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Loss-of-function mutations in PINK1 or PARKIN are the most common causes of autosomal recessive Parkinson's disease. Both gene products, the Ser/Thr kinase PINK1 and the E3 Ubiquitin ligase Parkin, functionally cooperate in a mitochondrial quality control pathway. Upon stress, PINK1 activates Parkin and enables its translocation to and ubiquitination of damaged mitochondria to facilitate their clearance from the cell. Though PINK1-dependent phosphorylation of Ser65 is an important initial step, the molecular mechanisms underlying the activation of Parkin's enzymatic functions remain unclear. Using molecular modeling, we generated a complete structural model of human Parkin at all atom resolution. At steady state, the Ub ligase is maintained inactive in a closed, auto-inhibited conformation that results from intra-molecular interactions. Evidently, Parkin has to undergo major structural rearrangements in order to unleash its catalytic activity. As a spark, we have modeled PINK1-dependent Ser65 phosphorylation in silico and provide the first molecular dynamics simulation of Parkin conformations along a sequential unfolding pathway that could release its intertwined domains and enable its catalytic activity. We combined free (unbiased) molecular dynamics simulation, Monte Carlo algorithms, and minimal-biasing methods with cell-based high content imaging and biochemical assays. Phosphorylation of Ser65 results in widening of a newly defined cleft and dissociation of the regulatory N-terminal UBL domain. This motion propagates through further opening conformations that allow binding of an Ub-loaded E2 co-enzyme. Subsequent spatial reorientation of the catalytic centers of both enzymes might facilitate the transfer of the Ub moiety to charge Parkin. Our structure-function study provides the basis to elucidate regulatory mechanisms and activity of the neuroprotective Parkin. This may open up new avenues for the development of small molecule Parkin activators through targeted drug design.

Breast cancer is the most frequent type of nonskin malignancy among women worldwide. In general, conventional cancer treatment options (i.e., surgery, radiotherapy, chemotherapy, biological therapy, and hormone therapy) are not completely effective. Recurrence and other pathologic situations are still an issue in breast cancer patients due to side effects, toxicity of drugs in normal cells, and aggressive behaviour of the tumours. From this point of view, breast cancer therapy and adjuvant methods represent a promising and challenging field for researchers. In the last few years, the use of some types of complementary medicines by women with a history of breast cancer has significantly increased such as phytotherapeutic products and nutritional supplements. Despite this, the use of such approaches in oncologic processes may be problematic and patient’s health risks can arise such as interference with the efficacy of standard cancer treatment. The present review gives an overview of the most usual phytotherapeutic products and nutritional supplements with application in breast cancer patients as adjuvant approach. Regardless of the contradictory results of scientific evidence, we demonstrated the need to perform additional investigation, mainly well-designed clinical trials in order to establish correlations and allow for further validated outcomes concerning the efficacy, safety, and clinical evidence-based recommendation of these products.

Leprosy, or Hansen’s disease, is a Neglected Tropical Disease (NTD) caused by Mycobacterium leprae that mainly affects the skin and peripheral nerves, causing neuropathy to varying degrees. It can result in physical disabilities and functional loss and is particularly prevalent amongst the most vulnerable populations in tropical and subtropical regions worldwide. The persistent stigma and social exclusion associated with leprosy complicate eradication efforts exacerbate the wider challenges faced by NTDs in sourcing the necessary resources and attention for control and elimination. The introduction of Multidrug Therapy (MDT) significantly lowers the global disease burden. Despite this breakthrough in the treatment of leprosy, over 200,000 new leprosy cases are reported annually across more than 120 countries, emphasizing the need for ongoing detection and management efforts. Artificial Intelligence (AI) has the potential to transform leprosy care by accelerating early detection, improving accurate diagnosis, and enabling predictive modeling to improve the quality for those affected. The potential of AI to provide information to assist healthcare professionals in interventions that reduce the risk of disability, and consequently stigma, particularly in endemic regions, presents a promising path to reducing the incidence of leprosy and improving integration social status of patients. This systematic literature review (SLR) examines the state of the art in research on the use of AI for leprosy care. From an initial 657 works from six scientific databases (ACM Digital Library, IEEE Xplore, PubMed, Scopus, Science Direct and Springer), only 30 relevant works were identified, after analysis of three independent reviewers. We have excluded works due duplication, couldn’t be retrieved and quality assessment. Results show that current research is focused primarily on the identification of symptoms using image based classification using three main techniques, neural networks, convolutional neural networks, and support vector machines; a small number of studies focus on other thematic areas of leprosy care. A comprehensive systematic approach to research on the application of AI to leprosy care can make a meaningful contribution to a leprosy-free world and help deliver on the promise of the Sustainable Development Goals (SDG).

Abstract Extracts of species from the Cordia genus have been reported with potential biological activities, such as antioxidant, antimicrobial, antiviral, and antiparasitic. The aim of this study was to develop microemulsions containing ethanolic extracts of C. glabrata leaves and to evaluate their stability and biological activities. The five developed microemulsions presented physicochemical stability and presented Newtonian behavior when submitted to rheological analysis. The diameter values of the globules ranged between 225.74 and 273.33 nm and the zeta potential of the formulations remained between -22.40 and -25.08. All phenolic acids of the extract, quantified by HPLC, showed consistency after being microemulsified. The EC50 values for the antioxidant activity by the DPPH scavenging method ranged between 38.13 and 45.54 µgmL-1, and between 34.46 and 39.60 mM for the ABTS+ scavenging method. The virucidal activity presented a CV50 <0.195 µgmL-1 and a selectivity index greater than 20. The photoprotection results ranged between 2.14 to 2.84. The study revealed stable microemulsions and potentiation of the antioxidant effect in the microemulsified extracts. Resumo Extratos de espécies do gênero Cordia têm sido relatados com potencial atividade biológica, como antioxidante, antimicrobiana, antiviral e antiparasitária. O objetivo deste estudo foi desenvolver microemulsões contendo extratos etanólicos de folhas de C. glabrata e avaliar sua estabilidade e atividades biológicas. As cinco microemulsões desenvolvidas apresentaram estabilidade físico-química e apresentaram comportamento newtoniano quando submetidas à análise reológica. Os valores de diâmetro dos glóbulos variaram entre 225,74 e 273,33 nm e o potencial zeta das formulações permaneceu entre -22,40 e -25,08. Todos os ácidos fenólicos do extrato, quantificados por CLAE, apresentaram consistência após serem microemulsionados. Os valores de EC50 para a atividade antioxidante pelo método de eliminação DPPH variaram entre 38,13 e 45,54 µgmL-1, e entre 34,46 e 39,60 mM para o método de eliminação ABTS+. A atividade viricida apresentou CV50 <0,195 µgmL-1 e índice de seletividade maior que 20. Os resultados da fotoproteção variaram entre 2,14 a 2,84. O estudo revelou microemulsões estáveis e potencialização do efeito antioxidante nos extratos microemulsionados.

Introduction and objectivesThe possibility of performing remote-surgery has been the goal to achieve, since the early development of the first surgical robotic platforms. This systematic review aims to analyse the state of the art in the field and to provide an overview of the possible growth of this technology.MethodsAll English language publications on Telementoring and Telesurgery for minimally invasive urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed®, Scopus®, and Web of Science™ databases (up to June 2019).ResultsOur electronic search identified a total of 124 papers in PubMed, Scopus, and Web of Science. Of these, 81 publications were identified for detailed review, which yielded 22 included in the present systematic review. Our results showed that remote surgery has been under-utilised until today, mostly due to the lack of appropriate telecommunication technologies.ConclusionRemote live surgery is a growing technology that is catalyzing incremental interest. Despite not being yet reliable today on a regular basis in its most advanced applications, thanks to the advent of novel data-transmission technologies, telepresence might become a critical educational methodology, highly impacting the global healthcare system

