"Instead of Being on a Screen You Can Be More Out There and Enjoy Your Life": Young People's Understandings of Physical Activity for Health.

BACKGROUND: Despite documented evidence of the benefits of leading a physically active life, it is reported that less than half of young people in Europe meet the physical activity recommendations. Schools, and in particular physical education (PE), are viewed to be at the forefront of addressing inactive lifestyles and educating young people about physical activity. Nonetheless, given advancements in technology, young people are increasingly exposed to physical activity information "beyond the school gates". Consequently, if PE teachers are to support young people to understand the information they receive surrounding physical activity online, then they need to be able to address any misconceptions about health they may have. METHODS: In this study, fourteen young people (7 boys and 7 girls) in year 9 (13-14 years old) from two secondary schools in England participated in a digitally-based activity and semi-structured interviews which aimed to explore their conceptions of physical activity for health. RESULTS: It was found that the young people had limited and narrow conceptions of what it means to be physically active. CONCLUSIONS: It was suggested the findings could be partly attributed to limitations in students' learning and experiences with respect to physical activity and health in the PE curriculum.

Direct Oral Anticoagulants Versus Warfarin for Venous Thromboembolism Prophylaxis in Patients With Nephrotic Syndrome: A Retrospective Cohort Study.

BACKGROUND: Evidence supporting venous thromboembolism (VTE) prophylaxis with direct oral anticoagulants (DOACs) in patients with nephrotic syndrome (NS) is limited to case reports. OBJECTIVE: The purpose of this study was to compare bleeding and thromboembolic events in this population. METHODS: A retrospective cohort study was conducted in adults with NS initiated on a DOAC or warfarin for VTE prophylaxis between January 2013 and July 2021 within the Ochsner Health System. Patients with study drug exposure within the preceding 7 days, acute VTE within the preceding 6 months, or ≤7 days of study drug exposure were excluded. The primary outcome was the composite rate of major bleeding and clinically relevant nonmajor bleeding. Secondary outcomes included time to major bleeding and rate of new thromboembolic events. This study was approved by the Ochsner Health System Institutional Review Board. RESULTS: Twenty-five DOAC and 19 warfarin patients were included. The primary outcome occurred in 8% vs 26.3% (P = 0.21) of patients treated with a DOAC or warfarin, respectively, and was driven by major bleeding (4% vs 21%, P = 0.25). Other secondary outcomes were similar between cohorts. The study was limited by a small sample size. CONCLUSION AND RELEVANCE: Use of DOACs for VTE prophylaxis resulted in a nonstatistically significant, but clinically relevant lower rate of major bleeding compared to warfarin. This study provides comparative data showing safe and effective use of DOACs in patients with NS. Prospective, randomized studies are needed to confirm results.

Direct Oral Anticoagulants Versus Warfarin for Treatment of Thrombosis or Atrial Fibrillation in Patients With Cirrhosis: A Retrospective Cohort Study.

BACKGROUND: Evidence for direct oral anticoagulants (DOACs) in patients with cirrhosis is limited. Few patients with Child-Turcotte-Pugh (CTP) class B and C cirrhosis have been studied. OBJECTIVE: To compare major bleeding rates in patients with cirrhosis receiving a DOAC versus warfarin. METHODS: A retrospective cohort study was conducted in adults with cirrhosis receiving a DOAC versus warfarin for venous thromboembolism, portal-vein thrombosis, or atrial fibrillation. The primary outcome was the rate of major bleeding. Secondary outcomes included time to major bleeding, clinically relevant nonmajor bleeding, all bleeding, gastrointestinal bleeding, intracranial bleeding, and new thromboembolic events. The study was approved by the Ochsner Health System Institutional Review Board. RESULTS: A total of 44 patients receiving a DOAC and 41 patients receiving warfarin were included. Major bleeding occurred in 4 patients receiving a DOAC and 6 patients receiving warfarin (9.1% vs 14.6%; P = 0.881). Rates of major bleeding were similar in 24 DOAC and 17 warfarin patients with CTP Class B (4.2% vs 17.6%; P = 0.37) and 8 DOAC and 9 warfarin patients with CTP Class C (37.5% vs 11.1%; P = 0.41) cirrhosis. Secondary bleeding and efficacy outcomes were similar between cohorts. The study was limited by a small sample size. CONCLUSION AND RELEVANCE: Treatment with DOACs in patients with cirrhosis was associated with a similar rate of major bleeding compared with warfarin. Inclusion of CTP class C patients in future studies remains valuable to evaluate safety and efficacy of DOACs in this population.

Atividade física para saúde, covid-19 e mídias sociais: o quê, onde e por quê? / Actividad física para la salud, covid-19 y medios sociales: ¿qué, dónde y por qué? / Physical activity for health, covid-19 and social media: what, where and why?

Resumo Este estudo concentra-se no uso de mídias sociais por professores de Educação Física (EF) para o ensino de atividade física para saúde durante a pandemia de covid-19. Com base na pesquisa apreciativa e utilizando uma metodologia de teoria fundamentada em dados (Grounded Theory), a análise de duas entrevistas e uma tarefa digital permitem apresentar três principais temas: (1) Mídias Sociais como Ferramenta de Ensino; (2) Um Legado Digital Duradouro?, e; (3) Desigualdade do Aprendizado Remoto. Esses temas destacam a urgência em utilizar mídias sociais quando os espaços físicos da EF foram removidos, o reconhecimento de que o ensino poderia ser diferente no futuro e os desafios inerentes aos espaços digitais. Em conclusão: (1) defendemos a efetiva formação inicial e continuada de professores e no uso positivo de tecnologias digitais; (2) sugerimos que atividades on-line futuras incorporadas ao aprendizado, e; (3) exigir aos governos ações para nivelar as desigualdades tecnológicas.

Resumen Este estudio se centra en el uso de los medios sociales por parte de los profesores de Educación Física (EF) para enseñar actividad física para la salud durante la pandemia de covid-19. Con base en la investigación apreciativa y utilizando una metodología teórica fundamentada en datos (Grounded Theory), el análisis de dos entrevistas y una tarea digital permiten presentar tres temas principales: (1) Medios Sociales como Herramienta de Enseñanza, (2) ¿Un Legado Digital Duradero?, y (3) Desigualdad del Aprendizaje Remoto. Estos temas destacan la urgencia de utilizar medios sociales cuando los espacios físicos de la EF fueron suspendidos, el reconocimiento de que la enseñanza podría ser diferente en el futuro y los desafíos inherentes a los espacios digitales. En conclusión, (1) abogamos por la efectiva formación inicial y continua de profesores en el uso positivo de las tecnologías digitales, (2) sugerimos que actividades online futuras sean incorporadas al aprendizaje, y (3) demandar a los gobiernos acciones para nivelar las desigualdades tecnológicas.

Abstract This study focuses on Physical Education (PE) teachers' use of social media to teach physical activity for health during the covid-19 pandemic. Drawing on appreciative inquiry and utilising a grounded theory methodology, analysis of two interviews and a digital task allow us to present three main themes: (1) Social Media as a Teaching Tool, (2) A Lasting Digital Legacy?, and (3) Inequity of Remote Learning. These themes highlight the rush to utilise social media when the physical spaces of PE were removed, the recognition that teaching could be different in the future, and challenges inherent to digital spaces. In concluding we: (1) advocate for effective initial teacher education and ongoing professional development in the positive use of digital technologies, (2) suggest that future online activities incorporate learning, and (3) urge governments to do more in terms of levelling out technological inequalities.

Safety and Efficacy of Apixaban Versus Warfarin in Patients With Advanced Chronic Kidney Disease.

BACKGROUND: Because of a lack of comparative data on anticoagulant use in the advanced chronic kidney disease (CKD) population, guidelines recommend warfarin for atrial fibrillation and venous thromboembolism (VTE) treatment in these patients. However, apixaban has specific dosing recommendations in CKD leading to use in clinical practice. OBJECTIVE: To evaluate major bleeding, stroke, and thromboembolism rates in patients with CKD stage 4, stage 5, and dialysis on apixaban or warfarin therapy. METHODS: This was a retrospective cohort study of patients with advanced CKD receiving apixaban or warfarin. The primary outcome was the occurrence of major bleeding at 3 months after enrollment. Secondary outcomes included occurrence of major bleeding, occurrence of ischemic stroke, and recurrence of VTE at 3 to 6 and 6 to 12 months. RESULTS: A total of 604 patients were included in the analysis. The percentage of apixaban and warfarin patients with a major bleed at 0 to 3, 3 to 6, and 6 to 12 months were 8.3% versus 9.9% ( P=0.48), 1.4% versus 4% ( P=0.07), and 1.5% versus 8.4% ( P<0.001), respectively. There were no differences in rates of ischemic stroke or recurrent VTE at any time period. Conclusion and Relevance: Patients with advanced CKD taking apixaban had similar bleeding rates at 3 months compared with those taking warfarin. However, those who continued therapy had higher major bleeding rates with warfarin between 6 and 12 months. This study provides knowledge on the effects of a direct oral anticoagulant in a population that was excluded from all major trials.

