Temporal association between atrial fibrillation and ischemic stroke: Systematic review and meta-analysis.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is strongly associated with ischemic stroke. Continuous cardiac implantable electronic devices (CIEDs) can assess PAF episodes over prolonged periods. Studies that attempted to find a temporal association between PAF and ischemic stroke were inconclusive. Thus, we performed a systematic review and meta-analysis to assess this relationship. AIMS: This study aimed to assess the temporal association between AF episodes and stroke within 30 days of the arrhythmic episode. The secondary outcome is a temporal association within a 90-day period. SUMMARY OF REVIEW: A total of 2804 studies that discussed the temporal relationship between PAF and ischemic stroke were screened, and 7 studies were included in the meta-analysis. Among the 4041 patients included in these studies, there were 138 patients with device detected PAF episodes and stroke. Four studies used a 30-day window for temporality and the pooled odds ratio (OR) showed a significant association (OR 4.11 (95% CI 1.03-16.40)). The three studies reporting on AF and stroke within a 90-day window did not find a significant temporal relationship (OR 0.43 (95% CI 0.13-1.41)). Finally, the pooled result of those seven studies did not show a significant association (OR 1.51 (95% CI 0.44-5.17)). CONCLUSION: This meta-analysis supports a temporal relationship between PAF and ischemic stroke within a 30-day window. Establishing this relationship is important for individualized risk prediction and targeted anticoagulation treatment. DATA ACCESS STATEMENT: The data will be made available upon reasonable request.

Interleukin-6 and -27 as potential novel biomarkers for human pleural tuberculosis regardless of the immunological status.

Tuberculosis (TB) is the leading cause of pleural exudative effusions. Inflammatory markers, such as IFNγ and ADA, have been used as proxies for its diagnosis. We evaluated ex vivo levels of several cytokines in 83 pleural effusion specimens from patients with TB (including 10 with HIV co-infection) and 26 patients with other pleuritis using multiplex and ELISA assays. IL-6 and IL-27 levels were higher (p ≤ 0.04) in TB patients, regardless of the HIV status and the approach. IL-2, IL-4, IL-8, IFNγ, TNF and G-CSF showed variable results depending on the assay. This warranty these markers to be further validated.

Caracterização da letalidade dos venenos de serpentes Bothrops jararaca e Crotalus durissus terrificus, por meio de ensaio em ovos embrionados de galinha

Em 2017, a Organização Mundial da Saúde voltou a considerar o ofidismo como uma doença tropical negligenciada de maior prioridade. As serpentes do gênero Bothrops têm destaque por serem responsáveis por mais de 90% dos acidentes ocorridos no Brasil. Já o gênero Crotalus apresenta um percentual de 7,7%, com letalidade maior nos acidentes crotálicos (1,87%) (Fundação Nacional de Saúde, 1988). O ensaio em ovos embrionados de galinha (OEG), representa um modelo in vivo, alternativo ao teste convencional em camundongos para teste de letalidade, sendo um método bastante eficaz e versátil para estudos pré-clínicos, podendo também atuar de forma complementar aos testes in vitro. Sendo assim, o presente estudo teve como objetivo analisar, por meio de ensaio em OEG, a determinação da letalidade induzida pelos venenos, obtidos do laboratório de Herpetologia do Instituto Butantan de Bothrops jararaca e Crotalus durissus terrificus. Foi feita a avaliação da aplicabilidade de doses desafio desses venenos para calcular a dose letal 50% (DL50). Nesta pesquisa, foram utilizados 300 ovos fertilizados de galinhas da linhagem Novogen White, SPF, em embriões de 6 e 7 dias de desenvolvimento. Os OEG foram incubados a 37oC e 62% de umidade relativa até o momento de inoculação. Nos OEG, foram inoculados na cavidade alantoide, os venenos de B. jararaca (VBj) as concentrações de VBj: 84,2 μg a 2,63125 μg/ovo e C. durissus terrificus (VCdt) as concentrações de VCdt: 5,74 μg a 0,179375 μg/ovo, tendo como grupos controles o crescimento de ovos sem qualquer inoculação (GC) e controles inoculados com salina (GS) em paralelo. Os embriões foram analisados por meio de ovoscopia manual, após os tempos de incubação, nos intervalos de 24 horas e 48 horas, para avaliação da função vascular. Foi realizada a inspeção macroscópica das lesões dos embriões mortos e registro fotográfico. Os resultados obtidos de dose letal 50% (DL50) em OEG no teste de VCdt foram de DL50=0,8035 μg/ovo nos embriões de 6 dias e DL50=0,09113 μg/ovo nos embriões de 7 dias de desenvolvimento. Já o teste para VBj os valores estimados de DL50 foram de DL50=21,91 μg/ovos nos embriões de 6 dias e DL50=24,37 μg /ovo em embriões de 7 dias de vida embrionária. Os valores de DL50 obtidos em OEG ao serem comparados com os valores de DL50 em camundongos, demostraram ter boa correspondência entres as metodologias. A partir do uso dessa técnica, verificou-se que os OEG podem ser utilizados como alternativo ao método convencional em camundongos.

Unraveling Transformative Effects after tDCS and BCI Intervention in Chronic Post-Stroke Patient Rehabilitation-An Alternative Treatment Design Study.

Stroke is a debilitating clinical condition resulting from a brain infarction or hemorrhage that poses significant challenges for motor function restoration. Previous studies have shown the potential of applying transcranial direct current stimulation (tDCS) to improve neuroplasticity in patients with neurological diseases or disorders. By modulating the cortical excitability, tDCS can enhance the effects of conventional therapies. While upper-limb recovery has been extensively studied, research on lower limbs is still limited, despite their important role in locomotion, independence, and good quality of life. As the life and social costs due to neuromuscular disability are significant, the relatively low cost, safety, and portability of tDCS devices, combined with low-cost robotic systems, can optimize therapy and reduce rehabilitation costs, increasing access to cutting-edge technologies for neuromuscular rehabilitation. This study explores a novel approach by utilizing the following processes in sequence: tDCS, a motor imagery (MI)-based brain-computer interface (BCI) with virtual reality (VR), and a motorized pedal end-effector. These are applied to enhance the brain plasticity and accelerate the motor recovery of post-stroke patients. The results are particularly relevant for post-stroke patients with severe lower-limb impairments, as the system proposed here provides motor training in a real-time closed-loop design, promoting cortical excitability around the foot area (Cz) while the patient directly commands with his/her brain signals the motorized pedal. This strategy has the potential to significantly improve rehabilitation outcomes. The study design follows an alternating treatment design (ATD), which involves a double-blind approach to measure improvements in both physical function and brain activity in post-stroke patients. The results indicate positive trends in the motor function, coordination, and speed of the affected limb, as well as sensory improvements. The analysis of event-related desynchronization (ERD) from EEG signals reveals significant modulations in Mu, low beta, and high beta rhythms. Although this study does not provide conclusive evidence for the superiority of adjuvant mental practice training over conventional therapy alone, it highlights the need for larger-scale investigations.

Assessment of inter-rater reliability of screening tools to identify patients at risk of medication-related problems across the emergency department continuum of care.

BACKGROUND: Following a national multicentre study, two emergency department (ED) screening tools were developed to determine risk of medication-related problems; one for use at ED presentation and another at ED discharge to the community. This study aimed to determine the inter-rater reliability amongst ED health professionals when applying these screening tools to a series of case scenarios. METHODS: A prospective, cross-sectional study was undertaken in the ED of a major metropolitan hospital. Twelve case scenarios were developed following ED observation of a range of patients, which were incorporated into a questionnaire and distributed to 50 health professionals. Inter-rater reliabilities of each explanatory variable of the screening tools and overall assessment were calculated using Fleiss' multi-rater kappa. RESULTS: The questionnaire was completed by 15 doctors, 19 nurses and 16 pharmacists. Fleiss' kappa showed an overall inter-rater reliability for the ED presentation tool of 0.83 (95% CI 0.83-0.84), indicating near perfect agreement. Fleiss' kappa for the ED discharge tool was 0.83 (95% CI 0.83-0.85), which also showed near perfect agreement. CONCLUSIONS: The screening tools produced favourable inter-rater reliability amongst ED health professionals. These results have important implications for ensuring consistency of ED decision-making in screening patients at risk of developing medication-related problems.

