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Abstract Background Distal femur osteotomies are a well known and valuable treatment option to manage valgus malalignment with unicompartmental arthritis. Early postoperative complications are well known, and risk factors, such as pulmonary diseases, smoke, high dependent functional status, and body mass index, have been studied, but no study is available about osteotomies when gait is abnormal because of neurodegenerative conditions or when mineral density is below the normal rate. Case presentation We report the case of a 44 year-old female Mediterranean patient who underwent a biplanar distal femur opening wedge osteotomy surgery following a lateral meniscus total removal, which led to the subsequent development of lateral compartment osteoarthritis and pain, despite general comorbidities, such as multiple sclerosis. Additionally, 2 months later a supracondylar femur fracture above the previously applied Tomofix® plate was reported. Fracture was treated by applying a LCP condylar 16 hole (336 mm) plate, a structural fibular graft, and strut fibular graft on the opposite side. Conclusion The overall aim of this case report is to provide a lesson to surgeons who want to perform a realignment surgery of the lower limb in patients with abnormal gait. Not only mechanical axes are to be considered, but also bone density, patient’s gait, and load force distribution along the bone stock. Emerging literature on three-dimensional cutting guides fails to account for these factors, thus promoting a standardized approach to surgery across all patients. The present case highlights a patient with low bone density and abnormal force distribution resulting from a pathologic neurodegenerative gait. In such cases, treatment decisions must carefully consider the biomechanical vulnerabilities of the native bone and the distribution of vector forces. These conditions must lead the choice toward a longer plate if an osteotomy is indicated, because surgery is more likely to fail.

Abstract Extracellular vesicles (EVs) are a new mechanism of cellular communication, by delivering their cargo into target cells to modulate molecular pathways. EV-mediated crosstalk contributes to tumor survival and resistance to cellular stress. However, the role of EVs in B-cell Acute Lymphoblastic Leukaemia (B-ALL) awaits to be thoroughly investigated. We recently published that ActivinA increases intracellular calcium levels and promotes actin polymerization in B-ALL cells. These biological processes guide cytoskeleton reorganization, which is a crucial event for EV secretion and internalization. Hence, we investigated the role of EVs in the context of B-ALL and the impact of ActivinA on this phenomenon. We demonstrated that leukemic cells release a higher number of EVs in response to ActivinA treatment, and they can actively uptake EVs released by other B-ALL cells. Under culture-induced stress conditions, EVs coculture promoted cell survival in B-ALL cells in a dose-dependent manner. Direct stimulation of B-ALL cells with ActivinA or with EVs isolated from ActivinA-stimulated cells was even more effective in preventing cell death. This effect can be possibly ascribed to the increase of vesiculation and modifications of EV-associated microRNAs induced by ActivinA. These data demonstrate that ActivinA boosts EV-mediated B-ALL crosstalk, improving leukemia survival in stress conditions.

Introduction Addressing childhood obesity risk factors like home environment, parental roles, excess weight, physical activity and healthy eating among Latino/Hispanic (L/H) families living in rural communities is an important priority. However, evidence supporting these interventions among L/H families living in rural communities is missing. Our trial will use cultural adaptation and implementation science frameworks to evaluate the feasibility of delivering a culturally appropriate family-based childhood obesity (FBCO) programme via an automated telephone system (interactive voice response) to L/H families in rural Nebraska.Methods and analysis A mixed-methods feasibility trial for L/H families with overweight or obese children. Aim 1 will focus on collaboratively adapting and evaluating all intervention materials to fit the rural L/H community profile better, including translation of materials to Spanish, culturally relevant content and images, and use of health communication strategies to address different levels of health literacy. In aim 2, a 6-month feasibility trial with contextual evaluation will randomise 48 dyads (parent and child) to either Family Connections (FC; n=29) or a waitlist standard-care group (n=29) to determine overall study reach, preliminary effectiveness in reducing child body mass index (BMI) z-scores, potential for programme adoption, implementation and sustainability through local health departments (RE-AIM outcomes). We will also evaluate health department perceptions of the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) constructs (innovation, context, recipient characteristics) and FC participants’ view of the intervention (ie, relative advantage, observability, trialability, complexity, compatibility). The study will answer three critical questions: (1) is a telephone-delivered FBCO programme in rural Nebraska culturally relevant, usable and acceptable by L/H families?; (2) is a telephone-delivered FBCO programme effective at reducing BMI z-scores in L/H children living in rural Nebraska? and (3) what real-world institutional and contextual factors influence the impact of the intervention and might affect its potential ability to sustainably engage a meaningful population of L/H families who stand to benefit?Ethics and dissemination This protocol was approved by the University of Nebraska Medical Center Institutional Review Board (IRB#:0745-20-EP). Dissemination of findings will occur through ClinicalTrials.gov, in scientific forums and to the local rural communities, pilot data to inform the design of a larger clinical trial.Trial registration number NCT04731506.

Resumen: La apnea obstructiva del sueño (AOS) es una enfermedad frecuente que produce síntomas diurnos, deterioro en la calidad de vida, mayor riesgo de morbi-mortalidad cardio y cerebrovascular, deterioro neuro cognitivo y mayor accidentabilidad de tránsito. La terapia con presión positiva continua en la vía aérea (CPAP) es altamente eficaz y ha sido el tratamiento de elección en los pacientes con enfermedad grave y aquellos con enfermedad moderada con síntomas diurnos y/o comorbilidad cardiovascular, sin embargo, la CPAP tiene limitaciones en términos de aceptación y adherencia al tratamiento. Existen diversas opciones de tratamiento, como la pérdida de peso, el uso de dispositivos orales, medidas posturales, cirugía y la terapia miofuncional. Estos tratamientos personalizados han demostrado buenos resultados, especialmente en pacientes con AOS leve a moderada o en aquellos que buscan alternativas efectivas al tratamiento convencional. Se reconoce cada vez más que la AOS es un trastorno multifactorial con diversas presentaciones clínicas, fisiopatología y comorbilidades. Una mejor comprensión de la heterogeneidad de los pacientes permitirá enfoques de tratamiento más personalizados y garantizará la efectividad de las intervenciones mediante una medicina avanzada y de precisión. Esta revisión proporciona una descripción de los enfoques actuales para el tratamiento no quirúrgico de la AOS leve a moderada en pacientes sin indicación de tratamiento con CPAP o que rechazan dicha opción, además de proponer un algoritmo terapéutico para orientar el manejo de estos pacientes. Abstract: Obstructive sleep apnea (OSA) is a common disease that causes daytime symptoms, decreased quality of life, increased risk of cardio and cerebrovascular morbidity and mortality, neurocognitive impairments, and higher traffic accident rates. Continuous positive airway pressure therapy (CPAP) is highly effective and has been the treatment of choice for patients with severe disease and those with moderate disease accompanied by daytime symptoms and/or cardiovascular comorbidity. However, CPAP has limitations in terms of acceptance and treatment adherence. There are various treatment options available, such as weight loss, the use of oral devices, positional devices, surgery and emerging therapies like myofunctional therapy. These personalized treatments have shown promising results, particularly in patients with mild to moderate OSA or those seeking an effective alternative to standard treatment. It is increasingly recognized that OSA is a disorder with diverse risk factors, clinical presentations, pathophysiology, and comorbidities. A better understanding of patient heterogeneity will allow for more personalized treatment approaches and ensure the effectiveness of interventions through advanced and precision medicine. This review provides an overview of current approaches to non-surgical treatment of mild to moderate OSA in patients without an indication for CPAP treatment or who reject that option. Additionally, it proposes a therapeutic algorithm to guide the management of these patients.

Abstract Bladder cells face a challenging biophysical environment: mechanical cues originating from urine flow and regular contraction to enable the filling voiding of the organ. To ensure functional adaption, bladder cells rely on high biomechanical compliance, nevertheless aging or chronic pathological conditions can modify this plasticity. Obviously the cytoskeletal network plays an essential role, however the contribution of other, closely entangled, intracellular organelles is currently underappreciated. The endoplasmic reticulum (ER) lies at a crucial crossroads, connected to both nucleus and cytoskeleton. Yet, its role in the maintenance of cell mechanical stability is less investigated. To start exploring these aspects, T24 bladder cancer cells were treated with the ER stress inducers brefeldin A (10-40nM BFA, 24 h) and thapsigargin (0.1-100nM TG, 24 h). Without impairment of cell motility and viability, BFA and TG triggered a significant subcellular redistribution of the ER; this was associated with a rearrangement of actin cytoskeleton. Additional inhibition of actin polymerization with cytochalasin D (100nM CytD) contributed to the spread of the ER toward cell periphery, and was accompanied by an increase of cellular stiffness (Young´s modulus) in the cytoplasmic compartment. Shrinking of the ER toward the nucleus (100nM TG, 2 h) was related to an increased stiffness in the nuclear and perinuclear areas. A similar short-term response profile was observed also in normal human primary bladder fibroblasts. In sum, the ER and its subcellular rearrangement seem to contribute to the mechanical properties of bladder cells opening new perspectives in the study of the related stress signaling cascades. Video Abstract

Abstract Machine learning has become a popular tool for learning models of complex dynamics from biomedical data. In Type 1 Diabetes (T1D) management, these models are increasingly been integrated in decision support systems (DSS) to forecast glucose levels and provide preventive therapeutic suggestions, like corrective insulin boluses (CIB), accordingly. Typically, models are chosen based on their prediction accuracy. However, since patient safety is a concern in this application, the algorithm should also be physiologically sound and its outcome should be explainable. This paper aims to discuss the importance of using tools to interpret the output of black-box models in T1D management by presenting a case-of-study on the selection of the best prediction algorithm to integrate in a DSS for CIB suggestion. By retrospectively “replaying” real patient data, we show that two long-short term memory neural networks (LSTM) (named p-LSTM and np-LSTM) with similar prediction accuracy could lead to different therapeutic decisions. An analysis with SHAP—a tool for explaining black-box models’ output—unambiguously shows that only p-LSTM learnt the physiological relationship between inputs and glucose prediction, and should therefore be preferred. This is verified by showing that, when embedded in the DSS, only p-LSTM can improve patients’ glycemic control.

Abstract This study aimed to assess the impact of a commercial blend of functional oils, specifically cashew nutshell liquid and castor oil (FO), in two physical forms (solid: P; liquid: S), in comparison to a combination of virginiamycin and anticoccidials on the gut health of broilers challenged with coccidiosis. A total of 1760 1-day-old male chicks were randomly distributed in a study design with eight treatments. The treatments included: a control group (without additive), OFS_0.75_kg/t (FO spray), OFP_1.0_kg/t (FO powder), OFP_1.5_kg/t (FO liquid spray), Sal (anticoccidials), Sal_Vir (virginiamycin and anticoccidials), Sal_OFS_0.5_ kg/t (anticoccidials plus FO spray), and Sal_OFP_1.0_kg/t (anticoccidials plus FO powder). All birds were challenged with Eimeria spp. at 14 days. The physical form of FO did not affect performance and intestinal health parameters. At 42 days, broilers from the control and OFS_0.75 treatments were the lightest, while those from the Sal_Vir and Sal_OFP_1.0 treatments were the heaviest (P

A new series of compounds planned by molecular hybridization of the nucleobases uracil and thymine, or the xanthine theobromine, with coumarins, and linked through 1,2,3-triazole heterocycles were evaluated for their in vitro anticancer activity against the human tumor cell lines: colon carcinoma (HCT116), laryngeal tumor cells (Hep-2), and lung carcinoma cells (A549). The hybrid compound 9a exhibited better activity in the series, showing an IC50 of 24.19 ± 1.39 μM against the HCT116 cells, with a selectivity index (SI) of 6, when compared to the cytotoxicity against the non-tumor cell line HaCat. The in silico search for pharmacological targets was achieved through molecular docking studies on all active compounds, which suggested that the synthesized compounds possess a high affinity to the Topoisomerase 1–DNA complex, supporting their antitumor activity. The in silico toxicity prediction studies suggest that the compounds present a low risk of causing theoretical mutagenic and tumorigenic effects. These findings indicate that molecular hybridization from natural derivative molecules is an interesting approach to seek new antitumor candidates.

Abstract Background Extracellular vesicles (EVs) from Gram-positive bacteria have gained considerable importance as a novel transport system of virulence factors in host–pathogen interactions. Bacillus cereus is a Gram-positive human pathogen, causing gastrointestinal toxemia as well as local and systemic infections. The pathogenicity of enteropathogenic B. cereus has been linked to a collection of virulence factors and exotoxins. Nevertheless, the exact mechanism of virulence factor secretion and delivery to target cells is poorly understood. Results Here, we investigate the production and characterization of enterotoxin-associated EVs from the enteropathogenic B. cereus strain NVH0075-95 by using a proteomics approach and studied their interaction with human host cells in vitro. For the first time, comprehensive analyses of B. cereus EV proteins revealed virulence-associated factors, such as sphingomyelinase, phospholipase C, and the three-component enterotoxin Nhe. The detection of Nhe subunits was confirmed by immunoblotting, showing that the low abundant subunit NheC was exclusively detected in EVs as compared to vesicle-free supernatant. Cholesterol-dependent fusion and predominantly dynamin-mediated endocytosis of B. cereus EVs with the plasma membrane of intestinal epithelial Caco2 cells represent entry routes for delivery of Nhe components to host cells, which was assessed by confocal microscopy and finally led to delayed cytotoxicity. Furthermore, we could show that B. cereus EVs elicit an inflammatory response in human monocytes and contribute to erythrocyte lysis via a cooperative interaction of enterotoxin Nhe and sphingomyelinase. Conclusion Our results provide insights into the interaction of EVs from B. cereus with human host cells and add a new layer of complexity to our understanding of multicomponent enterotoxin assembly, offering new opportunities to decipher molecular processes involved in disease development. Video Abstract

Abstract Cholangiocarcinoma (CCA) is a rare cancer characterized by a global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Of note, higher dihydroceramide content was associated with vascular invasion. Cancer-derived EVs induced the release of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory activity of iCCA-derived EVs, demonstrating a role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may promote iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.

Abstract Cannabidiol (CBD) is a substance derived from Cannabis sativa, widely studied in medicine for controlling neural diseases in humans. Besides the positive effects on humans, it also presents anxiolytic proprieties and decreases aggressiveness and stress in mammals. Therefore, CBD has the potential to increase welfare in reared animals, as it seems to reduce negative states commonly experienced in artificial environments. Here, we tested the effect of different CBD doses (0, 1, 10 and 20 mg/kg) on aggressiveness, stress and reproductive development of the Nile tilapia (Oreochromis niloticus) a fish reared worldwide for farming and research purposes. CBD mixed with fish food was offered to isolated fish for 5 weeks. The 10 mg/kg dose decreased fish’s aggressiveness over time, whereas 20 mg/kg attenuated non-social stress. Both doses decreased the baseline cortisol level of fish and increased the gonadosomatic index. However, CBD 1 and 10 mg/kg doses decreased the spermatozoa number. No CBD dose affected feeding ingestion and growth variables, showing that it is not harmful to meat production amount. Despite the effect on spermatozoa, CBD supplementation exhibits high potential to benefit animals’ lives in artificial environments. Therefore, we showed for the first time that CBD could be used as a tool to increase non-mammal welfare, presenting a great potential to be explored in other husbandry and captivity species.

Objetivo: analisar as principais características dos aplicativos móveis, disponíveis em lojas virtuais, que tratam sobre a temática da realização de procedimentos cirúrgicos. Método: Prospecção tecnológica, de abordagem qualitativa do tipo exploratória, realizada por busca de aplicativos nas lojas virtuais Apple Store® e Google Play®, utilizando as palavras-chave: Centro Cirúrgico, Cirurgia, Simulador de cirurgia e Jogos de cirurgia, em português, inglês e espanhol. Realizou-se análise temática categorial dos achados. Resultados: 67 ocorrências foram classificadas em quatro categorias: ‘Aplicativos destinados à orientação para procedimento cirúrgico’, ‘Aplicativos sobre o trabalho em centro cirúrgico’, ‘Aplicativos voltados à equipe de saúde’, e ‘Aplicativos relacionados a jogos de entretenimento’. Considerações finais: os aplicativos voltam-se tanto para indivíduos que buscam orientações sobre procedimentos, quanto a profissionais da área da saúde. No entanto, há uma lacuna referente à orientações pré-operatórias específicas para pediatria, onde nenhuma ocorrência foi registrada.

Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Available therapy causes severe side effects, has unacceptable prices for some specific formulations, and the existence of drug-resistant parasites limits the use of the currently available arsenal of antiparasitic drugs. Therefore, natural products serve as one of the main sources to develop new and effective alternative drugs against leishmaniasis. In this sense, the present study evaluated the potential of the triterpene Lupeol (Lu) entrapped in nanostructured lipid carriers (NLCs) for the treatment of experimental visceral leishmaniasis. The therapeutic efficacy of Lu or Lu entrapped in NLC (Lu-NLC) was investigated in golden hamsters infected with Leishmania (Leishmania) infantum. Lu-NLC presented a mean particle size of 265.3 ± 4.6 nm, a polydispersity index of Leishmania IgG2 isotype. These data indicate that NLC potentialized Lu efficacy in experimental visceral leishmaniasis. This work suggests that Lu and nanoformulations carrying this compound may be considered as an important tool to be included in the alternative therapy of leishmaniasis.

Humans are constantly exposed to mixtures of different xenobiotics through their diet. One emerging concern is the Alternaria mycotoxin alternariol (AOH), which can occur in foods typically contaminated by the process contaminant acrylamide (AA). AA is a byproduct of the Maillard reaction produced in carbohydrate-rich foods during thermal processing. Given the genotoxic properties of AOH and AA as single compounds, as well as their potential co-occurrence in food, this study aimed to assess the cytotoxic, genotoxic, and mutagenic effects of these compounds in combination. Genotoxicity was assessed in HepG2 cells by quantifying the phosphorylation of the histone γ-H2AX, induced as a response to DNA double-strand breaks (DSBs). Mutagenicity was tested in Salmonella typhimurium strains TA98 and TA100 by applying the Ames microplate format test. Our results showed the ability of AOH and AA to induce DSBs and increase revertant numbers in S. typhimurium TA100, with AOH being more potent than AA. However, no synergistic effects were observed during the combined treatments. Notably, the results of the study suggest that the compounds exert mutagenic effects primarily through base pair substitutions. In summary, the data indicate no immediate cause for concern regarding synergistic health risks associated with the consumption of foods co-contaminated with AOH and AA.

PurposeCongenital myopathies are a heterogeneous group of diseases affecting the skeletal muscles and characterized by high clinical, genetic, and histological variability. Magnetic Resonance (MR) is a valuable tool for the assessment of involved muscles (i.e., fatty replacement and oedema) and disease progression. Machine Learning is becoming increasingly applied for diagnostic purposes, but to our knowledge, Self-Organizing Maps (SOMs) have never been used for the identification of the patterns in these diseases. The aim of this study is to evaluate if SOMs may discriminate between muscles with fatty replacement (S), oedema (E) or neither (N).MethodsMR studies of a family affected by tubular aggregates myopathy (TAM) with the histologically proven autosomal dominant mutation of the STIM1 gene, were examined: for each patient, in two MR assessments (i.e., t0 and t1, the latter after 5 years), fifty-three muscles were evaluated for muscular fatty replacement on the T1w images, and for oedema on the STIR images, for reference. Sixty radiomic features were collected from each muscle at t0 and t1 MR assessment using 3DSlicer software, in order to obtain data from images. A SOM was created to analyze all datasets using three clusters (i.e., 0, 1 and 2) and results were compared with radiological evaluation.ResultsSix patients with TAM STIM1-mutation were included. At t0 MR assessments, all patients showed widespread fatty replacement that intensifies at t1, while oedema mainly affected the muscles of the legs and appears stable at follow-up. All muscles with oedema showed fatty replacement, too. At t0 SOM grid clustering shows almost all N muscles in Cluster 0 and most of the E muscles in Cluster 1; at t1 almost all E muscles appear in Cluster 1.ConclusionOur unsupervised learning model appears to be able to recognize muscles altered by the presence of edema and fatty replacement.

Despite the increased access to scientific publications and data as a result of open science initiatives, access to scientific tools remains limited. Uncrewed aerial vehicles (UAVs, or drones) can be a powerful tool for research in disciplines such as agriculture and environmental sciences, but their use in research is currently dominated by proprietary, closed source tools. The objective of this work was to collect, curate, organize and test a set of open source tools for aerial data capture for research purposes. The Open Science Drone Toolkit was built through a collaborative and iterative process by more than 100 people in five countries, and comprises an open-hardware autonomous drone and off-the-shelf hardware, open-source software, and guides and protocols that enable the user to perform all the necessary tasks to obtain aerial data. Data obtained with this toolkit over a wheat field was compared to data from satellite imagery and a commercial hand-held sensor, finding a high correlation for both instruments. Our results demonstrate the possibility of capturing research-grade aerial data using affordable, accessible, and customizable open source software and hardware, and using open workflows.

Introdução: A sífilis é uma doença infectocontagiosa que pode ser adquirida durante o período gravídico-puerperal e apresenta altas taxas de transmissão vertical, sendo considerada uma doença de fácil prevenção. Objetivo: Traçar o perfil epidemiológico dos casos notificados de sífilis congênita e sífilis gestacional, bem como verificar possíveis relações entre fatores sociodemográficos e clínicos associados às notificações de sífilis congênita. Material e Métodos: Estudo observacional, transversal com delineamento descritivo, usando abordagem quantitativa-analítica em que foram incluídas todas as fichas de notificação de sífilis congênita (2009 a 2015) e sífilis gestacional (2008 a 2014) do Sistema de Informação de Agravos de Notificação, do município de Maringá/Paraná/Brasil. As características maternas foram comparadas por meio de frequências relativas, consideradas diferenças estatisticamente significativas pelo teste do qui-quadrado bicaudal (p < 0,05). A força das associações foi determinada pelo odds ratio, com intervalos de confiança de 95% na análise de regressão logística. Posteriormente, aplicou-se o teste HL nas variáveis que apresentaram associação ao menos moderada (p < 0,25) com a variável que indica a aderência ao tratamento pelo teste qui-quadrado. Resultados: Foram notificados 120 casos de sífilis gestacional e 103 de sífilis congênita. Destes, observou-se tendência crescente na incidência a partir do ano de 2012, com aumento de 200% nas notificações de sífilis congênita de 2014 para 2015. Os casos de sífilis gestacional foram mais frequentes em mães de 20 a 30 anos (50,49%) e com baixa escolaridade (86,41%). Observou-se que 94,17% das crianças notificadas com sífilis gestacional nasceram de mães que realizaram o pré-natal, mas apenas 42,72% dos casos as mães foram tratadas adequadamente. As análises demonstraram que 61% dos filhos das gestantes notificadas com sífilis gestacional não foram notificados com sífilis congênita. Conclusão: Encontrou-se alta incidência de casos no município estudado. Os fatores associados à sífilis congênita sugerem falhas na assistência pré-natal, especialmente no tratamento inadequado das gestantes e seus parceiros, indicando a necessidade de reorientação das estratégias para reduzir a incidência desta morbidade.

Objective: In this study, we aim to assess the current situation of postgraduate medical education in obstetrics and gynaecology in Germany, Austria and Switzerland. In addition, we aim to determine transferable advantages amongst the countries. Study design: We performed a survey through a digital questionnaire with a total of 40 questions. The survey was advertised via communication channels of the German, Austrian and Swiss gynaecological societies; the participants were enrolled anonymously. Results: A total of 422 trainees took part in the survey. Differences within the three countries where found regarding the workload and the training of sub-specialties. Generally, the participants described to spend the majority of their daily working hours on documentation. Concerning assessment of current training regulations, more than half of trainees stated that they were actually faced with notable difficulties to fulfil the required obligatory numbers of self-performed interventions being documented. When asked for their intrinsic feeling of safety, around two-third of trainees felt “confident to very confident” during standard interventions. These numbers were up to 12% higher in the group of trainees who experienced simulation training during their education. Conclusion: With the help of this survey, weak points can be identified such as workload and implementation of current training regulations. Projects and ideas as EBCOG PACT, EPAs, the reduction of bureaucracy through digitization and deepening skills through simulation make a valuable contribution to compensate for these deficits and to adapt to future requirements.

Abstract Oxidative stress and reactive oxygen species (ROS) are central to many physiological and pathophysiological processes. However, due to multiple technical challenges, it is hard to capture a comprehensive readout of the cell, involving both biochemical and functional status. We addressed this problem by developing a fully parallelized workflow for metabolomics (providing absolute quantities for > 100 metabolites including TCA cycle, pentose phosphate pathway, purine metabolism, glutathione metabolism, cysteine and methionine metabolism, glycolysis and gluconeogenesis) and live cell imaging microscopy. The correlative imaging strategy was applied to study morphological and metabolic adaptation of cancer cells upon short-term hydrogen peroxide (H2O2) exposure in vitro. The combination provided rich metabolic information at the endpoint of exposure together with imaging of mitochondrial effects. As a response, superoxide concentrations were elevated with a strong mitochondrial localization, and multi-parametric image analysis revealed a shift towards fragmentation. In line with this, metabolism reflected both the impaired mitochondrial function and shifts to support the first-line cellular defense and compensate for energy loss. The presented workflow combining high-end technologies demonstrates the applicability for the study of short-term oxidative stress, but it can be suitable for the in-depth study of various short-term oxidative and other cellular stress-related phenomena.

This study assessed the efficacy of a pulmonary rehabilitation (PR) on pulmonary and respiratory muscle function and thickness of quadriceps femoris and diaphragm of patients with post-COVID-19 syndrome. This series of cases followed nine patients who performed PR twice a week for six weeks. Patients received the following PR program: lung expansion therapy; respiratory muscle training; upper limb strength exercises; aerobic exercises on a treadmill. After the program, we observed increased peak expiratory flow (26.03%), forced vital capacity (FVC) (7.14%), forced expiratory volume in the first second (FEV1) (9.55%), and ratio between FEV1/FVC (6.19%). All parameters of respiratory muscle strength and endurance were improved. Diaphragmatic thickening fraction and thickness of quadriceps femoris also improved, whereas echo intensity of quadriceps reduced. Thus, RP protocol improved pulmonary function, respiratory muscle strength and endurance, and thickness of diaphragm and quadriceps femoris, and reduced echo intensity of quadriceps in patients with post-COVID-19 syndrome.

Objetivos: Investigar a compreensão de fisioterapeutas sobre cuidados paliativos na Unidade de Terapia Intensiva(UTI), elencar dificuldades e apontar potencialidades/obstáculos quanto à assistência fisioterapêutica. Método: Pesquisa exploratória de natureza qualitativa, realizada por 11 fisioterapeutas da UTI de um Hospital Universitário da cidade de João Pessoa-PB. Para coleta de dados foi utilizado um formulario contendo questões pertinentes ao conteúdo do estudo. O material empírico foi analisado pela técnica do Discurso do Sujeito Coletivo(DSC). Resultados: Obtiveram-se como ideias centrais: Os cuidados paliativos buscam oferecer qualidade de vida, conforto e alívio do sofrimento para doentes incuráveis; atuação na perspectiva da ortotanásia; importância do fisioterapeuta em proporcionar conforto; dificuldades na tomada de decisão e adoção de estratégias como elaboração de protocolos e educação continuada. Conclusão: O DSC dos profissionais revelou a compreensão destes sobre os CP na UTI e possíveis dificuldades na assistência a estes pacientes, portanto, espera-se a realização de mais estudos nesta temática.

Objectives Among occupational sectors, construction is still one of the branches with the highest reported numbers of work-related injuries and diseases, which can even lead to death and in many cases induce permanent health consequences. The vast majority of these occupational injuries and diseases are preventable; accordingly, an improvement in preventive strategies, also through a better knowledge of the main factors involved in these events, is one of the most important objectives for better occupational health and safety in the construction sector. Considering the individual factors associated with a higher risk of work-related adverse health effects in workers, an inadequate perception of occupational risks is among the most relevant issues. Risk perception can vary according to different cultural backgrounds, highly influenced by ethnicity, and it affects the relations between workers in the work environment, and the way by with they undergo the specific occupational tasks and manage risky situations frequently occurring on construction sites. Accordingly, the aim of the authors was to develop a new tool for the assessment of risk perception in construction workers with different ethnic backgrounds. Material and Methods A team of health and safety experts involved in the training of construction workers from various ethnic backgrounds and in different regions of Italy developed and validated a questionnaire-based tool for the evaluation of their risk perception. Furthermore, through a factor analysis, a reference model defining various dimensions of occupational risk perception, relevant for the different ethnicities, was identified. Results The final tool included 12 items aimed to assess the associations between the ethnic background and occupational risk perception of construction workers. The authors identified 4 relevant dimensions: behavioral control, work conditions, safety climate and personal attitude. Conclusions The proposed tool should be considered to explore the appropriate ways for the development of effective preventive strategies for construction workers with different ethnic backgrounds in Italy. Int J Occup Med Environ Health. 2020;33(2):163–72

Abstract Aim To study the influence on the healing of the placement of particulate autogenous bone in the antrostomy and in the subjacent region after maxillary sinus elevation. Material and methods Sixteen New Zealand rabbits were undergone to bilateral maxillary sinus floor augmentation with 4 × 4 mm antrostomy dimension. The sinus mucosa was elevated, and the space obtained was filled with xenograft. In the test site (treated sites), autogenous bone was harvested from the tibia and was placed either in the antrostomy and the subjacent region while the control site was left untreated. Antrostomy was covered bilaterally with collagen membranes. Animals were euthanized after 1 and 8 weeks of healing, with 8 rabbits in each group. Histomorphometric evaluations were done. The Wilcoxon test is used for statistical analysis, for a 5% statistical significance. Results After 1 week of healing, the new bone proportion in the antrostomy was 7.7 ± 11.2% and 6.1 ± 6.4% in the treated and untreated sites, respectively. In the subjacent region (close-to-window region), hardly any new bone was assessed. In the elevated region, 2.7–2.8% of total new bone was found in both sites. In the antrostomy region, after 8 weeks of healing, 35.5 ± 20.9% of new bone in the treated sites, and 28.6 ± 24.1% in the untreated sites was observed (p = 0.499). In the close-to-window region, the respective proportions were 25.8 ± 16.1% and 17.6 ± 16.3% (p = 0.018). In the elevated region, the total new bone reached fractions of 27.9 ± 12.9% and 23.6 ± 15.2% in the treated and untreated sites, respectively (p = 0.128). Conclusions The placement of autogenous bone in the antrostomy and the subjacent region after maxillary sinus elevation, slightly enhanced bone formation compared with sites only grafted with xenograft. Though, only the subjacent close-to-window region showed a statistical significance at 8 weeks of healing. Despite the limitations of the present study, due to its preclinical nature, findings should be extrapolated to humans with caution.

Objective To evaluate whether telomere length (TL), mitochondrial-DNA (mt-DNA) or epigenetic age estimators based on DNA methylation (DNAm) pattern could be considered reliable predictors of in-vitro-fertilization (IVF) success in terms of live birth rate. Design Prospective cohort study Setting Infertility Unit of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Patients 181 women aged 37–39 years who underwent IVF at a single-centre between January 2017 and December 2018. Interventions On the day of recruitment, blood samples were collected, and genomic DNA was isolated from white blood cells. TL, mt-DNA and DNAm assessment was performed using quantitative real-time polymerase chain reaction (qPCR). Biological age (DNAm age) was computed as the algorithm based on methylation pattern of five genes. Epigenetic age acceleration was estimated from the residuals of the linear model of epigenetic age regressed on chronological age. Long Interspersed Nuclear Elements (LINE)-1 methylation pattern was used as a surrogate for global DNA methylation. Main outcome measures This study investigated whether peripheral TL, mt-DNA and DNAm could predict live birth in IVF cycles. Results TL, mt-DNA and LINE-1 methylation were not associated with IVF success. Conversely, DNAm age resulted significantly lower in women who had a live birth compared to women who did not (36.1 ± 4.2 and 37.3 ± 3.3 years, respectively, p = 0.04). For DNAm age, odds ratio (OR) for live birth per year of age was 0.90 (95%CI: 0.82–0.99, p = 0.036) after adjusting for FSH and antral follicle count (AFC) and 0.90 (95%CI: 0.82–0.99, p = 0.028) after adjusting also for number of oocytes retrieved. A significant association also emerged for epigenetic age acceleration after adjustments (OR = 0.91, 95%CI: 0.83–1.00, p = 0.048). Conclusion DNAm age is associated with IVF success but the magnitude of this association is insufficient to claim a clinical use. However, our findings are promising and warrant further investigation. Assessment of biological age using different epigenetic clocks or focusing on different tissues may reveal new predictors of IVF success.

BackgroundSickle cell disease (SCD) incurs vaso-occlusive episodes and organ damage, including nephropathy. Despite displaying characteristics of vascular dysfunction, SCD patients tend to present relatively lower systemic blood pressure (BP), via an unknown mechanism. We investigated associations between BP and renin-angiotensin-system (RAS) components in SCD and determined whether an inhibitor of angiotensin converting enzyme (ACE; often used to slow SCD glomerulopathy) further modulates BP and RAS components in a murine model of SCD.MethodsBP was compared in human subjects and mice with/without SCD. Plasma angiotensin II, ACE and renin were measured by immunoassay. BP was reevaluated after treating mice with enalapril (25 mg/kg, 5x/week) for 5 weeks; plasma and organs were stored for angiotensin II and ACE activity measurement, and quantitative real-time PCR.ResultsDiastolic BP and systolic BP were significantly lower in patients and mice with SCD, respectively, compared to controls. Reduced BP was associated with increased plasma renin and markers of kidney damage (mice) in SCD, as well as significantly decreased plasma ACE concentrations and ACE enzyme activity. As expected, enalapril administration lowered BP, plasma angiotensin II and organ ACE activity in control mice. In contrast, enalapril did not further reduce BP or organ ACE activity in SCD mice; however, plasma angiotensin II and renin levels were found to be significantly higher in enalapril-treated SCD mice than those of treated control mice.ConclusionRelative hypotension was confirmed in a murine model of SCD, in association with decreased ACE concentrations in both human and murine disease. Given that ACE inhibition has an accepted role in decreasing BP, further studies should investigate mechanisms by which ACE depletion, via both Ang II-dependent and alternative pathways, could contribute to reduce BP in SCD and understand how ACE inhibition confers Ang II-independent benefits on kidney function in SCD.

Infectious disease outbreaks are a primary contributor to coral reef decline worldwide. A particularly lethal disease, black band disease (BBD), was one of the first coral diseases reported and has since been documented on reefs worldwide. BBD is described as a microbial consortium of photosynthetic cyanobacteria, sulfate-reducing and sulfide-oxidizing bacteria, and heterotrophic bacteria and archaea. The disease is visually identified by a characteristic dark band that moves across apparently healthy coral tissue leaving behind bare skeleton. Despite its virulence, attempts to effectively treat corals with BBD in the field have been limited. Here, we developed and tested several different therapeutic agents on Pseudodiploria spp. corals with signs of active BBD at Buck Island Reef National Monument in St. Croix, USVI. A variety of therapies were tested, including hydrogen peroxide-based treatments, ointment containing antibiotics, and antiviral/antimicrobial-based ointments (referred to as CoralCure). The CoralCure ointments, created by Ocean Alchemists LLC, focused on the dosing regimen and delivery mechanisms of the different active ingredients. Active ingredients included carbamide peroxide, Lugol's iodine solution, along with several proprietary essential oil and natural product blends. Additionally, the active ingredients had different release times based on treatment: CoralCure A-C had a release time of 24 hours, CoralCure D-F had a release time of 72 hours. The ointments were applied directly to the BBD lesion. Also, jute rope was saturated with a subset of these CoralCure ointment formulations to assist with adhesion. These ropes were then applied to the leading edge of the BBD lesion for one week to ensure sufficient exposure. Corals were revisited approximately three to five months after treatment application to assess disease progression rates and the presence/absence of lesions-the metrics used to quantify the efficacy of each treatment. Although most of the treatments were unsuccessful, two CoralCure rope formulations-CoralCure D rope and CoralCure E rope, eliminated the appearance of BBD in 100% of the corals treated. As such, these treatments significantly reduced the likelihood of BBD occurrence compared to the untreated controls. Additionally, lesions treated with these formulations lost significantly less tissue compared with controls. These results provide the mechanisms for an easily employable method to effectively treat a worldwide coral disease.

The key role played by host-microbiota interactions on human health, disease onset and progression, and on host response to treatments has increasingly emerged in the latest decades. Indeed, dysbiosis has been associated to several human diseases such as obesity, diabetes, cancer and also neurodegenerative disease, such as Parkinson, Huntington and Alzheimer's disease (AD), although whether causative, consequence or merely an epiphenomenon is still under investigation. In the present study, we performed a metabologenomic analysis of stool samples from a mouse model of AD, the 3xTgAD. We found a significant change in the microbiota of AD mice compared to WT, with a longitudinal divergence of the F/B ratio, a parameter suggesting a gut dysbiosis. Moreover, AD mice showed a significant decrease of some amino acids, while data integration revealed a dysregulated production of desaminotyrosine (DAT) and dihydro-3-coumaric acid. Collectively, our data show a dysregulated gut microbiota associated to the onset and progression of AD, also indicating that a dysbiosis can occur prior to significant clinical signs, evidenced by early SCFA alterations, compatible with gut inflammation.

Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe an individual host and its microbial community, may pave the way towards a better understanding of kidney disease pathogenesis and progression. Microbiota-modulating or -derived interventions include probiotics, prebiotics, synbiotics and postbiotics. As of 2019, the concept of postbiotics was updated by the International Scientific Association of Probiotics and Prebiotics (ISAPP) to refer to preparations of inanimate microorganisms and/or their components that confer a health benefit to the host. By explicitly excluding purified metabolites without a cellular biomass, any literature making use of such term is potentially rendered obsolete. We now review the revised concept of postbiotics concerning their potential clinical applications and research in kidney disease, by discussing in detail several formulations that are undergoing preclinical development such as GABA-salt for diet-induced hypertension and kidney injury, sonicated Lactobacillus paracasei in high fat diet-induced kidney injury, GABA-salt, lacto-GABA-salt and postbiotic-GABA-salt in acute kidney injury, and O. formigenes lysates for hyperoxaluria. Furthermore, we provide a roadmap for postbiotics research in kidney disease to expedite clinical translation.

ABSTRACT: Introduction: Vascular erectile dysfunction (ED) is a burdensome condition, associated with increased cardiovascular risk. Peak systolic velocity (PSV) represents the maximum pulse velocity in the cavernous artery measured by a penile color doppler ultrasonography (PCDU) during a pharmacologically induced erection and is considered a reliable parameter for the diagnosis of vascular ED. However, the cut-off value of standard PSV (30 cm/s) provides high sensitivity only in the diagnosis of advanced arteriogenic disease. Thus, an age-adjusted PSV (6.73 + 0.7 x age cm/s) has been proposed to offer a more accurate diagnosis of vascular ED. Aim: In this study it was aimed to answer the following question: “Is there any positive association between indexes of vascular erectile dysfunction and cardiorespiratory fitness?” Main Outcome Measure And Methods: 25 patients with a medical history of ED (median age 55.3 years) underwent PCDU after pharmacological stimulation. Subsequently, a functional evaluation with ECG-monitored, incremental, maximal cardiopulmonary exercise testing was performed. Results: Peak oxygen uptake (VO2 peak), peak oxygen uptake per body weight (VO2 peak/kg) and Watt/kg correlated with standard PSV, even when corrected for age and BMI (p < 0.05). No differences emerged in cardiopulmonary fitness between pathological and healthy patients (4 vs 21) identified using the standard PSV cut-off. Conversely, the age-adjusted PSV cut-off identified a greater number of patients as pathological (18 vs 7), presenting a significantly lower cardiopulmonary fitness, exercise capacity and efficiency when compared to patients with normal age-adjusted PSV (all p < 0.05). Conclusion: Data showed an age and BMI independent association between vascular disfunction of cavernous artery and cardiopulmonary fitness, a known solid predictor of all-cause and disease-specific mortality. Moreover, the age-adjusted PSV better identified a subgroup of patients with vascular ED presenting impaired cardiorespiratory fitness and thus increased cardiovascular risk. De Rocco Ponce M, Vecchiato M, Neunhaeuserer D, et al. Association Between Penile Color Doppler Ultrasonography and Cardiorespiratory Fitness in Patients With Vascular Erectile Dysfunction. Sex Med 2021;9:100347.

