Effects of initial telomere length distribution on senescence onset and heterogeneity

Replicative senescence, induced by telomere shortening, exhibits considerable asynchrony and heterogeneity, the origins of which remain unclear. Here, we formally study how telomere shortening mechanisms impact on senescence kinetics and define two regimes of senescence, depending on the initial telomere length variance. We provide analytical solutions to the model, highlighting a non-linear relationship between senescence onset and initial telomere length distribution. This study reveals the complexity of the collective behavior of telomeres as they shorten, leading to senescence heterogeneity

Insights into the variability of nucleated amyloid polymerization by a minimalistic model of stochastic protein assembly

Self-assembly of proteins into amyloid aggregates is an important biological phenomenon associated with human diseases such as Alzheimer’s disease. Amyloid brils also have potential applications in nano-engineering of biomaterials. The kinetics of amyloid assembly show an exponential growth phase preceded by a lag phase, variable in duration as seen in bulk experiments and experiments that mimic the small volumes of cells. Here, to investigate the origins and the properties of the observed variability in the lag phase of amyloid assembly currently not accounted for by deterministic nucleation dependent mechanisms, we formulate a new stochastic minimal model that is capable of describing the characteristics of amyloid growth curves despite its simplicity. We then solve the stochastic di erential equations of our model and give mathematical proof of a central limit theorem for the sample growth trajectories of the nucleated aggregation process. These results give an asymptotic description for our simple model, from which closed form analytical results capable of describing and predicting the variability of nucleated amyloid assembly were derived. We also demonstrate the application of our results to inform experiments in a conceptually friendly and clear fashion. Our model o ers a new perspective and paves the way for a new and e cient approach on extracting vital information regarding the key initial events of amyloid formation

Hypoxia induces a glycolytic complex in intestinal epithelial cells independent of HIF-1-driven glycolytic gene expression

The metabolic adaptation of eukaryotic cells to hypoxia involves increasing dependence upon glycolytic adenosine triphosphate (ATP) production, an event with consequences for cellular bioenergetics and cell fate. This response is regulated at the transcriptional level by the hypoxia-inducible factor-1(HIF-1)-dependent transcriptional upregulation of glycolytic enzymes (GEs) and glucose transporters. However, this transcriptional upregulation alone is unlikely to account fully for the levels of glycolytic ATP produced during hypoxia. Here, we investigated additional mechanisms regulating glycolysis in hypoxia. We observed that intestinal epithelial cells treated with inhibitors of transcription or translation and human platelets (which lack nuclei and the capacity for canonical transcriptional activity) maintained the capacity for hypoxia-induced glycolysis, a finding which suggests the involvement of a nontranscriptional component to the hypoxia-induced metabolic switch to a highly glycolytic phenotype. In our investigations into potential nontranscriptional mechanisms for glycolytic induction, we identified a hypoxia-sensitive formation of complexes comprising GEs and glucose transporters in intestinal epithelial cells. Surprisingly, the formation of such glycolytic complexes occurs independent of HIF-1-driven transcription. Finally, we provide evidence for the presence of HIF-1α in cytosolic fractions of hypoxic cells which physically interacts with the glucose transporter GLUT1 and the GEs in a hypoxia-sensitive manner. In conclusion, we provide insights into the nontranscriptional regulation of hypoxia-induced glycolysis in intestinal epithelial cells.</p

The International Pharmacy Game:A Comparison of Implementation in Seven Universities World-Wide

The utilization of serious games and simulations in health professional education has increased. The Pharmacy Game is one such concept that intersects gamification and simulation, in which pharmacy student teams competitively manage simulated pharmacies; a concept included in the pharmacy curricula of seven international universities. This study aimed to compare the implementation and conduct of the Pharmacy Game of participant universities and their students’ performance in the same educational task. Data were collected via a questionnaire completed by academic staff in April 2020, and the collation of results of the same patient case was conducted at each university (April 2020 to March 2021). The main results reflected differences in the game frequencies and the curricular approach (standalone or integrated course) and in the learning outcomes for the Pharmacy Game. Other differences were identified in the extent to which students of other professions were part of the game such as medical students or pharmacy assistants. Student case outcomes revealed similar strengths across the universities in patient communication and focus on safety, with variations identified as areas for improvement. Collation of the international utilization of the Pharmacy Game identified a broad spectrum of similar learning outcomes, inspiring a model of international core and aspirational learning outcomes. While the Pharmacy Game has been implemented with flexibility regarding the numbers of teams (4–10) and the duration of activity (12–36 days), all universities reported positive experiences and student outcomes, suggesting that the intervention represents a potential tool to deliver capstone learning experiences, promote interprofessional education, reinforce patient safety, and prepare pharmacy graduates for future practice

Sex Differences in Reported Adverse Drug Reactions to Angiotensin-Converting Enzyme Inhibitors

Sex differences in adverse drug reactions (ADRs) associated with angiotensin-converting enzyme inhibitors (ACEIs) remain poorly understood owing to a lack of sex-specific ADR data from clinical trials. 1 Postmarketing pharmacovigilance data, containing structured and detailed ADR information, may play an important role in such analyses. However, these data are often not corrected for prescription numbers and therefore cannot separate sex differences in ADR risk from sex differences in prescription rates. To investigate whether women report more ACEI-related ADRs than men after correction for sex-specific prescription and describe sex differences in reported ADR types, we combined data from the global pharmacovigilance database VigiBase and the prescription-corrected Dutch pharmacovigilance database Lareb

Sex Differences in Reported Adverse Drug Reactions to Angiotensin-Converting Enzyme Inhibitors

This cross-sectional study investigates differences by sex in reporting of adverse drug reactions associated with angiotensin-converting enzyme inhibitors combining global and prescription-corrected databases

Le projet CRUMBEL et l'apport de la recherche l'archéométrique

The CRUMBEL project aims to investigate the mobility of the former population in Belgium from the Neolithic period until the Early Middle Ages. To reach these research goals different topics will be studied. In a preliminary phase, the ancient collections of cremated bone will be documented. A selection of these funerary sites will be studied to understand the mobility using different archaeometric approaches as stable isotopes and radiocarbon dating to obtain reliable information on earlier mobility in Belgium

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups