Blood-brain barrier dysfunction in aging is mediated by brain endothelial senescence.

BBB dysfunction during aging is characterized by an increase in its permeability and phenotypic alterations of brain endothelial cells (BECs) including dysregulation of tight junction's expression. Here we have investigated the role of BEC senescence in the dysfunction of the BBB. Our results suggest that the transition from young to aged BBB is mediated, at least in part by BEC senescence.

Morphometric Assessment of the Hip Joint in a Functional Dysplastic Rabbit Model.

The present study investigates the morphometric changes in the hip joint in a surgically induced rabbit model of hip dysplasia through the sectioning of the ligamentum capitis femoris and pelvic limb immobilization. A total of seventeen rabbits were evaluated using radiographic and computed tomographic imaging to measure the following parameters: the femoral angles of anteversion and inclination, length and width indexes of the neck of the femur, and acetabular depth and ventroversion. Significant differences in femoral anteversion angle and acetabular depth were observed, particularly in the group of hip instability surgery with pelvic limb immobilization. The results have shown the influence of hip joint instability in the promotion of femoral anteversion and acetabular shallowing. These findings provide a foundation for future research on naturally occurring or experimentally induced hip dysplasia in rabbits and underscore the model's potential for studying the biomechanical and developmental aspects of hip joint disorders.

Establishment of an ultrasound-guided protocol for the assessment of hip joint osteoarthritis in rabbits-A sonoanatomic study.

Ultrasound (US) has emerged as one of the most applied imaging tools to diagnose musculoskeletal disorders and assist in guided intra-articular administrations. Nevertheless, in evaluating the rabbit hip joint, there is a need for an ultrasonographic approach. Therefore, this study aimed to describe the hip sonoanatomy, develop and validate a US-guided protocol to assess the hip joint in rabbits and apply this protocol in vivo. This study was carried out in three phases, phase I: a pilot cadaveric study, to assess the applicability of different US approaches in the hip of rabbits and, consequently, develop a detailed US-guided protocol (2 rabbit cadavers, n = 4 hips); phase II: validation of the established US-guided protocol through a numerical scoring system in healthy joints (11 rabbit cadavers, n = 22 hips), and, lastly, phase III: application of the US-guided protocol in vivo in osteoarthritic joints (5 rabbits, n = 5 hips). A total of six planes were validated, two in the ventral approach and four in the dorsal approach. The ventral transverse plane was deemed more informative regarding the hip joint sonoanatomy, enabling the identification of a greater number of structures when compared to the other planes. Nevertheless, this study suggested that the isolated application of a plane was deemed insufficient for a complete and detailed evaluation of the hip joint anatomy, rendering it necessary to employ other planes complementarily. Furthermore, the established US-guided protocol allowed a definitive diagnosis of OA, and osteophytes and capsular hypertrophy were among the defects most frequently detected. This novel study provided US anatomical landmarks for forthcoming therapeutic research and monitoring of OA development, granting the accurate identification of osseous and cartilaginous defects.

High-throughput screening of nanoparticles in drug delivery.

The use of pharmacologically active compounds to manage and treat diseases is of utmost relevance in clinical practice. It is well recognized that spatial-temporal control over the delivery of these biomolecules will greatly impact their pharmacokinetic profile and ultimately their therapeutic effect. Nanoparticles (NPs) prepared from different materials have been tested successfully in the clinic for the delivery of several biomolecules including non-coding RNAs (siRNA and miRNA) and mRNAs. Indeed, the recent success of mRNA vaccines is in part due to progress in the delivery systems (NP based) that have been developed for many years. In most cases, the identification of the best formulation was done by testing a small number of novel formulations or by modification of pre-existing ones. Unfortunately, this is a low throughput and time-consuming process that hinders the identification of formulations with the highest potential. Alternatively, high-throughput combinatorial design of NP libraries may allow the rapid identification of formulations with the required release and cell/tissue targeting profile for a given application. Combinatorial approaches offer several advantages over conventional methods since they allow the incorporation of multiple components with varied chemical properties into materials, such as polymers or lipid-like materials, that will subsequently form NPs by self-assembly or chemical conjugation processes. The current review highlights the impact of high-throughput in the development of more efficient drug delivery systems with enhanced targeting and release kinetics. It also describes the current challenges in this research area as well as future directions.

Quality of Sleep among Portuguese Anaesthesiologists: A Cross-Sectional Study.