This study aimed to report the contribution of strategies for monitoring and effecting the flow of care to those who had been detained in a psychiatric hospital at the Center for Psychosocial Care. In the results, 496 outpatients from psychiatric hospitalization were contacted, of whom 95 were admitted to CAPS, 22 were re-admitted, 108 attended another point in the Health Network, 89 were hospitalized for problems related to the use and abuse of psychoactive substances, 19 refused to attend CAPS II, 93 phones were not answered, 70 others. It is concluded that the effectiveness of the flow for follow-up of egresses requires innovation with mental health management plans that include this theme, also collective constructions of instruments with indicators of follow-up in the information system and innovation in the elaboration of technological resources as a digital platform with real-time access by distinguished and involved service professionals.

Abstract Background HMG-CoA reductase inhibitors (statins) are cholesterol-lowering drugs widely used to treat hypercholesterolemia and prevent cardiovascular disease. Statins are generally well tolerated, but adverse reactions may occur, particularly myopathy and new onset of diabetes. The exact mechanism of statin-induced myopathy and diabetes has not been fully elucidated. We have previously shown that treatment of hypercholesterolemic (LDLr−/−) mice with pravastatin for 2 months decreased pancreatic islet insulin secretion and increased oxidative stress and cell death, but no glucose intolerance was observed. The purpose of the current work was to study long-term pravastatin effects on glucose homeostasis, insulin sensitivity, muscle protein turnover and cell viability. Methods LDLr−/− mice were treated with pravastatin for 3, 6 and 10 months. Glucose tolerance, insulin resistance and glucose-stimulated insulin secretion were evaluated. The rates of protein synthesis and degradation were determined in gastrocnemius muscle after 10 months of treatment. Insulin signalling, oxidative stress and cell death were analysed in vitro using C2C12 myotubes. Results After 6 and 10 months of treatment, these mice became glucose intolerant, and after 10 months, they exhibited marked insulin resistance. Reduced islet glucose-stimulated insulin secretion was observed after the 3rd month of treatment. Mice treated for 10 months showed significantly decreased body weight and increased muscle protein degradation. In addition, muscle chymotrypsin-like proteasomal activity and lysosomal cathepsin were markedly elevated. C2C12 myotubes exposed to increasing concentrations of pravastatin presented dose-dependent impairment of insulin-induced Akt phosphorylation, increased apoptotic markers (Bax protein and cleaved caspase-3) and augmented superoxide anion production. Conclusions In addition to reduced insulin secretion, long-term pravastatin treatment induces insulin resistance and muscle wasting. These results suggest that the diabetogenic effect of statins is linked to the appearance of myotoxicity induced by oxidative stress, impaired insulin signalling, proteolysis and apoptosis.

Abstract Introduction Cervical vestibular-evoked myogenic potentials (cVEMPs) are biphasic, short latency potentials, which represent the inhibition of the contraction of the sternocleidomastoid muscle (SCM) mediated by the saccule, the inferior vestibular nerve, the vestibular nuclei and the medial vestibular spinal tract. Objective To evaluate the response of cVEMPs in individuals with profound prelingual bilateral cochlear hearing loss. Methods A prospective case-control study. A total of 64 volunteers, divided into a study group (31 patients with profound prelingual sensorineural hearing loss) and a control group (33 subjects matched for age and gender with psychoacoustic thresholds of ≤ 25 dB HL between 500 and 8,000 Hz) were submitted to the cVEMP exam. The causes of hearing loss were grouped by etiology and the involved period. Results The subjects of the study group are more likely to present changes in cVEMPs compared to the control group (35.5% versus 6.1% respectively; p = 0.003), with an odds ratio (OR) of 8.52 (p = 0.009). It means that they had 8.52-fold higher propensity of presenting altered cVEMP results. There were no statistically significant differences between the latencies, the interamplitude and the asymmetry index. Regarding the etiology, there was a statistically significant difference when the cause was infectious, with an OR of 15.50 (p = 0.005), and when the impairment occurred in the prenatal period, with an OR of 9.86 (p = 0.009). Conclusion The present study showed abnormalities in the sacculocolic pathway in a considerable portion of individuals with profound prelingual sensorineural hearing loss due to infectious and congenital causes, as revealed by the cVEMP results.

Objetivos: Investigar a compreensão de fisioterapeutas sobre cuidados paliativos na Unidade de Terapia Intensiva(UTI), elencar dificuldades e apontar potencialidades/obstáculos quanto à assistência fisioterapêutica. Método: Pesquisa exploratória de natureza qualitativa, realizada por 11 fisioterapeutas da UTI de um Hospital Universitário da cidade de João Pessoa-PB. Para coleta de dados foi utilizado um formulario contendo questões pertinentes ao conteúdo do estudo. O material empírico foi analisado pela técnica do Discurso do Sujeito Coletivo(DSC). Resultados: Obtiveram-se como ideias centrais: Os cuidados paliativos buscam oferecer qualidade de vida, conforto e alívio do sofrimento para doentes incuráveis; atuação na perspectiva da ortotanásia; importância do fisioterapeuta em proporcionar conforto; dificuldades na tomada de decisão e adoção de estratégias como elaboração de protocolos e educação continuada. Conclusão: O DSC dos profissionais revelou a compreensão destes sobre os CP na UTI e possíveis dificuldades na assistência a estes pacientes, portanto, espera-se a realização de mais estudos nesta temática.

Objectives In Italy, the pandemic of COVID-19 resulted in congestion of hospitals and laboratories and probably determined an underestimation of the number of infected subjects, as the molecular diagnosis of SARS-CoV-2 infection was mainly performed on hospitalised patients. Therefore, limited data are available about the number of asymptomatic/paucisymptomatic subjects in the general population across time. To understand SARS-CoV-2 infection in the general population, we have developed a cross-sectional study (the ‘UNIversity against CORoNavirus study’) to investigate infection trends in asymptomatic/paucisymptomatic subjects in Milan (Italy), between March and June 2020.Participants The study population included 2023 subjects asymptomatic at the enrolment.Primary outcome measures A nasal mid-turbinate swab for the detection of SARS-CoV-2 RNA and blood specimen for testing serum antibodies (immunoglobulin M (IgM) and IgG) were collected.Results Subjects showing positivity for the SARS-CoV-2 RNA and/or for anti-SARS-CoV-2 Ig is 237 (11.7%). Only 1.2% (n=25) of the total population had a positive nasal swab for SARS-CoV-2 and the large majority (21/25) of them were observed in March. A total of 226 subjects (11%) had IgM (n=19; 0.9%), IgG (n=155; 7.7%) or both (n=52; 2.6%) against SARS-CoV-2. Subjects with a present or past SARS-CoV-2 infection did not differ from other subjects as regards the number of cohabiting family members, travels, fever and upper and lower respiratory infection episodes.Conclusions Results from the present study support the hypothesis that the actual spread of the virus in Lombardy was underestimated in the official records. However, as it is not known how long Ig persist, numbers should be taken cautiously.

