In Cellulo Bioorthogonal Catalysis by Encapsulated AuPd Nanoalloys. Overcoming Intracellular Deactivation

Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed AuPd nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media. We also show that the intracellular catalytic performance of these nanoalloys is significantly enhanced by protecting them following two different encapsulation methods. Encapsulation in mesoporous silica nanorods resulted in augmented catalyst reactivity, whereas the use of a biodegradable PLGA matrix increased nanoalloy delivery across the cell membrane. The functional potential of encapsulated AuPd was demonstrated by releasing the potent chemotherapy drug paclitaxel inside cancer cells. Nanoalloy encapsulation provides a novel methodology to develop nanoreactors capable of mediating new-to-life reactions in cell

Health enhancing strength training in nonagenarians (STRONG): rationale, design and methods

<p>Abstract</p> <p>Background</p> <p>The Health Enhancing Strength Training in Nonagenarians (STRONG) is a randomised control trial to assess the effectiveness of an aerobic and strength training program for improving muscle strength, functional capacity and quality of life in nonagenarians.</p> <p>Methods</p> <p>Sixty (51 women) nonagenarians (age range: 90–102 years) who live in a geriatric nursing home will be randomly assigned to either a usual care (control) group (n = 30) or an intervention (training) group (n = 30). Participants allocated in the usual care group will receive general physical activity guidelines and participants allocated in the intervention group will also enrol in three weekly non-consecutive individualized training sessions (~45–50 min each) during 8 weeks. The exercise program will consist of muscular strength [with a special focus on leg press at 30% (start of the program) to 70% 1 repetition maximum (end)] and aerobic exercises (cycle-ergometry during 3–5 to 15 minutes at 12–14 points in the rate of perceived exertion scale).</p> <p>Results</p> <p>Results from STRONG will help to better understand the potential of regular physical activity for improving the well-being of the oldest population groups.</p> <p>Conclusion</p> <p>The increase in life expectancy together with the dramatic decrease in birth rates in industrialized countries calls the attention to health care systems and public health policymakers to focus attention on promoting healthy lifestyle in the highest sector of the population pyramid. Our study attempts to improve functional capacity and QOL of nonagenarians by implementing an individualised aerobic and strength training program in a geriatric residential care. Results from STRONG will help to better understand the potential of regular physical activity for improving the well being even in persons aged 90 years or over.</p> <p>Trail Registration</p> <p>ClinicalTrials.gov ID: NCT00848978</p

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Dermatomicosis en deportistas Dermatomycoses in sports-practicing persons

Con el fin de evaluar la relación entre la práctica de un deporte determinado y la presencia de dermatomicosis se estudiaron, entre octubre y diciembre de 1990, 389 personas, entre 16 y 46 años, vinculadas a la Universidad de Antioquia, divididas en tres grupos de deportistas y uno de controles; los deportistas se subdividieron en calzados, descalzos y húmedos según las circunstancias de su práctica deportiva. En 177 personas (45.5%) se detectó la presencia de alguna dermatomicosis mediante exámenes directos o cultivos. El grupo más afectado fue el de los deportistas calzados cuya frecuencia de estas entidades (54.3%) fue significativamente mayor que la del grupo control (34.7%) (p &lt;0.05 ). La frecuencia en los grupos de deportistas descalzos y húmedos fue 46.4% y 41.6% respectivamente (NS). Cuando el análisis se concretó a las dermatomicosis de los pies se halIó una frecuencia significativamente mayor en los deportistas en general (p= 0.03) y en los calzados (p= 0.004) y descalzos (p= 0.04) en particular. Cuatro de los cultivos obtenidos de los zapatos (1 %) fueron positivos para dermatofitos y correspondieron a pacientes con infección en los pies por el mismo agente hallado en el zapato. Hubo 13 casos de infecciones de los pies por hongos no dermatofíticos (HND), 11 de ellos localizados en espacios Interdigitales. El examen directo tuvo alta sensibilidad diagnóstica (77 .3%) frente al cultivo. Se postula que el calor y la humedad generados por el uso de zapatos Influyen favorablemente en la aparición de dermatomicosis de los pies. &lt;p class="MsoNormal"&gt;&lt;span style="font-size: 9pt; font-family: Arial"&gt;The relationship between practice of sports (at least 6 hours per week) and the presence of dermatomycoses was evaluated In 389 persons, aged 16-46, most of them university students; according to the kind of sport 4 subgroups were defined, namely: 1) 129 footwear-users (football, basketball, athletics); 2) 84 barefooted (taekwondo, Judo, karate); 3) 101 ";wet"; (swimming and diving); 4) 75 controls (persons who practiced sports less than 2 hours per week). In 177 persons (45.5%) a dermatomicosis was found by either direct examination or culture. The frequency was significantly higher (p &lt; 0.05) In the foot wear users (54.3%) than In the controls (34.7%). The corresponding figures for the barefooted and the ";wet"; were 46.4% and 41.6% respectively &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: Arial"&gt;(NS}. When statistical analysis was restricted to the feet dermatomycoses It was found that the frequency was significantly higher In the sport practicing population as a whole (p= 0.03} and, partlcularly, In the footwear-users (p= 0.004) and the barefooted (p= 0.04}. Four of 389 cultures obtained from the shoes were positive for dermatophytes; the agents Isolated from the shoes were identical to those recovered from the corresponding persons. Thirteen cases of feet infection with a non-dermatophytic agent were found. sensitivity of the direct examination was 17 .3% when compared with the culture. It Is postulated that heat and humidity generated by footwear wearing favorably Influence the appearance of mycotic infections in feet.&lt;/span&gt;&lt;span&gt;&lt;/span&gt;&lt;/p&gt