A Knack to Know an Honest Man

Alzheimer’s disease (AD) is a multifactorial disorder with several target proteins contributing to its etiology. In search for multifunctional anti-AD drug candidates, taking into account that the acetylcholinesterase (AChE) and beta-amyloid (Aβ) aggregation are particularly important targets for inhibition, the tacrine and benzothiazole (BTA) moieties were conjugated with suitable linkers in a novel series of hybrids. The designed compounds (7a–7e) were synthesized and in vitro as well as in ex vivo evaluated for their capacity for the inhibition of acetylcholinesterase (AChE) and Aβ self-induced aggregation, and also for the protection of neuronal cells death (SHSY-5Y cells, AD and MCI cybrids). All the tacrine–BTA hybrids displayed high in vitro activities, namely with IC50 values in the low micromolar to sub-micromolar concentration range towards the inhibition of AChE, and high percentages of inhibition of the self-induced Aβ aggregation. Among them, compound 7a, with the shortest linker, presented the best inhibitory activity of AChE (IC50 = 0.34 μM), while the highest activity as anti-Aβ42 self-aggregation, was evidenced for compound 7b (61.3%, at 50 μM. The docking studies demonstrated that all compounds are able to interact with both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Our results show that compounds 7d and 7e improved cell viability in cells treated with Aβ42 peptide. Overall, these multi-targeted hybrid compounds appear as promising lead compounds for the treatment of Alzheimer’s disease

New Horizons in the Treatment of Corneal Endothelial Dysfunction

The treatment of corneal endothelial dysfunction has experienced a revolutionary change in the past decades with the emergence of endothelial keratoplasty techniques: descemet stripping automated endothelial keratoplasty (DSAEK) and descemet membrane endothelial keratoplasty (DMEK). Recently, new treatments such as cultivated endothelial cell therapy, Rho-kinase inhibitors (ROCK inhibitors), bioengineered grafts, and gene therapy have been described. These techniques represent new lines of treatment for endothelial dysfunction. Their advantages are to help address the shortage of quality endothelial tissue, decrease the complications associated with tissue rejection, and reduce the burden of postoperative care following transplantation. Although further randomized clinical trials are required to validate these findings and prove the long-term efficacy of the treatments, the positive outcomes in preliminary clinical studies are a stepping stone to a promising future. Our aim is to review the latest available alternatives and advancements to endothelial corneal transplant

Uma rodada de perguntas com os membros do Grupo de Trabalho Linguagem e Tecnologias (ANPOLL)

This text is the result of an interview conducted by the magazine Linguagem em Foco with researchers from the Language and Technologies Working Group (WG), from the National Association of Graduate Studies and Research in Letters and Linguistics (ANPOLL). We proposed, by e-mail, a round of three questions to all GT researchers. The questions were as follows: (1) from your perspective of studies and research, what would you say we lack to know about the relationship between language and technology? In other words, what theoretical, methodological, and / or practical gaps remain to be filled? (2) how far or how close are we to filling these gaps? What do we need to fill them? (3) in which the knowledge acquired with the mentioned researches would help the Language and Technology area, the teacher, the student, in short, the citizen? Of the twenty-six researchers who make up the WG, eleven teachers responded. The answers were organized in alphabetical order and arranged below each question in a sequential manner. The discussions compiled in this interview give us the dimension of the current research that is being done in the ​​Language and Technology area.Este texto é resultado de uma entrevista feita pela revista Linguagem em Foco com pesquisadores do Grupo de Trabalho (GT) Linguagem e Tecnologias, da Associação Nacional de Pós-Graduação e Pesquisa em Letras e Linguística (ANPOLL). Propusemos, por e-mail, uma rodada de três perguntas a todos os pesquisadores do GT. As perguntas foram as seguintes: (1) a partir da sua perspectiva de estudos e pesquisas, o que você diria que falta sabermos sobre as relações entre linguagem e tecnologia? Em outras palavras, que lacunas teóricas, metodológicas e/ou práticas faltam ser preenchidas?; (2) quão longe ou perto estamos de preencher essas lacunas? De que precisamos para preenchê-las?; (3) em que os conhecimentos adquiridos com as pesquisas mencionadas ajudariam a área de Linguagem e Tecnologia, o professor, o aluno, enfim, o cidadão? Dos vinte e seis pesquisadores que compõem o GT, obtivemos a resposta de onze professores. As respostas foram organizadas em ordem alfabética e dispostas abaixo de cada pergunta de forma sequencial. As discussões compiladas nesta entrevista nos dão a dimensão das atuais pesquisas que estão sendo feitas na área de Linguagem e Tecnologia.&nbsp

Perfil epidemiológico dos acidentes por animais peçonhentos em Alagoas de 2020 a 2023

Introdução:Os incidentes resultantes da interação com animais venenosos representam um desafio significativo para a saúde pública, contribuindo para um considerável número de problemas de saúde em todo o mundo. A pesquisa sobre esse assunto é limitada em Alagoas, destacando a urgência de investigar esses incidentes, pois são essenciais para orientar as estratégias de vigilância tanto epidemiológica quanto ambiental. Objetivo: Descrever  o  perfil epidemiológico  dos  acidentes  com  animais  peçonhentos  no Estado  de  Alagoas, entre 2020 a 2023. Metodologia: Este estudo adotou uma abordagem ecológica e descritiva, com foco quantitativo. Os dados foram obtidos do Sistema de Informação de Agravos de Notificação, vinculado ao Departamento de Informática do Sistema Único de Saúde, referentes aos casos notificados de acidentes com animais peçonhentos entre os anos de 2020 e 2023 em Alagoas. Resultados:Houve um total de 51.656 notificações de acidentes causados por animais peçonhentos em Alagoas.Os principais responsáveis por incidentes foram os Escorpiões, com uma incidência de 84,08%, ainda 45,06% eram mulheres. Conclusão:A importância dos incidentes envolvendo animais venenosos destaca a necessidade de um planejamento abrangente, envolvendo medidas coordenadas de vigilância epidemiológica em conjunto com agências ambientais, visando a redução do número de fatalidades

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Botulinum toxin type B for cervical dystonia : systematic review

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2015Background: This is an update of a previous review (Costa 2004). Cervical dystonia is a frequent and disabling disorder characterized by painful involuntary posturing of the head. Botulinum toxin type A (BtA) is the first line therapy for this condition, although Botulinum toxin type B (BtB) is an alternative option. Objectives: To compare the efficacy and safety of BtB versus placebo in cervical dystonia. Search methods: Cochrane Movement Disorders Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and conference proceedings. In addition, we contacted pharmaceutical companies. Selection criteria: Randomised placebo-controlled trials (RCTs) assessing efficacy and safety of BtB in cervical dystonia. Main results: We included 4 studies (n = 441) with an overall moderate methodological quality. BtB was associated with an improvement of 15% in the patients’ baseline clinical status as assessed by investigators, reducing 7 points in TWSTRS-total score at week 4 (95% CI: 4.43 to 9.01). Mean difference in TWSTRS-pain score at week 4 was 2.41 (95% CI: 0.82 to 4.01). Subjective clinician and patient assessments of change favoured BtB over placebo. BtB-treated patients had a 7.65 (95% CI: 2.75 to 21.32) and a 6.78 (95% CI: 2.42 to 19.05) increased risk of dry mouth and dysphagia, respectively.Introdução: Esta é uma atualização de uma revisão previamente publicada (Costa 2004). A distonia cervical é uma doença frequente e debilitante, caracterizada por um posicionamento involuntário doloroso da cabeça. A toxina botulínica tipo A (BtA) é a primeira linha terapêutica, mas a toxina botulínica tipo B (BtB) é uma alternativa. Objetivos: Comparar a eficácia e segurança da BtB versus placebo na distonia cervical. Métodos de pesquisa: Cochrane Movement Disorders Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, artigos de referência e livros de resumos de congressos. Contactámos companhias farmacêuticas. Critérios de seleção: Ensaios clínicos aleatorizados e controlados por placebo avaliando a eficácia e segurança da BtB na distonia cervical. Resultados principais: Incluímos 4 estudos (n = 441) com moderada qualidade metodológica global. BtB foi associada a uma melhoria de 15% do estado clínico basal dos doentes segundo avaliado pelos investigadores, reduzindo 7 pontos na escala TWSTRS-total na semana 4 (95% CI: 4.43 to 9.01). A diferença média na escala TWSTRS-pain na semana 4 foi 2.41 (95% CI: 0.82 to 4.01). Avaliações subjetivas pelo clínico e doente favoreceram BtB. Os doentes tratados com BtB tiveram um aumento no risco de xerostomia e disfagia de 7.65 (95% CI: 2.75 to 21.32) e 6.78 (95% CI: 2.42 to 19.05), respetivamente

DMEK versus DSAEK for Fuchs’ endothelial dystrophy : a meta-analysis

© The Author(s) 2018. Reprints and permissions: sagepub.co.uk/journalsPermissions.navPurpose: To compare the safety and efficacy profiles of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in adult patients with Fuchs’ endothelial dystrophy. Methods: Electronic database search on MEDLINE and CENTRAL from inception to August 2017. We included all comparative studies of DMEK versus DSAEK in patients with diagnosed Fuchs’ endothelial dystrophy. Studies assessing rescue procedures were excluded to minimize bias. Primary outcome: mean difference in best-corrected visual acuity (BCVA) at 3, 6, and 12months postoperatively. Secondary outcomes: rates of graft primary failure, rejection, and rebubbling; other graft-related issues; mean difference in endothelial cell density; subjective visual outcomes; and patient satisfaction. Results: A total of 10 retrospective studies of moderate methodological quality were included (n=947 eyes, 646 DMEK). BCVA was better with DMEK at all evaluated time points (0.16 logMAR at 12months) comparing to DSAEK (0.30 logMAR; p<0.001). DMEK had a 60% lower rate of rejection (risk ratio (RR) 0.4, 95% CI (0.24, 0.67), p=0.0005), but required more rebubblings (RR=2.48, 95% CI (1.32, 4.64), p=0.005). DMEK had more primary graft failures and less endothelial cell density loss, but statistical difference was not reached. More patients were satisfied after DMEK (odds ratio=10.29, 95% CI (3.55, 29.80), p<0.0001). Conclusion: DMEK showed better postoperative results regarding BCVA, patient satisfaction, and graft-related issues. However, the small number of studies with short follow-up times and other methodological issues prompt us to interpret these results carefully.info:eu-repo/semantics/publishedVersio

The effect of glaucoma treatment using high-intensity focused ultrasound on total and corneal astigmatism: a prospective multicentre study

Ultrasound cycloplasty (UCP) acts through the selective coagulation of the ciliary body using high-intensity focused ultrasound (HIFU) technology. The aim of this study was to investigate whether the application of ultrasound beams targeting the ciliary body using an external probe influences astigmatism

The effect of glaucoma treatment using high-intensity focused ultrasound on total and corneal astigmatism: a prospective multicentre study

PURPOSE: Ultrasound cycloplasty (UCP) acts through the selective coagulation of the ciliary body using high-intensity focused ultrasound (HIFU) technology. The aim of this study was to investigate whether the application of ultrasound beams targeting the ciliary body using an external probe influences astigmatism. METHODS: Multicentre, prospective, single-arm, open-label study in adult patients with primary open-angle glaucoma and moderately uncontrolled intraocular pressure (IOP) under glaucoma medication. The primary outcome was induced corneal astigmatism, calculated from topography, and assessed statistically through vector analysis. Secondary outcomes included induced total astigmatism and mean changes from baseline in best-corrected visual acuity (logMAR) and IOP. Subgroup analysis was performed to assess the impact of device centring on corneal and total induced astigmatism. RESULTS: Fifty eyes were enrolled. Mean age was 69.6 ± 11.3 years. At 1, 3 and 6 months postprocedure, HIFU-induced corneal astigmatism was 0.88 D × 93°, 0.87 D × 106° and 1.16 D × 97°, respectively, while induced total astigmatism was 0.62 D × 103°, 0.42 × 106° and 0.39 × 107°. By the last follow-up, the percentage of patients with <0.50, <1.00, <1.50 and <2.00 D of induced corneal versus total astigmatism was 8.3% versus 46%, 29% versus 66%, 62.5% versus 88% and 79% versus 94%. Visual acuity was statistically significantly impaired at 1 month, but no difference remained by 3 and 6 months postprocedure. CONCLUSION: Ultrasound cycloplasty procedure is associated with increased corneal astigmatism. However, its impact on total refractive astigmatism is less pronounced.status: publishe

Heavy elements in the phosphorite from Kalaat Khasba mine (North-western Tunisia): Potential implications on the environment and human health

Tunisia is one of the largest phosphate producers in the world (more than 10 million tons per year since the early nineties). The Kalaat Khasba mine (NW of Tunisia) has operated from 1893 until 1993 and data demonstrate that, in the phosphorites of Kalaat Khasba, Cd is enriched 105-208 times, when compared with shales, and U is enriched by a factor varying between 18 and 44. The general trend shows an increase in heavy elements content with decreasing particle size. On the other hand, concentrations of Sr, Cr and U exhibit the same distribution for the different size fractions. It was found that Cd concentrations exceed the allowed EC soil limits for growing crops. Hence, owing to the tailings exposure and to the mobilisation of the finest particles by rainfall and wind. Cd could have detrimental effects on human health and on the environment because a significant portion of Cd was found in the exchangeable form. (C) 2010 Elsevier B.V. All rights reserved.GRICES (Portugal)INRST (Tunisia)Research Center GeoBioTecFC