Nanostar based platforms for enhanced blood brain barrier crossing

The availability of drugs to treat diseases of the central nervous systems is severely restricted by the presence of the blood brain barrier (BBB). The blood-brain barrier prevents the passage of more than 98% of small molecules and 100% of large molecule pharmaceutics. With the rapid progression of neurodegenerative conditions arising with the increase in life expectancy, central nervous system disorders are now the leading cause of death in the United Kingdom, highlighting the urgent need to develop new strategies to effectively cross the blood brain barrier. Nanoscale particles have shown great potential for specifically identifying and binding to the BBB and are currently being investigated for enhanced brain penetration. In this work, the effect of a complex multispiked nanoparticle morphology on BBB penetration is investigated as an alternative to the conventionally used spherical nano-vehicles. Specifically, a platform matrix of plasmonic gold nanoparticles in the shape of gold stars were designed for specific brain targeting and effective transcytosis. The nanostars were synthesised with a highly controllable spectrum of properties including size, surface spikiness and morphology. Successful conformal surface biofunctionalisation with the BBB targeting protein transferrin was achieved for the complex stars and conformational changes due to packing was observed at high concentration of protein. The shape and functional properties of the nanostars was thus preserved after coating. The high surface area of the nanostars enabled superior loading capacity with the transferrin targeting moieties. In transwell transport studies the human brain endothelial cell line hCMEC/D3 showed preferential uptake of AuStrs over spherical nanoparticles. It was found that AuStrs with high aspect ratio, and spiky surface topology constituted the best transcytotic agents. TEM analysis demonstrated that AuStrs penetrate through the cells, not through the tight junctions, thus validating a transcellular transport mechanism. It is demonstrated that the extent of transcytosis and cell uptake can be tuned based on nanostructure geometry and surface biofunctionalization. This thesis provides important insights of the nano-bio interface for the future design of BBB penetrating agents.Open Acces

Determinants of the Use of Health and Fitness Mobile Apps by Patients With Asthma : Secondary Analysis of Observational Studies

Background: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients' daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities. Objective: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage. Methods: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R. Results: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were <= 40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83). Conclusions: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users' general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use

Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas – 2023

Note: These guidelines are for information purposes and should not replace the clinical judgment of a physician, who must ultimately determine the appropriate treatment for each patient

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN