Designing Antitrypanosomal and Antileishmanial BODIPY Derivatives: A Computational and In Vitro Assessment.

Leishmaniasis and Human African trypanosomiasis pose significant public health threats in resource-limited regions, accentuated by the drawbacks of the current antiprotozoal treatments and the lack of approved vaccines. Considering the demand for novel therapeutic drugs, a series of BODIPY derivatives with several functionalizations at the meso, 2 and/or 6 positions of the core were synthesized and characterized. The in vitro activity against Trypanosoma brucei and Leishmania major parasites was carried out alongside a human healthy cell line (MRC-5) to establish selectivity indices (SIs). Notably, the meso-substituted BODIPY, with 1-dimethylaminonaphthalene (1b) and anthracene moiety (1c), were the most active against L. major, displaying IC50 = 4.84 and 5.41 µM, with a 16 and 18-fold selectivity over MRC-5 cells, respectively. In contrast, the mono-formylated analogues 2b and 2c exhibited the highest toxicity (IC50 = 2.84 and 6.17 µM, respectively) and selectivity (SI = 24 and 11, respectively) against T. brucei. Further insights on the activity of these compounds were gathered from molecular docking studies. The results suggest that these BODIPYs act as competitive inhibitors targeting the NADPH/NADP+ linkage site of the pteridine reductase (PR) enzyme. Additionally, these findings unveil a range of quasi-degenerate binding complexes formed between the PRs and the investigated BODIPY derivatives. These results suggest a potential correlation between the anti-parasitic activity and the presence of multiple configurations that block the same site of the enzyme.

The Magnitude of Crohn's Disease Direct Costs in Health Care Systems (from Different Perspectives): A Systematic Review.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn's disease (CD) for health care systems from different perspectives: regional, economic, and temporal. METHODS: We searched for original real-world studies examining direct medical health care costs in Crohn's disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY. RESULTS: A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was €6295.28 (95% CI, €4660.55-€8503.41). The pooled mean hospitalization cost PPY for CD patients was €2004.83 (95% CI, €1351.68-€2973.59). The major contributors for the total health expenditure were biologics (€5554.58) and medications (€3096.53), followed by hospitalization (€2004.83) and surgery (€1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010. CONCLUSIONS: Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries.

Lipid-based nanostructures as a strategy to enhance curcumin bioaccessibility: Behavior under digestion and cytotoxicity assessment.

The aim of this study was to evaluate the behavior of different lipid-based nanostructures during in vitro digestion, in particular on curcumin's bioaccessibility, and to access their potential toxicity. Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE) were submitted to harmonized static in vitro digestion and their cytotoxicity and cellular transport were evaluated using Caco-2 cell line. NE presented the highest curcumin's bioaccessibility followed by NLC and SLN, 71.1%, 63.7% and 53.3%, respectively. Free fatty acids percentage increased in the following order: NLC ≤ NE < SLN. Non-digested nanostructures and excipients presented no cytotoxicity; however, digested NE and NLC presented cytotoxicity due to MCT oil, which presented cytotoxicity after digestion. The apparent permeability coefficient of NLC was higher than SLN and NE. These results showed that lipid-based nanostructures' physical state and composition have a high influence on particles' behavior during digestion, and on their cytotoxicity/intestinal permeability, and highlights the importance of conducting cytotoxicity assessments after in vitro digestion. This work contributes to a better understanding of the behavior of lipid-based nanostructures under digestion/adsorption, and this knowledge will be useful in design of nanostructures that afford both safety and an increased bioactive compounds' bioavailability.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels.

OBJECTIVE: Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. DESIGN: Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. RESULT: GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. CONCLUSIONS: GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

Tradução e adaptação cultural de uma medida de avaliação da sabedoria: a 3D-WS-19 / Translation and cultural adaptation of a measure of wisdom assessment: the 3D-WS-19 / Traducción y adaptación cultural de una medida de evaluación de la sabiduría: 3D-WS-19

Partindo do compromisso da Gerontologia Social de tentar explicar as diferenças interindividuais que se amplificam com o aumento da idade, e no sentido de melhorar a compreensão e intervenção gerontológica, o presente estudo assumiu como objetivo avaliar as qualidades psicométricas da Three-Dimensional Wisdom Scale (3D-WS; Ardelt, 2003), enquanto medida de avaliação das características associadas à sabedoria. Os resultados sugerem uma nova solução fatorial, a 3D-WS-19, que se apresenta como um instrumento de medida válido, fiável e adequado à população adulta portuguesa.

Based on the commitment of the Social Gerontology to try to explain the interindividual differences that amplify with the increase of age and to improve the gerontological understanding and intervention, the present study assumed the goal of evaluate the psychometric qualities of the Three Dimensional Wisdom Scale (3D- WS; Ardelt, 2003) as a measure of evaluation of the characteristics associated with wisdom. The results suggest a new factorial solution, the 3D-WS-19, which presents itself as a valid, reliable and suitable instrument for the Portuguese adult population.

A partir de el compromiso de la Gerontología Social de intentar explicar las diferencias interindividuales que se amplifican con el aumento de la edad y para mejorar la comprensión y la intervención gerontológica, este estudio se llevó a evaluar las propiedades psicométricas de la Three Dimensional Wisdom Scale (3D-WS; Ardelt, 2003) como una medida de la evaluación de las características asociadas con la sabiduría. Los resultados sugieren una nueva solución factorial, el 3D-WS-19, que se presenta como un instrumento de medición válido, fiable y adecuado a la población adulta portuguesa.

Assessment of muscle shortening and static posture in children with persistent asthma.

Asthmatic patients experience an increase in airway resistance that overburdens both respiratory and non-respiratory muscles. The objective of the present study was to determine whether children with persistent asthma present muscle shortening and postural changes. The 60 boys evaluated, aged 7-12 (pubertal ages up to Tanner stage G2) were divided into three age- and BMI-matched groups of equal number: CON (no history of asthma or allergy); MPA (mild persistent asthma); SPA (severe persistent asthma). Pulmonary function, muscle shortening and static posture were evaluated. The SPA group presented higher protraction of the head and shoulder compared with the CON group [9.5 (6.0-12.0) degrees vs 5.5 (0.0-12.0) degrees, P < 0.05; 0.89 (0.80-0.94) anterior/posterior ratio vs 0.94 (0.87-1.1) anterior/posterior ratio, P < 0.01)]. Severe asthmatic patients also presented shortening of arm flexor and posterior muscle of the thigh compared with the CON group [18.0 (10.0-24.0) degrees vs 12.0 (6.0-16.0) degrees, P < 0.05; and 16.5 (10.0-38.5) cm vs 8.0 (0.0-21.0) cm, respectively, P < 0.05]. Chest expansion at axillar and xiphoid levels were limited in SPA subjects compared with CON subjects [3.7 (1.5-6.5) cm vs 5.5 (2.0-8.0) cm and 4.7 (1.5-6.5) vs 6.0 (3.5-8.0) cm, respectively, P < 0.01]. SPA subjects also presented a higher incidence of lumbar spine straightening compared with CON and MPA subjects. Moderate asthmatic subjects presented intermediate values compared with severe and control subjects in five out nine evaluated outcomes. Our data suggest that severe asthmatic children present postural adaptations and muscle shortening that seem to be related to disease severity.

Avaliação dos critérios médicos para o encaminhamento de pacientes com disfunções neurológicas para atendimento fisioterapêutico / Assessment of medical criteria for referring neurological patients to physical therapy treatment

Este estudo objetivou investigar critérios utilizados por neurologistas para o encaminhamento de pacientes para o atendimento fisioterapêutico. Foram convidados os 44 neurologistas de um hospital universitário que atuam em todos os níveis do atendimento terciário à saúde...

The aim of the present study was to investigate the criteria used by neurologists to refer patients to physical therapy treatement. All (44) neurologists from a university hospital were contacted, Thirthy physicians answered a questionnaire composed by 12 multiple choice and four open ones, in view of assessing both their referral criteria...

[Garbage, work, and health: a case study of garbage pickers at the metropolitan landfill in Rio de Janeiro, Brazil]. / Lixo, trabalho e saúde: um estudo de caso com catadores em um aterro metropolitano no Rio de Janeiro, Brasil.

This article presents the results of a study on the lives, work, and health conditions of garbage pickers in the largest metropolitan landfill in Rio de Janeiro, Brazil. Using a semi-structured questionnaire with open-ended and closed questions, the study interviewed these individuals and developed a discussion of their daily lives, work, and health conditions. According to a quantitative-qualitative analysis, the garbage pickers identified garbage as a source of survival and defined health simply as the ability to work. They thus tended to neglect the relationship between work and health. However, the risks and reported morbidity highlighted the hazardous nature of this activity, aggravated by their living and housing conditions. Finally, the article emphasizes the importance of establishing public policies that integrate different dimensions of the problem, such as social inclusion, environmental preservation, public health, and the dignity of these workers.