Pharmacological Efficacy of Repurposing Drugs in the Treatment of Prostate Cancer.

Worldwide, prostate cancer (PC) is the second most frequent cancer among men and the fifth leading cause of death; moreover, standard treatments for PC have several issues, such as side effects and mechanisms of resistance. Thus, it is urgent to find drugs that can fill these gaps, and instead of developing new molecules requiring high financial and time investments, it would be useful to select non-cancer approved drugs that have mechanisms of action that could help in PC treatment, a process known as repurposing drugs. In this review article, drugs that have potential pharmacological efficacy are compiled to be repurposed for PC treatment. Thus, these drugs will be presented in the form of pharmacotherapeutic groups, such as antidyslipidemic drugs, antidiabetic drugs, antiparasitic drugs, antiarrhythmic drugs, anti-inflammatory drugs, antibacterial drugs, antiviral drugs, antidepressant drugs, antihypertensive drugs, antifungal drugs, immunosuppressant drugs, antipsychotic drugs, antiepileptic and anticonvulsant drugs, bisphosphonates and drugs for alcoholism, among others, and we will discuss their mechanisms of action in PC treatment.

The use of the functional independence measure in elderly. / O emprego da medida de independência funcional em idosos.

OBJECTIVES: To analyze in scientific publications how the Functional Independence Measure (FIM) has been employed to evaluate the elderly. METHODS: Integrative review of periodical publications between 2011 and 2015, available online in full-text in Portuguese, English and Spanish. RESULTS: 129 articles were found; after the application of the criteria, they resulted in 21. The studies were categorized into two groups: A) follow or compare scores in FIM (cohort studies, case-control, clinical trials), focusing on rehabilitation, evaluation of programs and changes in the functional level after procedures/interventions; and B) measure/associate the functionality of the elderly (cross-sectional studies), focused on evaluation protocols in elderly health and associations to the caregiver burden, hospital stay, balance, satisfaction with life, cognition and clinical/socio-demographic aspects. CONCLUSION: The FIM was used in several scenarios of healthcare for the elderly, particularly in rehabilitation and outpatient clinics or health centers.

[Handgrip strength and physical activity in frail elderly]. / Força de preensão manual e atividade física em idosos fragilizados.

OBJECTIVE: To investigate the association between handgrip strength (HS) and physical activity in physical frailty elderly. METHOD: Cross-sectional quantitative study with a sample of 203 elderly calculated based on the population estimated proportion. Tests were applied to detect cognitive impairment and assessment of physical frailty. Descriptive statistics and multivariate analysis by binary logistic regression were used, and also Student's t-test and Fisher's exact test. RESULTS: A total of 99 (64.3%) elderly showed decreased handgrip strength and 90 (58.4%) elderly presented decrease in physical activity levels. There was a statistically significant difference between these two components (p=0.019), in which elderly who have decreased HS have lower levels of physical activity. For low levels of physical activity and decreased HS, there was no evidence of significant difference in the probability of the classification as frail elderly (p<0.001). CONCLUSION: The components handgrip strength and physical activity are associated with the frail elderly. The joint presence of low levels of physical activity and decreased handgrip strength leads to a significantly higher probability of the elderly to be categorized as frailty.

Comparative analysis on natural spawning of F1 meagre, Argyrosomus regius, with wild broodstock spawns in Portugal.

The purpose of this study was to describe and compare the reproductive success and egg and larvae quality between wild and first-generation (F1) breeders of Argyrosomus regius. Wild broodstock were adapted to captivity, and good-quality spawns were obtained in 2009-2010, after GnRH treatment. In 2012, the F1 meagre (3 years old) spawned naturally at IPMA's Aquaculture Research Station facilities. From each spawning event, the following parameters were determined: number of floating and non-floating eggs, egg size, hatching success and larval total length. Eggs size and percentage of hatching obtained from F1 breeders (1.04 ± 0.10 mm and 90.5 ± 6.4%) were significantly higher when compared with wild breeders (0.97 ± 0.13 mm and 17.0 ± 12.7%). Although wild breeder spawns exhibited 2.7 ± 0.2 mm for larval total length, F1 breeder spawns presented 2.6 ± 0.2 mm. The wild and F1 breeder spawns exhibit a good egg and larval quality, indicating a promising starting point for a successful meagre hatchery production.