INTRODUCTION: Sleeping is essential to maintain proper relationships with others, keep alertness, and execute responsibilities, among many other functions. In the medical profession, there are several studies linking sleep deprivation with a decrease in responsiveness, cognition and attention. With this study we intended to characterize the sleep pattern of Portuguese anaesthesiologists and identify independent factors associated with sleep quality in this population. MATERIAL AND METHODS: An observational, cross-sectional study of senior and resident anesthesiologists working in Portugal was carried out through an online questionnaire. Individuals working exclusively in intensive care units, emergency departments or with previously diagnosed sleep disorders were excluded. Socio-demographic data, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Perceived Stress Scale were applied. Statistical significance was assessed using the Mann-Whitney test and the chi-square test. A multivariable analysis was performed to examine the association between the Pittsburgh Sleep Quality Index and certain variables. RESULTS: Among 256 respondents, 46.1% reported "poor" quality of sleep (Pittsburgh Sleep Quality Index > 5). Within these individuals, 77.1% slept less than 7 hours per night (p < 0.001). Excessive daytime sleepiness (Epworth Sleepiness Scale > 10) was present in 41.0% of the sample, and the median Perceived Stress Scale score was 17.0. The independent factors associated with worse quality ofsleep were the number of working hours/week (OR 1.03, 95% CI 1,01 to 1,06), perceived stress (OR 1.18, 95% CI 1.11 to 1.26), taking sleep medication (OR 14.72, 95% CI 5.55 to 39.08), and sleep hours/night (OR 0.25, 95% CI 0.15 to 0.42). DISCUSSION: This fraction of Portuguese anaesthesiologists presented a poorer quality of sleep, with excessive daytime somnolence, perceived stress and higher sedative use compared to previously studied populations. CONCLUSION: Our study characterizes sleep patterns and identifies potential risk factors linked to sleep disturbances in a sample of Portuguese anaesthesiologists. Government and institutional policies can endorse sleep hygiene practices and habits, promoting healthier working environments.

Introdução: O sono é essencial para executar tarefas, manter o estado de alerta, executar tarefas, entre outras funções. Diversos estudos na área médica relacionam a privação de sono com a redução da capacidade de resposta, cognição e nível de atenção. Os objetivos deste estudo foram a caracterização do padrão de sono dos anestesiologistas Portugueses e identificação de fatores de risco independentes para pior qualidade de sono. Material e Métodos: Efetuámos um estudo observacional e transversal em anestesiologistas e internos de formação específica em Anestesiologia a trabalhar em Portugal. Foram excluídos profissionais que trabalham exclusivamente em unidades de cuidados intensivos, serviços de urgência ou com patologias do sono previamente diagnosticadas. Foram colhidos dados sócio-demográficos e aplicadas as escalas de Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) e Perceived Stress Scale (PSS). A significância estatística foi analisada recorrendo aos testes de Mann-Whitney e qui-quadrado. A associação entre o Pittsburgh Sleep Quality Index e demais variáveis foi testada através de uma regressão logística. Resultados: Dos 256 casos admitidos, 46,1% apresentaram "má" qualidade de sono (Pittsburgh Sleep Quality Index > 5). Nestes, 77,1% dormiram menos de 7 horas por noite (p < 0,001). A sonolência diurna excessiva (Epworth Sleepiness Scale > 10) surgiu em 41,0% da amostra e a mediana da Perceived Stress Scale foi 17,0. Os fatores de risco independentes para "má" qualidade de sono foram: número de horas de trabalho semanais (OR 1,03, IC 95% 1,01 a 1,06), stress percecionado (OR 1,18, IC 95% 1,11 a 1,26), toma de medicamentos para dormir (OR 14,72, IC 95% 5,55 a 39,08) e número de horas dormidas por noite (OR 0,25, IC 95% 0,15 a 0,42). Discussão: A nossa amostra de anestesiologistas Portugueses apresentou pior qualidade de sono, com sonolência diurna excessiva, stress percecionado e uso de sedativos superiores a outras populações previamente estudadas. Conclusão: O presente estudo caracteriza o padrão de sono e identifica potenciais factores de risco relacionados com distúrbios do sono, numa amostra de Anestesiologistas Portugueses. Políticas de saúde governamentais e institucionais poderão ser orientadas para a promoção da higiene do sono, levando a ambientes de trabalho mais saudáveis.