Kinetic Basis of Carbohydrate-Mediated Inhibition of Human Glucokinase by the Glucokinase Regulatory Protein.

The glucokinase regulatory protein (GKRP) is a competitive inhibitor of glucokinase (GCK), triggering its localization to the hepatocyte nucleus upon glucose deprivation. Here we establish the kinetic mechanism of GKRP action by analyzing its association with a genetically encoded, fluorescent variant of human GCK. Our results demonstrate that binding of GKRP to GCK involves two steps, formation of an initial encounter complex followed by conformational equilibration between two GKRP-GCK states. Fructose 6-phosphate, a known enhancer of GKRP action, promotes formation of the initial encounter complex via a 2.6-fold increase in kon and stabilizes the complex through a 60-fold decrease in koff.

"I just remember rugby": Re-membering Physical Education as More Than a Sport.

PURPOSE: The purpose of this article was to investigate how boys communicate previous experiences of cultural norms in physical education (PE) practice. This was done by analyzing what boys (from a school in the United Kingdom) remember about PE 2 years after they last participated. Making use of autobiographical memory theory and John Dewey's notions of reactualization of experience and collateral learning, we discuss the results of the study in terms of re-membering. METHOD: The participants in this study were 20 boys from a secondary school in the United Kingdom. At the time of the study, 11 of the boys were aged 16 to 17 years old and 9 were aged 17 to 18 years old. These boys were interviewed using a semistructured approach to explore their autobiographical memories of PE. RESULTS: The overarching "logic" of memories of PE was sport. Almost all of the boys' articulated memories were of doing sports, albeit in various capacities. Beyond the main theme, the article positions the boys' recollections against established cultural norms of PE as a social practice and explores three subthemes: (a) just doing the game in a traditional curriculum though a multiactivity sport discourse; (b) learning the games in a technical sport discourse; and (c) learning beyond the game around an educational sport discourse. CONCLUSIONS: These boys reactualized memories of learning within an educational discourse, which suggests that what they learned goes beyond the simple consequence of participating.

An evolutionarily conserved alternate metal ligand is important for activity in α-isopropylmalate synthase from Mycobacterium tuberculosis.

Members of the DRE-TIM metallolyase superfamily rely on an active-site divalent cation to catalyze various reactions involving the making and breaking of carbon-carbon bonds. While the identity of the metal varies, the binding site is well-conserved at the superfamily level with an aspartic acid and two histidine residues acting as ligands to the metal. Previous structural and bioinformatics results indicate that the metal can adopt an alternate architecture through the addition of an asparagine residue as a fourth ligand. This asparagine residue is strictly conserved in all members of the DRE-TIM metallolyase superfamily except fungal homocitrate synthase (HCS-lys) where it is replaced with isoleucine. The role of this additional metal ligand in α-isopropylmalate synthase from Mycobacterium tuberculosis (MtIPMS) has been investigated using site-directed mutagenesis. Substitution of the asparagine ligand with alanine or isoleucine results in inactive enzymes with respect to α-isopropylmalate formation. Control experiments suggest that the substitutions have not drastically affected the enzyme's structure indicating that the asparagine residue is essential for catalysis. Interestingly, all enzyme variants retained acetyl CoA hydrolysis activity in the absence of α-ketoisovalerate, similar to the wild-type enzyme. In contrast to the requirement of magnesium for α-isopropylmalate formation, hydrolytic activity could be inhibited by the addition of magnesium chloride in wild-type, D81E, and N321A MtIPMS, but not in the other variants studied. Attempts to rescue loss of activity in N321I MtIPMS by mimicking the fungal HCS active site through the D81E/N321I double variant were unsuccessful. This suggests epistatic constraints in evolution of function in IPMS and HCS-lys enzymes.

Mechanistic and bioinformatic investigation of a conserved active site helix in α-isopropylmalate synthase from Mycobacterium tuberculosis, a member of the DRE-TIM metallolyase superfamily.

The characterization of functionally diverse enzyme superfamilies provides the opportunity to identify evolutionarily conserved catalytic strategies, as well as amino acid substitutions responsible for the evolution of new functions or specificities. Isopropylmalate synthase (IPMS) belongs to the DRE-TIM metallolyase superfamily. Members of this superfamily share common active site elements, including a conserved active site helix and an HXH divalent metal binding motif, associated with stabilization of a common enolate anion intermediate. These common elements are overlaid by variations in active site architecture resulting in the evolution of a diverse set of reactions that include condensation, lyase/aldolase, and carboxyl transfer activities. Here, using IPMS, an integrated biochemical and bioinformatics approach has been utilized to investigate the catalytic role of residues on an active site helix that is conserved across the superfamily. The construction of a sequence similarity network for the DRE-TIM metallolyase superfamily allows for the biochemical results obtained with IPMS variants to be compared across superfamily members and within other condensation-catalyzing enzymes related to IPMS. A comparison of our results with previous biochemical data indicates an active site arginine residue (R80 in IPMS) is strictly required for activity across the superfamily, suggesting that it plays a key role in catalysis, most likely through enolate stabilization. In contrast, differential results obtained from substitution of the C-terminal residue of the helix (Q84 in IPMS) suggest that this residue plays a role in reaction specificity within the superfamily.

V-type allosteric inhibition is described by a shift in the rate-determining step for α-isopropylmalate synthase from Mycobacterium tuberculosis.

The kinetic parameters affected by allosteric mechanisms contain collections of rate constants that vary based on differences in the relative rates of individual steps in the reaction. Thus, it may not be useful to compare enzymes with similar allosteric mechanisms unless the point of regulation has been identified. Rapid reaction kinetics and kinetic isotope effects provide a detailed description of V-type feedback allosteric inhibition in α-isopropylmalate synthase from Mycobacterium tuberculosis, an evolutionarily conserved model allosteric system. Results are consistent with a shift in the rate-determining step from product release to the hydrolytic step in catalysis in the presence of the effector.

The slow-onset nature of allosteric inhibition in α-isopropylmalate synthase from Mycobacterium tuberculosis is mediated by a flexible loop.

The identification of structure-function relationships in allosteric enzymes is essential to describing a molecular mechanism for allosteric processes. The enzyme α-isopropylmalate synthase from Mycobacterium tuberculosis (MtIPMS) is subject to slow-onset, allosteric inhibition by l-leucine. Here we report that alternate amino acids act as rapid equilibrium noncompetitive inhibitors of MtIPMS failing to display biphasic inhibition kinetics. Amino acid substitutions on a flexible loop covering the regulatory binding pocket generate enzyme variants that have significant affinity for l-leucine but lack biphasic inhibition kinetics. Taken together, these results are consistent with the flexible loop mediating the slow-onset step of allosteric inhibition.

Heteroduplex molecules cause sexing errors in a standard molecular protocol for avian sexing.

Molecular methods are a necessary tool for sexing monomorphic birds. These molecular approaches are usually reliable, but sexing protocols should be evaluated carefully because biochemical interactions may lead to errors. We optimized laboratory protocols for genetic sexing of a monomorphic shorebird, the upland sandpiper (Bartramia longicauda), using two independent sets of primers, P2/P8 and 2550F/2718R, to amplify regions of the sex-linked CHD-Z and CHD-W genes. We discovered polymorphisms in the region of the CHD-Z intron amplified by the primers P2/P8 which caused four males to be misidentified as females (n = 90 mated pairs). We cloned and sequenced one CHD-W allele (370 bp) and three CHD-Z alleles in our population: Z° (335 bp), Z' (331 bp) and Z″ (330 bp). Normal (Z°Z°) males showed one band in agarose gel analysis and were easily differentiated from females (Z°W), which showed two bands. However, males heterozygous for CHD-Z alleles (Z'Z″) unexpectedly showed two bands in a pattern similar to females. While the Z' and Z″ fragments contained only short deletions, they annealed together during the polymerase chain reaction (PCR) process and formed heteroduplex molecules that were similar in size to the W fragment. Errors previously reported for molecular sex-assignment have usually been due to allelic dropout, causing females to be misidentified as males. Here, we report evidence that events in PCRs can lead to the opposite error, with males misidentified as females. We recommend use of multiple primer sets and large samples of known-sex birds for validation when designing protocols for molecular sex analysis.