Legislation and policy for involuntary mental healthcare across countries in the FOSTREN network: rationale, development of mapping survey and protocol.

BACKGROUND: Several countries are currently revising or have already revised their mental health laws to align with the global movement to reduce the use of coercive care. No government has yet fully implemented the recommendation of the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) to eliminate the use of coercion in mental healthcare. Consequently, the international field of mental health law and policy is in a degree of flux. AIMS: To describe the rationale, development and protocol for a project that will map and examine how mental health laws, policies and service capacity across European countries relate to the use of coercive measures, including involuntary admissions and treatment, restraints and seclusion. This will help to better understand the current situation and explore future directions of policies regarding coercive care. METHOD: The project is being carried out under the purview of the European Cooperation in Science and Technology (COST) action network, entitled FOSTREN (Fostering and Strengthening Approaches to Reducing Coercion in European Mental Health Services). A multidisciplinary group of experts developed a comprehensive survey assessing mental health laws, policies and service frameworks, based on World Health Organization and UNCRPD recommendations. The survey was piloted in three countries, revised and disseminated to 30 FOSTREN country representatives. The survey will provide data for three strands of work on legislation, policies and service-level context. A comprehensive evaluation will be conducted, drawing on findings from all work packages. CONCLUSIONS: The project could inform the development of strategies, interventions and legislation to address gaps and promote compliance with international standards.

Entecavir: A Review and Considerations for Its Application in Oncology.

Entecavir (ETV) is a drug used as a first-line treatment for chronic hepatitis B (CHB) virus infection because it is a guanosine nucleoside analogue with activity against the hepatitis B virus polymerase. The ETV dosage can range from 0.5 mg to 1 mg once a day and the most common side effects include headache, insomnia, fatigue, dizziness, somnolence, vomiting, diarrhea, nausea, dyspepsia, and increased liver enzyme levels. In addition to its conventional use, ETV acts as an inhibitor of lysine-specific demethylase 5B (KDM5B), an enzyme that is overexpressed in breast, lung, skin, liver, and prostate tumors and is involved in the hormonal response, stem cell regeneration, genomic stability, cell proliferation, and differentiation. The KDM5B enzyme acts as a transcriptional repressor in tumor suppressor genes, silencing them, and its overexpression leads to drug resistance in certain tumor types. Furthermore, the literature suggests that KDM5B activates the PI3K/AKT signaling pathway, while reducing KDM5B expression decreases AKT signaling, resulting in decreased tumor cell proliferation. In silico studies have demonstrated that ETV can inhibit tumor cell proliferation and induce apoptosis by reducing KDM5B expression. ETV also appears to inhibit PARP-1, has a high genetic barrier, reducing the chance of resistance development, and can also prevent the reactivation of the hepatitis B virus in cancer patients, which have proven to be significant advantages regarding its use as a repurposed drug in oncology. Therefore, ETV holds promise beyond its original therapeutic indication.

[Functional capacity in elderly longevity: an integrative review]. / Capacidade funcional no idoso longevo: uma revisão integrativa.

This is an integrated literature review intended to get to know the Brazilian scientific production regarding the functional capacity of the elderly. BDENF, LILACS, MEDLINE and SciELO databases were consulted in the sampling period from January, 2001, to September, 2010. Eight articles were selected with nursing professionals (4) as the main authors of such publications. Publication year of the articles is between 2006 and 2010, with predomination of quantitative research focused on the multidimensionality of the elderly. Questionnaires and scales were used to assess the functional capacity of the elderly and constraining factors for its performance were also indicated. Scientific studies on the theme are incipient, which evidences the need for further research aiming to improve the quality of life of the elderly.