Development and Characterization of High-Absorption Microencapsulated Organic Propolis EPP-AF® Extract (i-CAPs).

The demand for organic and functional food continues to increase yearly. Among the available functional foods, propolis is a bee product that has various beneficial properties, including antimicrobial, antioxidant, and anti-inflammatory activities. However, it generally is only available in ethanol solution, which has poor bioavailability, as it is relatively insoluble in water. The use of such ethanol extracts is often objectionable because of the alcohol content and because they have a strong and striking taste. Development of alternatives that can efficiently and safely increase solubility in water, and that meet organic production specifications, has been a challenge. To address these concerns, microcapsules were developed using spray-dryer technology from an emulsion based on EPP-AF® propolis and gum arabic (i-CAPS). These propolis-loaded microcapsules were characterized using FT-IR, SEM, TGA, HPLC, and spectrophotometric techniques, along with determination of antimicrobial, antioxidant, antitumor, anti-inflammatory, and antihypercholesterolemic activities, as well as permeability in in vitro models. The production system resulted in microcapsules with a spherical shape and an encapsulation efficiency of 93.7 ± 0.7%. They had IC50s of 2.654 ± 0.062 and 7.342 ± 0.058 µg/mL by FRAP and DPPH antioxidant methods, respectively. The EPP-AF® i-CAPS also had superior antimicrobial activity against Gram-positive bacteria. Antitumor activity was calculated based on the concentration that inhibited 50% of growth of AGS, Caco-2, and MCF-7 cell strains, giving results of 154.0 ± 1.0, 117 ± 1.0, and 271.0 ± 25 µg/mL, respectively. The microcapsule presentation reduced the permeation of cholesterol by 53.7%, demonstrating antihypercholesterolemic activity, and it improved the permeability of p-coumaric acid and artepillin C. The IC50 for NO production in RAW 264.7 cells was 59.0 ± 0.1 µg/mL. These findings demonstrate the potential of this new propolis product as a food and pharmaceutical ingredient, though additional studies are recommended to validate the safety of proposed dosages.

Development and Characterization of New Green Propolis Extract Formulations as Promising Candidates to Substitute for Green Propolis Hydroalcoholic Extract.

The technologies used to produce the different dosage forms of propolis can selectively affect the original propolis compounds and their biological activities. The most common type of propolis extract is hydroethanolic. However, there is considerable demand for ethanol-free propolis presentations, including stable powder forms. Three propolis extract formulations were developed and investigated for chemical composition and antioxidant and antimicrobial activity: polar propolis fraction (PPF), soluble propolis dry extract (PSDE), and microencapsulated propolis extract (MPE). The different technologies used to produce the extracts affected their physical appearance, chemical profile, and biological activity. PPF was found to contain mainly caffeic and p-Coumaric acid, while PSDE and MPE showed a chemical fingerprint closer to the original green propolis hydroalcoholic extract used. MPE, a fine powder (40% propolis in gum Arabic), was readily dispersible in water, and had less intense flavor, taste, and color than PSDE. PSDE, a fine powder (80% propolis) in maltodextrin as a carrier, was perfectly water-soluble and could be used in liquid formulations; it is transparent and has a strong bitter taste. PPF, a purified solid with large amounts of caffeic and p-Coumaric acids, had the highest antioxidant and antimicrobial activity, and therefore merits further study. PSDE and MPE had antioxidant and antimicrobial properties and could be used in products tailored to specific needs.

Leishmanicidal and immunomodulatory properties of Brazilian green propolis extract (EPP-AF®) and a gel formulation in a pre-clinical model.

Leishmaniasis is a widespread group of neglected vector-borne tropical diseases that possess serious therapeutic limitations. Propolis has been extensively used in traditional medical applications due to its range of biological effects, including activity against infectious agents. Here we evaluated the leishmanicidal and immunomodulatory properties of Brazilian green propolis extract (EPP-AF®) and a gel formulation incorporating EPP-AF®, in both in vitro and in vivo models of Leishmania amazonensis infection. Propolis extract, obtained from a standardized blend following hydroalcoholic extraction, showed the characteristic fingerprint of Brazilian green propolis as confirmed by HPLC/DAD. A carbopol 940 gel formulation was obtained containing propolis glycolic extract at 3.6% w/w. The release profile, assessed using the Franz diffusion cell protocol, demonstrated a gradual and prolonged release of p-coumaric acid and artepillin C from the carbomer gel matrix. Quantification of p-coumaric acid and artepillin C in the gel formulation over time revealed that p-coumaric acid followed the Higuchi model, dependent on the disintegration of the pharmaceutical preparation, while artepillin C followed a zero-order profile with sustained release. In vitro analysis revealed the ability of EPP-AF® to reduce the infection index of infected macrophages (p < 0.05), while also modulating the production of inflammatory biomarkers. Decreases in nitric oxide and prostaglandin E2 levels were observed (p < 0.01), suggesting low iNOS and COX-2 activity. Furthermore, EPP-AF® treatment was found to induce heme oxygenase-1 antioxidant enzyme expression in both uninfected and L. amazonensis-infected cells, as well as inhibit IL-1ß production in infected cells (p < 0.01). ERK-1/2 phosphorylation was positively correlated with TNF-α production (p < 0.05), yet no impact on parasite load was detected. In vivo analysis indicated the effectiveness of topical treatment with EPP-AF® gel alone (p < 0.05 and p < 0.01), or in combination with pentavalent antimony (p < 0.05 and p < 0.001), in the reduction of lesion size in the ears of L. amazonensis-infected BALB/c mice after seven or 3 weeks of treatment, respectively. Taken together, the present results reinforce the leishmanicidal and immunomodulatory effects of Brazilian green propolis, and demonstrate promising potential for the EPP-AF® propolis gel formulation as a candidate for adjuvant therapy in the treatment of Cutaneous Leishmaniasis.

Novel Dual AChE and ROCK2 Inhibitor Induces Neurogenesis via PTEN/AKT Pathway in Alzheimer's Disease Model.

Alzheimer's disease (AD) is a progressive and complex neurodegenerative disease. Acetylcholinesterase inhibitors (AChEIs) are a major class of drugs used in AD therapy. ROCK2, another promising target for AD, has been associated with the induction of neurogenesis via PTEN/AKT. This study aimed to characterize the therapeutic potential of a novel donepezil-tacrine hybrid compound (TA8Amino) to inhibit AChE and ROCK2 protein, leading to the induction of neurogenesis in SH-SY5Y cells. Experiments were carried out with undifferentiated and neuron-differentiated SH-SY5Y cells submitted to treatments with AChEIs (TA8Amino, donepezil, and tacrine) for 24 h or 7 days. TA8Amino was capable of inhibiting AChE at non-cytotoxic concentrations after 24 h. Following neuronal differentiation for 7 days, TA8Amino and donepezil increased the percentage of neurodifferentiated cells and the length of neurites, as confirmed by ß-III-tubulin and MAP2 protein expression. TA8Amino was found to participate in the activation of PTEN/AKT signaling. In silico analysis showed that TA8Amino can stably bind to the active site of ROCK2, and in vitro experiments in SH-SY5Y cells demonstrate that TA8Amino significantly reduced the expression of ROCK2 protein, contrasting with donepezil and tacrine. Therefore, these results provide important information on the mechanism underlying the action of TA8Amino with regard to multi-target activities.

Pomegranate Extract Potentiates the Anti-Demineralizing, Anti-Biofilm, and Anti-Inflammatory Actions of Non-Alcoholic Mouthwash When Associated with Sodium-Fluoride Trimetaphosphate.

This study investigated the anti-caries and anti-inflammatory effects of mouthwash formulations containing Punica granatum (pomegranate) peel extract (PPE), sodium-trimetaphosphate, and low concentrations of fluoride. PPE was characterized using high-performance liquid chromatography (ellagic acid and punicalagin). Total phenolics were quantified among formulations, and their stability was analyzed for 28 days. The formulation effects were evaluated as follows: (1) inorganic component concentration and reduced demineralization on bovine enamel blocks subjected to pH cycling; (2) anti-biofilm effect on dual-biofilms of Streptococcus mutans ATCC 25175 and Candida albicans ATCC 10231 treated for 1 and 10 min, respectively; and (3) cytotoxicity and production of inflammatory mediators (interleukin-6 and tumor necrosis factor-alpha). The formulation containing 3% PPE, 0.3% sodium-trimetaphosphate, and 225 ppm of fluoride resulted in a 34.5% surface hardness loss; a 13% (treated for 1 min) and 36% (treated for 10 min) biofilm reduction in S. mutans; a 26% (1 min) and 36% (10 min) biofilm reduction in C. albicans; absence of cytotoxicity; and anti-inflammatory activity confirmed by decreased interleukin-6 production in mouse macrophages. Thus, our results provide a promising prospect for the development of an alcohol-free commercial dental product with the health benefits of P. granatum that have been recognized for a millennium.

Physiotherapy in lymphangioleiomyomatosis: a systematic review.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is associated with progressive dyspnoea and exercise intolerance, but despite the central role of physiotherapy on pulmonary rehabilitation, there is a huge lack of physiotherapy approaches used specifically for LAM patients. OBJECTIVE: to identify the physiotherapeutic strategies used in the treatment of patients with LAM. MATERIALS AND METHODS: This is a systematic review of literature. Searches were performed (in PubMed, Lilacs, Embase and PEDro databases) with the keywords "Lymphangioleiomyomatosis" and "Physiotherapy," and its variations. Articles describing physiotherapy interventions were included in the study. Data extracted from the studies were authors, year, country of publication, sample size, physiotherapy intervention, time/frequency/duration of intervention protocols, instruments used to measure results and main findings. Methodological quality of studies was evaluated by PEDro Scale (clinical trials), Newcastle-Ottawa Scale (NOS; observational studies) and CARE checklist (case reports), respectively. RESULTS: A total of 82 articles identified, three duplicates were removed, 71 studies were excluded after title and abstract reading and four after full-text reading, all due to absence of association with the study topic. Four studies were included in the present review. Cardiorespiratory physiotherapy with endurance and resistance training were identified as physiotherapeutic strategies to improve lung function, functional capacity, depression symptoms and quality of life in LAM. CONCLUSIONS: Endurance and resistance training is the keystone for physiotherapy in patients with LAM, but despite the reported benefits, there is a huge lack of studies related to the modalities, safety and dosage of physiotherapy prescription for patients with LAM.KEY MESSAGESLymphangioleiomyomatosis (LAM), a rare disease, leads to progressive dyspnoea and exercise intolerance;Physiotherapy can improve dyspnoea and exercise intolerance in LAM through endurance and resistance exercises.

Structural plasticity in roots of the hemiepiphyte Vanilla phaeantha Rchb.f. (Orchidaceae): a relationship between environment and function.

The aerial environment appears to structurally modify roots, which frequently show specializations for absorbing water and nutrients. Among those specializations are the velamen, a multiseriate epidermis generally composed of dead mature cells, and greater degrees of lignification in the endodermis, exodermis, and pith. Vanilla phaeantha is a hemiepiphyte used here as a model of study to determine which root characteristics demonstrate the most plasticity in response to aerial and terrestrial environments. It produces roots growing under three conditions: (1) aerial and free, growing from the highest branches towards the ground; (2) aerial roots attached to the phorophyte; and (3) terrestrial. Samples taken 3 cm from the apices were used to prepare histological slides. The tissues and other anatomical structures were measured and histochemically characterized. The most plastic characteristics were the external periclinal thicknesses of the exodermis and the total area occupied by the aerenchyma lacunae. The free roots were the longest, did not evidence root hairs, and had the largest number of the aerenchyma lacunae; they also evidenced greater thicknesses of the exodermis in contact with the epidermis walls that helped maintain their shapes. Terrestrial roots had root hairs around the entire circumference and intense infestations of mycorrhiza, indicating their involvement in nutrient acquisition. The adhering roots evidenced free regions similar to those of aerial roots, as well as adhering regions showed characteristics similar to terrestrial roots (with root hairs and mycorrhiza infestations).

Cytotoxic CD4+ T cells driven by T-cell intrinsic IL-18R/MyD88 signaling predominantly infiltrate Trypanosoma cruzi-infected hearts.

