125 research outputs found
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 âcytokine stormâ 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 âexerciseâ 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 spĂ©cialistes sont les mieux placĂ©s pour enseigner lâĂ©ducation physique au primaire. Nous nous sommes penchĂ©s sur deux questions: (a) les spĂ©cialistes offrent-ils plus de cours dâĂ©ducation physique et dâoccasions de pratiquer des activitĂ©s physiques modĂ©rĂ©es ou vigoureuses ?, et (b) les obstacles Ă la participation aux activitĂ©s physiques scolaires et extra-scolaires dans les Ă©coles primaires de lâOntario sont-ils les mĂȘmes pour les enseignants spĂ©cialistes et les enseignants non-spĂ©cialistes ? Dans le contexte dâun modĂšle croisĂ©, nous avons envoyĂ© un questionnaire Ă des rĂ©pondants clĂ©s dans 599 Ă©coles primaires sĂ©lectionnĂ©es au hasard en Ontario. Notre taux de rĂ©ponse a Ă©tĂ© de 85%. La majoritĂ© (63%) des cours dâĂ©ducation physique en Ontario sont offerts par des non spĂ©cialistes. Les rĂ©sultats nâindiquent aucune diffĂ©rence entre les enseignants spĂ©cialistes et les enseignants non-spĂ©cialistes quant aux critĂšres suivants: le nombre de cours dâĂ©ducation physique offerts par semaine, la durĂ©e des cours dâĂ©ducation physique et la mesure dans laquelle les cours impliquent de lâactivitĂ© physique modĂ©rĂ©e ou vigoureuse. Par rapport aux rĂ©pondants des Ă©coles oĂč les cours dâĂ©ducation physique se donnaient par des spĂ©cialistes, ceux des Ă©coles oĂč ces cours se donnaient par des gĂ©nĂ©ralistes ont indiquĂ© que le manque de formation constituait un obstacle plus important Ă lâenseignement de lâĂ©ducation physique. Compte tenu du rĂŽle important de la connaissance de la matiĂšre dans lâenseignement efficace, il faudrait continuer Ă promouvoir lâenseignement de lâĂ©ducation physique par des spĂ©cialistes dans les Ă©coles primaires. Toutefois, les prĂ©occupations portant sur lâenseignement par des spĂ©cialistes semblent secondaires face aux facteurs plus gĂ©nĂ©raux et complexes en matiĂšre dâenseignement de lâĂ©ducation physique dans les Ă©coles 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 physicianâs 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 Ă 10â5 and c.2702T > G [p.V901G], MAF 2.51 Ă 10â3). 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 1.05â13.52). 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 Ă 10â8), viability (P = 8.9 Ă 10â7), 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 Ă 10â4) 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 Ă 10â5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia
The alkaline anthraquinone-2-sulfonate-H2O2-catalyzed oxidative degradation of lactose: An improved Spengler-Pfannenstiel oxidation
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
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