Temporally extended goal recognition in fully observable non-deterministic domain models: Temporally extended goal recognition in FOND planning.

Goal Recognition is the task of discerning the intended goal that an agent aims to achieve, given a set of goal hypotheses, a domain model, and a sequence of observations (i.e., a sample of the plan executed in the environment). Existing approaches assume that goal hypotheses comprise a single conjunctive formula over a single final state and that the environment dynamics are deterministic, preventing the recognition of temporally extended goals in more complex settings. In this paper, we expand goal recognition to temporally extended goals in Fully Observable Non-Deterministic (fond) planning domain models, focusing on goals on finite traces expressed in Linear Temporal Logic (ltlf) and Pure-Past Linear Temporal Logic (ppltl). We develop the first approach capable of recognizing goals in such settings and evaluate it using different ltlf and ppltl goals over six fond planning domain models. Empirical results show that our approach is accurate in recognizing temporally extended goals in different recognition settings.

Predictors of Mortality and Functional recovery after severe traumatic brain injury: protocol for a prospective cohort study

Introduction: traumatic brain injury is a global public health problem due to its severity and high rates of morbimortality worldwide. Identifying predictors associated with increased mortality and unfavorable functional outcomes after the traumatic brain injury event is crucial for minimizing morbidity and mortality rates. Therefore, this study aims to establish a protocol to investigate the predictors of mortality and functional recovery after severe traumatic brain injury in Brazil.Methods: The study will include all patients admitted for severe traumatic brain injury (Glasgow Coma Scale ≤ 8) at the State Hospital of Urgency and Emergency, which is the referral trauma hospital of Espirito Santo. The outcomes of interest are hospital mortality and functional recovery 24 months after hospital discharge. Subjects will be followed up at seventy-two hours, three months, six months, twelve months, and twenty-four months after the trauma. Morbidity will be determined by assessing: 1) the level of motor and cognitive disability, 2) functional impairment and quality of life, and 3) aspects of rehabilitation treatment. Additionally, the traumatic brain injury load, estimated by the years of life lost, will be calculated. Discussion: the results of this study will help identify variables that can predict morbidity and mortality, as well as diagnostic and therapeutic targets for patients with severe traumatic brain injury. Furthermore, the findings will have practical implications for: 1) the development of public policies, 2) investments in hospital infrastructure 3) understanding the socioeconomic impact of functional loss in the individuals.Study registration: the study received approval from the Ethics Committee of the Federal University of Espirito Santo under protocol number 4.222.002 on August 18, 2020.

Introdução: traumatismo cranioencefálico é um problema global de saúde pública devido à sua gravidade e altas taxas de morbimortalidade em todo o mundo. Identificar preditores associados ao aumento da mortalidade e desfechos funcionais desfavoráveis após o evento do traumatismo craniencefálico é primordial para minimizar as taxas de morbidade e mortalidade. Portanto, este estudo tem como objetivo estabelecer um protocolo para investigar os preditores de mortalidade e recuperação funcional após traumatismo cranioencefálico grave no Brasil. Métodos: este estudo tem como objetivo investigar os preditores de mortalidade e recuperação funcional em pacientes com traumatismo cranioencefálico, além de fornecer uma visão geral do traumatismo cranioencefálico no estado do Espírito Santo. O estudo abrangerá todos os pacientes internados por traumatismo cranioencefálico grave (Escala de Coma de Glasgow ≤ 8) no Hospital Estadual de Urgência e Emergência, o hospital de referência para traumas no Espírito Santo. Os desfechos de interesse incluem mortalidade hospitalar e recuperação funcional após 24 meses da alta hospitalar. Os participantes serão acompanhados em setenta e duas horas, três meses, seis meses, doze meses e vinte e quatro meses após o trauma. A morbidade será determinada pela avaliação de: 1) nível de incapacidade motora e cognitiva, 2) comprometimento funcional e qualidade de vida, e 3) aspectos do tratamento e reabilitação. Além disso, a carga de traumatismo cranioencefálico, estimada em anos de vida perdidos, será calculada. Discussão: os resultados deste estudo ajudarão a identificar variáveis que podem predizer a morbidade e a mortalidade após traumatismo cranioencefálico grave. Além disso, as descobertas terão implicações práticas para: 1) o desenvolvimento de políticas públicas, 2) investimentos em infraestrutura hospitalar e 3) compreensão do impacto socioeconômico da perda funcional nesses indivíduos. Registro do estudo: o estudo recebeu aprovação do Comitê de Ética da Universidade Federal do Espírito Santo sob o número de protocolo 4.222.002 em 18 de agosto de 2020

Global Leadership Initiative on Malnutrition criteria for the diagnosis of malnutrition and prediction of mortality in patients awaiting liver transplant: A validation study.

OBJECTIVES: The Global Leadership Initiative on Malnutrition (GLIM) is a framework aiming to standardize malnutrition diagnosis. However, it still needs to be validated, in particular for patients with chronic liver disease. This study aimed to validate the GLIM criteria in patients with liver cirrhosis awaiting liver transplant (LTx). METHODS: This was a retrospective observational study carried out with adult patients on the waiting list for LTx, consecutively evaluated between 2006 and 2021. The phenotypic criteria were unintentional weight loss, low body mass index, and reduced muscle mass (midarm muscle circumference [MAMC]). The etiologic criteria were high Model for End-Stage Liver Disease (MELD) and MELD adjusted for serum sodium (MELD-Na) scores, the Child-Pugh score, low serum albumin, and low food intake and/or assimilation. Forty-three GLIM combinations were tested. Sensitivity (SE), specificity (SP), positive and negative predictive values, and machine learning (ML) techniques were used. Survival analysis with Cox regression was carried out. RESULTS: A total of 419 patients with advanced liver cirrhosis were included (median age, 52.0 y [46-59 y]; 69.2% male; 68.8% malnourished according to the Subjective Global Assessment [SGA]). The prevalence of malnutrition by the GLIM criteria ranged from 3.1% to 58.2%, and five combinations had SE or SP >80%. The MAMC as a phenotypic criterion with MELD and MELD-Na as etiologic criteria were predictors of mortality. The MAMC and the presence of any phenotypic criteria associated with liver disease parameters and low food intake or assimilation were associated with malnutrition prediction in ML analysis. CONCLUSIONS: The MAMC and liver disease parameters were associated with malnutrition diagnosis by SGA and were also predictors of 1-y mortality in patients with liver cirrhosis awaiting LTx.

Extra virgin coconut oil (Cocos nucifera L.) intake shows neurobehavioural and intestinal health effects in obesity-induced rats.

The present study aimed to evaluate the effect of E-VCO on the neurobehaviour and intestinal health parameters of obesity-induced rats, focusing on food consumption, body composition, bacterial and faecal organic acids and histological analyses in the hippocampus and colon. A total of 32 male Wistar rats were randomized into healthy (HG, n = 16) and obese groups (OG, n = 16), which consumed a control or cafeteria diet for eight weeks, respectively. After this period, they were subdivided into four groups: healthy (HG, n = 8); healthy treated with E-VCO (HGCO, n = 8); obese (OG, n = 8); obese treated with E-VCO (OGCO, n = 8), continuing for another eight weeks with their respective diets. The treated groups received 3000 mg kg-1 of E-VCO and control groups received water via gavage. Food preference, body weight gain, body composition, anxiety- and depression-like behaviour were evaluated. Bacteria and organic acids were evaluated in faeces, and histological analyses of the hippocampus and M1 and M2 macrophages in the colon were performed. E-VCO reduced energy intake (16.68%) and body weight gain (16%), although it did not reduce the fat mass of obese rats. E-VCO showed an antidepressant effect, increased lactic acid bacteria counts and modulated organic acids in obese rats. Furthermore, E-VCO protected the hippocampus from neuronal degeneration caused by the obesogenic diet, decreased the M1 macrophage and increased the M2 macrophage population in the gut. The results suggest neurobehavioural modulation and improved gut health by E-VCO, with promising effects against obesity-related comorbidities.

A machine learning model to assess potential misdiagnosed dengue hospitalization.

Dengue, like other arboviruses with broad clinical spectra, can easily be misdiagnosed as other infectious diseases due to the overlap of signs and symptoms. During large outbreaks, severe dengue cases have the potential to overwhelm the health care system and understanding the burden of dengue hospitalizations is therefore important to better allocate medical care and public health resources. A machine learning model that used data from the Brazilian public healthcare system database and the National Institute of Meteorology (INMET) was developed to estimate potential misdiagnosed dengue hospitalizations in Brazil. The data was modeled into a hospitalization level linked dataset. Then, Random Forest, Logistic Regression and Support Vector Machine algorithms were assessed. The algorithms were trained by dividing the dataset in training/test set and performing a cross validation to select the best hyperparameters in each algorithm tested. The evaluation was done based on accuracy, precision, recall, F1 score, sensitivity, and specificity. The best model developed was Random Forest with an accuracy of 85% on the final reviewed test. This model shows that 3.4% (13,608) of all hospitalizations in the public healthcare system from 2014 to 2020 could have been dengue misdiagnosed as other diseases. The model was helpful in finding potentially misdiagnosed dengue and might be a useful tool to help public health decision makers in planning resource allocation.

Machine Learning-Based Routine Laboratory Tests Predict One-Year Cognitive and Functional Decline in a Population Aged 75+ Years.

BACKGROUND: Cognitive and functional decline are common problems in older adults, especially in those 75+ years old. Currently, there is no specific plasma biomarker able to predict this decline in healthy old-age people. Machine learning (ML) is a subarea of artificial intelligence (AI), which can be used to predict outcomes Aim: This study aimed to evaluate routine laboratory variables able to predict cognitive and functional impairment, using ML algorithms, in a cohort aged 75+ years, in a one-year follow-up study. METHOD: One hundred and thirty-two older adults aged 75+ years were selected through a community-health public program or from long-term-care institutions. Their functional and cognitive performances were evaluated at baseline and one year later using a functional activities questionnaire, Mini-Mental State Examination, and the Brief Cognitive Screening Battery. Routine laboratory tests were performed at baseline. ML algorithms-random forest, support vector machine (SVM), and XGBoost-were applied in order to describe the best model able to predict cognitive and functional decline using routine tests as features. RESULTS: The random forest model showed better accuracy than other algorithms and included triglycerides, glucose, hematocrit, red cell distribution width (RDW), albumin, hemoglobin, globulin, high-density lipoprotein cholesterol (HDL-c), thyroid-stimulating hormone (TSH), creatinine, lymphocyte, erythrocyte, platelet/leucocyte (PLR), and neutrophil/leucocyte (NLR) ratios, and alanine transaminase (ALT), leukocyte, low-density lipoprotein cholesterol (LDL-c), cortisol, gamma-glutamyl transferase (GGT), and eosinophil as features to predict cognitive decline (accuracy = 0.79). For functional decline, the most important features were platelet, PLR and NLR, hemoglobin, globulin, cortisol, RDW, glucose, basophil, B12 vitamin, creatinine, GGT, ALT, aspartate transferase (AST), eosinophil, hematocrit, erythrocyte, triglycerides, HDL-c, and monocyte (accuracy = 0.92). CONCLUSIONS: Routine laboratory variables could be applied to predict cognitive and functional decline in oldest-old populations using ML algorithms.

Adverse events of COVID-19 vaccines in pregnant and postpartum women in Brazil: A cross-sectional study.

BACKGROUND: By the fact that pregnant and postpartum women are currently using COVID-19 vaccines, ensure their safety is critical. So, more safety evidence is crucial to include this new technology to their vaccine's calendar and to develop public policies regarding the support and training of Health Care Personnel. This study aims to describe the adverse events (AE) of COVID-19 vaccines in pregnant and postpartum women in the early stage of vaccination campaign in Brazil. METHODS: An observational cross-sectional study using data from the Brazilian surveillance information system to characterize the AE of COVID-19 vaccines (Sinovac/Butantan, Pfizer/BioNTech, AstraZeneca and Janssen) in Brazilian pregnant and postpartum women from April to August 2021. Frequency and incidence rate of AE for COVID-19 vaccines were assessed. RESULTS: 3,333 AE following immunization were reported for the study population. AE incidence was 309.4/100,000 doses (95% CI 297.23, 321.51). Within the vaccines available, Sinovac/Butantan had the lowest incidence (74.08/100,000 doses; 95% CI 63.47, 84.69). Systemic events were the most frequent notified (82.07%), followed by local (11.93%) and maternal (4.74%), being most of them classified as non-severe (90.65%). CONCLUSION: Our results corroborate the recommendation of vaccination for these groups. Even though, further studies appraising a longer observation time are still needed to provide a broader safety aspect for the vaccines currently under use for this population.

Acerola fruit by-product alleviates lipid, glucose, and inflammatory changes in the enterohepatic axis of rats fed a high-fat diet.

Acerola (Malpighia emarginata) by-product (ABP) has various bioactive compounds with hypoglycaemic, antioxidant and anti-inflammatory activity. The ABP effects on the biochemical changes in the enterohepatic axis caused by a high-fat diet (HFD) remains unclear. This study assessed whether the ABP or fenofibrate administration for 28 days interferes in lipid, glucose, or inflammatory changes in the enterohepatic axis of rats fed HFD. ABP induced in the rats fed HFD a reduction in body weight, serum lipids, blood glucose, and liver fat accumulation; increased insulin tolerance, and faecal bile acid excretion; regulated organic acid synthesis, faecal and colonic microbial growth; reduced M1 macrophage and increased M2 macrophage infiltration in the colon and liver, respectively. The fenofibrate did not improve the lipid or glucose alterations in enterohepatic axis of rats fed HFD. ABP has functional/nutraceutical potential in treating HFD-induced metabolic disorders with beneficial effects on lipid and glucose metabolism, and reduction of inflammation.

Adverse events of COVID-19 vaccines in pregnant and postpartum women in Brazil: a cross-sectional study

Background By the fact that pregnant and postpartum women are currently using COVID-19 vaccines, ensure their safety is critical. So, more safety evidence is crucial to include this new technology to their vaccine’s calendar and to develop public policies regarding the support and training of Health Care Personnel. This study aims to describe the adverse events (AE) of COVID-19 vaccines in pregnant and postpartum women in the early stage of vaccination campaign in Brazil. Methods An observational cross-sectional study using data from the Brazilian surveillance information system to characterize the AE of COVID-19 vaccines (Sinovac/Butantan, Pfizer/BioNTech, AstraZeneca and Janssen) in Brazilian pregnant and postpartum women from April to August 2021. Frequency and incidence rate of AE for COVID-19 vaccines were assessed. Results 3,333 AE following immunization were reported for the study population. AE incidence was 309.4/100,000 doses (95% CI 297.23, 321.51). Within the vaccines available, Sinovac/Butantan had the lowest incidence (74.08/100,000 doses; 95% CI 63.47, 84.69). Systemic events were the most frequent notified (82.07%), followed by local (11.93%) and maternal (4.74%), being most of them classified as non-severe (90.65%). Conclusion Our results corroborate the recommendation of vaccination for these groups. Even though, further studies appraising a longer observation time are still needed to provide a broader safety aspect for the vaccines currently under use for this population.

Leishmania (L.) infantum BH401 strain induces classic renal lesions in dogs: Histological and confocal microscopy study.