Abstract Species of the genus Cordia have shown biological activities, such as anti-inflammatory, analgesic, antioxidant, antiviral, and antifungal activities. The species Cordia glabrata (MART) A.DC. Has no information concerning its phytochemical profile and possible biological activities. Thus, this study aimed to evaluate this profile in ethanolic extracts of young, adult and senescent leaves, as well as their antioxidant, photoprotective, antimicrobial, and virucidal potentials. Phytochemical analysis was performed by TLC (thin-layer chromatography) and showed the presence of flavonoids, tannins, and terpenes. The evaluation by UPLC-MS/MS (Ultra performance liquid chromatography - tandem mass spectrometer) evidenced the presence of caffeic (3.89 mgL-1), p-cumaric (6.13 mgL-1), and ferulic (0.58 mgL-1) acids, whilst, in GC/MS (Gas chromatography–mass spectrometry) analysis there was a greater amount of palmitic (51.17%), stearic (20.34%), linoleic (9.62%), and miristic (8.16%) fatty acids. The DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS+ (2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radicals were used to verify the potential antioxidant activity, observing a better activity for the leaf extract in the adult phenological stage: 54.63 ± 1.06 µgmL-1 (DPPH) and 44.21 ± 1.69 mM (ABTS). The potential photoprotective activity of the extracts was determined by spectrophotometry and the in vitro values of SPF (Sun Protection Factor) in young and adult leaves (5.47 and 5.41, respectively) showed values close to the minimum SPF of 6.0 required by ANVISA (Brazilian Health Regulatory Agency). It was not observed an antimicrobial activity for Staphylococcus aureus with a minimum inhibitory concentration of 2000 μgmL-1, however the anti-herpetic assay against the Herpes simplex virus type 2 (HSV-2) showed a potent virucidal activity at the tested concentrations with CV50 value <0.195 μgmL-1 and a Selectivity Index (SI = CC50 / CV50) greater than 448. The results obtained in this study suggest that extracts of leaves of C. glabrata in their adult phenological stage have potential antioxidant, photoprotective and virucidal activity, considering in vitro test results. Resumo Espécies do gênero Cordia apresentam atividades biológicas, como anti-inflamatória, analgésica, antioxidante, antiviral e antifúngica. Para a espécie Cordia glabrata (MART) A.DC., ainda não existem informações sobre seu perfil fitoquímico e possíveis atividades biológicas, deste modo, o presente estudo teve como objetivo avaliar este perfil em extratos etanólicos de folhas jovens, adultas e senescentes, bem como o potencial antioxidante, fotoprotetor, antimicrobiano e virucida. A análise fitoquímica foi realizada por CCD (Cromatografia em Camada Delgada), mostrando a presença de flavonóides, taninos e terpenos. Na avaliação por CLAE EM/EM (Cromatografia Líquida de Ultra Eficiência acoplada a Espectrometria de Massas) foi evidenciado a presença dos ácidos caféico (3,89 mgL-1), p-cumárico (6,13 mgL-1) e ferúlico (0,58 mgL-1), paralelamente, na CG/EM (Cromatografia Gasosa acoplada a Espectrometria de Massas) verificou-se maior quantidade dos ácidos graxos palmítico (51,17%), esteárico (20,34%), linoléico (9,62%) e mirístico (8,16%). Os radicais DPPH (2,2-Difenil-1-picrilhidrazil) e ABTS+ (2′-Azino-bis (ácido 3-etilbenzotiazolina-6-sulfônico)) foram utilizados para verificar o potencial antioxidante, observando-se uma atividade superior para o extrato da folha em sua fase fenológica adulta: 54,63 ± 1,06 µgmL-1 (DPPH) e 44,21 ± 1,69 mM (ABTS+). A potencial atividade fotoprotetora dos extratos foi determinada espectrofotometricamente e os valores in vitro de FPS (Fator de Proteção Solar) em folhas jovens e adultas (5,47 e 5,41 respectivamente) apresentaram valores próximos ao FPS mínimo de 6,0 exigido pela ANVISA (Agência Nacional de Vigilância Sanitária). Não foi observada atividade antimicrobiana para Staphylococcus aureus sendo a concentração inibitória mínima de 2000 μgmL-1, no entanto o ensaio anti-herpético contra o vírus Herpes simplex tipo 2 (HSV-2) mostrou uma potente atividade virucida nas concentrações testadas com um valor de CV50 <0,195 μgmL-1 e um Índice de Seletividade (IS = CC50 / CV50) maior que 448. Os resultados obtidos neste estudo sugerem que extratos de folhas de C. glabrata em seu estágio fenológico adulto apresentam potencial antioxidante, fotoprotetora e virucida, considerando os resultados de testes in vitro.

Recent evidence suggests that some seizures are preceded by preictal changes that start from minutes to hours before an ictal event. Nevertheless an adequate statistical evaluation in a large database of continuous multiday recordings is still missing. Here, we investigated the existence of preictal changes in long-term intracranial recordings from 53 patients with intractable partial epilepsy (in total 531 days and 558 clinical seizures). We describe a measure of brain excitability based on the slow modulation of high-frequency gamma activities (40–140 Hz) in ensembles of intracranial contacts. In prospective tests, we found that this index identified preictal changes at levels above chance in 13.2% of the patients (7/53), suggesting that results may be significant for the whole group (p < 0.05). These results provide a demonstration that preictal states can be detected prospectively from EEG data. They advance understanding of the network dynamics leading to seizure and may help develop novel seizure prediction algorithms.