Introdução: Cirurgia bariátrica é um importante tratamento para a obesidade severa. Como ansiedade e estratégias de enfrentamento insatisfatórias estão associadas à obesidade, é importante avaliar o comportamento de pacientes candidatos e submetidos à cirurgia bariátrica, uma vez que esta pode ter impacto negativo sobre os resultados desse procedimento. Objetivo: avaliar ansiedade, depressão, estratégias de enfrentamento e qualidade de vida pré e pós-cirurgia bariátrica a partir dos dados da avaliação psicológica. Método: Estudo descritivo, longitudinal, com 118 pacientes atendidos no Ambulatório de Cirurgia Bariátrica de um hospital de ensino de alta complexidade, que realizaram o procedimento entre janeiro/2011 e janeiro/2015. Foram utilizados dados primários (avaliação psicológica pós-cirurgia) e secundários (relatório da avaliação psicológica pré-cirurgia). A avaliação psicológica incluiu: questionário socioeconômico, Escala Hospitalar de Ansiedade e de Depressão (HAD), Questionário de Qualidade de Vida SF-36 e Escala de Modos de Enfrentamento de Problemas (EMEP). Resultados: A média de idade dos pacientes foi 40,1 anos e houve predomínio de mulheres (n = 105, 89%). Houve redução significante dos sintomas de depressão após a cirurgia (p

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p

Modelo de estudo: Estudo observacional e transversal com dados coletados a partir de questionários aplicados aos idosos em visitas domiciliares, sobre acesso a serviços de saúde. Objetivo: Analisar a percepção de idosos independentes sobre questões fonoaudiológicas e odontológicas nos serviços de Atenção Primária à Saúde do Sistema Único de Saúde. Métodos: Foram analisadas frequências absolutas das variáveis de estudo relacionadas a questões fonoaudiológicas e odontológicas através do teste do Qui-quadrado e Teste Exato-de-Fisher, ambos com nível de 0,05% de significância. Resultados: Os idosos entrevistados foram predominantemente mulheres (76,5%), cor branca (73,5%), com no mínimo ensino médio de escolaridade (64,7%). Destes idosos, 92,6% afirmaram não possuir dificuldades para se alimentar, apesar de 51,5% nunca ter feito uma avaliação fonoaudiológica. Houve maior proporção indicando que os idosos não necessitaram de consulta com fonoaudióloga (73,5%). Quanto à utilização de serviços da atenção primária, 68,7% utilizavam o sistema público e desses, 94,1% autoperceberam sua condição de saúde bucal como regular/ruim. Conclusão: Sugere-se o fortalecimento do cuidado dos idosos de forma interdisciplinar e integral, a fim de abranger as necessidades e especificidades dessa população. A baixa percepção da importância do cuidado sugere a necessidade do fortalecimento dos serviços de fonoaudiologia para a saúde da população idosa brasileira.

Due to COVID-19 outbreak, to lighten the burden of acute and critical care hospitals, some respiratory rehabilitation departments have been used to host patients with COVID-19 in the post-acute phase. This new and unexpected situation required a change of roles and scheduling of the rehabilitation teams. In this manuscript we describe the unexpected and urgent organizational change of the Cardio-Pulmonary Rehabilitation (CPR) service during the COVID-19 emergency in a Northern Italian rehabilitation hospital, focusing on the Respiratory Physiotherapists’ (RPTs) role. A quick three-days complete reorganization of the entire hospital was needed. A COVID-19 care team including a multidisciplinary panel of physicians, nurses, and RPTs was quickly performed to manage 90 beds for post acute patients with COVID-19. Within the team, the RPTs changed their shifts, so as to be available 16h per day, 7 days out of 7. Remodelled tasks in charge of RPTs were: oxygen therapy daily monitoring, non invasive ventilation (NIV) and continuous positive airways pressure (CPAP) delivery, pronation and postural changes to improve oxygenation, reconditioning with leg/arm cranking and exercises, initial and final patients’ functional assessment by short-physical performance battery (SPPB) and 1-minute sit-to-stand test (1-STS) to evaluate motor conditions and exercise-induced oxygen desaturation. Three “what-to-do” algorithms were developed to guide: i) oxygen de-escalation by reducing inhaled fraction of oxygen (FiO2); ii) oxygenation improvement through the use of Venturi mask; iii) reconditioning and physical activity. One-hundred seventy patients were treated in one month. As main topics, RPTs have been involved in oxygen therapy management in almost a third of the admitted patients, reconditioning exercises in 60% of the cases, and initial and final functional motor capacity assessment in all patients. Details of activities performed by the RPT in one typical working day are also shown. Our reorganization has exploited the professional skills and clinical expertise of the RPTs. This re-organization can provide practical insights to other facilities that are facing this crisis, and may be a starting point for implementing post-COVID-19 rehabilitation. Future studies will have to improve and review this organization.

Food contaminants of bacterial or fungal origin frequently contaminate staple foods to various extents. Among others, the bacterial toxin cereulide (CER) and the mycotoxin deoxynivalenol (DON) co-occur in a mixed diet and are absorbed by the human body. Both toxins exert dis-tinctive mitotoxic potential. As damaged mitochondria are removed via autophagy, mitochondrial and lysosomal toxicity were assessed by applying low doses of single and combined toxins (CER 0.1–50 ng/mL; DON 0.01–5 µg/mL) to HepG2 liver cells. In addition to cytotoxicity assays, RT-qPCR was performed to investigate genes involved in lysosomal biogenesis and autophagy. CER and DON caused significant cytotoxicity on HepG2 cells after 5 and 24 h over a broad concentration range. CER, alone and in combination with DON, increased the transcription of the autophagy related genes coding for the microtubule associated protein 1A/1B light chain 3 (LC3) and sequestome 1 (SQSTM1) as well as LC3 protein expression which was determined using immunocytochemistry. DON increased LC3 protein expression without induction of gene transcription, hence it seems plausible that CER and DON act on different pathways. The results support the hypothesis that CER induces autophagy via the LC3 pathway and damaged mitochondria are therefore eliminated.

O acesso aos serviços básicos de saúde ainda mostra-se como um processo em construção e que necessita de esforços conjuntos do poder público, dos profissionais e de pesquisadores da saúde coletiva para descrever, traçar planos para o enfrentamento dos problemas e construir acesso universal ao que se considera, dentro das políticas públicas, como essencial a saúde do cidadão brasileiro nos grandes centros urbanos. Nestes pressupostos, o objetivo deste estudo foi analisar o acesso aos serviços de Atenção Primária à Saúde (APS) por meio da percepção do usuário adulto em três Gerências Distritais de Porto Alegre/RS. Estudo de base populacional realizado com 214 usuários. Utilizou-se questionário construído especificamente para a pesquisa contendo o atributo Acesso de Primeiro Contato do Primary Care Assessment Tool/PCATool, versão adulta, que foi aplicado através de um aplicativo para tablets. Como resultado 65,0% dos participantes eram usuários dos serviços básicos de saúde ofertado no Sistema Único de Saúde. No geral, o acesso foi insatisfatório. Em contraste, Acesso de Primeiro-Contato/Utilização foi percebido como satisfatório. Além disso, Acesso de Primeiro-Contato/Acessibilidade e o Escore Acesso apresentaram um desempenho insatisfatório. Destaca-se a importância de analisar dados sociodemográficos para o funcionamento da APS. Enfatiza-se a necessidade do município em direcionar esforços para a parte da população que percebeu o acesso como um atributo insatisfatório.

Sin resumen

The study aimed to evaluate biomarkers facilitating early diagnosis of axial spondyloarthritis (axSpA) and correlations between them and disease activity parameters and imaging indexes. Patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early SPACE study underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ). An expert rheumatologist formulated axSpA diagnosis in accordance with Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers using the SPARCC, mSASSS and NY-criteria. Patients were classified as: subjects with signs of radiographic sacroiliitis (r-axSpA), subjects with signs of sacroiliitis on SIJ-MRI but not on X-rays (nr-axSpA MRI SIJ+) or subjects with no signs of sacroiliitis on MRI/X-rays but with >2 SpA features and signs of bone oedema on MRI spine (nr-axSpA MRI SIJ-/undifferentiated SpA). Significant differences were found in the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ scores. Biomarker levels were not significantly increased in any of the patient groups. The correlations between IL-17 and IL-23 and other indices were not significant; correlations were found between IL-22 and BASFI, BASG1, HAQ, VAS pain, between mSASSS and MMP3, and between the latter and hsCRP. Although not significantly higher in any of the three groups, IL-22, MMP3 and hsCRP values were correlated with some disease activity indexes and with mSASSS. Large observational studies are required to confirm these preliminary findings.

Abstract We have described a novel C-to-T mutation in the APP gene that corresponds to an alanine to valine substitution at position 673 in APP (A673V), or position 2 of the amyloid-β (Aβ) sequence. This mutation is associated with the early onset of AD-type dementia in homozygous individuals, whereas it has a protective effect in the heterozygous state. Correspondingly, we observed differences in the aggregation properties of the wild-type and mutated Aβ peptides and their mixture. We have carried out neutron diffraction (ND) and x-ray diffraction (XRD) experiments on magnetically-oriented fibers of Aβ1-28WT and its variant Aβ1-28A2V. The orientation propensity was higher for Aβ1-28A2V suggesting that it promotes the formation of fibrillar assemblies. The diffraction patterns by Aβ1-28WT and Aβ1-28A2V assemblies differed in shape and position of the equatorial reflections, suggesting that the two peptides adopt distinct lateral packing of the diffracting units. The diffraction patterns from a mixture of the two peptides differed from those of the single components, indicating the presence of structural interference during assembly and orientation. The lowest orientation propensity was observed for a mixture of Aβ1-28WT and a short N-terminal fragment, Aβ1-6A2V, which supports a role of Aβ’s N-terminal domain in amyloid fibril formation.