Extracellular matrix (ECM) alterations in visceral leishmaniasis are related mainly to collagen deposition (fibropoiesis). In canine visceral leishmaniasis (CVL), an intense fibrosis associated to chronic inflammation in organs such as kidneys is described. However, renal fibropoiesis has not been described in natural or experimental infections with L. (L.) infantum. We aimed to characterize renal nephropathies by histology and confocal microscopy comparing renal lesions in dogs naturally and experimentally infected with L. (L.) infantum. Sixty-two mixed-breed symptomatic dogs naturally infected with L. (L.) infantum, sixteen beagles experimentally infected with two strains of L. infantum (eleven dogs with the BH400 strain and five dogs with the BH401 strain), and five uninfected beagles (controls) were used. Samples were stained with hematoxylin & eosin for routine histology. Congo red was used to visualize amyloid protein deposits, periodic acid-Schiff to identify glomerular basal membrane anomalies, Masson's trichrome for collagen deposits, and Jones' methenamine silver to reveal membranous glomerulonephropathy. Immunohistochemistry was used to identify Leishmania amastigotes, and confocal microscopy was used for macrophage characterization (L1/calprotectin and CD163 antigen receptors). The most common lesions were chronic glomerular and interstitial nephritis, which was found in all naturally infected dogs and dogs experimentally infected with L. infantum strain BH401 but not with the BH400 strain. Glomeruloesclerosis was the main lesion presented in all BH401 group. Morphometric analysis revealed positive correlation of renal glomeruli tufts with cellular expression of L1/calprotectin and CD163 antigens. Leishmania infantum strain BH401 shows pathogenicity that may be sufficient to induce classic chronic visceral renal leishmaniasis.

Predicting in vitro fertilization success in the Brazilian public health system: a machine learning approach.

Infertility has become a global health problem, increasing the number of couples looking for in vitro fertilization (IVF). Despite advances and technical improvements, some couples remain childless due to the high complexity of the technique. The use of machine learning (ML) in the prediction of pregnancy, computing factors that could interfere in the effectiveness of the treatment, is an important tool to optimize these factors and reach the success of pregnancy. The aim of this study was to apply ML models to determine variables related to pregnancy after IVF in a public health service, including pre-implantation variables. This study included 771 women who underwent IVF treatment at Hospital das Clínicas, Federal University of Minas Gerais, between 2013 and 2019. We used the following Machine Learning algorithms: Logistic Regression, Random Forest, XG Boost and Support Vector Machines. The Random Forest algorithm achieved the best performance, with better accuracy, sensitivity and area under the ROC curve to predict the success of IVF evaluated by pregnancy frequency. We also trained a specific model only for women older than 35 years old. Variables in the Random Forest model related to pregnancy after in vitro fertilization.

Adoption of new therapies in the treatment of Hepatitis: a verification of the accuracy of budget impact analysis to guide investment decisions.

OBJECTIVES: While there are good Budget Impact Analysis (BIA) guidelines, studies still register potential bias. To do this, we compared the results between theoretical and real-world evidence (RWE) expenditures for medicines for Hepatitis C: boceprevir (BOC) and telaprevir (TVR). While both are not currently recommended in treatment guidelines following recent developments, this is an emblematic case because for 4 years these medicines consumed considerable resources. METHODS: Theoretical results and RWE expenditures were compared regarding the incorporation of BOC and TVR in 2013-2014 into the Brazilian Public Health System. Theoretical values were extracted from Commission for Technology Incorporation Report and RWE expenditures were extracted from the administrative data records using deterministic-probabilistic linkage. RESULTS: The estimated number of patients treated (BOC+TVR) was 13,012 versus 7,641 (real). The estimated purchase price for BOC was US$6.20 versus US$11.07 (real) and for TVR was US$42.21 versus US$84.09 (average/real). The estimated budget impact was US$285.16 million versus US$128.58 million (real). CONCLUSION: This study demonstrates appreciable divergence (US$156.58 million) between the theoretical budget impact and RWE expenditures due to underestimated purchase prices and overestimated populations. The greater the degree of accuracy the more reliable and usable BIAs become for decision-making.

Budget impact analysis of medicines: estimated values versus real-world evidence and the implications.

OBJECTIVES: Budget Impact Analyses (BIA) of medicines helps managers in promoting health systems' sustainability when assessing the role and value of new medicines. However, it is not clear whether BIAs typically underestimate or overestimate the impact on real-world budgets. This retroactive analysis seeks to compare estimated values obtained by a BIA and Real-World Evidence (RWE) to guide discussions. METHODS: The estimated values were obtained through a BIA concerning the incorporation of adalimumab for the treatment of Rheumatoid Arthritis into the Brazilian Unified Health System (SUS) carried out retroactively and per international guidelines. RWE data was extracted from SUS computerized systems. We subsequently compared the number of treatments, costs, and Incremental Budget Impact (IBI). RESULTS: - The total number of treatments was underestimated by 10% (6,243) and the total expenditure was overestimated by 463% (US$ 4.7 billion). In five years, the total difference between the estimated values and real IBI reached US$ 1.1 billion. A current expenditure of US$ 1.0 was observed for every US$ 5.60 of estimated expenditure. CONCLUSION: - The higher estimates from the BIA might cause decision makers to be more cautious with the introduction of a new medicine to reduce the opportunity costs for other interventions.

Cost-minimization analysis of teledermatology versus conventional care in the Brazilian National Health System.

Aims: Cost-minimization analysis (CMA) comparing the teledermatology service of the State of Santa Catarina, Brazil with the provision of conventional care, from the societal perspective. Patients & methods: All costs related to direct patient care were considered in calculation of outpatient costs. The evaluation was performed using the parameters avoided referrals and profile of hospitalizations. The economic analysis was developed through a decision tree. Results: Totally, 40% of 79,411 tests performed could be managed in primary care, avoiding commuting and expanding the patients' access. The CMA showed the teledermatology service had a cost per patient of US$196.04, and the conventional care of US$245.66. Conclusion: In this scenario, teledermatology proved to be a cost-saving alternative to conventional care, reducing commuting costs.

Lay abstract Diagnosis and treatment of skin diseases through teledermatology avoid patient referrals, improves accessibility to specialized care, as well as the skin care provided by physicians. This study compared the costs of the teledermatology service of the State of Santa Catarina, Brazil with the costs of the provision of conventional care, to check which of them was more efficient. All costs related to direct patient care were considered in the calculation of costs. Totally, 40% of 79,411 dermatological tests performed could be locally managed in primary care, avoiding commuting, and expanding the patients' access to care. The teledermatology service had a cost per patient of US$196.04, compared with the cost of conventional care of US$245.66. In this evaluation, teledermatology proved to be cheaper than conventional care, reducing commuting costs.

Capacidade de exercício e nível de atividade física diária de crianças e adolescentes com fibrose cística: associação com estado nutricional, função pulmonar, hospitalização e uso de antibióticos / Capacidad de ejercicio y nivel de actividad física diaria de niños y adolescentes con fibrosis quística: asociación con estado nutricional, función pulmonar, hospitalización y uso de antibióticos / Exercise capacity and daily physical activity levels in children and adolescents with cystic fibrosis: association with nutritional status, lung function, hospitalization and antibiotic use

RESUMO O objetivo deste trabalho é avaliar a capacidade de exercício e nível de atividade física diária de crianças e adolescentes com fibrose cística e associar com estado nutricional, função pulmonar, tempo de hospitalização e uso de antibióticos. Trata-se de estudo transversal em indivíduos com fibrose cística entre 6 e 18 anos, registrando-se informações sobre perfil clínico, histórico de hospitalizações e uso de antibióticos. Os participantes foram submetidos à espirometria, bioimpedância, avaliação da capacidade de exercício com teste de Shuttle modificado (MST), o nível da atividade física foi medido por meio do questionário internacional de atividade física (IPAQ) e usando acelerômetro por 5 dias. Participaram 30 indivíduos com idade de 11,2 ± 3,6 anos e volume expirado forçado (VEF1) de 68,0 ± 24,8%. A mediana da distância percorrida no MST foi de 820 metros (66,3%) e demonstrou associação com a função pulmonar (r = 0,78), estado nutricional (r = 0,38), tempo de hospitalização (r = -0,42) e uso de antibióticos (r = -0,46). De acordo com o questionário, 20 pacientes (64,6%) foram classificados como sedentários, o acelerômetro revelou que os indivíduos passam 354,2 minutos em atividades sedentárias e apenas 14,9 minutos em atividades moderadas a vigorosas por dia. Quanto maior a porcentagem de tempo em atividade física moderada a vigorosa, maior o índice de massa corpórea (IMC) e menor o tempo de hospitalização. Assim, a capacidade de exercício e nível de atividade física em crianças e adolescentes com fibrose cística apresentou-se reduzida e associada com menores valores de IMC e aumento do tempo de hospitalização.