The impact of the COVID-19 pandemic on the mental health of Portuguese university students.

Worldwide, the COVID-19 pandemic has had a disruptive effect on daily routines, especially for university students. This study aimed to compare pre-pandemic domains of students' mental health during the pandemic lockdown. One cross-sectional study was conducted in two waves with academic students from 20 Portuguese universities, in March 2020 before the COVID-19 pandemic (n = 3579) and 2 months after the first lockdown in May 2020 (n = 1228). The Positive Mental Health Questionnaire (PMHQ), the Mental Health Knowledge Questionnaire, the Mental Health-promoting knowledge, and the Psychological Vulnerability Scale were used. Statistical analyses were performed by bivariate associations and multiple linear regression models. Students were mostly women (79%), with an average age of 23.2 years (SD = 6.6), displaced from their family environment (43%), out-of-home (43%), and scholarship holders (37%). Higher scores found in the PVS were associated with decreased PMHQ in both moments (P < 0.01). These cross-sectional studies showed a slight variation in the mental health variables studied in the period before and during the COVID-19 outbreak. Being a woman, younger, out-of-home, and having a scholarship (P < 0.01) seem to increase susceptibility to mental health variation before and during the pandemic. Universities should develop strategies that promote students' mental health.

Handgrip strength in older adults and driving aptitude.

OBJECTIVE: to analyze handgrip strength as a predictor of the inability to drive in older adults. METHOD: a cross-sectional study conducted in traffic clinics with 421 older adults in Curitiba-Paraná from January 2015 to December 2018. A sociodemographic and clinical questionnaire, handgrip strength test, and queries from the National Registry of Qualified Drivers form were applied. RESULTS: Reduced handgrip strength was not a predictor of inaptitude for vehicular driving (p=0.649). The predictors of inaptitude were: low education (p=0.011), incomplete elementary education (p=0.027), and cognition (p=0.020). CONCLUSION: reduced handgrip strength was not shown to predict for loss of driving skills in older adults. Low education level and reduced cognition level are conditions that were shown to be predictors for loss of vehicular driving license.

Predictive Model of the Psychological Well-Being of Nursing Students During the COVID-19 Lockdown.

Introduction: Lockdowns due to the COVID-19 pandemic radically changed nursing education. Along with social isolation, the transition to distance education affected the well-being of students in several countries, particularly Portugal and Spain. Objectives: To identify which variables are predictors of psychological well-being for Portuguese and Spanish nursing students during mandatory lockdowns. Methods: A multicenter, cross-sectional, descriptive, correlational study involving a sample of 1075 students (944 women, mean age 22.46 + /-4.95 years). Data were collected from an online questionnaire which applied the following scales: Perceived Stress Scale (α = .820); Brief COPE-14 Subscales (α = .430 < 0.930); Well-being Manifestations Measure Scale (α = .940); Herth Hope Index (α = .850). A multiple regression model was created to predict the psychological well-being of nursing students. Results: The following predictor variables were identified in the model of the psychological well-being of students during the COVID-19 pandemic: perceived stress (ß = .405; p ≤ .001); hope (ß = .404; p ≤ .001); and the mechanisms of active coping (ß = .405; p ≤ .001), planning (ß = .097; p ≤ .001), and positive reinterpretation (ß = .053; p = .12). These five variables predicted 62.0% of the nursing students' psychological well-being (R 2 = .620; F = 350.82; p ≤ .001). Conclusion: Promoting students' mental health is essential, especially in periods of great adversity, such as a pandemic. Our results lead the way for the design and validation of an intervention program that addresses the five variables identified as predictors of students' psychological well-being.

The clinical effectiveness of transurethral incision of the prostate: a systematic review of randomised controlled trials.

