i.e., total day, home, school, transport, and other locations). Walking to and/or from school was associated with higher MVPA in all space-time domains except home, where no associations were found. After subtracting commuting time to/from school from total day domain, the associations in favour of walking to/from school were maintained compared to those using other commuting modes, and in transport domain these associations dissipated. The study suggests the importance of promoting walking to/from school for increasing MVPA levels.

Low molecular weight acids and OATP1B mediated hepatic clearance: In vitro and in vivo evaluation using novel hypoxia-inducible factor prolyl hydroxylase inhibitors (Dustats).

Organic anion transporting polypeptide (OATP1B) plays a key role in the hepatic clearance of a majority of high molecular weight (MW) acids and zwitterions. Here, we evaluated the role of OATP1B-mediated uptake in the clearance of novel hypoxia-inducible factor prolyl hydroxylase inhibitors ("Dustats"), which are typically low MW (300-400 daltons) aliphatic carboxylic acids. Five acid dustats, namely daprodustat, desidustat, enarodustat, roxadustat and vadadustat, showed specific transport by OATP1B1/1B3 in transporter-transfected HEK293 cells. Neutral compound, molidustat, was not a substrate to OATP1B1/1B3. None of the dustats showed transport by other hepatic uptake transporters, including NTCP, OAT2 and OAT7. In the primary human hepatocytes, uptake of all acids was significantly reduced by rifampin (OATP1B inhibitor); with an estimated fraction transported by OATP1B (ft ,OATP1B) of up to >80% (daprodustat). Molidustat uptake was minimally inhibited by rifampin; and low permeability acids (desidustat and enarodustat) also showed biliary efflux in sandwich culture human hepatocytes. In vivo, intravenous pharmacokinetics of all 5 acids was significantly altered by a single-dose rifampin (30 mg/kg) in Cynomolgus monkey. Hepatic clearance (non-renal) was about 4-fold (vadadustat) to >11-fod (daprodustat and roxadustat) higher in control group compared to rifampin-treated subjects. In vivo ft ,OATP1B was estimated to be ~70-90%. In the case of molidustat, rifampin had a minimal effect on overall clearance. Rifampin also considerably reduced volume of distribution of daprodustat and roxadustat. Overall, OATP1B significantly contribute to the hepatic clearance and pharmacokinetics of several dustats, which are low MW carboxylic acids. OATP1B activity should therefore by evaluated in this property space. Significance Statement Our in vitro and in vivo results suggest that OATP1B-mediated hepatic uptake play a significant role in the pharmacokinetics of low MW acidic dustats, which are being developed or approved for the treatment of anemia in chronic kidney disease. Significant active uptake mechanisms are not apparent for the neutral compound, molidustat. Characterization of uptake mechanisms is therefore important in predicting human pharmacokinetics and evaluating drug-drug interactions for low MW acids.

Exploring the K+ binding site and its coupling to transport in the neurotransmitter:sodium symporter LeuT.

The neurotransmitter:sodium symporters (NSSs) are secondary active transporters that couple the reuptake of substrate to the symport of one or two sodium ions. One bound Na+ (Na1) contributes to the substrate binding, while the other Na+ (Na2) is thought to be involved in the conformational transition of the NSS. Two NSS members, the serotonin transporter (SERT) and the Drosophila dopamine transporter (dDAT), also couple substrate uptake to the antiport of K+ by a largely undefined mechanism. We have previously shown that the bacterial NSS homologue, LeuT, also binds K+, and could therefore serve as a model protein for the exploration of K+ binding in NSS proteins. Here, we characterize the impact of K+ on substrate affinity and transport as well as on LeuT conformational equilibrium states. Both radioligand binding assays and transition metal ion FRET (tmFRET) yielded similar K+ affinities for LeuT. K+ binding was specific and saturable. LeuT reconstituted into proteoliposomes showed that intra-vesicular K+ dose-dependently increased the transport velocity of [3H]alanine, whereas extra-vesicular K+ had no apparent effect. K+ binding induced a LeuT conformation distinct from the Na+- and substrate-bound conformation. Conservative mutations of the Na1 site residues affected the binding of Na+ and K+ to different degrees. The Na1 site mutation N27Q caused a >10-fold decrease in K+ affinity but at the same time a ~3-fold increase in Na+ affinity. Together, the results suggest that K+ binding to LeuT modulates substrate transport and that the K+ affinity and selectivity for LeuT is sensitive to mutations in the Na1 site, pointing toward the Na1 site as a candidate site for facilitating the interaction with K+ in some NSSs.

Results from Ireland North and South's 2022 report card on physical activity for children and adolescents.

Background: The Ireland North and South Report Card on Physical Activity (PA) for Children and Adolescents aims to monitor progress in PA participation across a range of internationally established indicators. Methods: Data were collated for 11 indicators and graded following the harmonised Active Healthy Kids Global Alliance report card process. Six representative studies (sample size range n = 898 to n = 15,557) were primarily used in the grading, with many indicators supplemented with additional studies and reports. Data collected since the implementation of COVID-19 public health measures in March 2020 were excluded. Results: Grades were awarded as follows: 'Overall physical activity', C-; 'Organised Sport and Physical Activity', C; 'Active Play', INC; 'Sedentary Behaviours', C-; 'Physical Fitness', INC; 'Family and Peers', D+; 'School', C-; 'Physical Education', D; 'Community and Environment', B+ and 'Government', B. Separate grades were awarded for disability as follows; 'Overall physical activity', F; 'Organised Sport and Physical Activity', D; 'Sedentary Behaviours', C-; 'Family and Peers', C; 'School', C- and 'Government', B. 'Active Play', 'Physical Fitness', 'Physical Education' and 'Community and Environment' were all graded INC for disability. Since the last report card in 2016, four grades remained the same, three increased ('Overall physical activity', 'School' and 'Physical Education') and two ('Family and Peers,' and 'Government') were awarded grades for the first time. Conclusion: Grades specific to children and adolescents with disability were generally lower for each indicator. While small improvements have been shown across a few indicators, PA levels remain low across many indicators for children and adolescents.

Effects of Aqueous Boundary Layers and Paracellular Transport on the Efflux Ratio as a Measure of Active Transport Across Cell Layers.

The efflux ratio (ER), determined by Caco-2/MDCK assays, is the standard in vitro metric to establish qualitatively whether a compound is a substrate of an efflux transporter. However, others have also enabled the utilisation of this metric quantitatively by deriving a relationship that expresses the ER as a function of the intrinsic membrane permeability of the membrane (P0) as well as the permeability of carrier-mediated efflux (Ppgp). As of yet, Ppgp cannot be measured directly from transport experiments or otherwise, but the ER relationship provides easy access to this value if P0 is known. However, previous derivations of this relationship failed to consider the influence of additional transport resistances such as the aqueous boundary layers (ABLs) and the filter on which the monolayer is grown. Since single fluxes in either direction can be heavily affected by these experimental artefacts, it is crucial to consider the potential impact on the ER. We present a model that includes these factors and show both mathematically and experimentally that this simple ER relationship also holds for the more realistic scenario that does not neglect the ABLs/filter. Furthermore, we also show mathematically how paracellular transport affects the ER, and we experimentally confirm that paracellular dominance reduces the ER to unity and can mask potential efflux.

ATP1A1-linked diseases require a malfunctioning protein product from one allele.

Heterozygous germline variants in ATP1A1, the gene encoding the α1 subunit of the Na+/K+-ATPase (NKA), have been linked to diseases including primary hyperaldosteronism and the peripheral neuropathy Charcot-Marie-Tooth disease (CMT). ATP1A1 variants that cause CMT induce loss-of-function of NKA. This heterodimeric (αß) enzyme hydrolyzes ATP to establish transmembrane electrochemical gradients of Na+ and K+ that are essential for electrical signaling and cell survival. Of the 4 catalytic subunit isoforms, α1 is ubiquitously expressed and is the predominant paralog in peripheral axons. Human population sequencing datasets indicate strong negative selection against both missense and protein-null ATP1A1 variants. To test whether haploinsufficiency generated by heterozygous protein-null alleles are sufficient to cause disease, we tested the neuromuscular characteristics of heterozygous Atp1a1+/- knockout mice and their wildtype littermates, while also evaluating if exercise increased CMT penetrance. We found that Atp1a1+/- mice were phenotypically normal up to 18 months of age. Consistent with the observations in mice, we report clinical phenotyping of a healthy adult human who lacks any clinical features of known ATP1A1-related diseases despite carrying a plasma-membrane protein-null early truncation variant, p.Y148*. Taken together, these results suggest that a malfunctioning gene product is required for disease induction by ATP1A1 variants and that if any pathology is associated with protein-null variants, they may display low penetrance or high age of onset.

Intermediaries and intermediation in building local transformative capacity for active and sustainable transport.

Intermediation and transformative capacity building are identified as important issues in sustainability transformations. Yet the connection of these two concepts has not been systematically analysed. This empirical, qualitative case study on active transport in Finland investigates intermediation in building local transformative capacity. The study shows that intermediaries are a heterogeneous group of actors that support transformative capacity building by facilitating the flows of knowledge, linking actors, forming ties across different scales, and supporting visioning and strategic planning. Intermediation manifests in five of the seven elements of local transformative capacity building. Our study, thus, contrasts with previous understanding wherein intermediation is considered only as a criterion for multiform governance. As intermediation is central in building transformative capacity, it should be better acknowledged, particularly by authorities and policymakers to secure legitimacy, operational capabilities, and funding for intermediaries.

Does active transport create a win-win situation for environmental and human health: the moderating effect of leisure and tourism activity.