RESUMEN El propósito de este trabajo fue evaluar la capacidad de ejercicio y el nivel de actividad física diaria de los niños y adolescentes con fibrosis quística, así como asociarlos con el estado nutricional, la función pulmonar, la duración de la permanencia hospitalaria y el uso de antibióticos. Este es un estudio transversal realizado con individuos con fibrosis quística con edades comprendidas entre los 6 y los 18 años, y que registra información sobre el perfil clínico, los antecedentes de hospitalizaciones y el uso de antibióticos. Los participantes se sometieron a la espirometría, la bioimpedancia, la evaluación de la capacidad de ejercicio con la prueba de Shuttle modificada (MST); para medir el nivel de actividad física se aplicó el Cuestionario Internacional de Actividad Física (IPAQ) y el uso del acelerómetro durante 5 días. Participaron 30 personas de entre 11,2 ± 3,6 años de edad y volumen espirado forzado (VEF1) de 68,0 ± 24,8%. La mediana de la distancia recorrida en el MST fue de 820 metros (66,3%) y se mostró asociación con la función pulmonar (r=0,78), el estado nutricional (r=0,38), la duración de la permanencia hospitalaria (r=-0,42) y el uso de antibióticos (r=-0,46). El cuestionario reveló que 20 pacientes (64,6%) estaban sedentarios, y el acelerómetro evidenció que ellos pasan 354,2 minutos en actividades sedentarias y solo 14,9 minutos en actividades moderadas a intensas al día. Cuanto mayor sea el porcentaje de tiempo dedicado a la actividad física moderada a intensa, mayor será el índice de masa corporal (IMC) y menor la duración de la permanencia hospitalaria. Por lo tanto, la capacidad de ejercicio y el nivel de actividad física de niños y adolescentes con fibrosis quística fueron menores y están asociadas con bajos valores de IMC y con una permanencia hospitalaria más prolongada.

ABSTRACT To evaluate the exercise capacity and daily physical activity level among children and adolescents with cystic fibrosis, and its association with nutritional status, lung function, hospitalization time, and days taking antibiotics. This is a cross-sectional study in individuals with cystic fibrosis aged 6 to 18 years. Information on clinical profile, history of hospitalizations and antibiotic use were collected. Participants were submitted to spirometry, bioimpedance, and an assessment of exercise capacity with modified shuttle test (MST), and the level of physical activity was measured with the International Physical Activity Questionnaire (IPAQ) using an accelerometer for 5 days. In total, 30 individuals participated, aged 11.2±3.6 years, and 68.0±24.8% in forced expired volume in the first second (FEV1). The median distance covered in the MST was 820 meters (66.3%), showing association with lung function (r=0.78), nutritional status (r=0.38), hospitalization time (r=-0.42) and antibiotic use (r=-0.46). According to the questionnaire, 20 patients (64.6%) were classified as sedentary, the accelerometer revealed that the individuals spend 354.2 minutes in sedentary activities and only 14.9 minutes in moderate to vigorous activities per day. The higher the percentage of time in moderate to vigorous physical activity, the higher the body mass index (BMI) and the shorter the hospitalization time. Exercise capacity and level of physical activity in children and adolescents with cystic fibrosis is reduced and associated with lower BMI values and with an increase in hospitalization time.

MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice.