Increasing attention has been directed to cytotoxic CD4+ T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite Trypanosoma cruzi. CD4CTLs display parallel kinetics to Th1 cells in the spleen, mediate specific cytotoxicity against cells presenting pathogen-derived antigens and express immunoregulatory and/or exhaustion markers. We demonstrate that CD4CTL absolute numbers and activity are severely reduced in both Myd88-/- and Il18ra-/- mice. Of note, the infection of mixed-bone marrow chimeras revealed that wild-type (WT) but not Myd88-/- cells transcribe the CD4CTL gene signature and that Il18ra-/- and Myd88-/- CD4+ T cells phenocopy each other. Moreover, adoptive transfer of WT CD4+GzB+ T cells to infected Il18ra-/- mice extended their survival. Importantly, cells expressing the CD4CTL phenotype predominate among CD4+ T cells infiltrating the infected mouse cardiac tissue and are increased in the blood of Chagas patients, in which the frequency of CD4CTLs correlates with the severity of cardiomyopathy. Our findings describe CD4CTLs as a major player in immunity to a relevant human pathogen and disclose T-cell intrinsic IL-18R/MyD88 signaling as a key pathway controlling the magnitude of the CD4CTL response.

Neuroprotective Effects of Cholinesterase Inhibitors: Current Scenario in Therapies for Alzheimer's Disease and Future Perspectives.

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease conceptualized as a continuous process, ranging from mild cognitive impairment (MCI), to the mild, moderate, and severe clinical stages of AD dementia. AD is considered a complex multifactorial disease. Currently, the use of cholinesterase inhibitors (ChEI), such as tacrine, donepezil, rivastigmine, and galantamine, has been the main treatment for AD patients. Interestingly, there is evidence that ChEI also promotes neuroprotective effects, bringing some benefits to AD patients. The mechanisms by which the ChEI act have been investigated in AD. ChEI can modulate the PI3K/AKT pathway, which is an important signaling cascade that is capable of causing a significant functional impact on neurons by activating cell survival pathways to promote neuroprotective effects. However, there is still a huge challenge in the field of neuroprotection, but in the context of unravelling the details of the PI3K/AKT pathway, a new scenario has emerged for the development of more efficient drugs that act on multiple protein targets. Thus, the mechanisms by which ChEI can promote neuroprotective effects and prospects for the development of new drug candidates for the treatment of AD are discussed in this review.

Intervenção com o método Pilates em trabalhadores com LER/DORT / Intervention with the Pilates method in workers with RSI/WMSD

O presente estudo é do tipo quase experimental e teve como objetivo verificar os efeitos da intervenção com o Método Pilates (MP) na presença e intensidade dos sintomas musculoesqueléticos, na força de preensão palmar e na flexibilidade toracolombar de trabalhadores com lesões por esforços repetitivos/distúrbios osteomusculares relacionados ao trabalho (LER/DORT). Participaram trabalhadores encaminhados para atendimento fisioterapêutico a um serviço municipal de nível secundário de atenção à saúde. Foi disponibilizada aos pesquisadores uma lista com 605 usuários com diagnóstico de afecções musculoesqueléticas (sem referência se as afecções tinham ou não relação com o trabalho). Realizou-se contato telefônico para identificar quais eram trabalhadores, convidando-os a participar da pesquisa. Os 244 trabalhadores que aceitaram foram agendados; e, destes, 166 compareceram, sendo avaliados os aspectos sociodemográficos, ocupacionais, história clínica detalhada, sintomas musculoesqueléticos e exame físico, permitindo o estabelecimento do nexo causal (diagnóstico de LER/DORT) para 142 desses trabalhadores. Destes, 17 apresentaram disponibilidade para participar da intervenção nos dias e horários disponibilizados para a aplicação do MP. O protocolo foi constituído por 12 exercícios, por seis semanas, com duração de 60 minutos. Os resultados do MP foram significantes (p<0,05) na redução do número de trabalhadores com sintomas nas regiões dos ombros e punhos/mãos, redução significante da intensidade dos sintomas em oito das nove regiões corporais avaliadas e aumento significante da força da mão não dominante. O MP proporcionou efeitos positivos na redução dos sintomas das LER/DORT.

