High-fat diet elicits sex-based differences in liver inflammatory cytokines and redox homeostasis.

Sex differences in metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Oxidative stress and inflammation are involved in the progression of MASLD. Thus, we aimed to evaluate liver redox homeostasis and inflammation in male and female rats fed a high-fat diet (HFD). Male and female Wistar rats were divided into the following groups: standard chow diet (SCD) or HFD during 12 weeks. HFD groups of both sexes had higher hepatocyte injury, with no differences between the sexes. Portal space liver inflammation was higher in females-HFD compared to females-SCD, whereas no differences were observed in males. Lobular inflammation and overall liver inflammation were higher in HFD groups, regardless of sex. TNF-α, IL-6, and IL-1ß levels were higher in males-HFD compared to males-SCD, but no differences were observed in females. Catalase activity was higher in males compared to females, with no differences between the SCD and HFD groups of both sexes. Glutathione peroxidase activity was higher in females compared to males, with no differences between the SCD and HFD groups in both sexes. Lipid peroxidation was higher in female-SCD when compared to male-SCD, and in both male- and female-HFD compared to SCD groups. Furthermore, both cytoplasmic and nuclear NRF2 staining were lower in the HFD group compared to the SCD group in males. However, female-HFD exhibited reduced nuclear NRF2 staining compared to the female-SCD group. In conclusion, our study demonstrated that while both male and female rats developed metabolic dysfunction-associated steatohepatitis after 12 weeks of HFD, the alterations in inflammatory cytokines and redox balance were sexually dimorphic.

Melatonin supplementation enhances pulmonary rehabilitation outcomes in COPD: a randomized, double-blind, placebo-controlled study.

Melatonin (MLT), the main product of the pineal gland, is involved in muscle tissue repair and regeneration, besides several other important physiologic functions. In COPD, MLT administration can improve lung oxidative stress and sleep quality, but its potential effects on the outcomes of pulmonary rehabilitation (PR) have not been previously investigated. A randomized controlled trial was undertaken to test the hypothesis that a combined approach of rehabilitative exercise training and MLT supplementation could maximize functional performance, health status and quality of life in patients with COPD. Thirty-nine individuals with COPD referred to a supervised PR program at the Federal University of Ceara, Brazil, were randomized to receive MLT (3 mg/day; n = 18) or placebo (n = 21). Exercise capacity (6-min walk test - 6MWT), health status (COPD assessment test), and quality of life (airways questionnaire 20) were investigated as primary outcomes. No differences were observed at baseline in demographic, anthropometric and clinical characteristics between MLT and placebo groups. At the end of PR, superiority of the MLT group was demonstrated in improvement in the distance covered in the 6MWT (71 ± 26 vs. 25 ± 36 m; p < 0.01), health status (-11 ± 6 vs. -3 ± 5; p < 0.01), and quality of life (-6.9 ± 3.0 vs. -1.9 ± 2.4; p < 0.01), compared to the placebo group. In conclusion, MLT supplementation during the course of 12 weeks of PR can improve functional capacity, health status and quality of life in patients with COPD. These findings may have significant implications for the management of this condition.

A New Full-Face Mask for Multifunctional Non-Invasive Ventilation.

Background: Noninvasive ventilation (NIV) provides positive pressure through different interfaces. A multifunctional full-face mask prototype was developed to provide NIV from three sources: ICU ventilators, portable ventilators, and high-flow medical gas pipeline systems. This study aimed to evaluate the usability of this prototype mask. Methods: This was a quantitative experimental study, conducted in two phases: the development of a full-face mask prototype NIV interface, and the evaluation of its usability by health professionals (evaluators) using a heuristic approach. The Wolf Mask prototype is a multifunctional full-face mask that makes it possible to deliver positive pressure from three different sources: microprocessor-controlled ICU ventilators, portable ventilators with single-limb circuits, and high-flow medical gas. The evaluation was conducted in three stages: presentation of the prototype to the evaluators; skills testing via simulation in a clinical environment; and a review of skills. Results: The prototype was developed by a multidisciplinary team and patented in Brazil. The evaluators were 10 health professionals specializing in NIV. Seven skills related to handling the prototype were evaluated. Three of the ten evaluators called for (non-urgent) changes to improve recognition of the components of the prototype. Only one evaluator called for (non-urgent) changes to improve recognition of the pieces, assembly, and checking the mask. Conclusions: The newly developed multifunctional full-face mask prototype demonstrated excellent usability for providing noninvasive ventilation from multiple sources. Minor modifications may further improve the design.

Effect of virgin coconut oil on body weight, white fat depots, and biochemical and morphological parameters in mice fed standard or high-fat diets.