PURPOSE: Transurethral incision of the prostate gland (TUIP) is perceived as a less morbid surgical alternative to standard transurethral resection of the prostate gland (TURP) for treatment of symptomatic mild to moderate benign prostate enlargement (BPE). We aimed to evaluate comparative clinical effectiveness of the two procedures. METHODS: Systematic review and meta-analysis of short- and long-term data from randomised controlled trials comparing TUIP with TURP. RESULTS: This review considered data from 795 randomised participants across 10 RCTs of moderate to poor quality 8 of which stated an upper limit for prostate size. No difference in the degree of symptomatic improvement was seen between the two procedures. Improvement in peak urine flow rate was lower for TUIP compared to TURP whilst the rate of blood transfusion and TUR syndrome was higher after TURP. Urinary retention, urinary tract infection, strictures and incontinence did not differ between the two approaches, although clinically important differences could not be ruled-out. TUIP was associated with a shorter duration of operation and length of hospital stay but a higher re-operation rate. CONCLUSION: TUIP and TURP appear to offer equivalent symptomatic improvement for men with mild to moderate BPE. Choosing TUIP involves a trade-off between the lower risk of peri-operative morbidity and the higher risk of subsequent re-operation.

The fate of conference abstracts: systematic review and meta-analysis of surgical treatments for men with benign prostatic enlargement.

OBJECTIVE: From the literature search for a government-commissioned systematic review on surgical treatments for benign prostatic enlargement (BPE), we identified the relevant conference abstracts of randomised controlled trials (RCTs) which failed to reach full publication and their data were not utilised. We aimed to ascertain, first, the reasons of failure to reach full publication and second, to estimate the impact of including the abstracts' data. DESIGN: A two-part study, consisting of a questionnaire survey and a sensitivity analysis of the above said review. METHODS: An ad hoc questionnaire was sent to each author of the relevant abstracts, as to determine the reasons of failure to reach full publication. The data from the abstracts were then extracted and incorporated into sensitivity analysis of the review. RESULTS: Forty-seven questionnaires were completed for 47 abstracts. Of these abstracts, 32 of them were claimed to have reached full publication. A number of reasons of failure to reach full publication were identified, for example: 'being written up' and 'lack of time'. Utilizable, relevant data were obtained from eight of the 47 abstracts, and put into sensitivity analysis. There were small changes in effect sizes and directions for three of 14 reviews' secondary outcomes. CONCLUSION: Common reasons of failure to reach full publication were also identified in the context for the BPE review. Inclusion of abstract data did not affect primary outcome defined in the original review. Identification, summarisation of conference abstracts and other grey literature should form an essential exercise for any systematic review.

Biofloc-Based Enhanced Survival of Litopenaeus vannamei Upon AHPND-Causing Vibrio parahaemolyticus Challenge Is Partially Mediated by Reduced Expression of Its Virulence Genes.

The biofloc system is a relatively new aquaculture technology that offers practical solution to maintain culture water quality by recycling nutrients and improves the health status and resistance of shrimps against microbial infection, yet the mode of action involved remains unclear. This study aimed to unravel the underlying mechanism behind the protective effect of a biofloc system using Litopenaeus vannamei and acute hepatopancreatic necrosis disease (AHPND)-causing Vibrio parahaemolyticus M0904 strain as a host-pathogen model. The results showed that a biofloc system maintained at a C/N ratio of 15, improves the water quality and contributes to the nutrition of cultured animals as bioflocs might serve as an additional protein source. Furthermore, the study demonstrated that the biofloc system enhances the survival of L. vannamei upon challenge with a V. parahaemolyticus AHPND strain. Remarkably, the results highlight that in the biofloc system, AHPND-causing V. parahaemolyticus possibly switch from free-living virulent planktonic phenotype to a non-virulent biofilm phenotype, as demonstrated by a decreased transcription of flagella-related motility genes (flaA, CheR, and fliS), Pir toxin (PirB VP ), and AHPND plasmid genes (ORF14) and increased expression of the phenotype switching marker AlkPhoX gene in both in vitro and in vivo conditions. Taken together, results suggest that biofloc steer phenotype switching, contributing to the decreased virulence of V. parahaemolyticus AHPND strain toward shrimp postlarvae. This information reinforces our understanding about AHPND in a biofloc setting and opens the possibility to combat AHPND not only by trying to eliminate the AHPND-causing V. parahaemolyticus from the system but rather to steer the phenotypic switch.

Review of nursing diagnosis validation studies: caregiver role strain.

OBJECTIVE: To analyze the nursing diagnosis NANDA-I - Caregiver Role Strain validation studies. METHODS: Integrative literature review. Research of studies carried out between 2000 and 2018 with the descriptors: caregivers, nursing diagnosis and validation study in the following databases: Web of Science, EBESCOhost, Scielo Brasil and Portugal, LILACS, RCAAP, CAPES, NANDA-I website, and in the bibliographic references of the articles. Articles in Portuguese, English or Spanish were included. RESULTS: The sample consisted of seven validation studies, with heterogeneity in the methodologies used. The populations where the diagnosis was clinically validated focused on caregivers for the elderly and people with chronic illness. The most prevalent defining characteristics were Stress and Apprehension related to the future. CONCLUSIONS: This diagnosis requires further validation studies among different populations in search of greater accuracy and a reduction in the number of defining characteristics, facilitating the use of taxonomy.

Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury.

Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.

Gait speed associated factors in elderly subjects undergoing exams to obtain the driver's license. / Fatores associados à velocidade da marcha em idosos submetidos aos exames para habilitação veicular.

OBJECTIVE: to analyze the factors associated with gait speed in elderly subjects undergoing physical and mental fitness tests to obtain a driver's license. METHOD: a cross-sectional quantitative study conducted in transit agencies. The probabilistic sample included 421 elderly (≥ 60 years old). The study was developed through application of questionnaires and tests that assess the frailty phenotype. For evaluating gait speed, the time spent by each participant to walk a 4.6 meter distance at normal pace on a flat surface was timed. Data were analyzed by using multiple linear regression and the stepwise method. The R statistical program version 3.4.0 was adopted. RESULTS: there was a significant association between gait speed and paid work (<0.0000), body mass index (<0.0000), Mini-Mental State Examination (=0.0366), physical frailty (pre-frail =0.0063 and non-frail <0.0000), age (<0.0000), sex (=0.0255), and manual grip strength (<0.0000). CONCLUSION: elderly drivers who do not work, women of advanced age, high body mass index, low score in the Mini-Mental State Examination, low hand grip strength, and frail tend to decrease gait speed and should be a priority of interventions.

Laparoscopic surgery for colorectal cancer: safe and effective? - A systematic review.

OBJECTIVE: To determine the clinical effectiveness of laparoscopic and laparoscopically assisted surgery in comparison with open surgery for the treatment of colorectal cancer. BACKGROUND: Open resection is the standard method for surgical removal of primary colorectal tumours. However, there is significant morbidity associated with this procedure. Laparoscopic resection (LR) is technically more difficult but may overcome problems associated with open resections (OR). METHODS: Systematic review and meta-analysis of short- and long-term data from randomised controlled trials (RCTs) comparing LS with OR. RESULTS: Highly sensitive searches of nine databases identified 19 primary RCTs describing data from over 4,500 participants. Length of hospital stay is shorter, blood loss and pain are less, and return to usual activities is likely to be faster after LR than after OR, but duration of operation is longer. Lymph node retrieval, completeness of resection and quality of life do not appear to differ. No statistically significant differences were observed in rates of anastomotic leakage, abdominal wound breakdown, incisional hernia, wound and urinary tract infections, operative and 30-day mortality, and recurrences, nor in overall and disease-free survival up to three years. CONCLUSIONS: LR is associated with a quicker recovery in terms of return to usual activities and length of hospital stay with no evidence of a difference in complications or long-term outcomes in comparison to OR, up to three years postoperatively.

Fatores sociodemográficos e clínicos associados à força de preensão manual de idosos condutores de veículos / Sociodemographic and clinical factors associated with handgrip strength in elderly automobile drivers / Factores sociodemográficos y clínicos asociados a la fuerza de prensión de la mano en conductores de vehículos de ancianos

Objetivo: investigar a associação entre força de preensão manual e características sociodemográficas e clínicas de idosos condutores de veículos automotores. Método: estudo transversal, realizado em clínicas de medicina de tráfego na cidade de Curitiba/Paraná, com 421 idosos (≥ 60 anos). Realizou-se análise estatística pelo modelo de Regressão Logística e Teste de Wald, considerando intervalo de confiança de 95% e valores de p <0,05 como significativos. Resultados: oitenta e quatro (20%) idosos apresentaram força de preensão manual reduzida. A força de preensão manual reduzida foi associada à faixa etária (p=0,001) e à hospitalização no último ano (p=0,002). Conclusão: houve associação significativa entre a força de preensão manual de idosos motoristas e as variáveis idade e hospitalização no último ano. Dessa forma, torna-se essencial a inclusão de avaliações específicas, centradas nas variáveis sociodemográficas e clínicas próprias da pessoa idosa, durante o exame de aptidão para dirigir veículos automotores.(AU)

Objective: to investigate the association between handgrip strength and sociodemographic and clinical characteristics of elderly automobile drivers. Method: cross-sectional study, carried out in traffic medicine clinics in the city of Curitiba/Paraná, with 421 elderly people (≥ 60 years old). Statistical analysis was performed using the Logistic Regression model and the Wald Test, considering a 95% confidence interval and p values <0.05 as significant. Results: eighty-four (20%) seniors had reduced handgrip strength. Reduced handgrip strength was associated with age group (p=0.001) and hospitalization in the last year (p=0.002). Conclusion: there was a significant association between the handgrip strength of elderly drivers and the variables age and hospitalization in the last year. Thus, it is essential to include specific assessments, centered on sociodemographic and clinical variables specific to the elderly person, during the aptitude test to drive automobiles.(AU)

Objetivo: investigar la asociación entre la fuerza de prensión de la mano y las características sociodemográficas y clínicas de los ancianos conductores de vehículos automotores. Método: estudio transversal, realizado en clínicas de medicina de tránsito de la ciudad de Curitiba/Paraná, con 421 ancianos (≥ 60 años). El análisis estadístico fue realizado por el modelo de Regresión Logística y Test de Wald, considerando intervalo de confianza de 95% y valores de p <0,05 como significativos. Resultados: 84 (20%) sujetos ancianos presentaron reducción de la fuerza de prensión de la mano. La reducción de la fuerza de prensión de la mano se asoció al grupo de edad (p=0,001) y a la hospitalización en el último año (p=0,002). Conclusión: hubo una asociación significativa entre la fuerza de prensión de la mano de los conductores ancianos y las variables edad y hospitalización en el último año. Así pues, es esencial incluir evaluaciones específicas, centradas en las variables sociodemográficas y clínicas de los ancianos, durante el examen de aptitud para conducir vehículos automotores.(AU)

Handgrip strength in older adults and driving aptitude / Fuerza de prensión manual y aptitud para conducción vehicular de adultos mayores / Força de preensão manual em idosos e a aptidão para condução veicular

ABSTRACT Objective: to analyze handgrip strength as a predictor of the inability to drive in older adults. Method: a cross-sectional study conducted in traffic clinics with 421 older adults in Curitiba-Paraná from January 2015 to December 2018. A sociodemographic and clinical questionnaire, handgrip strength test, and queries from the National Registry of Qualified Drivers form were applied. Results: Reduced handgrip strength was not a predictor of inaptitude for vehicular driving (p=0.649). The predictors of inaptitude were: low education (p=0.011), incomplete elementary education (p=0.027), and cognition (p=0.020). Conclusion: reduced handgrip strength was not shown to predict for loss of driving skills in older adults. Low education level and reduced cognition level are conditions that were shown to be predictors for loss of vehicular driving license.

RESUMEN Objetivo: analizar la fuerza de prensión manual como factor predictivo de inaptitud para la conducción vehicular de adultos mayores. Método: se trata de un estudio transversal llevado a cabo en clínicas de tránsito de Curitiba, Paraná, entre 421 adultos mayores, de enero de 2015 a diciembre de 2018. Se aplicaron los cuestionarios sociodemográfico y clínico, la prueba de fuerza de prensión manual y se consultó el formulario del Registro Nacional de Conductores Habilitados. Resultados: la fuerza de prensión manual reducida no fue un factor predictivo de la incapacidad para conducir (p=0,649). Los predictores de inaptitud fueron: baja educación (p=0,011), estudios primarios incompletos (p=0,027) y cognición (p=0,020). Conclusión: la fuerza de prensión manual reducida no demostró ser predictora de la pérdida de habilidades de conducción vehicular en adultos mayores. El nivel de escolaridad bajo y el nivel cognitivo reducido despuntaron como predictores de la pérdida de habilitación en la conducción vehicular.

RESUMO Objetivo: analisar a força de preensão manual como preditora de inaptidão para condução veicular de idosos. Método: estudo transversal realizado em clínicas de trânsito com 421 idosos em Curitiba-Paraná de janeiro de 2015 a dezembro de 2018. Aplicaram-se questionários sociodemográfico e clínico, teste de força preensão manual e consultas ao formulário de Registro Nacional de Condutores Habilitados. Resultados: A força de preensão manual reduzida não se mostrou preditora de inaptidão para a direção veicular (p=0,649). Os preditores de inaptidão foram: baixa escolaridade (p=0,011), ensino primário incompleto (p=0,027) e cognição (p=0,020). Conclusão: a força de preensão manual reduzida não se mostrou preditora para perda da habilitação na condução veicular de idosos. O baixo nível de escolaridade, o nível de cognição reduzida, são condições que se mostraram preditoras para a perda da habilitação na condução veicular.

The 9H-Fluoren Vinyl Ether Derivative SAM461 Inhibits Bacterial Luciferase Activity and Protects Artemia franciscana From Luminescent Vibriosis.

Vibrio campbellii is a major pathogen in aquaculture. It is a causative agent of the so-called "luminescent vibriosis," a life-threatening condition caused by bioluminescent Vibrio spp. that often involves mass mortality of farmed shrimps. The emergence of multidrug resistant Vibrio strains raises a concern and poses a challenge for the treatment of this infection in the coming years. Inhibition of bacterial cell-to-cell communication or quorum sensing (QS) has been proposed as an alternative to antibiotic therapies. Aiming to identify novel QS disruptors, the 9H-fluroen-9yl vinyl ether derivative SAM461 was found to thwart V. campbellii bioluminescence, a QS-regulated phenotype. Phenotypic and gene expression analyses revealed, however, that the mode of action of SAM461 was unrelated to QS inhibition. Further evaluation with purified Vibrio fischeri and NanoLuc luciferases revealed enzymatic inhibition at micromolar concentrations. In silico analysis by molecular docking suggested binding of SAM461 in the active site cavities of both luciferase enzymes. Subsequent in vivo testing of SAM461 with gnotobiotic Artemia franciscana nauplii demonstrated naupliar protection against V. campbellii infection at low micromolar concentrations. Taken together, these findings suggest that suppression of luciferase activity could constitute a novel paradigm in the development of alternative anti-infective chemotherapies against luminescent vibriosis, and pave the ground for the chemical synthesis and biological characterization of derivatives with promising antimicrobial prospects.