Objectives The purpose was to administer the NEO-FFI personality test to patients who did and did not want to have their teeth bleached and before and after bleaching to the participants who accepted the treatment. The research question is to correlate styles and personality factors with bleaching. Materials and methods There were 128 patients eligible for bleaching; 58 accepted (AB) while 70 refused (RB). The test was administered to both groups (AB-RB). The group AB was administered before and 1 week after the end of the bleaching. For each personality domain comparison, the Mann-Whitney test was used. For the group AB, the results for each domain before and after bleaching were compared using the Wilcoxon test. Results There was a significant difference between the groups (AB-RB) in the extraversion factor ( p  = 0.01). There was no significant difference between any of the personality items before and after bleaching ( p  > 0.1). The comparison between groups by sex revealed significant differences in extraversion and neuroticism factors. Males who AB scored higher in extraversion than males who RB ( p  < 0.05). Females scored higher in neuroticism than males who AB ( p  < 0.05). Conclusions There were personality differences between people who decided to bleach compared with those who did not want the bleaching, which was mainly in the extroversion factor. This stereotypes the patients, who could be described as more sociable, extroverted, and concerned about esthetics and cleanliness. The bleaching protocol, however, cannot modify any of the personality factors. Clinical significance It is important to understand a patient’s behavior to meet their needs and to determine the type of patients who would like to have their teeth bleached.

Aging related alterations in body composition are associated with higher all-cause mortality risk. To examine the associations between 10-year mortality risk with both BMI and body composition, as well as to establish whether these relationships are modified by age and gender, using data from community-dwelling older Brazilian adults. We used data from two waves i.e., 2000 and 2010 of the SABE (Health, Well-being, and Aging) study conducted in São Paulo, Brazil, involving a probabilistic sample of community-dwelling older adults aged 60 years and older. The variables of the study were: mortality (in 10-year follow-up period), body mass index (BMI), body composition (waist circumference, waist hip ratio, triceps skinfold thickness, mid-upper arm circumference, calf circumference, and arm muscle area) and covariables (sociodemographic characteristics, life style, self-reported health conditions, number of chronic diseases, Mini mental state exam, and Geriatric depression scale). Poisson regression estimates with STATA statistical software were used for statistical analyses, considering all p-values < 0.05. Over the 10-year follow-up period, there were 769 deaths (40.2%). The mortality rate was 61.0 for men and 111.8 for the ≥80 age group. In the fully adjusted model, statistically significant hazard ratios were found for low muscle mass (IRR: 1.33), underweight (IRR: 1.29), and low fat mass (IRR: 1.31) with mortality. Men in extreme BMI categories (underweight - IRR: 1.47; obesity I - IRR: 1.66; and obesity II - IRR: 1.91) and women with low muscle and low fat mass were significantly associated with mortality risk. In the ≥80 age group it was observed that low muscle mass (IRR: 168.7), inadequate body reserves (IRR: 1.63), low fat mass (IRR: 140.7), and underweight (IRR: 142.9) were associated with mortality risk. Waist circumference demonstrated protection for mortality in the high-risk categorization for the ≥80 age group. Our results showed that underweight, low fat mass, and low muscle mass were associated with mortality risk, presenting different roles considering gender and age in older Brazilian adults over a 10-year follow-up period.

The increasing use of the Learning Management Systems (LMSs) is making available an ever-growing, volume of data from interactions between teachers and students. This study aimed to develop a model capable of predicting students' academic performance based on indicators of their self-regulated behavior in LMSs. To accomplish this goal, the authors analyzed behavioral data from an LMS platform used in a public University for distance learning courses, collected during a period of seven years. With this data, they developed, evaluated, and compared predictive models using four algorithms: Decision Tree (CART), Logistic Regression, SVM, and Naïve Bayes. The Logistic Regression model yielded the best results in predicting students' academic performance, being able to do so with an accuracy rate of 0.893 and an area under the ROC curve of 0.9574. Finally, they conceived and implemented a dashboard-like interface intended to present the predictions in a user-friendly way to tutors and teachers, so they could use it as a tool to help monitor their students' learning process.