Introdução: Acidentes de trânsito (AT) são uma das principais causas de trauma no mundo. No Brasil, a taxa de mortalidade de motociclistas envolvidos em AT aumentou de forma significante entre 2004 e 2014: de 2,8 para 6,2 óbitos respectivamente por 100 mil habitantes. Objetivos: caracterizar o perfil sociodemográfico e clínico de motociclistas vítimas de Acidentes de Trânsito atendidos no Hospital de Base de São José do Rio Preto (2016 a 2018); identificar o perfil comportamental desses pacientes e rastrear sintomas de transtornos mentais. Métodos: pacientes envolvidos em acidentes com motocicleta (motoristas), atendidos no Pronto Atendimento da Cirurgia do Hospital de Base de São José do Rio Preto, SP, Brasil, foram convidados a participar do estudo e responderam aos seguintes instrumentos: Mini International Neuropsychiatric Interview (MINI) e Inventário de Auto-Avaliação para Adultos (ASR). O Banco de Dados da Unidade de Trauma do Hospital de Base forneceu as infomações do prontuário para a construção do perfil sociodemográfico e clínico (referentes às lesões do trauma) do paciente. Resultados: Os participantes (n = 40) eram principalmente do sexo masculino, com média de idade de 33,83 anos (± 12,95) e baixa escolaridade; 13 relataram dirigir após ingestão de bebida alcoólica. A maioria apresentou lesões leves. Foram identificados (ASR e MINI) problemas externalizantes e internalizantes, violação de regras, queixas somáticas, abuso de álcool e de crack. Conclusão: Entre os motociclistas acidentados houve predominância de jovens do sexo masculino com baixa escolaridade, maior prevalência de lesões nas extremidades e no abdomem, uso de álcool associado à direção e presença de sintomas de transtornos mentais internalizantes e externalizantes.

Enquadramento: Grupo de gestão autónoma da medicação (GGAM) é uma abordagem em grupo com usuários de medicação psiquiátrica que partilham experiências, no qual o usuário é protagonista e corresponsável pelas decisões relacionadas com o seu tratamento. Objetivo: Descrever a experiência dos usuários participantes do GGAM de um Centro de atenção psicossocial no Brasil. Metodologia: O estudo é qualitativo, exploratório e descritivo, com recurso à entrevista semiestruturada em que a análise seguiu o referencial teórico proposto por Minayo. Foram indicados 6 usuários pela equipa multiprofissional que possuem transtorno mental com prescrição de psicofármacos há mais de 6 meses e que participaram no GGAM. Resultados: Emergiram como categorias o Contexto, a Experiência e os Efeitos da vivência dos usuários no GGAM. A descrição das experiências dos usuários mostrou o reconhecimento do grupo como um espaço de fala e escuta. Conclusão: A participação no GGAM proporcionou ampliação do conhecimento relativo à medicação psiquiátrica, à sua relação com o tratamento, fortalecimento das relações, do protagonismo e autonomia e contribuição na apropriação sobre o projeto terapêutico singular.

Cetacean morbillivirus (CeMV) is a major natural cause of morbidity and mortality in cetaceans worldwide and results in epidemic and endemic fatalities. The pathogenesis of CeMV has not been fully elucidated, and questions remain regarding tissue tropism and the mechanisms of immunosuppression. We compared the histopathologic and viral immunohistochemical features in molecularly confirmed CeMV-infected Guiana dolphins (Sotalia guianensis) from the Southwestern Atlantic (Brazil) and striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) from the Northeast-Central Atlantic (Canary Islands, Spain) and the Western Mediterranean Sea (Italy). Major emphasis was placed on the central nervous system (CNS), including neuroanatomical distribution of lesions, and the lymphoid system and lung were also examined. Eleven Guiana dolphins, 13 striped dolphins, and 3 bottlenose dolphins were selected by defined criteria. CeMV infections showed a remarkable neurotropism in striped dolphins and bottlenose dolphins, while this was a rare feature in CeMV-infected Guiana dolphins. Neuroanatomical distribution of lesions in dolphins stranded in the Canary Islands revealed a consistent involvement of the cerebrum, thalamus, and cerebellum, followed by caudal brainstem and spinal cord. In most cases, Guiana dolphins had more severe lung lesions. The lymphoid system was involved in all three species, with consistent lymphoid depletion. Multinucleate giant cells/syncytia and characteristic viral inclusion bodies were variably observed in these organs. Overall, there was widespread lymphohistiocytic, epithelial, and neuronal/neuroglial viral antigen immunolabeling with some individual, host species, and CeMV strain differences. Preexisting and opportunistic infections were common, particularly endoparasitism, followed by bacterial, fungal, and viral infections. These results contribute to understanding CeMV infections in susceptible cetacean hosts in relation to factors such as CeMV strains and geographic locations, thereby establishing the basis for future neuro- and immunopathological comparative investigations.

Interactive relationships among metabolism, mitochondrial dysfunction and inflammation at skeletal muscle level play a key role in the pathogenesis of disorders related to oxidative stress. Mitochondrial dysfunction and oxidative stress result in cellular energy deficiency, inflammation and cell death inducing a vicious cycle that promotes muscle wasting. The histidine-containing dipeptides, carnosine and anserine, are carbonyl scavengers whose cytoprotective contributions extend beyond the antioxidant defence, but the physiological meaning of these capacities is actually limited. In the present study, we compared and investigated the potential protective effects of three different histidine-containing dipeptides: carnosine, anserine and carnosinol, a carnosine-mimetic new compound, against oxidative stress induction in rat L6 skeletal muscle cells. The hydrogen peroxide induced-oxidative stress significantly altered cell morphology, induced apoptosis, oxidative stress and inflammation, decreased mitochondrial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/sirtuin3 pathway and the antioxidant system. Notably, all three investigated dipeptides in the present study, with a different extent and in a concentration-dependent manner, reduced myotube oxidative stress, apoptosis and inflammation. The present study underlined that carnosinol, maintaining the safety condition of carnosine and anserine, was the more efficient studied dipeptide in the preservation of mitochondrial environment mediated by PGC-1α and sirtuin3 expression and thereby in the reduction of oxidative stress-related alterations in this in vitro skeletal muscle model. Furthermore, we observed that carnosinol's antioxidant effects are not blocked inhibiting sirtuin3, but are maintained with almost the same extend, indicating its multiple capacities of reactive carbonyl species-scavenging and of mitochondrial modulation through PGC-1α. In conclusion, carnosinol retained and surpassed the efficacy of the well-known investigated histidine-containing dipeptides improving oxidative stress, inflammation and also cell metabolism and so becoming a greatly promising therapeutic carnosine derivate.

The human intestine is regularly exposed to ingested food contaminants, such as fungal and bacterial toxins, which have been described to co-occur in a mixed diet. Thus, it is of utmost importance to understand possible interactions between contaminants of different origin. Hence, we investigated the single and combined effects of one of the most abundant mycotoxins, deoxynivalenol (DON; 0.1 to 10 µg/mL), and the bacterial toxin cereulide (CER; 1 to 100 ng/mL) on differentiated human Caco-2 (C2BBe1) cells cultured in a transwell system. We tested the capacity of the two toxins to alter the intestinal integrity and further investigated the uptake of both compounds and the formation of selected DON metabolites. CER alone (10 and 100 ng/mL) and in combination with DON (10 ng/mL CER with 1 µg/mL DON) was found to alter the barrier function by increasing the transepithelial electrical resistance and the expression of the tight junction protein claudin-4. For the first time, DON-3-sulfate was identified as a metabolite of human intestinal cells in vitro. Moreover, co-incubation of CER and DON led to an altered ratio between DON and DON-3-sulfate. Hence, we conclude that co-exposure to CER and DON may alter the intestinal barrier function and biotransformation of intestinal cells.