The aim of the present quasi-experimental study was to verify the effects of intervention with the Pilates Method (PM) on the presence and intensity of musculoskeletal symptoms, handgrip strength and thoracolumbar flexibility of workers with Repetitive Strain Injuries/Musculoskeletal Disorders Work Related (LER/DORT). Workers referred for physical therapy care to a municipal service at the secondary level of health care participated. A list of 605 users with a diagnosis of musculoskeletal disorders was made available to the researchers (without reference to whether the disorders were related to work or not). Telephone contact was made to identify which workers were, inviting them to participate in the research. The 244 workers who accepted were scheduled and, of these, 166 attended, and the sociodemographic, occupational, detailed medical history, musculoskeletal symptoms and physical examination were evaluated, allowing the establishment of the causal link (RSI/WMSD diagnosis) for 142 of these workers. Of these, 17 were available to participate in the intervention on the days and times available for the application of the MP. The protocol consisted of 12 exercises, for six weeks, lasting 60 minutes. The MP results were significant for a reduction in the number of workers with symptoms for the shoulder and wrist/hand regions, a significant reduction in the intensity of symptoms for eight of the nine body regions evaluated, and a significant increase in the strength of the non-dominant hand. MP provided positive effects in reducing RSI/WMSD symptoms.

Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia.

Type 2 diabetes (T2D) is a complex multifactorial disease that emerges from the combination of genetic and environmental factors, and obesity, lifestyle, and aging are the most relevant risk factors. Hyperglycemia is the main metabolic feature of T2D as a consequence of insulin resistance and ß-cell dysfunction. Among the cellular alterations induced by hyperglycemia, the overproduction of reactive oxygen species (ROS) and consequently oxidative stress, accompanied by a reduced antioxidant response and impaired DNA repair pathways, represent essential mechanisms underlying the pathophysiology of T2D and the development of late complications. Mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation are also closely correlated with insulin resistance and ß-cell dysfunction. This review focus on the mechanisms by which oxidative stress, mitochondrial dysfunction, ER stress, and inflammation are involved in the pathophysiology of T2D, highlighting the importance of the antioxidant response and DNA repair mechanisms counteracting the development of the disease. Moreover, we indicate evidence on how nutritional interventions effectively improve diabetes care. Additionally, we address key molecular characteristics and signaling pathways shared between T2D and Alzheimer's disease (AD), which might probably be implicated in the risk of T2D patients to develop AD.

Dioctophyme renale in wandering dogs in Pelotas, South of Brasil.

This study aimed to verify the occurrence of Dioctophyme renale in stray dogs in the city of Pelotas, in the state of Rio Grande do Sul, Brazil. The Laboratório Regional de Diagnóstico of the Universidade Federal de Pelotas received 146 wandering dogs for necropsy, sent by the City Hall of Pelotas from March 2012 to January 2020. Among the necropsied animals, seventeen dogs (11.64%) were diagnosed with dioctophymosis. Among these dogs, 11 were parasitized with one specimen in the right kidney, two dogs presented two specimens in the right kidney, and in other two dogs, the parasites were in the abdominal cavity. In one dog, two parasites were found in the left kidney; in another dog, both kidneys were parasitized, with two parasites in the right kidney and one in the left kidney. The data obtained in this study showed that the occurrence of D. renale in stray dogs in the city of Pelotas is high, and D. renale mainly parasitizes the right kidney.

Transcript Expression Profiles and MicroRNA Regulation Indicate an Upregulation of Processes Linked to Oxidative Stress, DNA Repair, Cell Death, and Inflammation in Type 1 Diabetes Mellitus Patients.

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing ß-cells leading to impaired insulin secretion and hyperglycemia. T1D is accompanied by DNA damage, oxidative stress, and inflammation, although there is still scarce information about the oxidative stress response and DNA repair in T1D pathogenesis. We used the microarray method to assess mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of 19 T1D patients compared to 11 controls and identify mRNA targets of microRNAs that were previously reported for T1D patients. We found 277 differentially expressed genes (220 upregulated and 57 downregulated) in T1D patients compared to controls. Analysis by gene sets (GSA and GSEA) showed an upregulation of processes linked to ROS generation, oxidative stress, inflammation, cell death, ER stress, and DNA repair in T1D patients. Besides, genes related to oxidative stress responses and DNA repair (PTGS2, ATF3, FOSB, DUSP1, and TNFAIP3) were found to be targets of four microRNAs (hsa-miR-101, hsa-miR148a, hsa-miR-27b, and hsa-miR-424). The expression levels of these mRNAs and microRNAs were confirmed by qRT-PCR. Therefore, the present study on differential expression profiles indicates relevant biological functions related to oxidative stress response, DNA repair, inflammation, and apoptosis in PBMCs of T1D patients relative to controls. We also report new insights regarding microRNA-mRNA interactions, which may play important roles in the T1D pathogenesis.

Combined training increases thermogenic fat activity in patients with overweight and type 2 diabetes.

BACKGROUND: Exercise is an important strategy in the management of diabetes. Experimental studies have shown that exercise acts, at least in part, by inducing the production of myokines that improve metabolic control and activate brown/beige adipose tissue depots. Combined training (CT) is recommended by the major diabetes guidelines due to its metabolic and cardiovascular benefits, however, its impact on brown/beige adipose tissue activities has never been tested in humans with overweight and type 2 diabetes (T2D). Here, we evaluated the effects of 16-week combined training (CT) program on brown adipose tissue activity; browning and autophagy markers, and serum pro-thermogenic/inflammatory inducers in patients with overweight and T2D. METHODS: Thirty-four patients with overweight and T2D were assigned to either a control group (CG) or a combined training group (CTG) in a randomized and controlled study. Functional/fitness parameters, anthropometry/body composition parameters, blood hormone/biochemical parameters, thermogenic/autophagic gene expression in subcutaneous adipose tissue were evaluated before and at the end of the intervention. In addition, cold-induced 18-Fluoroxyglucose Positron Emission Computed Tomography (18F-FDG PET/CT) was performed in the training group before and after the end of the intervention. RESULTS: CT increased cervical/supraclavicular brown adipose tissue (BAT) thermogenic activity (p = 0.03) as well as in perirenal adipose tissue (p = 0.02). In addition, CT increased the expression of genes related to thermogenic profile (TMEM26: + 95%, p = 0.04; and EPSTI1: + 26%, p = 0.03) and decreased autophagic genes (ULK1: -15%, p = 0.04; LC3: -5%, p = 0.02; and ATG4: -22%, p < 0.001) in subcutaneous adipose tissue. There were positive correlations between Δ% BAT activity with Δ% of post training energy expenditure cold exposure, HDL-c, IL4, adiponectin, irisin, meteorin-like, and TMEM26 and ZIC1 genes, besides negative correlations with LDL-c, total cholesterol and C-reactive protein. CONCLUSION: This is the first evidence of the beneficial actions of CT on adipose tissue thermogenic activity in humans, and it adds important support for the recommendation of CT as a strategy in the management of diabetes.

Caracterização da força e da função muscular nas disferlinopatias em amostra brasileira / Characterization of muscle strength and function in dysferlinopathy in a Brazilian sample

Estudo de caracterização da força e da função muscular nas disferlinopatias para estabelecer biomarcadores de habilidades motoras com amostra de 40 pacientes, tendo sido avaliados força muscular (Medical Research Council - MRC), percentual de MRC, tempo de execução para deambular e escores nas Escalas de Vignos, Egen Klassifikation, Avaliação Funcional para Distrofia Muscular de Duchenne (FES-DMD) e North Star Ambulatory Assessment adaptada. Prevalência da disferlinopatia de 25,5% na amostra total de distrofias (1340), idade média de 36,5 anos, 52,5% do sexo masculino e 75% deambuladores. Músculos mais fracos: abdominal, glúteos, íliopsoas, isquiotibial, quadríceps femoral, tibial anterior e deltoide médio. Correlação forte entre MRC e tempo para deambular (r = 0,77) e, muito forte da MRC distal de membros inferiores com aNSAA (r = 0,90). Interação da MRC dos membros superiores e inferiores nos segmentos proximal e distal (p < 0,001), sendo mais evidente em membros superiores que inferiores. Taxa variável de progressão da doença com 60% dos pacientes moderadamente ou gravemente afetados, com mais de 12 anos de doença. Estudo mostra que padrão de fraqueza muscular dos brasileiros com disferlinopatia é proximal e distal dos MMII, com comprometimento associado da região proximal dos MMSS, além de elucidar as habilidades motoras em relação ao processo de locomoção e disfunções cardiorrespiratórias. (AU).