This study investigated the effects of virgin coconut oil (VCO) on body weight, white fat depots, and biochemical and morphological parameters in male Swiss mice fed standard (SD) or high-fat (HFD) diets. Thirty-three adult animals were assigned to one of four groups, as follows: SD, SD plus VCO (SDCO), HFD, and HFD plus VCO (HFDCO). VCO had no effects on the Lee index, subcutaneous fat, periepididymal fat, retroperitoneal fat, area under the curve for glucose, or pancreas weight, all of which were increased by HFD. Low-density lipoprotein cholesterol increased in the SDCO group compared with the SD group and decreased in the HFDCO group compared with the HFD group. VCO increased total cholesterol only in the SDCO group compared with the SD group, with no differences between the HFD and HFDCO groups. In conclusion, low-dose VCO supplementation did not improve obesity, had no effects on hepatic or renal function, and had beneficial effects on the lipid profile only in animals fed HFD.

Profile of patients hospitalized by COVID-19: the importance of hospital epidemiological surveillance / Perfil dos pacientes internados por COVID-19: a importância da vigilância epidemiológica hospitalar / Perfil de pacientes hospitalizados por COVID-19: la importancia de la vigilancia epidemiológica hospitalaria

Rationale: Since December 2019, the novel coronavirus SARS-Cov-2, also called COVID-19, has spread rapidly across countries, making it one of the biggest health challenges of this century. In Brazil, it was declared a public health emergency in March 2020. The aim of this study was to describe the profile of patients hospitalized by COVID-19 in an emergency hospital in the city of Rio de Janeiro, as well as the factors associated with in-hospital death. Methods: Retrospective observational study, which included patients hospitalized between March and December 2020 with a confirmed diagnosis of COVID-19. The epidemiological, clinical, and laboratory aspects were extracted from the epidemiological investigation files and the hospital chart. Results: 582 suspected cases of COVID-19 were hospitalized and 317 were confirmed, of which 182 (57.5%) were male, and most were residents in the north of Rio de Janeiro (42.5%). Main tomographic or radiological findings: ground glass (34.7%) and pulmonary infiltrate (15.4%), and more than half of those hospitalized (64.0%) had at least one comorbidity. Among hospitalized patients, the overall lethality was 53.6%, and among those admitted to the ICU, this percentage was 84.5%. Age and use of ventilatory support and ICU were the variables that showed a statistically significant association with in-hospital mortality. Conclusion: This study reinforces the importance of epidemiological surveillance, in a hospital setting, especially for diseases in which the passive surveillance system may not be able to adequately report, as in the case of COVID-19.(AU)

Justificativa: Desde dezembro de 2019, o novo coronavírus SARS-Cov-2, também chamado COVID-19, tem se espalhado rapidamente pelos países, tornando-se um dos maiores desafios sanitários deste século. No Brasil, ele foi declarado como una emergência de saúde pública em março de 2020. O objetivo deste estudo foi descrever o perfil dos pacientes hospitalizados por COVID-19 em um hospital de emergência no município de Rio de Janeiro, bem como os fatores associados ao óbito hospitalar. Métodos: Estudo observacional retrospectivo, que incluiu pacientes internados entre março e dezembro de 2020 com um diagnóstico confirmado de COVID-19. Os aspectos epidemiológicos, clínicos, e laboratoriais foram extraídos das fichas de investigação epidemiológica e do prontuário hospitalar. Resultados: Foram internados 582 casos suspeitos de COVID-19 e 317 foram confirmados, dos quais 182 (57,5%) eram do sexo masculino, e a maioria era residente na zona norte do Rio de Janeiro (42,5%). Principais achados 'tomográficos ou radiológicos': vidro fosco (34,7%) e infiltrado pulmonar (15,4%), e mais da metade dos hospitalizados (64,0%) apresentava pelo menos uma comorbidade. Entre os pacientes hospitalizados, a letalidade geral foi de 53,6% sendo que entre os internados na UTI esse percentual foi de 84,5%. Idade e uso de suporte ventilatório e UTI foram as variáveis que mostraram associação estatisticamente significante com mortalidade intra-hospitalar. Conclusão: Este estudo reforça a importância da vigilância epidemiológica, em âmbito hospitalar, principalmente para as doenças em que o sistema de vigilância passivo pode não ser capaz de reportar adequadamente, como no caso da COVID-19.(AU)

Justificación: Desde diciembre de 2019, el coronavirus SARS-Cov-2, también llamado COVID-19, se ha extendido rápidamente por los países, convirtiéndose en uno de los mayores retos sanitarios de este siglo. En Brasil, se declaró una emergencia de salud pública en febrero de 2020. El objetivo de este estudio es describir el perfil de los casos hospitalizados por COVID-19 en un hospital de urgencias de la ciudad de Río de Janeiro, así como los factores asociados a la muerte hospitalaria. Métodos: Estudio observacional, retrospectivo, que incluyó pacientes hospitalizados entre marzo y diciembre de 2020 con diagnóstico confirmado de COVID-19. Los aspectos epidemiológicos, clínicos y de laboratorio fueron extraídos del formulario de investigación epidemiológica y de los registros hospitalarios. Resultados: Se hospitalizaron 582 casos sospechosos de COVID-19 y se confirmaron 317, de los cuales 203 (57,5%) eran hombres, la mayoría residentes en el norte de Río de Janeiro (42,5%). Los principales hallazgos tomográficos o radiológicos: vidrio deslustrado (34,7%) e infiltrado pulmonar (15,4%) y más de la mitad de los hospitalizados (64%) tenían al menos 1 comorbilidad. La letalidad global entre los hospitalizados fue del 53,6% y entre los ingresados en la UCI, este porcentaje fue del 84,5%. Las variables que mostraron una asociación estadísticamente significativa con la mortalidad intrahospitalaria fueron la edad, el uso de soporte ventilatorio y el uso de la UCI. Conclusiones: El estudio refuerza la importancia de la vigilancia epidemiológica en el ámbito hospitalario, especialmente para aquellas enfermedades en las que el sistema de vigilancia pasiva puede no informar adecuadamente, como es el caso de la COVID-19.(AU)

MG-Pe: A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine.

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.

Improvement of 2,2'-Azobis(2-Methylpropionamidine) Dihydrochloride-Induced Hepatic Redox Imbalance in Swiss Mice and HepG2 Cells by Rutin.

Redox imbalance can lead to irreversible damages to biological functions. In this context, rutin stands out for its antioxidant potential. The objective of this study was to evaluate the acute and chronic effect of rutin on the hepatic redox imbalance. The study was performed according to three different protocols. First, healthy male Swiss mice were divided into two groups: control and rutin, the second of which received chronic oral supplementation of rutin (10 mg/kg). The second involved evaluation of the generation of reactive oxygen species (ROS) by HepG2 cells, incubated or not with rutin (20 and 40 µg/mL) for 3 h. The final protocol involved assessment of the acute effect of rutin (10 mg/kg) in mice with oxidative stress induced by 2,2'-azobis(2-methylpropionamidine) dihydrochloride (ABAP). After the in vivo treatments, the livers were collected to analyze the oxidative damage by thiol, and the antioxidant defense by catalase, superoxide dismutase, and glutathione peroxidase. In the HepG2 cells, the following probes were employed to assess the ROS production: dichlorofluorescein, MitoSOX, dihydroethidium, and Amplex Red. Rutin administered chronically improved the antioxidant defense in healthy animals, and when administered acutely both inhibited the increased production of ROS in HepG2 cells and improved the redox imbalance parameters in mice with induced oxidative stress. This study suggests rutin as a protective agent for restoration of hepatic redox homeostasis in redox injury induced by ABAP in Swiss mice and HelpG2 cells.

Influences of assisted breathing and mechanical ventilator settings on tidal volume and alveolar pressures in acute respiratory distress syndrome: a bench study. / Influência da ventilação assistida e dos ajustes do ventilador mecânico sobre o volume corrente e as pressões alveolares na síndrome do desconforto respiratório agudo: um estudo de bancada.

OBJECTIVE: To evaluate the influences of respiratory muscle efforts and respiratory rate setting in the ventilator on tidal volume and alveolar distending pressures at end inspiration and expiration in volume-controlled ventilation and pressure-controlled ventilation modes in acute respiratory distress syndrome. METHODS: An active test lung (ASL 5000™) connected to five intensive care unit ventilators was used in a model of acute respiratory distress syndrome. Respiratory muscle efforts (muscle pressure) were configured in three different ways: no effort (muscle pressure: 0cmH2O); inspiratory efforts only (muscle pressure:-5cmH2O, neural inspiratory time of 0.6s); and both inspiratory and expiratory muscle efforts (muscle pressure:-5/+5cmH2O). Volume-controlled and pressure-controlled ventilation modes were set to deliver a target tidal volume of 420mL and positive end-expiratory pressure of 10cmH2O. The tidal volume delivered to the lungs, alveolar pressures at the end of inspiration, and alveolar pressures at end expiration were evaluated. RESULTS: When triggered by the simulated patient, the median tidal volume was 27mL lower than the set tidal volume (range-63 to +79mL), and there was variation in alveolar pressures with a median of 25.4cmH2O (range 20.5 to 30cmH2O). In the simulated scenarios with both spontaneous inspiratory and expiratory muscle efforts and with a mandatory respiratory rate lower than the simulated patient's efforts, the median tidal volume was higher than controlled breathing. CONCLUSION: Adjusting respiratory muscle effort and pulmonary ventilator respiratory rate to a value above the patient's respiratory rate in assisted/controlled modes generated large variations in tidal volume and pulmonary pressures, while the controlled mode showed no variations in these outcomes.

OBJETIVO: Avaliar a influência dos esforços musculares respiratórios e do ajuste da frequência respiratória no ventilador sobre o volume corrente e as pressões de distensão alveolar ao final da inspiração e expiração com ventilação sob os modos controle por volume e controle por pressão na síndrome do desconforto respiratório agudo. MÉTODOS: Utilizou-se um simulador mecânico de pulmão (ASL 5000™) conectado a cinco tipos de ventiladores utilizados em unidade de terapia intensiva, em um modelo de síndrome do desconforto respiratório agudo. Os esforços musculares respiratórios (pressão muscular) foram configurados de três formas distintas: sem esforço (pressão muscular: 0cmH2O), apenas esforços inspiratórios (pressão muscular: - 5cmH2O, tempo inspiratório neural de 0,6 segundos) e esforços musculares inspiratórios e expiratórios (pressão muscular:-5/+5cmH2O). Foram configuradas ventilação sob os modos controle por volume e ventilação com controle por pressão para oferecer um volume corrente de 420mL e pressão positiva expiratória final de 10cmH2O. Avaliaram-se o volume corrente fornecido aos pulmões, as pressões alveolares no final da inspiração e as pressões alveolares no final da expiração. RESULTADOS: Quando disparado pelo paciente simulado, o volume corrente mediano foi 27mL menor do que o volume corrente ajustado (variação-63 a +79mL), e ocorreu uma variação nas pressões alveolares com mediana de 25,4cmH2O (faixa de 20,5 a 30cmH2O). Nos cenários simulados com esforço muscular tanto inspiratório quanto expiratório e com frequência respiratória mandatória inferior à dos esforços do paciente simulado, o volume corrente mediano foi maior com ventilação controlada. CONCLUSÃO: O ajuste do esforço muscular respiratório e da frequência respiratória no ventilador em um valor acima da frequência respiratória do paciente nos modos de ventilação assistida/controlada gerou maiores variações no volume corrente e nas pressões pulmonares, enquanto o modo controlado não mostrou variações nesses desfechos.

Influência da ventilação assistida e dos ajustes do ventilador mecânico sobre o volume corrente e as pressões alveolares na síndrome do desconforto respiratório agudo: um estudo de bancada / Influences of assisted breathing and mechanical ventilator settings on tidal volume and alveolar pressures in acute respiratory distress syndrome: a bench study

RESUMO Objetivo: Avaliar a influência dos esforços musculares respiratórios e do ajuste da frequência respiratória no ventilador sobre o volume corrente e as pressões de distensão alveolar ao final da inspiração e expiração com ventilação sob os modos controle por volume e controle por pressão na síndrome do desconforto respiratório agudo. Métodos: Utilizou-se um simulador mecânico de pulmão (ASL 5000™) conectado a cinco tipos de ventiladores utilizados em unidade de terapia intensiva, em um modelo de síndrome do desconforto respiratório agudo. Os esforços musculares respiratórios (pressão muscular) foram configurados de três formas distintas: sem esforço (pressão muscular: 0cmH2O), apenas esforços inspiratórios (pressão muscular: - 5cmH2O, tempo inspiratório neural de 0,6 segundos) e esforços musculares inspiratórios e expiratórios (pressão muscular:-5/+5cmH2O). Foram configuradas ventilação sob os modos controle por volume e ventilação com controle por pressão para oferecer um volume corrente de 420mL e pressão positiva expiratória final de 10cmH2O. Avaliaram-se o volume corrente fornecido aos pulmões, as pressões alveolares no final da inspiração e as pressões alveolares no final da expiração. Resultados: Quando disparado pelo paciente simulado, o volume corrente mediano foi 27mL menor do que o volume corrente ajustado (variação-63 a +79mL), e ocorreu uma variação nas pressões alveolares com mediana de 25,4cmH2O (faixa de 20,5 a 30cmH2O). Nos cenários simulados com esforço muscular tanto inspiratório quanto expiratório e com frequência respiratória mandatória inferior à dos esforços do paciente simulado, o volume corrente mediano foi maior com ventilação controlada. Conclusão: O ajuste do esforço muscular respiratório e da frequência respiratória no ventilador em um valor acima da frequência respiratória do paciente nos modos de ventilação assistida/controlada gerou maiores variações no volume corrente e nas pressões pulmonares, enquanto o modo controlado não mostrou variações nesses desfechos.

ABSTRACT Objective: To evaluate the influences of respiratory muscle efforts and respiratory rate setting in the ventilator on tidal volume and alveolar distending pressures at end inspiration and expiration in volume-controlled ventilation and pressure-controlled ventilation modes in acute respiratory distress syndrome. Methods: An active test lung (ASL 5000™) connected to five intensive care unit ventilators was used in a model of acute respiratory distress syndrome. Respiratory muscle efforts (muscle pressure) were configured in three different ways: no effort (muscle pressure: 0cmH2O); inspiratory efforts only (muscle pressure:-5cmH2O, neural inspiratory time of 0.6s); and both inspiratory and expiratory muscle efforts (muscle pressure:-5/+5cmH2O). Volume-controlled and pressure-controlled ventilation modes were set to deliver a target tidal volume of 420mL and positive end-expiratory pressure of 10cmH2O. The tidal volume delivered to the lungs, alveolar pressures at the end of inspiration, and alveolar pressures at end expiration were evaluated. Results: When triggered by the simulated patient, the median tidal volume was 27mL lower than the set tidal volume (range-63 to +79mL), and there was variation in alveolar pressures with a median of 25.4cmH2O (range 20.5 to 30cmH2O). In the simulated scenarios with both spontaneous inspiratory and expiratory muscle efforts and with a mandatory respiratory rate lower than the simulated patient's efforts, the median tidal volume was higher than controlled breathing. Conclusion: Adjusting respiratory muscle effort and pulmonary ventilator respiratory rate to a value above the patient's respiratory rate in assisted/controlled modes generated large variations in tidal volume and pulmonary pressures, while the controlled mode showed no variations in these outcomes.

Phytomodulatory proteins isolated from Calotropis procera latex promote glycemic control by improving hepatic mitochondrial function in HepG2 cells.

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.

Acute effects of noninvasive ventilation on sleep physiology in patients with moderate to severe stable chronic obstructive pulmonary disease: a pilot study.

OBJECTIVE/BACKGROUND: Changes in sleep architecture in patients with Chronic Obstructive Pulmonary Disease (COPD) can be explained by a combination of physiological changes in breathing during sleep, with impairment of respiratory mechanics and reduction of arterial oxygenation. This study aimed to evaluate the acute effects of noninvasive ventilation (NIV) - compared to spontaneous breathing - on sleep latency and stages, and on the occurrence of sleep-related respiratory events, nocturnal hypoxemia, and changes in heart rate (HR) in patients with moderate to severe stable COPD. PATIENTS/METHODS: Patients completed two polysomnography (PSG) studies: one during spontaneous breathing and one while receiving NIV in bilevel mode and with backup respiratory rate (RR.) setting. Sleepware G3 software was used for the analysis of PSG and pressure, volume, and ventilator flow curves × time. RESULTS: Participants were 10 female patients with a mean age of 68.1 ± 10.2 years. NIV during sleep decreased sleep onset latency (17 ± 18.8 min vs 46.8 ± 39.5 min; p = 0.02), increased REM sleep time (41.2 ± 24.7 min vs 19.7 ± 21.7 min; p = 0.03), and decreased the obstructive apnea index (OAI) (0 vs 8.7 ± 18.8; p = 0.01). Lower mean HR (66.6 ± 4.1 bpm vs 70.6 ± 5.9 bpm; p = 0.03) and lower maximum HR (84.1 ± 7.3 bpm vs 91.6 ± 7.8 bpm; p = 0.03) were observed in PSG with NIV. CONCLUSIONS: The use of NIV in patients with moderate to severe stable COPD while they were sleeping increased REM sleep time and decreased sleep onset latency, the number of obstructive respiratory events, and the mean and maximum HR.

Scaling up of Eco-Bio-Social Strategy to Control Aedes aegypti in Highly Vulnerable Areas in Fortaleza, Brazil: A Cluster, Non-Randomized Controlled Trial Protocol.

Aedes aegypti is a cosmopolitan vector for arboviruses dengue, Zika and chikungunya, disseminated in all Brazilian states. The Eco-Bio-Social (EBS) strategy is vital in Aedes aegypti control as it mobilizes stakeholders (government, professionals, society, and academics) to promote healthy environments. This paper describes the rationale and methods of expanding the EBS strategy for Aedes aegypti control in Fortaleza, Northeast Brazil. A cluster, non-randomized controlled clinical trial was developed to analyze the strategy's effectiveness in vulnerable territories (high incidence of dengue and violent deaths; low HDI; substandard urban infrastructure, high population density, and water scarcity). We selected two intervention and two control groups, resulting in a sample of approximately 16,000 properties. The intervention consisted of environmental management by sealing large elevated water tanks, introduction of beta fish in waterholes, elimination of potential breeding sites, and mobilization and training of schoolchildren, endemic disease workers, health workers, social mobilizers, and community leaders; community surveillance of arboviruses; construction and validation of a booklet for the prevention of arboviruses in pregnant women. We analyzed the costs of arboviruses to government and households, the intervention cost-effectiveness, chikungunya's chronicity, and acceptance, sustainability, and governance of vector control actions. The primary outcome (infestation) was analyzed using the house, container, and Breteau indices. We hope that this study will help us understand how to scale up strategies to fight Aedes aegypti in vulnerable areas.

Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes.

BACKGROUND: Colorectal cancer (CRC) is among the deadliest cancers, wherein early dissemination of tumor cells, and consequently, metastasis formation, are the main causes of mortality and poor prognosis. Cofilin-1 (CFL-1) and its modulators, LIMK1/SSH1, play key roles in mediating the invasiveness by driving actin cytoskeleton reorganization in various cancer types. However, their clinical significance and prognostic value in CRC has not been fully explored. Here, we evaluated the clinical contribution of these actin regulators according to TNM and consensus molecular subtypes (CMSs) classification. METHODS: CFL-1, LIMK1 and SSH1 mRNA/protein levels were assessed by real-time PCR and immunohistochemical analyses using normal adjacent and tumor tissues obtained from a clinical cohort of CRC patients. The expression levels of these proteins were associated with clinicopathological features by using the chi square test. In addition, using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we determine how these actin regulators are expressed and distributed according to TNM and CMSs classification. Based on gene expression profiling, Kaplan-Meier survival analysis was used to evaluated overall survival. RESULTS: Bioinformatic analysis revealed that LIMK1 expression was upregulated in all tumor stages. Patients with high levels of LIMK1 demonstrated significantly lower overall survival rates and exhibited greater lymph node metastatic potential in a clinical cohort. In contrast, CFL-1 and SSH1 have expression downregulated in all tumor stages. However, immunohistochemical analyses showed that patients with high protein levels of CFL-1 and SSH1 exhibited greater lymph node metastatic potential and greater depth of local invasion. In addition, using the CMSs classification to evaluate different biological phenotypes of CRC, we observed that LIMK1 and SSH1 genes are upregulated in immune (CMS1) and mesenchymal (CMS4) subtypes. However, patients with high levels of LIMK1 also demonstrated significantly lower overall survival rates in canonical (CMS2), and metabolic (CMS3) subtypes. CONCLUSIONS: We demonstrated that CFL-1 and its modulators, LIMK1/SSH1, are differentially expressed and associated with lymph node metastasis in CRC. Finally, this expression profile may be useful to predict patients with aggressive signatures, particularly, the immune and mesenchymal subtypes of CRC.

Effect of an aqueous extract of Chrysobalanus icaco on the adiposity of Wistar rats fed a high-fat diet / Efecto del extracto acuoso de Chrysobalanus icaco sobre la adiposidad de ratas Wistar alimentadas con una dieta alta en grasas

OBJECTIVE: the purpose of this study was to investigate the effects of Chrysobalanus icaco on adiposity and its mechanism of action in the gene and protein expression of acetyl-CoA carboxylase (ACC), a key enzyme in lipogenesis. METHOD: Wistar rats were divided into a regular or control group (CG) and a high-fat diet (HFD) group. HFD was treated with saline or aqueous extract of Chrysobalanus icaco (AECI) for four weeks. Body weight and food intake were assessed. Subcutaneous, retroperitoneal and periepididymal adipose tissue samples were collected and weighed. Adipocytes from periepididymal tissue were isolated and analyzed. The gene and protein expression of ACC in subcutaneous tissue was determined. RESULTS: AECI showed no effect on intake or body weight. However, the weight of the fat pads and the gene and protein expression of ACC were lower, and glucose tolerance was improved. CONCLUSION: the aqueous extract of Chrysobalanus icaco proved beneficial for the treatment of obesity, preventing fat storage and improving glycemic homeostasis

OBJETIVO: el objetivo de este estudio fue investigar los efectos del extracto acuoso de Chrysobalanus icaco (AECI) en la adiposidad y su mecanismo de acción en la expresión génica y proteica de la acetil-CoA-carboxilasa (ACC), una enzima clave para la lipogénesis. MÉTODOS: se usaron ratones macho Wistar que se asignaron a una dieta estándar de control (CG) o a una rica en grasa (HFD). La HFD se trató con solución salina o con extracto acuoso de Chrysobalanus icaco (AECI) durante cuatro semanas. Se evaluaron el peso corporal y el consumo alimentario. Se aislaron y analizaron muestras de tejido adiposo subcutáneo, retroperitoneal y periepididímico. Se determinó la expresión génica y proteica de ACC en el tejido subcutáneo. RESULTADOS: el AECI no mostró ningún efecto sobre la ingesta de alimento y tampoco sobre el peso corporal. Sin embargo, el tratamiento con AECI redujo el peso de los tejidos adiposos y la expresión génica y proteica de ACC, y mejoró también la tolerancia a la glucosa. CONCLUSIÓN: Chrysobalanus icaco (AECI) resultó ser beneficioso para el tratamiento de la obesidad, previniendo el almacenamiento de grasa y mejorando la homeostasis glucémica

Effect of an aqueous extract of Chrysobalanus icaco on the adiposity of Wistar rats fed a high-fat diet.

INTRODUCTION: Objective: the purpose of this study was to investigate the effects of Chrysobalanus icaco on adiposity and its mechanism of action in the gene and protein expression of acetyl-CoA carboxylase (ACC), a key enzyme in lipogenesis. Method: Wistar rats were divided into a regular or control group (CG) and a high-fat diet (HFD) group. HFD was treated with saline or aqueous extract of Chrysobalanus icaco (AECI) for four weeks. Body weight and food intake were assessed. Subcutaneous, retroperitoneal and periepididymal adipose tissue samples were collected and weighed. Adipocytes from periepididymal tissue were isolated and analyzed. The gene and protein expression of ACC in subcutaneous tissue was determined. Results: AECI showed no effect on intake or body weight. However, the weight of the fat pads and the gene and protein expression of ACC were lower, and glucose tolerance was improved. Conclusion: the aqueous extract of Chrysobalanus icaco proved beneficial for the treatment of obesity, preventing fat storage and improving glycemic homeostasis.

INTRODUCCIÓN: Objetivo: el objetivo de este estudio fue investigar los efectos del extracto acuoso de Chrysobalanus icaco (AECI) en la adiposidad y su mecanismo de acción en la expresión génica y proteica de la acetil-CoA-carboxilasa (ACC), una enzima clave para la lipogénesis. Métodos: se usaron ratones macho Wistar que se asignaron a una dieta estándar de control (CG) o a una rica en grasa (HFD). La HFD se trató con solución salina o con extracto acuoso de Chrysobalanus icaco (AECI) durante cuatro semanas. Se evaluaron el peso corporal y el consumo alimentario. Se aislaron y analizaron muestras de tejido adiposo subcutáneo, retroperitoneal y periepididímico. Se determinó la expresión génica y proteica de ACC en el tejido subcutáneo. Resultados: el AECI no mostró ningún efecto sobre la ingesta de alimento y tampoco sobre el peso corporal. Sin embargo, el tratamiento con AECI redujo el peso de los tejidos adiposos y la expresión génica y proteica de ACC, y mejoró también la tolerancia a la glucosa. Conclusión: Chrysobalanus icaco (AECI) resultó ser beneficioso para el tratamiento de la obesidad, previniendo el almacenamiento de grasa y mejorando la homeostasis glucémica.

The Combination of Sulforaphane and Fernblock® XP Improves Individual Beneficial Effects in Normal and Neoplastic Human Skin Cell Lines.

Plenty of evidence supports the health effects exerted by dietary supplements containing phytochemicals, but the actual efficacy and safety of their combinations have been seldom experimentally evaluated. On this basis, we investigated in vitro the antioxidant/antineoplastic efficacy and anti-aging activity of a dietary supplement containing sulforaphane (SFN), a sulfur-isothiocyanate present in broccoli, combined with the patented extract Fernblock® XP (FB), obtained from the tropical fern Polypodium leucotomos. We evaluated the effect of SFN and FB, alone or in combination, on migration ability, matrix metalloproteinases (MMP) production, neoangiogenic potential and inflammasome activation in human WM115 and WM266-4 melanoma cells. Moreover, the effects on MMPs and reactive oxygen species production, and IL-1ß secretion were studied in human normal keratinocytes. The SFN/FB combination inhibited melanoma cell migration in vitro, MMP-1, -2, -3, and -9 production, inflammasome activation and IL-1ß secretion more efficiently than each individual compound did. In normal keratinocytes, SFN/FB was more efficient than SFN or FB alone in inhibiting MMP-1 and -3 production and IL-1ß secretion in the presence of a pro-inflammatory stimulus such as TNF-α. The potential use of SFN/FB based supplements for the prevention of skin aging and as adjuvants in the treatment of advanced melanoma is suggested.

Hypoglycaemic effect of resveratrol in streptozotocin-induced diabetic rats is impaired when supplemented in association with leucine.

Studies have shown synergistic and independent effects of leucine and resveratrol (RSV) as possible therapeutic agents to ameliorate metabolic disorders. Thus, the objective of this study was to investigate the effects of supplementation with leucine and RSV, alone and in combination, on metabolic changes in white adipose tissue of neonatally STZ-induced diabetic rats. After weaning, the rats were treated with trans-resveratrol (0.6 mg/kg/dose) and/or leucine (1.35 mg/kg/dose) administered orally. The animals were euthanized at age 16 weeks for blood analyses. Subcutaneous (SC), periepididymal (PE) and retroperitoneal (RP) fat pads were weighed. Adipocytes from PE and RP pads were isolated for morphometric analysis. Long-term supplementation with RSV promoted adiposity recovery, prevented hypoinsulinemia and improved the metabolic profile of the diabetic rats. However, some of these effects were impaired when RSV was associated with leucine. The diabetic rats supplemented with leucine alone showed no significant improvement in metabolic disorders.

Hipersensibilidade a drogas: um alerta em pacientes portadores de doenças autoimunes / Drug hypersensitivity: an alert in patients with autoimmune diseases

Objetivo: Avaliar a hipersensibilidade a medicamentos em pacientes com o diagnóstico de doenças autoimunes. Métodos: Estudo clínico, analítico, do tipo caso-controle. Foram selecionadas 35 mulheres com doenças autoimunes e 35 sem esse diagnóstico que participaram do protocolo de pesquisa sobre antecedentes de hipersensibilidade a drogas. Resultados: As pacientes apresentavam idade variando de 16 a 66 anos, com a mediana semelhante nos dois grupos. A doença autoimune mais prevalente foi o lupus eritematoso sistêmico, 24/35 (68,5%). A proporção de hipersensibilidade a medicamentos, nas pacientes com doenças autoimunes, foi de 14/35 (40%), e apenas 2/35 (5,7%) no grupo controle (p = 0,0029). As reações de hipersensibilidade do tipo tardia foram as mais frequentes, e na maioria dos casos precederam o diagnóstico de doença autoimune em um total de cinco pacientes, sendo que destas cinco, duas apresentaram síndrome de Stevens Johnson, duas exantema maculopapular, e uma eritema fixo pigmentar. O grupo de drogas mais envolvido foi os anti-inflamatórios não esteroides, seguidos pelos anticonvulsivantes. Conclusão: Hipersensibilidade a medicamentos foi mais frequente em pacientes portadoras de doenças autoimunes, e pode preceder o diagnóstico, especialmente se for do tipo tardia. Estudos adicionais multicêntricos para verificar uma eventual associação de hipersensibilidade a medicamentos e doenças autoimunes são necessários.

Objective: To evaluate drug hypersensitivity in patients with autoimmune diseases. Methods: In this clinical, analytical, casecontrol study, we selected 35 women with autoimmune diseases and 35 women without this diagnosis to participate in this research protocol on history of drug hypersensitivity. Results: Patients' age ranged from 16 to 66 years with similar median in both groups. The most prevalent autoimmune disease was systemic lupus erythematosus, in 24/35 (68.5%) patients. The proportion of drug hypersensitivity was 14/35 (40%) in the autoimmune disease group and only 2/35 (5.7%) in the control group (p = 0.0029). Delayed hypersensitivity reactions were most frequent and preceded the diagnosis of autoimmune disease in five patients, including two with Stevens-Johnson syndrome, two with maculopapular rash and one with fixed pigmented erythema. The most frequently involved group of drugs was nonsteroidal anti-inflammatory drugs, followed by anticonvulsants. Conclusion: Drug hypersensitivity was more common in patients with autoimmune diseases and may precede the diagnosis, especially in delayed-type. Additional multicenter studies are required to evaluate a possible association of drug hypersensitivity to autoimmune diseases.

Sex differences in subcutaneous adipose tissue redox homeostasis and inflammation markers in control and high-fat diet fed rats.

The development of obesity-related metabolic disorders is more evident in male in comparison with female subjects, but the mechanisms are unknown. Several studies have shown that oxidative stress is involved in the pathophysiology of obesity, but the majority of these studies were performed with male animals. The aim of this study was to evaluate the sex-related differences in subcutaneous adipose tissue redox homeostasis and inflammation of rats chronically fed a high-fat diet. NADPH oxidase (NOX), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities were evaluated in the subcutaneous adipose tissue (SC) of adult male and female rats fed either a standard chow (SCD) or a high-fat diet (HFD) for 11 weeks. NOX2 and NOX4 messenger RNA (mRNA) levels, total reduced thiols, interleukin (IL)-1ß, tumor necrosis factor α (TNF-α), and IL-6 were also determined. Higher antioxidant enzyme activities and total reduced thiol levels were detected in SC of control male compared with female rats. Chronic HFD administration increased NOX activity and NOX2 and NOX4 mRNA levels and decreased SOD and GPx activities only in male animals. IL-1ß, TNF-α, and IL-6 levels, as well as Adgre1, CD11b, and CD68 mRNA levels, were also higher in SC of males after HFD feeding. In SC of females, catalase activity was higher after HFD feeding. Taken together, our results show that redox homeostasis and inflammation of SC is sexually dimorphic. Furthermore, males show higher oxidative stress in SC after 11 weeks of HFD feeding owing to both increased reactive oxygen species (ROS) production through NOX2 and NOX4 and decreased ROS detoxification.

Combination of ω-3 fatty acids and cisplatin as a potential alternative strategy for personalized therapy of metastatic melanoma: an in-vitro study.

The recently developed therapeutic strategies have led to unprecedented improvements in the control of metastatic melanoma and in the survival of specific subgroups of patients. However, drug resistance, low response rates, and undesired side effects make these treatments not suitable or tolerable for all the patients, and chemotherapeutic treatments appear still indispensable, at least for subgroups of patients. New combinatory strategies are also under investigation as tailored treatments or salvage therapies, including combined treatments of immunotherapy with conventional chemotherapy. On this basis, and in consideration of the antineoplastic properties of ω-3 polyunsaturated fatty acids, we have here investigated the potential of these bioactive dietary factors to revert the resistance frequently exhibited by this form of cancer to cisplatin (CDDP, cis-diamminedichloroplatinum). We demonstrated that docosahexenoic acid (DHA, 22:6ω-3) sensitizes the cells to the CDDP-induced inhibition of cell growth and migration by reverting CDDP effects on DNA damage and ERCC1 expression, as well as on the DUSP6 and p-ERK expressions, which regulate ERCC1 activation upwardly. In line, DUSP6 gene silencing prevented the effect of DHA, confirming that DHA acted on the DUSP6/p-ERK/ERCC1 repair pathways to sensitize melanoma cells to the anticancer effect of CDDP. Similar effects were obtained also with eicosapentaenoic acid (20:5ω-3). Overall, our findings suggest that the combination of CDDP treatment with a dietary supplementation with ω-3 polyunsaturated fatty acids could potentially represent a new therapeutic strategy for overcoming CDDP resistance in metastatic melanoma.