SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing

Infection with SARs-COV-2 displays increasing fatality with age and underlying co-morbidity, in particular, with markers of the metabolic syndrome and diabetes, which seems to be associated with a “cytokine storm” and an altered immune response. This suggests that a key contributory factor could be immunosenescence that is both age-related and lifestyle-induced. As the immune system itself is heavily reliant on mitochondrial function, then maintaining a healthy mitochondrial system may play a key role in resisting the virus, both directly, and indirectly by ensuring a good vaccine response. Furthermore, as viruses in general, and quite possibly this new virus, have also evolved to modulate immunometabolism and thus mitochondrial function to ensure their replication, this could further stress cellular bioenergetics. Unlike most sedentary modern humans, one of the natural hosts for the virus, the bat, has to “exercise” regularly to find food, which continually provides a powerful adaptive stimulus to maintain functional muscle and mitochondria. In effect, the bat is exposed to regular hormetic stimuli, which could provide clues on how to resist this virus. In this paper, we review the data that might support the idea that mitochondrial health, induced by a healthy lifestyle, could be a key factor in resisting the virus, and for those people who are perhaps not in optimal health, treatments that could support mitochondrial function might be pivotal to their long-term recovery

Specialist or Nonspecialist Physical Education Teachers in Ontario Elementary Schools: Examining Differences in Opportunities for Physical Activity

Research supports the position that specialists are the preferred providers of physical education in elementary (primary) school settings. We examined whether specialists delivered more physical education lessons and provided greater opportunities for moderate and vigorous physical activity and whether barriers to curricular and extracurricular physical activity opportunities in Ontario elementary schools differed for specialist and nonspecialist teachers. Using a cross-sectional design, a questionnaire was mailed to key informants in 599 randomly selected elementary schools in Ontario, yielding an 85% response rate. Most physical education in Ontario elementary schools is delivered by nonspecialists (63%). No self-reported differences were found between specialists and generalist teachers in the number of physical education lessons delivered per week, the minutes per physical education class, or in the amount of reported moderate or vigorous physical activity in lessons. Compared with specialists, respondents in schools in which generalist teachers taught PE perceived lack of training as a greater barrier to delivering physical education. Given the importance of subject knowledge in teaching effectively, there is still need to advocate for specialist physical education teaching in elementary schools. However, concerns about teaching specialism may be secondary to broader and more complex factors surrounding the delivery of physical education in elementary schools.La recherche appuie le point de vue selon lequel les spécialistes sont les mieux placés pour enseigner l’éducation physique au primaire. Nous nous sommes penchés sur deux questions: (a) les spécialistes offrent-ils plus de cours d’éducation physique et d’occasions de pratiquer des activités physiques modérées ou vigoureuses ?, et (b) les obstacles à la participation aux activités physiques scolaires et extra-scolaires dans les écoles primaires de l’Ontario sont-ils les mêmes pour les enseignants spécialistes et les enseignants non-spécialistes ? Dans le contexte d’un modèle croisé, nous avons envoyé un questionnaire à des répondants clés dans 599 écoles primaires sélectionnées au hasard en Ontario. Notre taux de réponse a été de 85%. La majorité (63%) des cours d’éducation physique en Ontario sont offerts par des non spécialistes. Les résultats n’indiquent aucune différence entre les enseignants spécialistes et les enseignants non-spécialistes quant aux critères suivants: le nombre de cours d’éducation physique offerts par semaine, la durée des cours d’éducation physique et la mesure dans laquelle les cours impliquent de l’activité physique modérée ou vigoureuse. Par rapport aux répondants des écoles où les cours d’éducation physique se donnaient par des spécialistes, ceux des écoles où ces cours se donnaient par des généralistes ont indiqué que le manque de formation constituait un obstacle plus important à l’enseignement de l’éducation physique. Compte tenu du rôle important de la connaissance de la matière dans l’enseignement efficace, il faudrait continuer à promouvoir l’enseignement de l’éducation physique par des spécialistes dans les écoles primaires. Toutefois, les préoccupations portant sur l’enseignement par des spécialistes semblent secondaires face aux facteurs plus généraux et complexes en matière d’enseignement de l’éducation physique dans les écoles primaires

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root

A comparison of the pharmacokinetics of Aspen Ceftriaxone and Rocephin in community-acquired meningitis

BACKGROUND. Community-acquired bacterial meningitis (CABM) is a life-threatening condition that is common among immunocompromised individuals. Intravenous ceftriaxone, of which Rocephin (ROC) is the originator brand, is recommended as first-line therapy in South Africa. Despite concerns regarding therapeutic equivalence with generic agents, this is the first study that has been conducted comparing clinical pharmacokinetics (PK) of a generic ceftriaxone formulation with the originator. OBJECTIVE. To compare the PK and safety of Aspen Ceftriaxone (AC) and ROC in the treatment of adult CABM. METHODS. A total of 63 eligible patients were randomised 1:1 to receive 2 g of either medication twice daily for a duration based on the identity of the causative organism and their physician’s clinical judgment. The primary endpoint of this study was the comparison of clinical PK, specifically the concentrations of each drug in the cerebrospinal fluid with corresponding paired plasma samples. While this study was underpowered to assess efficacy, safety could be evaluated on the basis of reported adverse events. RESULTS. The two patient groups were epidemiologically similar. There were no statistically significant differences in PK between either agent, nor any difference with regard to safety. CONCLUSION. AC can be considered as equivalent to ROC with regard to PK and safety in patients with CABM.Aspen Pharmacare Ltd, SA.http://www.samj.org.zaam2014ay201

A hierarchy of heuristic-based models of crowd dynamics

International audienceWe derive a hierarchy of kinetic and macroscopic models from a noisy variant of the heuristic behavioral Individual-Based Model of Moussaid et al, PNAS 2011, where the pedestrians are supposed to have constant speeds. This IBM supposes that the pedestrians seek the best compromise between navigation towards their target and collisions avoidance. We first propose a kinetic model for the probability distribution function of the pedestrians. Then, we derive fluid models and propose three different closure relations. The first two closures assume that the velocity distribution functions are either a Dirac delta or a von Mises-Fisher distribution respectively. The third closure results from a hydrodynamic limit associated to a Local Thermodynamical Equilibrium. We develop an analogy between this equilibrium and Nash equilibia in a game theoretic framework. In each case, we discuss the features of the models and their suitability for practical use

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a