Unraveling the RAGE-NF-κB pathway: implications for modulating inflammation in diabetic neuropathy through photobiomodulation therapy.

Diabetic peripheral neuropathy (DPN) is a primary complication observed in diabetes that severely affects quality of life. Recent evidence suggests that photobiomodulation (PBM) is a promising therapy against painful conditions and nerve damage. However, the effects of PBM on DPN remains mostly unknown. In the present study, we investigated the efficacy of PBM therapy in modulating proinflammatory cytokine expression in both central and peripheral nervous systems of rats with Streptozotocin (STZ)-induced type 1 diabetes. Male Wistar rats were allocated into control (naïve), diabetic (STZ), and treatment (STZ + PBM) groups. A single intraperitoneal (i.p.) injection of STZ (85 mg/kg) was administered for the induction of diabetes. Animals were subjected to 10 treatment sessions, every other day. The results herein presented indicate that PBM treatment diminishes Receptor for Advanced Glycation End-products (RAGE) and Nuclear Factor Kappa B (NF-Ï°B) expression in peripheral nervous system and suppresses TNF-α expression in central nervous system tissues. Furthermore, PBM-therapy in diabetic rats also induces increased levels of the anti-inflammatory protein IL-10 in both peripheral and central nervous system. Collectively, our findings demonstrate compelling evidence that PBM-therapy modulates cytokine dynamics and influences RAGE/NF-Ï°B axis in a STZ-induced model of type 1 diabetes.

A Curated Cell Life Imaging Dataset of Immune-enriched Pancreatic Cancer Organoids with Pre-trained AI Models.

Tumor organoids are three-dimensional in vitro models which can recapitulate the complex mutational landscape and tissue architecture observed in cancer patients, providing a realistic model for testing novel therapies, including immunotherapies. A significant challenge in organoid research in oncology lies in developing efficient and reliable methods for segmenting organoid images, quantifying organoid growth, regression and response to treatments, as well as predicting the behavior of organoid systems. Up to now, a curated dataset of organoids co-cultured with immune cells is not available. To address this gap, we present a new public dataset, comprising both phase-contrast images of murine and patient-derived tumor organoids of one of the deadliest cancer types, the Pancreatic Ductal Adenocarcinoma, co-cultured with immune cells, and state-of-the-art algorithms for object detection and segmentation. Our dataset, OrganoIDNetData, encompassing 180 images with 33906 organoids, can be a potential common benchmark for different organoids segmentation protocols, moving beyond the current practice of training and testing these algorithms on isolated datasets.

Growth and physiological response of proactive and reactive juvenile "tambaqui" (Colossoma macropomum) in a recirculating aquaculture system.

This study evaluated the growth and physiological response of proactive and reactive Colossoma macropomum juveniles in a recirculating aquaculture system (RAS). In Phase 1 of the experiment (50 days of cultivation), juveniles, weighing 2.16 ± 0.52 g, were stocked in 12 28-L tanks to test the following treatments: proactive (PT), reactive (RT) and mixed (MT) composed of reactive (MRT) and proactive (MPT) animals. In Phase 2 of the experiment (40 days of cultivation), the animals were transferred to 175-L tanks with the same treatments as Phase 1. The animals were fed twice a day with commercial diet during both phases. After Phase 1, MPT animals showed higher growth than MRT animals (P < 0.05), and higher weight gain and daily weight than PT animals (P < 0.05). After Phase 2, PT animals showed higher weight gain and daily weight gain than RT and MT animals (P < 0.05), as did MPT animals compared to PT animals. Performance for RT animals was superior (P < 0.05) to that of MRT animals. Glucose (P < 0.04) and cholesterol (P < 0.01) were higher for RT animals compared to PT animals. Cholesterol was higher for MPT animals compared to MRT animals (P < 0.01), while plasma protein was lower (P < 0.001). Glucose (P < 0.001) and cholesterol (P < 0.01) were higher for MPT animals compared to PT animals and for MRT animals compared to RT animals (glucose P < 0.02, cholesterol P < 0.01). After 90 days of cultivation, proactive animals cultivated separately presented better performance. When cultivated together, reactive animals experienced a decrease in performance and both stress coping styles showed more signs of stress.

Arsenic bioaccumulation and biotransformation in different tissues of Nile tilapia (Oreochromis niloticus): A comparative study between As(III) and As(V) exposure and evaluation of antagonistic effects of selenium.

The speciation of arsenic in fish has been widely investigated, but bioaccumulation and biotransformation of inorganic As in different tissues of Nile tilapia (Oreochromis niloticus) are not fully understood. The present study aimed to investigate the bioaccumulation of As in Nile tilapia, as well as to evaluate the distribution of the main arsenic species (As(III), As(V), MMA, DMA, and AsB) in liver, stomach, gill, and muscle, after controlled exposures to As(III) and As(V) at concentrations of 5.0 and 10.0 mg L-1 during periods of 1 and 7 days. Total As was determined by inductively coupled plasma mass spectroscopy (ICP-MS). For both exposures (As(III) and As(V)), the total As levels after 7-day exposure were highest in the liver and lowest in the muscle. Overall, the Nile tilapia exposed to As(III) showed higher tissue levels of As after the treatments, compared to As(V) exposure. Speciation of arsenic present in the tissues employed liquid chromatography coupled to ICP-MS (LC-ICP-MS), revealing that the biotransformation of As included As(V) reduction to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to nontoxic arsenobetaine (AsB), which was the predominant arsenic form. Finally, the interactions and antagonistic effects of selenium in the bioaccumulation processes were tested by the combined exposure to As(III), the most toxic species of As, together with tetravalent selenium (Se(IV)). The results indicated a 4-6 times reduction of arsenic toxicity in the tilapia.

OrganoIDNet: a deep learning tool for identification of therapeutic effects in PDAC organoid-PBMC co-cultures from time-resolved imaging data.

PURPOSE: Pancreatic Ductal Adenocarcinoma (PDAC) remains a challenging disease due to its complex biology and aggressive behavior with an urgent need for efficient therapeutic strategies. To assess therapy response, pre-clinical PDAC organoid-based models in combination with accurate real-time monitoring are required. METHODS: We established stable live-imaging organoid/peripheral blood mononuclear cells (PBMCs) co-cultures and introduced OrganoIDNet, a deep-learning-based algorithm, capable of analyzing bright-field images of murine and human patient-derived PDAC organoids acquired with live-cell imaging. We investigated the response to the chemotherapy gemcitabine in PDAC organoids and the PD-L1 inhibitor Atezolizumab, cultured with or without HLA-matched PBMCs over time. Results obtained with OrganoIDNet were validated with the endpoint proliferation assay CellTiter-Glo. RESULTS: Live cell imaging in combination with OrganoIDNet accurately detected size-specific drug responses of organoids to gemcitabine over time, showing that large organoids were more prone to cytotoxic effects. This approach also allowed distinguishing between healthy and unhealthy status and measuring eccentricity as organoids' reaction to therapy. Furthermore, imaging of a new organoids/PBMCs sandwich-based co-culture enabled longitudinal analysis of organoid responses to Atezolizumab, showing an increased potency of PBMCs tumor-killing in an organoid-individual manner when Atezolizumab was added. CONCLUSION: Optimized PDAC organoid imaging analyzed by OrganoIDNet represents a platform capable of accurately detecting organoid responses to standard PDAC chemotherapy over time. Moreover, organoid/immune cell co-cultures allow monitoring of organoid responses to immunotherapy, offering dynamic insights into treatment behavior within a co-culture setting with PBMCs. This setup holds promise for real-time assessment of immunotherapeutic effects in individual patient-derived PDAC organoids.

CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial

Abstract Introduction: Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis. Interin-dividual variations in drug response, including single nucleotide polymorphisms, are related to pharmacokinetic and pharmacodynamic changes in these drugs and may lead to a poor therapeutic response. This study aimed to evaluate the influence of CYP2D6 isoenzyme and ABCB1 gene polymorphisms on the frequency of postoperative nausea and vomiting with the use of ondansetron or palonosetron. Methods: A randomized, double-blind clinical trial including 82 women aged 60 years or over undergoing laparoscopic cholecystectomy was conducted. Patients were randomized to receive either ondansetron or palonosetron for postoperative nausea and vomiting prophylaxis. DNA was extracted from saliva. Genetic polymorphisms were analyzed by real-time polymerase chain reaction. The following polymorphisms were analyzed: rs3892097 C/T, rs1128503 A/G, rs16947A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A, and rs20325821 C/A. Results: Overall, vomiting, and severe nausea occurred in 22.5% and 57.5% of patients, respectively. In the palonosetron group, patients with the GG genotype (rs16947 A/G) experienced more severe nausea (p = 0.043). In the ondansetron group, patients with the M genotype (rs16947 A/G) presented mild nausea (p = 0.034), and those with the AA genotype (rs1065852 A/G) experienced more vomiting (p = 0.034). Conclusion: A low antiemetic response was observed with ondansetron in the presence of the AA genotype (rs16947 A/G) and the AA genotype (rs1065852 A/G), and a low therapeutic response was found with palonosetron in the presence of the GG genotype (rs16947 A/G) in laparoscopic cholecystectomy. Register: ClinicalTrials.gov.

Mindful eating durante a gravidez: um estudo comparativo conforme a atenção pré-natal / Mindful eating during pregnancy: a comparative study according to prenatal care

Mudanças no estilo de vida global levaram a comportamentos alimentares disfuncionais durante a gravidez. Nesse sentido, a abordagem Mindful Eating é uma prática com potencial para influenciar positivamente os hábitos alimentares, com impacto benéfico na saúde das gestantes. Para avaliar os níveis de Mindful Eating de mulheres antes e durante a gravidez e associá-los ao tipo de assistência pré-natal (Sistema Único de Saúde ou Setor Privado), foi realizado um estudo transversal com 184 gestantes com idade ≥18 anos, acompanhadas por Sistema Único de Saúde (SUS) ou Setor Privado no município de Lavras-MG, Brasil. Foram coletados dados socioeconômicos e obstétricos e informações sobre Mindful Eating foram obtidas por meio do questionário autoaplicável de Mindful Eating. O Mindful Eating foi maior durante a gravidez do que durante o período pré-gestacional. As gestantes atendidas pelo SUS apresentaram menor nível de Mindful Eating em comparação às mulheres do setor privado. As atendidas pelo SUS obtiveram maiores valores durante o período gestacional na subescala Emocional. As gestantes que atenderam no setor privado obtiveram valores mais elevados durante o período gestacional nas subescalas Consciência, Distração e Desinibição. Durante a gravidez, as mulheres apresentaram níveis mais elevados de Mindful Eating, indicando uma melhoria no comportamento alimentar. A pontuação do Mindful Eating das mulheres atendidas no pré-natal pelo Setor Privado foi superior a das mulheres atendidas pelo SUS, necessitando de intervenção individualizada em cada setor para abranger os fatores socioeconômicos inerentes a cada grupo e sua influência na melhoria dos comportamentos alimentares.

Changes in the global lifestyle have led to dysfunctional eating behaviors during pregnancy. In this sense, the Mindful Eating approach is a practice with the potential to positively influence eating habits, with a beneficial impact on the health of pregnant women. To evaluate the levels of Mindful Eating of women before and during pregnancy and to associate them with the type of prenatal care (Unified Health System or Private Sector), a cross-sectional study was conducted with 184 pregnant women aged ≥18 years, accompanied by the Unified Health System (SUS) or the Private Sector in the municipality of Lavras-MG, Brazil. Socioeconomic and obstetric data were collected, and information on Mindful Eating was obtained through the self-administered Mindful Eating Questionnaire. Mindful Eating was higher during pregnancy than during the pre-gestational period. Pregnant women assisted by SUS showed lower Mindful Eating compared with women in the private sector. Those attended by SUS obtained higher values during the gestational period in the Emotional subscale. Pregnant women who attended in the private sector obtained higher values during the gestational period in the Awareness, Distraction and Disinhibition subscales. During pregnancy, women presented higher levels of Mindful Eating, indicating an improvement in eating behavior. The Mindful Eating score of women attended in prenatal care by the Private Sector was higher than that of women attended by SUS, requiring individualized intervention in each sector to cover the socioeconomic factors inherent to each group and their influence on the improvement of eating behaviors.

Teste de provocação oral com alimentos: o panorama brasileiro / Oral food challenge: a Brazilian panorama

Introdução: O teste de provocação oral (TPO) com alimentos é o padrão ouro para avaliação diagnóstica e de aquisição de tolerância em pacientes com alergia alimentar (AA). Exige, no entanto, equipe especializada e local apropriado para execução, uma vez que reações alérgicas, incluindo anafilaxia, podem acontecer. Foi recém-incorporado como procedimento reconhecido pelo Sistema Único de Saúde e pela Agência Nacional de Saúde, mas apenas no contexto da alergia ao leite de vaca para pacientes com até 24 meses de vida. Pouco se sabe sobre sua disponibilidade/execução no território brasileiro. Objetivos: Explorar o perfil de realização de TPO com alimentos em âmbito nacional, bem como as limitações para a sua não realização. Métodos: Inquérito virtual foi disponibilizado por e-mail aos 2.500 sócios cadastrados na Associação Brasileira de Alergia e Imunologia questionando sobre a prática de TPO, formação do profissional, limitações para sua não realização e possíveis soluções para sua execução. Resultados: Foram obtidas 290 respostas (11,6% dos associados), sendo a maioria deles proveniente da Região Sudeste (56,1%). Realizam TPO 54,5% (158/290) dos associados, 62% destes mais de 5 TPOs/mês, principalmente para leite e ovo. A execução de TPO na atualidade, majoritariamente na rede privada, esteve associada à prática do procedimento durante a especialização. Falta de recurso e ambiente apropriados são as maiores limitações para a não realização do TPO. Conclusões: Apesar do viés de seleção inerente à metodologia empregada do estudo, este inquérito pioneiro em território nacional tem importância por esclarecer e discutir a realização do TPO no âmbito do Brasil. Certamente este procedimento ainda é insuficientemente realizado no Brasil.

Background: Oral food challenge (OFC), the gold standard for diagnosing food allergy and determining tolerance levels, requires specialized staff and appropriate conditions since anaphylaxis may occur. In 2022, OFC was officially recognized in Brazilian public and private health systems, although only for milk allergy in children up to 24 months of age. Little is known about OFC practices in Brazil. Objectives: To explore OFC practices, barriers, and solutions among Brazilian allergists and immunologists. Methods: A survey was e-mailed to 2500 associates of the Brazilian Association of Allergy and Immunology regarding OFC practices, training experiences, barriers to this procedure, and workable solutions. Results: A total of 290 associates responded (11.6%), more than a half of whom (56.15) practiced in the southeast region: 158 (54.5%) reported performing OFC, of whom 62% performed > 5 procedures each month, mostly for cow milk and hen egg. OFCs were mostly performed in private practice and were associated with specialized training. Lack of an appropriate setting was seen as the main barrier to performing the procedure. Conclusions: Although this study's methodology involves intrinsic biases, this is the first exploration of OFC practice in Brazil. OFCs are still underperformed nationwide.

Homozygous CDH2 variant may be associated with hypopituitarism without neurological disorders.

Context: Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition. Objectives: The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant. Design: Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing. Results: One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected. Conclusion: A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations. Significance statement: A female patient with hypopituitarism was born from consanguineous parents and had a homozygous, likely pathogenic, CDH2 variant that impairs cell aggregation in vitro. No other likely pathogenic variants in CDH2 were identified in 145 hypopituitarism patients.

CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial.

INTRODUCTION: Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis. Interindividual variations in drug response, including single nucleotide polymorphisms, are related to pharmacokinetic and pharmacodynamic changes in these drugs and may lead to a poor therapeutic response. This study aimed to evaluate the influence of CYP2D6 isoenzyme and ABCB1 gene polymorphisms on the frequency of postoperative nausea and vomiting with the use of ondansetron or palonosetron. METHODS: A randomized, double-blind clinical trial including 82 women aged 60 years or over undergoing laparoscopic cholecystectomy was conducted. Patients were randomized to receive either ondansetron or palonosetron for postoperative nausea and vomiting prophylaxis. DNA was extracted from saliva. Genetic polymorphisms were analyzed by real-time polymerase chain reaction. The following polymorphisms were analyzed: rs3892097 C/T, rs1128503 A/G, rs16947 A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A, and rs20325821 C/A. RESULTS: Overall, vomiting, and severe nausea occurred in 22.5% and 57.5% of patients, respectively. In the palonosetron group, patients with the GG genotype (rs16947 A/G) experienced more severe nausea (p = 0.043). In the ondansetron group, patients with the AA genotype (rs16947 A/G) presented mild nausea (p = 0.034), and those with the AA genotype (rs1065852 A/G) experienced more vomiting (p = 0.034). CONCLUSION: A low antiemetic response was observed with ondansetron in the presence of the AA genotype (rs16947 A/G) and the AA genotype (rs1065852 A/G), and a low therapeutic response was found with palonosetron in the presence of the GG genotype (rs16947 A/G) in laparoscopic cholecystectomy. REGISTER: ClinicalTrials.gov.

The Mini Nutritional Assessment-Short Form is more effective in predicting clinical outcomes among hospitalised patients with overweight than the Nutritional Risk Screening-2002.

Understanding of the association between nutritional risk and clinical outcomes in hospitalised patients with overweight is still at an early stage. Given the lack of specific tools for the patient with overweight, the objective of this study was to compare two of the main general screening instruments for assessing nutritional risk in predicting clinical outcomes in a population of hospitalised patients with overweight. A retrospective study was carried out in a medium-sized hospital in Brazil, with patients ≥20 years old admitted between July 2017 and December 2019. Patients who were overweight and had records of Nutritional Risk Screening-2002 (NRS-2002) and Mini-Nutritional Assessment-Short Form (MNA-SF) in their medical files were included in the study. Clinical outcomes data (longer length of stay, readmission during the study period and mortality before the end of study or during hospitalisation) were obtained. The Kappa coefficient assessed agreement between both tools, and their performance for predicting outcomes was analysed using characteristic receiver operating curves (ROC). Data were collected from 643 patients. The prevalence of nutritional risk was 17.7% and 36.1% according to the NRS-2002 and MNA-SF (k = 0.390; p < 0.001), respectively. According to both tools, all clinical outcomes were significantly more common among individuals at nutritional risk (p < 0.05). Only the MNA-SF showed a significant percentage of predictions for readmission (57.2%) and death during hospitalisation (65.7%). For mortality until the end of the study, the area under the ROC curve was similar for MNA-SF (60.5%) and NRS-2002 (60.7%; p = 0.057). The MNA-SF detected a greater proportion of nutritional risk among hospitalised patients with overweight and better predicted all clinical outcomes compared to the NRS-2002 and should be used to screen patients with overweight for nutritional risk.

Brain damage serum biomarkers induced by COVID-19 in patients from northeast Brazil.

Neurological symptoms have been often reported in COVID-19 disease. In the present study, we evaluated brain damage associated with the increase of serum levels of neurological biomarkers S100B and neuron-specific enolase (NSE) induced by SARS-CoV-2 infection, in a population from Northeastern Brazil. Thirty-six healthy control (G1) individuals and 141 patients with confirmed COVID-19 were enrolled in this study. Positive-COVID-19 patients were divided into two groups according to the severity of illness by the National Institute of Health (NIH) criteria, 76 patients with mild symptoms for COVID-19 and (G2) and 65 with acute respiratory conditions requiring supplemental oxygenation via intensive care unit (ICU) admission (G3). A follow-up study was conducted with 23 patients from G2 14 (D14) and 21 (D21) days after the onset of symptoms. Serum levels of NSE and S100B were measured using the enzyme-linked immunoassay method (ELISA). Results revealed a significant positive association between G3 patients and S100B serum expression (p = 0.0403). The serum levels of NSE were also significantly enhanced in the G3 group compared to the control (p < 0.0001) and G2 group (p < 0.0001). In addition, clinical features such as symptoms and oxygenation status were not correlated with NSE or S100B serum expression. The follow-up study demonstrated a decrease over time (21 days) in NSE serum expression (p < 0.0001). These results suggest that brain damage is followed by acute virus exposure, with no long-term effects. Future work examining COVID-19 recovery will shed light on chronic neurological damage of SARS-CoV-2 infection.

Customized Photobiomodulation Modulates Pain and Alters Thermography Pattern in Patients with Knee Osteoarthritis: A Randomized Double-Blind Pilot Study.

Background: Photobiomodulation therapy (PBMT) modulates a wide variety of biological processes, leading to anti-inflammatory and analgesic effects. Understanding the mechanisms underlying therapeutic effects of PBMT remains challenging due to varying outcomes observed between wavelengths, dosage, and site of application. Our research group has dedicated close attention to customization and individualization of dosimetry for PBMT protocols. Preliminary data showed that using an individualized treatment could solve contradictory results reported by previous studies. Based on literature and our preliminary data on light absorption, the goal of the present pilot is to determine whether our individualized dosimetry is a feasible method to assist osteoarthritis (OA) pain control. Methods: This parallel two-arm controlled-pilot study aimed to assess whether personalized PBMT can be effective in the treatment of painful chronic knee OA. Thirty-one patients were randomly allocated into treatment and placebo group (sham irradiation), and the treatment procedure was performed twice a week, for 5 weeks. The PBMT was applied using 850 nm with continuous wave and a total of 526-1402 J each session. Individualized dosimetry was chosen based on each patient's body mass index and skin color. Quality-of-life (QOL) questionnaires and serum/urine analyses were performed before and after treatment was over. Both examiners and participants were blinded to group allocation. Results: Pain scores were reduced significantly in the 4th, 5th, and 10th sessions and remained lower 6 weeks posttherapy in the treatment group when compared to the placebo group. Moreover, the treatment group's results were improved in QOL questionnaires score, dopamine level, and in microcirculation. Conclusions: The present results provide initial evidence that customized photobiomodulation (PBM) reduce pain levels in short- and medium-term in patients with symptomatic knee OA when compared to placebo group. Furthermore, we have provided evidence that customized PBM is able to improve the QOL of those patients.

Serum biomarkers associated with SARS-CoV-2 severity.

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice.

Low-grade inflammation of the hypothalamus is associated with the disturbance of energy balance. The endocannabinoid system has been implicated in the development and maintenance of obesity as well as in the control of immune responses. The type 2 cannabinoid receptor (CB2) signaling has been associated with anti-inflammatory effects. Therefore, in high fat diet (HFD)-induced obese mice, we modulated CB2 signaling and investigated its effects on energy homeostasis and hypothalamic microgliosis/astrogliosis. We observed no effect on caloric intake and body weight gain in control diet-fed animals that received prolonged icv infusion of the CB2 receptor agonist HU308. Interestingly, we observed a decrease in glucose tolerance in HFD-fed animals treated with HU308. Prolonged icv infusion of HU308 increases astrogliosis in the ventromedial nucleus (VMH) of obese animals and reduced HFD-induced microgliosis in the hypothalamic arcuate (ARC) but not in the paraventricular (PVN) or VMH nuclei. These data indicate that central CB2 signaling modulates glucose homeostasis and glial reactivity in obesogenic conditions, irrespective of changes in body weight.

Flavanone Glycosides, Triterpenes, Volatile Compounds and Antimicrobial Activity of Miconia minutiflora (Bonpl.) DC. (Melastomataceae).

Chemical composition of the essential oils and extracts and the antimicrobial activity of Miconia minutiflora were investigated. The flavanone glycosides, pinocembroside and pinocembrin-7-O-[4″,6″-HHDP]-ß-D-glucose, were identified, along with other compounds that belong mainly to the triterpene class, besides the phenolics, gallic acid and methyl gallate. Sesquiterpenes and monoterpenes were the major compounds identified from the essential oils. Screening for antimicrobial activity from the methanolic extract of the leaves showed that the MIC and MMC values against the tested microorganisms ranged from 0.625 to 5 mg·mL−1 and that the extract was active against microorganisms, Staphyloccocus aureus, Escherichia coli, and Bacillus cereus.

Introdução dos alimentos no primeiro ano de vida e prevenção da alergia alimentar: quais as evidências? / Introduction of food in the first year of life and food allergy prevention: what is the evidence?

Objetivo: A incidência das doenças alérgicas cresceu nas últimas décadas. Na tentativa de conter o aumento da alergia alimentar (AA) ao longo dos anos, estratégias de prevenção vêm sendo implementadas. Para promover um melhor entendimento dos dilemas que permeiam a introdução alimentar no primeiro ano de vida, esse artigo trata de uma revisão bibliográfica narrativa sobre a introdução dos alimentos complementares no primeiro ano de vida e possíveis associações com a prevenção primária da alergia alimentar. Fonte dos dados: Publicações relevantes foram pesquisadas nas bases de dados Cochrane Library, MEDLINE, PubMed, Guidelines International Network, National Guidelines Clearinghouse e revisadas recomendações do guia e do consenso nacional de alergia alimentar. Resultados: Estudos observacionais diversos e ensaios clínicos randomizados estão disponíveis, bem como recomendações publicadas por organizações científicas; no entanto, de qualidade variável. Foram consideradas as recomendações de diretrizes de prática clínica classificadas como de alta qualidade e publicações recentes ainda não categorizadas de forma sistemática em sua qualidade, mas internacionalmente reconhecidas como relevantes para a atenção primária. Conclusão: Até o momento, não há evidências consistentes de que a introdução precoce, antes dos 6 meses, dos alimentos alergênicos, contribua para a prevenção de alergia a alimentos na população geral.

Objective: The incidence of allergic diseases has increased in recent decades. In an attempt to contain the increase in food allergy (AA) over the years, prevention strategies have been implemented. To promote a better understanding of the dilemmas that permeate the introduction of food in the first year of life, this article deals with a narrative literature review on the introduction of complementary foods in the first year of life and possible associations with the primary prevention of food allergy. Data source: Relevant publications were searched in the Cochrane Library, MEDLINE, PubMed, Guidelines International Network, National Guidelines Clearinghouse, and revised recommendations from the national food allergy guide and consensus. Results: Several observational studies and randomized controlled trials are available, as well as recommendations. published by scientific organizations; however, of variable quality. Recommendations from clinical practice guidelines classified as high quality and recent publications not yet systematically categorized in their quality, but internationally recognized as relevant to primary care, were considered. Conclusion: To date, there is no consistent evidence that the early introduction, before 6 months, of allergenic foods contributes to the prevention of food allergy in the general population.

An Alternative Technique for Monitoring the Live Interaction of Monocytes and Tumor Cells with Nanoparticles in the Mouse Lung.

Nanomaterials are increasingly used for the diagnosis and treatment of cancer, including lung cancer. For the clinical translation of nano-based theranostics, it is vital to detect and monitor their accumulation in the tumor, as well as their interaction with tumor, immune cells, and the tumor microenvironment (TME). While high resolution microscopy of fixed tumor specimens can provide some of this information from individual thin slices, it cannot capture cellular events over time and lacks 3D information of the tumor tissue. On the other hand, in vivo optical procedures either fall short of providing the necessary cellular resolution, as in the case of epifluorescence optical imaging, or are very demanding, as for instance intravital lung microscopy. We describe an alternative approach to investigate nanoparticle-cell interactions in entire mouse lung lobes, by longitudinal live cell confocal microscopy at nanometer resolution. By filling the lung ex vivo with 1% agarose, we were able to stabilize the lung lobes and visualize the interaction of fluorescent cells and nanoparticles for at least 4 hours post mortem. This high resolution ex vivo live cell imaging approach is an easy 4D tool for assessing several dynamic processes in tumor tissue, such as the traffic of cells, shedding of extracellular vesicles (EVs), and the accumulation of nanoparticles in tumor tissue. Graphic abstract: Schematic of the workflow for live cell imaging in the mouse lung.

Consumption of carbonated soft drinks, fruits and vegetables and association with macroeconomic indicators: the analysis of students from seventy-four countries (2003-2015).

This study aimed to compare fruits and vegetables (FV), and carbonated soft drink (CSD) consumption among adolescents from seventy-four countries, according to macroeconomic indicators. This is an ecological study, developed with countries evaluated through the Global School-based Student Health Survey (2003-2014) and the National School Health Survey (PeNSE-Brazil, 2015). The percentages of students in each country who consumed CSD and FV daily and their association with the Human Development Index (HDI) and the Gross National Income per capita (GNIpc) were assessed. Scatter plots were constructed for each marker, and a multilevel model was tested to consider the effects of region in the associations. The overall prevalence of daily CSD consumption was 54·1 %. CSD consumption was positively associated with HDI and GNIpc through multilevel models, and Central and South America showed a considerable higher consumption compared with other regions. Overall, FV daily consumption was 67·9 % and 74·6 %, respectively, and no associations with macroeconomic indicators were found. The study shows concerning rates of CSD consumption among adolescents, and a trend of increased consumption with the improvement of the country's development and GNIpc. This points for the importance of public policies that regulate food and beverage industries to reduce CSD consumption and related co-morbidities among adolescents.

Is the management of obesity in primary health care appropriate in Brazil?

This study aims to describe the adequacy of basic health units (UBS) in Brazil regarding structure and work process for obesity management and to evaluate user satisfaction with primary health care services. This cross-sectional study was conducted with data from the 2013-2014 National Program for Improving Primary Care Access and Quality (PMAQ) - an initiative to assess primary health care teams' performance. Data were collected between 2013 and 2014 through interviews with primary health care teams and users. All indicators of adequate care for obesity were defined within the article scope, based on data from the PMAQ. Of the 24,055 UBS analyzed, located in 4,845 different cities, only 7.6% had adequate structure for obesity management. Likewise, only 26.6% of the 114,615 users interviewed reported adequate access, and 27.8% of the UBS showed adequate service organization. Healthcare was considered as "good" or "very good" by 82.4% of users. These indicators varied according to geographic region, showing better results for the South and Southeast. Our results suggest that the country may still be at the initial stage of systematizing care with obesity, presenting significant disparities among regions.