The current environmental crisis is mostly due to global warming. Promoting walking and cycling requires both the availability of green public areas (such as parks, green paths, and greenways) and a mentality that values such active modes of transportation. Significant health advantages from increased physical activity (PA) are associated with transportation options like walking and cycling (sometimes known as "active transportation," AT): the health and environmental advantages of encouraging workers to use bicycles for transportation been widely acknowledged. The authors of this research set out to fill this information gap by investigating the theoretically theorized links between green public space awareness and attitudes toward active mobility, adapting to a changing environment, and improving one's mental and physical health, with leisure and tourist activities serving as a moderator. The data was collected quantitatively using purposive sampling and then analyzed using PLS-SEM. We surveyed Korean walkers (n = 282) and bikers (n = 315) online between May 25 and June 17, 2021, and used a partial least squares structural equation modeling (PLS-SEM) analysis to test our hypothesis. As stated in the findings, being conscious of green public space when using active transportation significantly affects how clean the air feels. Active transportation was shown to have a significant effect on health, and climate change mitigation efforts were found to have a significant effect on health. Those who used active transportation for tourism had a stronger connection between green public space awareness and air quality, in addition to environmental sustainability and ethical conduct mitigation, than those who used active transport for recreation. Therefore, the model may aid in locating transport and health scenarios that benefit both sectors.

Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial.

(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood-brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; p = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin p = 0.031 [0.023, 0.579]; conjugated bilirubin p = 0.001 [0.193, 0.683]; unconjugated p = 0.387 [-0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood-brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood-brain barrier.

Determinants of physical activity in community-dwelling older adults: an umbrella review.

INTRODUCTION: Physical activity (PA) is critical for disease prevention and maintaining functional ability with aging. Despite this, as many as 50% of older adults in populations worldwide are considered insufficiently active. There is a recognized need to mobilize policies targeted toward modifiable determinants of healthy aging like PA. This umbrella review aimed to summarize the evidence for determinants of PA in community-dwelling older adults. METHODS: A research librarian searched six databases. Systematic and scoping reviews were included if they investigated community-dwelling people with a mean age of 60 + years and examined a relationship between a determinant and any type of PA. Two independent reviewers screened and extracted data from all reviews. JBI methodology and Critical Appraisal Checklist for Systematic Reviews and Research Syntheses were followed and information on the quality of the evidence was extracted. RESULTS: From 17,277 records screened,11 reviews representing > 300 unique primary papers were ultimately included. Only 6% of studies included in all reviews had longitudinal designs. Included studies used a large variety of PA measures, with 76% using only self-report, 15% using only direct measures (e.g., accelerometry), 3% using both types, and 6% with no outcome measure reported. Only four reviews provided a definition of PA and there was substantial inconsistency in the way PA was categorised. Community level influences, which only included the physical environment, were the most commonly assessed (6/11) with more than 70% of the summarized relationships demonstrating null associations. Three out of four reviews reported a positive relationship between walkability and PA in general community-dwelling older adults. There was also evidence supporting relationships between presence of social support for PA, younger age, and men having higher PA from a single systematic review. None of the included reviews assessed the quality of evidence but over 60% performed a risk of bias assessment. CONCLUSIONS: Walkability, age, gender, and social support for PA were the most supported PA determinants identified. Further research should focus on interpersonal and intrapersonal influences and incorporate direct measures of PA with clear operational definitions. There is a need for longitudinal study designs to further understand determinants of PA behaviour trajectories.

School-based physical activity in relation to active travel - a cluster randomized controlled trial among adolescents enrolled in the school in motion study in Norway.

BACKGROUND: Active travel and school settings are considered ideal for promoting physical activity. However, previous research suggests limited effect of school-based interventions on overall physical activity levels among adolescents. The relationship between physical activity in different domains remains inconclusive. In this study, we examined the effects of adding two weekly hours of school-based physical activity on active travel rates. METHOD: We analyzed data from 1370 pupils in the 9th-grade participating in the cluster RCT; the School In Motion (ScIM) project. Intervention schools (n = 19) implemented 120 min of class-scheduled physical activity and physical education, in addition to the normal 2 hours of weekly physical education in the control schools (n = 9), for 9 months. Active travel was defined as pupils who reported walking or cycling to school, while motorized travel was defined as pupils who commuted by bus or car, during the spring/summer half of the year (April-September), or autumn/winter (October-February). The participants were categorized based on their travel mode from pretest to posttest as; maintained active or motorized travel ("No change"), changing to active travel (motorized-active), or changing to motorized travel (active-motorized). Multilevel logistic regression was used to analyze the intervention effect on travel mode. RESULTS: During the intervention period, most participants maintained their travel habits. In total, 91% of pupils maintained their travel mode to school. Only 6% of pupils switched to motorized travel and 3% switched to active travel, with small variations according to season and trip direction. The intervention did not seem to influence the likelihood of changing travel mode. The odds ratios for changing travel habits in spring/summer season were from active to motorized travel 1.19 [95%CI: 0.53-2.15] and changing from motorized to active travel 1.18 [0.30-2.62], compared to the "No change" group. These findings were consistent to and from school, and for the autumn/winter season. CONCLUSION: The extra school-based physical activity does not seem to affect rates of active travel among adolescents in the ScIM project. TRIAL REGISTRATION: Clinicaltrials.gov ID nr: NCT03817047. Registered 01/25/2019' retrospectively registered'.