The combined allergic rhinitis and asthma syndrome (CARAS) is a chronic airway inflammation of allergic individuals, with a type 2 immune response. Pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study was to evaluate the synthetic alkaloid, MHTP in the experimental model of CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with MHTP by intranasal or oral routes. Treated animals showed a decrease (p < 0.05) of sneezing, nasal rubbings, and histamine nasal hyperactivity. Besides, MHTP presented binding energy and favorable interaction for adequate anchoring in the histamine H1 receptor. MHTP treatment inhibited the eosinophil migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids. Histological analysis showed that the alkaloid decreased the inflammatory cells in the subepithelial and perivascular regions of nasal tissue and in the peribronchiolar and perivascular regions of lung tissue. The MHTP treatment also reduced the pulmonary hyperactivity by decreasing the smooth muscle layer hypertrophy and the collagen fiber deposition in the extracellular matrix. The immunomodulatory effect of the alkaloid was due to the decrease of cytokines like IL-5 and IL-17A (type 2 and 3), TSLP (epithelial), and the immunoregulatory cytokine, TGF-ß. These MHTP effects on granulocytes were dependent on the p38/ERK1/2 MAP kinase signaling pathway axis. Indeed, the synthetic alkaloid reduced the frequency of activation of both kinases independent of the NF-κB (p65) pathway indicating that the molecule shut down the intracellular transduction signals underlie the cytokine gene transcription.

Potentially obesogenic diets alter metabolic and neurobehavioural parameters in Wistar rats: a comparison between two dietary models.

BACKGROUND: Clinical studies related to the obesity pandemic have intensified in recent years, being the animal studies are also considered of great relevance. However, despite the fact that many diets have been reported in the literature to induce obesity in animal models, there is still a gap regarding evidence of the efficacy of these models, considering not only changes in somatic parameters, but also the triggering of comorbidities associated with obesity. In this scenario, the aim of this study was to compare the effectiveness of western and cafeteria diets as obesity-inducing protocols, focusing on the evaluation of metabolic, somatic, oxidative, histological and behavioural parameters of Wistar rats. METHODS: The rats were fed a control (CON), western (WTD) or cafeteria (CAF) diet for 16 weeks. RESULTS: The CAF diet caused anxiogenic-like behaviour. Body mass (BMI), Lee and adiposity indices increased in the CAF group. CAF and WTD diets reduced glucose and insulin tolerance, caused dyslipidemia, increased lipid peroxidation and decrease antioxidant capacity in the liver, kidneys and brain. The WTD and CAF groups shows greater IL-6 protein expression in adipose tissue, developed hepatic steatosis and ischaemic neurons, whereas interstitial nephritis was observed only in the CAF group. CONCLUSION: The CAF diet was most effective in inducing obesity, as shown both by the somatic parameters and by the greater number of obesity-related metabolic and neurobehavioural disorders in the evaluated rats.

Mucuna pruriens Administration Minimizes Neuroinflammation and Shows Anxiolytic, Antidepressant and Slimming Effects in Obese Rats.

This study evaluated the effect of Mucuna pruriens (MP) administration on neuroinflammation and behavioral and murinometric parameters in obese rats. Proximate composition, oligosaccharide and phenolic compound profile of MP were determined. Wistar adult male rats were randomized into healthy (HG) and obese group (OG). The HG consumed a control chow diet while OG consumed a cafeteria diet for eight weeks. Then, they were subdivided into: Healthy (HG); Healthy with MP administration (HGMP); Obese (OG); Obese with MP administration (OGMP), with the consumption of the respective diets remaining for another eight weeks, in addition to gavage with MP extract to supplemented groups (750 mg/kg weight). MP presented a composition rich in proteins and phenolic compounds, especially catechin, in addition to 1-kestose and levodopa. Supplementation reduced food intake, body weight, and thoracic and abdominal circumferences in obese rats. MP showed anxiolytic and antidepressant effects and reduced morphological damage and expression of interleukin 6 in the hippocampus of obese rats. MP treatment showed satietogenic, slimming, anxiolytic and antidepressant effects, besides to minimizing hippocampal neuroinflammation in obese rats. Our results demonstrated the potential anti-obesity of MP which are probably related to the high content of bioactive compounds present in this plant extract.

4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis.

The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 µg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 µL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5-50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome.