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The aim of this study was to assess the reliability and external validity of the Previous Day Food Questionnaire (PDFQ) designed to obtain a report of the foods eaten on the previous day by schoolchildren. Participants were 7-10-year-old school children of the first four grades of a public school in Southern Brazil (N=227). Test-retest reliability was evaluated by kappa coefficient for two administrations of the PDFQ on the same day to the same children. External validity of the PDFQ was evaluated via sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) using trained observers of the food eaten on the previous day as gold standard. The association between responses from observed food intake with those from reported food intake on PDFQ was evaluated by multivariate logistic regression, controlled for school grade, gender, time of the eating, and the variation between first and second PDFQ applications. For the reliability study, the analyses stratified by school eating occasions (3 a day) indicated that agreement level was moderate or better for all food categories. PDFQ's sensitivity ranged from 57.1% (vegetables) to 93.3% (rice), whereas its specificity ranged from 77.8% (bread/pasta) to 98% (meats). Both, PPV and NPV were reasonably high. PDFQ was highly associated with observed food intake, with effect magnitude several times larger than any other factor analyzed for all foods. PDFQ also showed good test-retest reliability, suggesting that it may generate reliable and valid data for assessing food intake at the group (school) level. [ABSTRACT FROM AUTHOR]

BACKGROUND: A population of over 12,000 mature subjects participated in a longitudinal study (8 years) of nutrition and health (the Su.Vi.Max Study). In this context, a specific cross-sectional study was carried out in a randomly selected subpopulation. AIM: To identify anthropometric, nutritional and biochemical correlates of spontaneous use of 'light' foods and drinks in a free-living population. DESIGN: Men (n = 2299) and women (n = 1979), 45-60 years, reported their food intakes over six non-consecutive days. Consumers of low-fat and low-sugar foods and drinks, and artificial sweeteners, were compared with non-consumers. RESULTS: Users of low-sugar products were heavier than non-users; female consumers of low-fat products, but not males, had higher body weight and BMI than non-consumers. Users of low-sugar products had higher triacylglycerols and glycaemia than non-users while biochemical parameters were not different in users and non-users of low-fat products. Use of low-sugar products led to increased diet density of a few micronutrients, including cholesterol. Low-fat product selection was associated with increased intake of most micronutrients, both in absolute value and in density. CONCLUSIONS: In mature adults, selection of fat-reduced products was associated with improved quality of the diet, while anthropometric and biological parameters appeared less favourable in consumers of low-sugar products vs. non-consumers. The longitudinal follow-up of the cohort in future years will help determine cause-and-effect relationships among these parameters. [ABSTRACT FROM AUTHOR]

Introduction: The Second Expert Report, Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective from World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR), features general and special recommendations for cancer prevention. Objective: To evaluate nutritional and lifestyle characteristics of newly diagnosed women with breast cancer according to WCRF/AICR Second Report recommendations. Methods: This is a cross-sectional study with a sample of 133 women. Diet data were obtained from a food frequency questionnaire and anthropometric data by standard procedures. The characteristics of study population were evaluated in comparison with the recommendations of the WCRF/AICR Second Report. Results: Mean age of participants was 51.6 ± 10.98 (range 28-78) years; 35% was obese and 51% had waist circumference higher than the maximum cut-off value. Regarding life style, 80% of participants were sedentary, 89% reported diet presenting energy density higher than 125 kcal/100 g, 51% reported consumption of fruits and vegetables lower than 400 g/day, and 47% reported high consumption of red or processed meat (≥ 500 g per week). Just 3% related consumption of alcoholic beverages above the recommendation (15 g/day), 82% presented the intake of sodium lower than the limit recommended (2.4 g/day), and the use of dietary supplements was reported by 11% of the subjects. Finally 51% of women reported breast feeding for less than 6 months. Conclusion: Inadequacies were observed related to behavior factors that can result in weight gain, such as inadequate physical activity and high energy density diet. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effect of breastfeeding on reducing Pentavalent vaccination pain in infants and to identify the necessary breastfeeding interval for antinociceptive action., Method: Open parallel randomized clinical trial. Ninety mother-infant dyads participated, distributed into intervention group 1 (n = 30), which breastfed five minutes before vaccination; intervention group 2 (n = 30), which breastfed five minutes before and during vaccination; and control group (n = 30), which did not breastfeed. The outcome variable was the pain level measured by the FLACC Scale. Data analysis was conducted using descriptive and inferential statistics, applying Fisher's Exact, Kolmogorov-Smirnov, Kruskal-Wallis and Dunn's multiple comparison tests, with 0.05 significance level., Results: Pain induced by the Pentavalent vaccine was reduced in intervention groups 1 and 2 (mean pain of 6.06 versus 3.83, respectively) compared to the control group (mean of pain of 7.43), which was significant for intervention group 2 (p < 0.001), indicating that, to achieve lower levels of pain, breastfeeding should be carried out before and during vaccination., Conclusion: Longer breastfeeding, conducted five minutes before and during vaccination, reduces the pain induced by the Pentavalent vaccine. No vaccination risks were identified to outweigh the benefits. These results endorse that health professionals should encourage breastfeeding at least five minutes before and during vaccine injection for an antinociception effect. Brazilian Clinical Trials Registry: RBR-9vh37wr.

Trichoderma erinaceum is a filamentous fungus that was isolated from decaying sugarcane straw at a Brazilian ethanol biorefinery. This fungus shows potential as a source of plant cell wall-degrading enzymes (PCWDEs). In this study, we conducted a comprehensive multiomics investigation of T. erinaceum to gain insights into its enzymatic capabilities and genetic makeup. Firstly, we performed genome sequencing and assembly, which resulted in the identification of 10,942 genes in the T. erinaceum genome. We then conducted transcriptomics and secretome analyses to map the gene expression patterns and identify the enzymes produced by T. erinaceum in the presence of different substrates such as glucose, microcrystalline cellulose, pretreated sugarcane straw, and pretreated energy cane bagasse. Our analyses revealed that T. erinaceum highly expresses genes directly related to lignocellulose degradation when grown on pretreated energy cane and sugarcane substrates. Furthermore, our secretome analysis identified 35 carbohydrate-active enzymes, primarily PCWDEs. To further explore the enzymatic capabilities of T. erinaceum , we selected a β-glucosidase from the secretome data for recombinant production in a fungal strain. The recombinant enzyme demonstrated superior performance in degrading cellobiose and laminaribiose compared to a well-known enzyme derived from Trichoderma reesei . Overall, this comprehensive study provides valuable insights into both the genetic patterns of T. erinaceum and its potential for lignocellulose degradation and enzyme production. The obtained genomic data can serve as an important resource for future genetic engineering efforts aimed at optimizing enzyme production from this fungus.

Context: A systematic study of hydrogen bonds in base pairs and the interaction of cisplatin with DNA fragments was carried out. Structure, binding energies, and electron density were analyzed. xTB has proven to be an accurate method for obtaining structures and binding energies in DNA structures. Our xTB values for DNA base binding energy were in the same order and in some cases better than CAM-B3LYP values compared to experimental values. Double-stranded DNA-cisplatin structures have been calculated and the hydrogen bonds of water molecules are a decisive factor contributing to the preference for the cisplatin-Guanine interaction. Higher values of the water hydrogen bonding energies were obtained in cisplatin-Guanine structures. Furthermore, the electrostatic potential was used to investigate and improve the analysis of DNA-cisplatin structures., Methods: We applied the xTB method and the CAM-B3LYP functional combined with def2-SVP basis set to perform and analyze of the bonding energies of the cisplatin interaction and the effects of the hydrogen bonds. Results were calculated employing the xTB and the ORCA software., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Functional constipation can lead to painful defecations, fecal incontinence, and abdominal pain, significantly affecting a child's quality of life. Treatment options include non-pharmacological and pharmacological approaches, but some cases are intractable and require alternative interventions like neuromodulation. A subtype of neuromodulation, called Transcutaneous Posterior Tibial Nerve Stimulation (TPTNS), comprises electrical stimulation at the ankle level, by means of electrodes fixed to the skin. TPTNS is a minimally invasive, easy-to-apply technique that can potentially improve constipation symptoms in the pediatric population by stimulating the sacral nerves., Aim: To evaluate the clinical results and applicability of TPTNS as an adjuvant treatment for children and adolescents with functional constipation., Methods: Between April 2019 and October 2021, 36 patients diagnosed with functional constipation according to the Rome IV Criteria were invited to participate in the study. The study followed a single-center, uncontrolled, prospective cohort design. Patients received TPTNS for 4 or 8 weeks, with assessments conducted immediately after the periods of TPTNS and 4 weeks after the end of the intervention period. The data normality distribution was determined by the Shapiro-Wilk test. The Wilcoxon test and Student's t -test for paired samples were used to compare quantitative variables, and the McNemar test was used to compare categorical variables., Results: Of the 36 enrolled patients, 28 children and adolescents with intractable function constipation completed the study, receiving TPTNS for 4 weeks. Sixteen patients (57.1%) extended the intervention period for 4 extra weeks, receiving 8 weeks of intervention. TPTNS led to significant improvements in stool consistency, frequency of defecation, and bowel function scores, with a reduction in abdominal pain. Quality of life across physical and psychosocial domains showed substantial enhancements. The quality of life-related to bowel habits also improved significantly, particularly in lifestyle, behavior, and embarrassment domains. The positive effects of this intervention are seen relatively early, detected after 4 weeks of intervention, and even 4 weeks after the end of the intervention. TPTNS was well-tolerated, with an adherence rate of approximately 78%, and no adverse effects were reported., Conclusions: TPTNS is an adjuvant treatment for intractable functional constipation, improving bowel function and quality of life. The effects of TPTNS were observed relatively early and sustained even after treatment cessation.

Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors., Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH., Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037)., Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

The upper body and trunk muscles are crucial to perform soccer kicks. Resistance training targeting these muscles may modify the pattern adopted during kicking. This study aimed to investigate the effect of resistance training of the arm and anterior trunk muscles on instep kicking kinematics. Twenty-six male participants were randomly allocated into a training group or control group. The training group underwent resistance training of arm and trunk muscles and practiced the instep kick for 8 weeks. The control group only practiced kicking during the same period. The trunk, hip, and knee kinematics were assessed during the instep kick before and after the intervention. Kinematics were analyzed according to their data distribution with statistical parametric or nonparametric mapping. The effect of the training on the 1-repetition maximum test was analyzed using a repeated-measures multivariate analysis of variance. The training group showed greater hip extension after the training during the backswing phase (Hedge g effect size of 0.316-0.321) and increased 1-repetition maximum for all exercises. There were no other differences. The present study documented the nonlocal effect of strengthening training in which arm and trunk muscle training resulted in changes in hip kinematics during the backswing phase of the instep kick.

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here., Competing Interests: The authors declare no conflict of interest.

Background: Propolis exhibits huge potential in the pharmaceutical industry. In the present study, its effects were investigated on dendritic cells (DCs) stimulated with a tumor antigen (MAGE-1) and retinoic acid (RA) and on T lymphocytes to observe a possible differential activation of T lymphocytes, driving preferentially to Th1 or Treg cells., Methods: Cell viability, lymphocyte proliferation, gene expression (T-bet and FoxP3), and cytokine production by DCs (TNF-α, IL-10, IL-6 and IL-1β) and lymphocytes (IFN-γ and TGF-β) were analyzed., Results: MAGE-1 and RA alone or in combination with propolis inhibited TNF-α production and induced a higher lymphoproliferation compared to control, while MAGE-1 + propolis induced IL-6 production. Propolis in combination with RA induced FoxP3 expression. MAGE-1 induced IFN-γ production while propolis inhibited it, returning to basal levels. RA inhibited TGF-β production, what was counteracted by propolis., Conclusion: Propolis affected immunological parameters inhibiting pro-inflammatory cytokines and favoring the regulatory profile, opening perspectives for the control of inflammatory conditions., Competing Interests: Competing interests: The authors declare that they have no conflicts of interest to disclose.

Mayaro virus (MAYV, Togaviridae) and Oropouche orthobunyavirus (OROV, Peribunyaviridae) are emerging enzootic arboviruses in Latin America. Outbreaks of febrile illness associated with MAYV and OROV have been reported among humans mainly in the northern region of Brazil since the 1980s, and recent data suggest these viruses have circulated also in more populated areas of western Brazil. MAYV shares mosquito vectors with yellow fever virus and it has been historically detected during yellow fever epidemics. Aiming to investigate the transmission of OROV and MAYV at the human-animal interface during a yellow fever, chikungunya and Zika outbreaks in Brazil, we conducted a retrospective molecular investigation in 810 wild and domestic animals, 106 febrile patients, and 22.931 vectors collected from 2016 to 2018 in Cuiaba and Campo Grande metropolitan regions, western Brazil. All samples tested negative for OROV and MAYV RNA by RT-qPCR. Findings presented here suggest no active circulation of MAYV and OROV in the sampled hosts. Active surveillance and retrospective investigations are instrumental approaches for the detection of cryptic and subclinical activity of enzootic arboviruses and together serve as a warning system to implement appropriate actions to prevent outbreaks., Competing Interests: The authors declare no conflict of interest., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: In the absence of direct therapy for COVID-19, extracorporeal blood treatment (EBT) could represent an option for cytokine removal., Objective: This study aimed to describe and compare cytokine removal during intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT) in COVID-19 patients with Acute Kidney Injury (AKI)., Methods: It was a cohort study that studied patients with COVID-19-related AKI according to KDIGO criteria and admitted at Intensive Care Unit (ICU). Blood samples were collected at the start and end of both IHD using high flux (HF) membranes (10 patients) and continuous venovenous haemodiafiltration (CVVHDF:10 patients) in two sessions for measuring 13 different plasma interleukins and calculating the cytokine removal rate., Results: There was no difference between the two groups regarding mechanical ventilation, vasoactive drug, age or prognostic scores. Patients treated by CRRT presented higher levels of IL-2 and IL-8 than patients treated by IHD at dialysis start. Cytokine removal ranged from 9% to 78%. Patients treated by CRRT presented higher cytokine removal for IL-2, IL-6 IL-8, IP-10 and TNF. The removal rates of IL-4, IL-10, IL-17A, IFN, MCP-1 and TGF-B1 were similar in two groups. After one session of CVVHDF (24 h), IL-2 and IL-1β levels did not vary significantly, whereas IL-4, IL-6, IL-8, IL-10, IL-17A, TNF, IFN, IP-10, MCP-1, IL-12p70 and TGF-B1 decreased by 33.8-76%, and this decrease was maintained over the next 24 h. In IHD groups, IL-2, IL-6, TNF, IP-10 and IL-1β levels did not decrease significantly whereas IL-4, IL-8, IL-10, IL-17A, IFN, MCP-1, IL-12p70 and TGF-B1 decreased by 21.8-72%; however, cytokine levels returned to their initial values after 24 h., Conclusion: Cytokine removal is lower in IHD using HF membranes than in CVVHDF, and in IHD the removal is transient and selective, which can be associated with mortality during cytokines storm-related COVID-19., Competing Interests: Prof. Dr. Alexandre Naime Barbosa reports grants and/or personal fees from GSK, Abbvie, Boehringer Ingelheim, Celltrion, Gilead, Janssen, Medictalks, MSD, Pfizer, Sanofi Pasteur, Takeda, Wyethand, and Dr. Reedy’s; non-financial support from Eurofarma, outside the submitted work. The authors declare that they have no other competing interests in this work., (© 2022 Ponce et al.)

Objective: The aim of this study was to evaluate allergenic labeling components of packaged foods for "What is the quality of food labels?" and "What is the group of Brazilian Food Pyramid that 'May contain' is predominant?.", Methods: The photographs of 916 products were obtained, of which 518 were analyzed. Data from each label were evaluated according to Brazilian Food Pyramid Groups (i.e., Cereals, Fruits, & Vegetables; Soybean & products; Milk & dairy products; Meat & eggs; Fats & oils; and Sugars & sweets). Ten items were analyzed in each label, namely, the presence of a list of ingredients, alert phrase for allergy sufferers, grouping of the alert phrase, phrase location, uppercase phrase, the phrase in bold, the color of alert phrase contrasting to the background, adequate font size, do not claim the absence for any allergen with the ingredients, and others factors that make it difficult to read. For the second question, a structured questionnaire was completed, and products were classified into two categories, namely, "Contain" and "May contain.", Results: The quality of the label was appropriate, and 69% of packaged foods had at least one allergen. The information "May contain" were higher in cow's milk (Cereals and Meat & eggs), soy (Soybean & products), and egg protein (Cereals). Soybean & products were the highest insecurity group., Conclusions: Brazilian health professionals can count on good-quality labeling of packaged products. Consequently, they could promote patients' and parents/caregivers' education to consult the labels and manage the risks in processed foods about precautionary allergen labeling. Soybean & products were the most significant insecurity for food choices between Brazilian Pyramid Groups.

Objective: To analyze the maternal burden related to the care of children diagnosed with autism spectrum disorder., Method: Study with a mixed-method sequential explanatory design held at the Association of Friends and Families of Special Children and in a WhatsApp® Messenger group, with 51 (quantitative phase) and six (qualitative phase) mothers, between January and October 2019. For data collection, in the quantitative phase, a sociodemographic, economic and child care characterization form and a Zarit Burden Interview instrument were used. Semi-structured interview was used in the qualitative phase. Descriptive bivariate and multivariate analysis (quantitative) and Bardin analysis (qualitative) were performed., Results: A total of 64.7% mothers felt burdened, with mild to moderate burden (52.9%). Four analytical categories on elements that trigger maternal burden emerged., Conclusions: There is an urgent need to identify maternal burden related to the care of children with autism spectrum disorder, during assistance in Primary Health Care.

Hepatitis C virus has infected over 71 million people worldwide, and it is the main cause of cirrhosis in the western world. Currently, the treatment involves direct-acting antiviral agents (DAAs) and its main goal is to achieve sustained virologic response (SVR). The aim of this study was to evaluate the impact of SVR using DAAs in the improvement of liver fibrosis using scores evaluation by indirect method, liver function, and inflammation indirect biomarkers. Patients with cirrhosis with SVR after treatment (n = 104) were evaluated using liver function scores, indirect fibrosis methods, alpha-fetoprotein, and ferritin at t-base and t-SVR. Statistically significant positive results in all parameters were observed: 54 patients were classified as 5 in the CP score in t-base, and 77 in t-SVR; a significant decrease was observed in MELD score, alpha-fetoprotein, ferritin, APRI, FIB-4 and liver stiffness in liver elastography. We did not observe difference in the liver function scores between regressors and non-regressors of liver stiffness, as well as in indirect inflammation biomarkers. The measurements of fibrosis using the indirect methods have significantly decreased in patients with cirrhosis treated who achieved SVR associated with decreased indirect inflammation biomarkers and improved liver function scores., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients' sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rosa, Krieck, Padula, Stievani, Rossi, Pfeifer, Basso, Braz, Golim and Alves.)

Background: Sexually transmitted diseases (STIs) are an important public health problem in all countries. Knowledge of their relationship with the various socioeconomic levels is necessary for an understanding of their epidemiology and behavior in society., Objective: To investigate the epidemiology of human immunodeficiency virus (HIV)-positive patients and to correlate education with history of sexually transmitted diseases, especially for syphilis., Design and Setting: Analytical cross-sectional study carried out in the city of Juiz de Fora, Minas Gerais, Brazil., Methods: The medical records of HIV/acquired immunodeficiency syndrome (AIDS) patients who started antiretroviral therapy (ART) between January 2010 and July 2018 were assessed. These patients were attended at the specialized assistance service for HIV/AIDS) of the Department of Sexually Transmitted Diseases (STD/AIDS) of the city of Juiz de Fora. In total, 335 patients were selected., Results: In our sample, 73.13% were male; 57.36% were aged between 25 and 45 years and 24.23% were over 45 years of age. Regarding sexual orientation, 61.78% were homosexual. Regarding education, 52.88% had "unskilled education", while 47.12% had "qualified education". Analysis on the relationship between schooling and syphilis, a positive relationship between qualified schooling and syphilis was observed: odds ratio = 3.588; 95% confidence interval: 1.090-11.808., Conclusion: Homosexual male patients are most affected by HIV. Furthermore, this disease is not limited only to individuals with low education. Syphilis should be suspected in all individuals.

Visceral leishmaniasis caused by Leishmania (Leishmania) infantum in Latin America progress with hepatosplenomegaly, pancytopenia, hypergammaglobulinemia, and weight loss and maybe lethal mainly in untreated cases. miRNAs are important regulators of immune and inflammatory gene expression, but their mechanisms of action and their relationship to pathogenesis in leishmaniasis are not well understood. In the present study, we sought to quantify changes in miRNAs associated with immune and inflammatory pathways using the L. (L.) infantum promastigote infected- human monocytic THP-1 cell model and plasma from patients with visceral leishmaniasis. We identified differentially expressed miRNAs in infected THP-1 cells compared with non-infected cells using qPCR arrays. These miRNAs were submitted to in silico analysis, revealing targets within functional pathways associated with TGF-β, chemokines, glucose metabolism, inflammation, apoptosis, and cell signaling. In parallel, we identified differentially expressed miRNAs in active visceral leishmaniasis patient plasma compared with endemic healthy controls. In silico analysis of these data indicated different predicted targets within the TGF-β, TLR4, IGF-I, chemokine, and HIF1α pathways. Only a small number of miRNAs were commonly identified in these two datasets, notably with miR-548d-3p being up-regulated in both conditions. To evaluate the potential biological role of miR-548d-3p, we transiently transfected a miR-548d-3p inhibitor into L. (L.) infantum infected-THP-1 cells, finding that inhibition of miR-548d-3p enhanced parasite growth, likely mediated through reduced levels of MCP-1/CCL2 and nitric oxide production. Further work will be required to determine how miR-548d-3p plays a role in vivo and whether it serves as a potential biomarker of progressive leishmaniasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramos-Sanchez, Reis, Souza, Muxel, Santos, Lagos, Pereira, Brito, Kaye, Floeter-Winter and Goto.)

Objective: Developing and validating a disease-specific instrument in the Brazilian Portuguese language to assess the Health-Related Quality of Life of children with functional constipation, applied to parents/caregivers., Methods: The process of developing the questionnaire was carried out in the following steps: items generation concerning functional constipation; elaboration of the preliminary questionnaire; assessment by health professionals; identifying problems or inconsistencies by the researchers; improvement of the questions; obtaining a final questionnaire named Pediatric Functional Constipation Questionnaire-Parent Form (PedFCQuest-PR) with 26 questions divided into four domains. Responses options use a Likert scale based on the events of the last four weeks. The process of validation was an observational, cross-sectional study in a sample of 87 parents/caregivers of children from 5 to 15 years of age diagnosed with Functional constipation according to the Rome IV Criteria. The questionnaire was applied simultaneously to the Pediatric Quality of Life Inventory 4.0 (PedsQL TM 4.0) as a control., Results: The questionnaire validation included 87 parents/caregivers. The children's median age was 8.2 years, with a long time of constipation symptoms associated with fecal incontinence in approximately two-thirds. Internal consistency reliability for the Total Scale Score of PedFCQuest-PR by Coefficient Alpha of Cronbach score was 0.86. Convergent and divergent validity of PedFCQuest-PR was demonstrated by correlating the domains of both questionnaires., Conclusion: This study provides evidence that PedFCQuest-PR is a reliable instrument. The results showed a high degree of internal consistency and validity of the instrument for future applications., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: In 2020, the COVID-19 pandemic brought a work and stress overload to healthcare workers, increasing their vulnerability to mental health impairments. In response, the authors created the COMVC-19 program. The program offered preventive actions and mental health treatment for the 22,000 workers of The Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). This paper aims to describe its implementation and share what we have learned from this experience., Methods: Workers were able to easily access the program through a 24/7 hotline. Additionally, a mobile phone app that screened for signs and symptoms of emotional distress and offered psychoeducation and/or referral to treatment was made available. Data from both these sources as well as any subsequent psychiatric evaluations were collected., Results: The first 20 weeks of our project revealed that most participants were female, and part of the nursing staff working directly with COVID-19 patients. The most frequently reported symptoms were: anxiety, depression and sleep disturbances. The most common diagnoses were Adjustment, Anxiety, and Mood disorders., Conclusions: Implementing a mental health program in a multimodal intervention was feasible in a major quaternary public hospital. Our data also suggests that preventive actions should primarily be aimed at anxiety and depression symptoms, with a particular focus on the nursing staff.

Cirrhotic patients with chronic hepatitis C should be monitored for the evaluation of liver function and screening of hepatocellular carcinoma even after sustained virological response (SVR). The stage of inflammatory resolution and regression of fibrosis is likely to happen, once treatment and viral clearance are achieved. However, liver examinations by elastography show that 30-40% of patients do not exhibit a reduction of liver stiffness. This work was a cohort study in cirrhotic patients whose purpose was to identify immunological factors involved in the regression of liver stiffness in chronic hepatitis C and characterize possible serum biomarkers with prognostic value. The sample universe consisted of 31 cirrhotic patients who underwent leukocyte immunophenotyping, quantification of cytokines/chemokines and metalloproteinase inhibitors in the pretreatment (M1) and in the evaluation of SVR (M2). After exclusion criteria application, 16 patients included were once more evaluated in M3 (like M1) and classified into regressors (R) or non-regressors (NR), decrease or not ≥ 25% stiffness, respectively. The results from ROC curve, machine learning (ML) and linear discriminant analysis showed that TCD4 + lymphocytes (absolute) are the most important biomarkers for the prediction of the regression (AUC = 0.90). NR patients presented levels less than R of liver stiffness since baseline, whereas NK cells were increased in NR. Therefore, it was concluded that there is a difference in the profile of circulating immune cells in R and NR, thus allowing the development of a predictive model of regression of liver stiffness after SVR. These findings should be validated in greater numbers of patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The effects, severity, and prognosis of COVID-19 infections do not follow a linear pattern in different locations, but change according to the epidemiological data and social issues in each region., Aims: The purpose of the current study is to provide the clinical and epidemiological standard of the population affected by COVID-19 in the city of Juiz de Fora, MG to better understand the disease and its risk factors, in order to enable more appropriate conduct for patients., Methods: A retrospective observational study was carried out from March to August of 2020, with 266 participants admitted to the emergency department of the Instituto de Clínicas e Cirurgia de Juiz de Fora-Hospital Monte Sinai. Data were tabulated, analyzed, and classified according to the outcome using an ordinal regression model., Results: Among the 266 admitted patients, the most common findings were ground-glass opacifications on chest CT (78.8%), cough (75.6%), fever (58.4%), and rhinorrhea (34.5%). There were greater severity and greater need for hospitalization and admission to the ICU in patients who were male, tachypneic at the time of admission, with older age, and with underlying diseases., Conclusion: Collected data allowed for a better understanding of the disease, its severity criteria, and its pattern of affection in Juiz de Fora, MG. More studies based on the analysis of the behavior of COVID-19 in different regions must be carried out, to improve treatment and support to local populations., Competing Interests: The authors have declared that no competing interests exist.

American Tegumentary Leishmaniasis (ATL) is an endemic disease in Latin America, mainly caused in Brazil by Leishmania (Viannia) braziliensis . Clinical manifestations vary from mild, localized cutaneous leishmaniasis (CL) to aggressive mucosal disease. The host immune response strongly determines the outcome of infection and pattern of disease. However, the pathogenesis of ATL is not well understood, and host microRNAs (miRNAs) may have a role in this context. In the present study, miRNAs were quantified using qPCR arrays in human monocytic THP-1 cells infected in vitro with L. (V.) braziliensis promastigotes and in plasma from patients with ATL, focusing on inflammatory response-specific miRNAs. Patients with active or self-healed cutaneous leishmaniasis patients, with confirmed parasitological or immunological diagnosis, were compared with healthy controls. Computational target prediction of significantly-altered miRNAs from in vitro L. (V.) braziliensis -infected THP-1 cells revealed predicted targets involved in diverse pathways, including chemokine signaling, inflammatory, cellular proliferation, and tissue repair processes. In plasma, we observed distinct miRNA expression in patients with self-healed and active lesions compared with healthy controls. Some miRNAs dysregulated during THP-1 in vitro infection were also found in plasma from self-healed patients, including miR-548d-3p, which was upregulated in infected THP-1 cells and in plasma from self-healed patients. As miR-548d-3p was predicted to target the chemokine pathway and inflammation is a central to the pathogenesis of ATL, we evaluated the effect of transient transfection of a miR-548d-3p inhibitor on L. (V.) braziliensis infected-THP-1 cells. Inhibition of miR-548d-3p reduced parasite growth early after infection and increased production of MCP1/CCL2, RANTES/CCL5, and IP10/CXCL10. In plasma of self-healed patients, MCP1/CCL2, RANTES/CCL5, and IL-8/CXCL8 concentrations were significantly decreased and MIG/CXCL9 and IP-10/CXCL10 increased compared to patients with active disease. These data suggest that by modulating miRNAs, L. (V.) braziliensis may interfere with chemokine production and hence the inflammatory processes underpinning lesion resolution. Our data suggest miR-548d-3p could be further evaluated as a prognostic marker for ATL and/or as a host-directed therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Souza, Ramos-Sanchez, Muxel, Lagos, Reis, Pereira, Brito, Zampieri, Kaye, Floeter-Winter and Goto.)

In this work, we evaluated the fermentative performance and metabolism modifications of a second generation (2G) industrial yeast by comparing an industrial condition during laboratory and industrial scale fermentations. Fermentations were done using industrial lignocellulosic hydrolysate and a synthetic medium containing inhibitors and analyses were carried out through transcriptomics and proteomics of these experimental conditions. We found that fermentation profiles were very similar, but there was an increase in xylose consumption rate during fermentations using synthetic medium when compared to lignocellulosic hydrolysate, likely due to the presence of unknown growth inhibitors contained in the hydrolysate. We also evaluated the bacterial community composition of the industrial fermentation setting and found that the presence of homofermentative and heterofermentative bacteria did not significantly change the performance of yeast fermentation. In parallel, temporal differentially expressed genes (tDEG) showed differences in gene expression profiles between compared conditions, including heat shocks and the presence of up-regulated genes from the TCA cycle during anaerobic xylose fermentation. Thus, we indicate HMF as a possible electron acceptor in this rapid respiratory process performed by yeast, in addition to demonstrating the importance of culture medium for the performance of yeast within industrial fermentation processes, highlighting the uniquenesses according to scales., (© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Propolis is a bee-made product used for centuries due to its diverse biological properties, including its immunomodulatory action. This work aimed at investigating whether propolis may affect monocyte functions challenged with retinoic acid (RA), B subunit of Escherichia coli heat-labile enterotoxin (EtxB), human melanoma-associated antigen-1 (MAGE-1) and lipopolysaccharide (LPS)., Methods: Monocytes from healthy donors were treated with the stimuli separately or in the presence of propolis. Cell viability was evaluated by MTT assay, cell marker expression was assessed by flow cytometry, cytokine production by ELISA, gene expression by RT-qPCR., Key Findings: Propolis alone maintained TLR-2, TLR-4, HLA-DR, CD40 and CD80 expression in the monocytes; however, its combination with either MAGE-1 or LPS decreased CD40 expression triggered by the stimuli. Propolis maintained RA action on cell marker expression. Propolis inhibited TNF-α (with either EtxB or MAGE-1) and IL-6 (with either RA or MAGE-1), and increased IL-10 (with MAGE-1) production. Propolis downmodulated LC3 expression induced by LPS. It also induced a lower NF-kB expression than control cells and its combination with RA induced a higher expression than the stimulus alone., Conclusions: Propolis potentially affected innate immunity by downmodulating the monocytes pro-inflammatory activity., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Transcutaneous parasacral nerve stimulation (TPNS) via electrodes placed over the sacrum can activate afferent neuronal networks noninvasively, leading to sacral reflexes that may improve colonic motility. Thus, TPNS can be considered a promising, noninvasive, and safe method for the treatment of constipation. However, there is no published study investigating its use in children with functional constipation. This is a single-center, prospective, longitudinal, and interventional study designed to assess the applicability and clinical outcomes of TPNS in functionally constipated children., Patient Concerns: Parents or guardians of patients will be informed of the purpose of the study and will sign an informed consent form. The participants may leave the study at any time without any restrictions., Diagnosis: Twenty-eight children (7-18 years old) who were diagnosed with intestinal constipation (Rome IV criteria) will be included., Interventions: The patients will be submitted to daily sessions of TPNS for a period of 4 or 8 weeks and will be invited to participate in semistructured interviews at 3 or 4 moments: 1 week before the beginning of TPNS; immediately after the 4 and/or 8 weeks of TPNS; and 4 weeks after the end of the intervention period. In these appointments, the aspects related to bowel habits and quality of life will be assessed., Outcomes: This study will evaluate the increase in the number of bowel movements and stool consistency, the decrease in the number of episodes of retentive fecal incontinence, and the indirect improvement in the overall quality of life., Conclusion: we expect that this study protocol can show the efficacy of this promising method to assist the treatment of children with functional constipation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: To evaluate the expressions of intracellular cytokines in CD4+ T lymphocytes and to investigate the correlation between biomarker expressions and clinical and functional characteristics of stable COPD patients., Patients and Methods: Peripheral blood was collected from 36 COPD patients, and the expression of cytokines (IL-8, IL-13, IL-17, IL-6, IL-2, IL-10, and TNF-α) in T lymphocytes CD4 + was investigated. In addition, lung function, dyspnea symptoms, quality of life, vital signs, body composition, level of physical activity, peripheral muscle strength, and functional capacity were assessed., Results: Individuals with greater bronchial obstruction present a higher proportion of CD4 + IL-2 + lymphocytes compared to individuals with less severe bronchial obstruction. We found a positive correlation between the expression of the cytokines IL-13, IL-17, IL-6, IL-2, IL-10, and TNF-α in CD4+ T lymphocytes. In addition, we found a positive correlation between CD4+ IL-10+ T lymphocytes and lower limb muscle strength and a negative correlation between CD4+ IL-8+ T lymphocytes and peripheral oxygen saturation and steps per day., Conclusion: Systemic CD4+IL-2+, IL-8+, and IL-10+ T lymphocytes presented a correlation with clinical characteristics and functional status in stable COPD., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Uzeloto et al.)

Fibrin scaffold fits as a provisional platform promoting cell migration and proliferation, angiogenesis, connective tissue formation and growth factors stimulation. We evaluated a unique heterologous fibrin biopolymer as scaffold to mesenchymal stem cells (MSCs) to treat a critical-size bone defect. Femurs of 27 rats were treated with fibrin biopolymer (FBP); FBP + MSCs; and FBP + MSC differentiated in bone lineage (MSC-D). Bone repair was evaluated 03, 21 and 42 days later by radiographic, histological and scanning electron microscopy (SEM) imaging. The FBP + MSC-D association was the most effective treatment, since newly formed Bone was more abundant and early matured in just 21 days. We concluded that FBP is an excellent scaffold for MSCs and also use of differentiated cells should be encouraged in regenerative therapy researches. The FBP ability to maintain viable MSCs at Bone defect site has modified inflammatory environment and accelerating their regeneration., Competing Interests: R.S.F.J. is a CNPq PQ1C fellow researcher [303224/20185]. C.F.Z.C. was a FAPESP fellow researcher [FAPESP 2013/02004-3]. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results”. The other authors have no conflicts of interest to disclose in relation to this article.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic fungi of the genus Paracoccidioides that affects predominantly 30-60-year-old male rural workers. The main clinical forms of the disease are acute/subacute, chronic (CF); almost all CF patients develop pulmonary fibrosis, and they also exhibit emphysema due to smoke. An important cytokine in this context, IL-1β, different from the others, is produced by an intracellular multimolecular complex called inflammasome that is activated by pathogens and/or host signs of damage. Inflammasome has been recognized for its contribution to chronic inflammatory diseases, from that, we hypothesized that this activation could be involved in paracoccidioidomycosis, contributing to chronic inflammation. While inflammasome activation has been demonstrated in experimental models of Paracoccidioides brasiliensis infection, no information is available in patients, leading us to investigate the participation of NLRP3-inflammasome machinery in CF/PCM patients from a Brazilian endemic area. Our findings showed increased priming in mRNA levels of NLRP3 inflammasome genes by monocytes of PCM patients in vitro than healthy controls. Similar intracellular protein expression of NLRP3, CASP-1, ASC, and IL-1β were also observed in freshly isolated monocytes of PCM patients and smoker controls. Increased expression of NLRP3 and ASC was observed in monocytes from PCM patients under hypoxia in comparison with smoker controls. For the first time, we showed that primed monocytes of CF-PCM patients were associated with enhanced expression of components of NLRP3-inflammasome due to smoke. Also, hypoxemia boosted this machinery. These findings reinforce the systemic low-grade inflammation activation observed in PCM during and after treatment., Competing Interests: Declaration of Competing Interest We declare that the manuscript does not present any potential conflicts of interest., (Copyright © 2019 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The immunogenic collagen V (Col V) and the proinflammatory cytokine interleukin (IL)-17 have been implicated in the pathogenesis of multiple autoimmune diseases. Col V is also up-regulated during adipogenesis and can stimulate adipocyte differentiation in vitro. Conditioned medium (CM) generated from adipose-derived mesenchymal stem cells (MSCs) reduces bleomycin (BLM)-induced lung injury in rats, suggesting a crucial role in situ of immunomodulatory factors secreted by MSCs in these beneficial effects. In the present work, we investigated this hypothesis, analyzing levels of plasma inflammatory mediators and inflammatory and fibrotic mediators in the lung tissue of BLM-injured rats after treatment with MSCs and CM. Pulmonary fibrosis was intratracheally induced by BLM. After 10 days, BLM animals were further randomized into subgroups receiving saline, MSCs, or CM intravenously. On days 14 and 21, the animals were euthanized, and the lungs were examined through protein expression of nitric oxide synthase (NOS), IL-17, transforming growth factor-β (TGF-β), vascular endothelial growth factor, endothelin-1, and the immunogenic Col V through histological quantitative evaluation and plasma levels of fibrinogen, Von Willebrand factor, and platelet-derived growth factor (PDGF). Rats that had been injected with MSCs and CM showed a significant increase in weight and significant improvements at 14 and 21 days after intravenous injection at both time points of analysis of plasma fibrinogen, PDGF, and Von Willebrand factor and NOS-2 expression, supporting an early anti-inflammatory action, thus reducing TGF-β and collagen I fibers. In contrast, intravenous injection of CM was able to significantly increase the deposition of Col V fibers and IL-17 on both day 14 and day 21 as compared with the amount observed in rats from the BLM group and MSC groups. In conclusion, this study reinforces previous observations on the therapeutic properties of MSCs and CM and is the first report to demonstrate the association of its actions with immunomodulatory biomarkers on lung tissue. We concluded that adipose-derived stem cells and adipose-derived stem cells-CM modulate an in situ imbalance between collagen I- and Col V-mediated IL-17 immune response, emerging as a promising therapeutic option for recovering from BLM pulmonary fibrosis.

The high diversity of species in the marine environment gives rise to compounds with unique structural patterns not found as natural products in other systems and with great potential for pharmacological, cosmetic and nutritional use. The genus Tubastraea (Class Anthozoa, Order Scleractinia, Family Dendrophylliidae) is characterized as a hard coral without the presence of zooxanthellae. In species of this genus alkaloids derived from the compound aplysinopsin with pharmacological activity are known. In Brazil T. coccinea and T. tagusensis are characterized as non-indigenous and invasive and are currently found along the Brazilian coast, from Santa Catarina to Bahia states. This study aims to analyze the mutagenic, cytotoxic and genotoxic potential of methanolic and ethanolic extracts from T. coccinea and T. tagusensis collected in Ilha Grande Bay, Rio de Janeiro state, Brazil. Bacterial reverse mutation assay on the standard strains TA97, TA98, TA100, TA102 and TA104, in vitro micronucleus formation test and colorimetric assays for cytotoxic signals on the cell lines HepG2 and RAW264.7 were used. We also synthesized an oxoaplysinopsin derivate alkaloid (APL01) for comparative purposes. No mutagenic (250; 312.5; 375; 437.5 and 500 μg/plate) or genotoxic (0.05; 0.5; 5.0; 50 and 500 μg/mL) effects were observed in any sample tested for all measured concentrations. Cytotoxic responses were observed for eukaryotic cells in all tested samples at 500 and 5000 μg/mL concentrations. Cytotoxicity found in the WST-1 assay was independent of the metabolism of substances present in samples compositions. The cytotoxicity observed in the LDH release assay depended on metabolism., (© 2019 John Wiley & Sons, Ltd.)

Background: Blood can be the target of microbial cells in the human body. Erythrocytes, platelets, and plasma concentrates in blood bags used in hemotherapy for blood transfusion are contamination targets, which can trigger serious diseases in blood. These infections can cause septicemia that can lead to death if not recognized rapidly and treated adequately. The aim of this study was to evaluate the photodynamic inactivation in the in vitro decontamination of Staphylococcus aureus in whole blood, erythrocytes and platelet-rich plasma., Methods: Photodynamic inactivation using light doses of 10, 15 and 30 J/cm 2 at 630 nm and an hematoporphyrin-derivative photosensitizer (Photogem®) solutions at 25 and 50 μg/mL were evaluated. Toxicity of treatment was determined by hemolysis and cell viability assays., Results: The S. aureus reduction in phosphate buffered saline (PBS), whole blood, erythrocytes and platelet-rich plasma at 15 J/cm 2 and 50 μg/mL were 7.2, 1.0, 1.3 and 0.4 log CFU/mL, respectively. Quantitative and qualitative analyses were performed in whole blood samples, and Photogem® showed a low risk of hemolysis (10.7%) in whole blood. However, 100% of erythrocytes suffered hemolysis in the absence of plasma. The cell viability assay showed 13.9% of apoptosis in erythrocytes, but normal platelet viability., Conclusion: S. aureus inactivation of whole blood samples using 50 μg/mL Photogem® and 15 J/cm 2 resulted in better outcomes, providing promising indications for treatment of bacterial contamination of blood, and in this work, alternative possibilities to apply the technique for blood decontamination are discussed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Bone tissue repair remains a challenge in tissue engineering. Currently, new materials are being applied and often integrated with live cells and biological scaffolds. The fibrin biopolymer (FBP) proposed in this study has hemostatic, sealant, adhesive, scaffolding and drug-delivery properties. The regenerative potential of an association of FBP, biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSCs) was evaluated in defects of rat femurs., Methods: Adult male Wistar rats were submitted to a 5-mm defect in the femur. This was filled with the following materials and/or associations: BPC; FBP and BCP; FBP and MSCs; and BCP, FBP and MSCs. Bone defect without filling was defined as the control group. Thirty and sixty days after the procedure, animals were euthanatized and subjected to computed tomography, scanning electron microscopy and qualitative and quantitative histological analysis., Results: It was shown that FBP is a suitable scaffold for bone defects due to the formation of a stable clot that facilitates the handling and optimizes the surgical procedures, allowing also cell adhesion and proliferation. The association between the materials was biocompatible. Progressive deposition of bone matrix was higher in the group treated with FBP and MSCs. Differentiation of mesenchymal stem cells into osteogenic lineage was not necessary to stimulate bone formation., Conclusions: FBP proved to be an excellent scaffold candidate for bone repair therapies due to application ease and biocompatibility with synthetic calcium-based materials. The satisfactory results obtained by the association of FBP with MSCs may provide a more effective and less costly new approach for bone tissue engineering., Competing Interests: Competing interests: Benedito Barraviera, Rui Seabra Ferreira Jr. and Claudia Vilalva Cassaro, authors of this article, are respectively editor-in-chief, associate and junior editors of Journal of Venomous Animals and Toxins including Tropical Diseases. They did not get involved in the peer review process of this manuscript.

Introduction: A vast majority of children with functional constipation respond to the standard medical treatment. However, a subset of patients may present with an unsatisfactory response and only minor improvement of symptoms. Transcutaneous posterior tibial nerve stimulation (PTNS) involves electrical stimulation of the posterior tibial nerve at the level of the ankle, transcutaneously through electrodes fixated on the overlying skin. Stimulation of the tibial nerve can modulate urinary and defecatory function through the stimulation of sacral nerves. Thus, transcutaneous PTNS can be considered a very promising, noninvasive, and safe method to be used in the pediatric age group. However, there is still no published study that has investigated its use in children for the treatment of intestinal constipation. This is a single-center, prospective, longitudinal, and interventional study designed to assess the applicability and clinical outcomes of transcutaneous PTNS in children with functional intestinal constipation. Children will be submitted to daily sessions of transcutaneous PTNS for a period of 4 weeks. All children will also be invited to participate in semistructured interviews, 1 in each of the 3 assessments: 1 week before the start of the intervention; immediately after the 4 weeks of intervention; and 4 weeks after the end of the intervention period. In these interviews, the aspects related to bowel habits and quality of life will be assessed. This project aims to evaluate the clinical outcomes of transcutaneous PTNS in children with functional intestinal constipation and the applicability of this kind of treatment., Conclusions: This protocol intended to demonstrate the efficacy of this promising method to increase the number of bowel movements and the stool consistency, to reduce the number of episodes of retentive fecal incontinence, and to indirectly improve the overall quality of life.

Osteoarthritis is an incapacitating disease characterized by pain and a progressive decrease in joint mobility. The implantation of mesenchymal stem cells (MSCs) has shown promising results for its treatment. The challenge remains to keep the cells longer at the site of action, increasing their therapeutic potential. The aim of this study was to evaluate the effectiveness of the Qtracker® 655 nanocrystal marking on allogeneic synovial membrane (SM) MSCs, encapsulated in alginate hydrogel, evaluating the migration of these cells. The 10 radiocarpal joints were submitted to arthroscopic surgery (D0), divided into two groups. The chondral defect was treated according to the group: GA free-labelled MSC SM and GB labelled MSC SM microcapsules. Seven days after lesion induction and implantation of labelled cells, biopsies of the lesion site were performed in two animals, and fragments of SM and joint capsule also collected, which were frozen and later processed for fluorescence microscopy. The synovial fluid of the three animals was analyzed by flow cytometry three times - 3, 7 and 21 days after application. The cellular marking with the nanocrystals allowed the visualization of the cells in cartilage, synovial membrane, synovial fluid and articular capsule, but with a predilection for the synovial membrane and the lesion site was scarce. The labelled MSC SM in microcapsules were scarce in the synovial fluid and could be related to the small quantity of MSCs leaving the pores of the microcapsules, also favorable results, as the cells release paracrine effects acting for a long period until the cellular differentiation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Chronic hepatitis C is a leading cause of liver disease. Infection triggers an immediate immune response in the host that is mediated by humoral/cellular mechanisms. T cells respond to infection via secretion of cytokines, which inhibit or stimulate one another, leading to cytokine imbalance and ultimately affecting treatment. Studies using interferon (IFN) and ribavirin (RBV) showed that TCD8+ cells and cytokine levels are associated with sustainable virological response (SVR). However, studies that investigated the effects of triple therapy (TT) are limited., Methods: The study included hepatitis C virus (HCV)+ RNA, naives, genotype 1, ≥18 years, and advanced fibrosis (F≥3) patients. Samples were collected at baseline and after 12 weeks (W12) of TT. Six cytokines were analyzed by flow cytometry., Results: Of 31 patients, four were excluded (two deaths, one interrupted TT, and one F2 patient). Of the 27 remaining patients, 21 (78%) were cirrhotic. SVR was achieved in 63% of the patients. The patients had a mean age of 55.11 ± 10.03 years. Analyses at baseline showed that the chemokine CCL5/Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) (p=0.04) and interleukin (IL)-6 (p=0.02), which was associated with SVR. RANTES (p=0.04) and IL-8 (p=0.01) levels were associated with SVR at W12., Conclusions: Similar to patterns observed during double therapy, IL-6, IL-8, and RANTES levels were associated with SVR in TT, indicating the potential role of interferon in immune response to hepatitis C virus.

In this study, we aimed to evaluate the immunomodulatory effects of crude leaf extracts from Piper gaudichaudianum Kunth, P. arboreum Aub., P. umbellata L., P. fuligineum Kunth, and Peperomia obtusifolia A. Dietr. on an in vitro model of inflammatory response. The crude extracts were previously obtained by maceration of the leaves. The half-maximal inhibitory concentration was determined by the MTT assay using human peripheral blood mononuclear cells. Human monocytes were simultaneously challenged with each crude extract and lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, to induce a strong inflammatory response. After 24 h of incubation, cell-free supernatants were used for evaluating the mediators involved in inflammation: H2O2, TNF-α, IL-8, IL-6, IL-1β, IL-10, IL-12, FGF-b, and TGF-β1. We also compared the results with the effects of ketoprofen, a well-known anti-inflammatory drug. The P. gaudichaudianum crude extract downmodulated the production of H2O2, IL-1β, IL-6, IL-8, and TGF-β1 by LPS-stimulated monocytes; P. arboreum, IL-1β, IL-6, IL-8, and TNF-α; P. umbellata and P. fuligineum, H2O2, IL-1β, IL-6, IL-8, IL-10, and TNF-α; and P. obtusifolia, H2O2, IL-6, IL-8, IL-10, and TNF-α. In general, the crude leaf extracts amplified the anti-inflammatory response when compared with ketoprofen, particularly reducing the production of IL-8, a mediator involved in neutrophil recruitment during tissue damage. Thus, the crude leaf extracts of P. gaudichaudianum, P. arboreum, P. umbellata, P. fuligineum, and Peperomia obtusifolia elicited an anti-inflammatory response against LPS-challenged monocytes. These findings show the anti-inflammatory properties of these crude leaf extracts and offer new perspectives for their use in the treatment of inflammatory diseases., Competing Interests: The authors have declared that no competing interests exist.

The palm tree Euterpe edulis , known as juçara, produces spherical and purple fruits, similar to those of the Euterpe oleracea and Euterpe precatoria palm trees, from which the common name açaí originates. Juçara fruit has been gaining prominence in the scientific world for its interesting nutritional composition, which is rich in antioxidants, and for its sustainable production model. Recently, relevant biological activities have been associated with the juçara fruit, and its use in alimentation has become an important nutritional, environmental, and economic alternative. The aim of this review is to compile recent scientific data about the phytochemical characterization and biological activities of E. edulis. A review of the literature was conducted in two electronic databases, Medline and Science Direct. The eligibility criteria were as follows: phytochemicals characterize of the E. edulis fruits and evaluate biological effects in vitro or in vivo with pulp, extract, juice, or product of juçara fruits. Investigations were excluded if they used other parts of the plant (seeds), did not assess biological activities, or have tested methodologies for compound extraction. From the identified reports, 25 articles were eligible for this study. The promotion of health benefits related to juçara fruits seems to have improved antioxidant activity in vivo, benefits to lipid and glycemic profiles, and modulation of inflammatory status in experimental studies in animals., Competing Interests: The authors declare no conflicts of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The main clinical forms of paracoccidioidomycosis (PCM) are the acute/subacute form (AF) and the chronic form (CF), and they both display considerable clinical variability. The immune responses of PCM patients, during and after treatment, remain neglected, mainly in the case of CF patients, due to the high prevalence of pulmonary sequelae., Objective: To evaluate the distribution of whole blood T cell subsets, serum cytokines, and biomarkers of pulmonary fibrosis in PCM patients, according to the clinical form and at different time points, during the antifungal therapy., Methods: Eighty-seven PCM patients, from an endemic area in Brazil, were categorised into groups, according to the clinical form (AF or CF) and the moment of treatment. The peripheral blood T lymphocyte subsets of these patients were analysed using fluorescence-activated cell sorting. The serum levels of cytokines, basic fibroblast growth factor and surfactant protein-D (SP-D) were also analysed., Findings: In the CF patients, an expansion of the peripheral blood TCD4+ cells was observed during the treatment, and this persisted even after two years of antifungal treatment. In addition, these patients showed high serum levels of SP-D., Conclusion: Our findings highlight the immunological changes CF patients undergo, during and after treatment, possibly due to the hypoxia triggered by pulmonary fibrosis and emphysema.

The aims of this study were to identify cross-sectional dietary patterns (DPs) in a representative sample of 7-10-year-old schoolchildren, to examine how scores for these DPs tracked over a time period of five years (from age 7-10 years to 12-15 years), and to investigate longitudinal associations between changes in DPs scores and changes in BMI (Body Mass Index) z-scores. Children aged 7-10-years were examined in 2007 ( n = 1158) and a subset of the sample participated in a follow-up in 2012 ( n = 458). Factor analysis (FA) was applied to derive DPs at baseline. The change in DP from childhood to adolescence was analyzed by comparing factor scores using the complete cases, in which factor loadings were the ones evaluated at baseline. Associations of BMI change with DP change were assessed by multivariate linear regression. At baseline, four DP were identified that explained 47.9% of the food intake variance. On average, the factor scores of "DP II" (salty snacks, French fries, fast-food, sugary beverages) decreased in follow-up, while no changes were observed for "DP I" (rice, cooked beans, beef/poultry, leafy vegetables), "DP III" (fruits, cooked and leafy vegetables, fruit juices, pasta, milk, cheese), and "DP IV" (milk, coffee with milk, cheese, breads/biscuits). No significant linear association was shown between changes in BMI z-scores and changes in DP scores from childhood to adolescence. In conclusion, three out of four DP scores identified at baseline tracked slightly in adolescence., Competing Interests: The authors declare no conflict of interest.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi from the genus Paracoccidioides in Latin America. PCM-patients (PCM-p) are classified as having acute/subacute or chronic (CF) clinical forms. CF is responsible for 75%-90% of all cases, affects mainly adults over 30 years old and the clinical manifestation are associated mainly with lungs and mucosa of upper airdigestive tract. In addition, the CF patients exhibit fibrosis of the lungs, oral mucous membranes and adrenals, and pulmonary emphysema. Consequently, CF PCM-p with active disease, as well as those that have been apparently cured, seem to be an interesting model for studies aiming to understand the long-term host-fungi relationship and hypoxia. Dendritic cells (DCs) constitute a system that serve as a major link between innate and adaptive immunity composed of several subpopulations of cells including two main subsets: myeloid (mDCs) and plasmacytoid (pDCs). The present study aimed to access the distribution of PBDC subsets of CF PCM-p who were not treated (NT) or treated (apparently cured - AC). CF PCM-p were categorized into two groups, consisting of 9 NTs and 9 ACs. Twenty-one healthy individuals were used as the control group. The determination of the PBDC subsets was performed by FACS (fluorescence-activated cell sorting) and the dosage of serum TNF-α, IL1β, IL-18, CCL3, IL-10 and basic fibroblast growth factor (bFGF) by ELISA (enzyme-linked immunosorbent assay). A high count and percentage of mDCs was observed before treatment, along with a low count of pDCs in treated patients. Furthermore, the mDC:pDC ratio and serum levels of TNF-α was higher in both of the PCM-p groups than in the control group. In conclusion, our findings demonstrated that active PCM influences the distribution of mDCs and pDCs, and after treatment, PCM-p retained a lower count of pDCs associated with pro-inflammatory profile. Therefore, we identified new evidences of persistent immunological abnormalities in PCM-p after treatment. Even these patients showing fungal clearance after successful antifungal treatment; the hypoxia, triggered by the persistent pulmonary sequelae, possibly continues to interfere in the immune response., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose:: To investigate the effects of cyclosporine A on renal ischemia-reperfusion injury during transient hyperglycemia in rats., Methods:: In a model of ischemia-reperfusion-induced renal injury and transiently induced hyperglycemia by intraperitoneal injection of glucose, 2.5 g.kg-1, Wistar rats were anesthetized with either isoflurane or propofol and received intravenous cyclosporine A, 5 mg.kg-1, five minutes before reperfusion. Comparison groups were isoflurane and propofol sham groups and isoflurane and propofol ischemia-reperfusion-induced renal injury. Renal tubular cell viability was quantitatively assessed by flow cytometry after cell culture and classified as early apoptosis, necrotic cells, and intact cells., Results:: Early apoptosis was significantly higher in isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury when compared to both cyclosporine A treated and sham groups. Necrosis percentage was significantly higher in propofol-anesthetized animals subjected to renal ischemia-reperfusion injury. The percentage of intact cells was lower in both, isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury., Conclusion:: In a model of ischemia-reperfusion-induced renal injury, cyclosporine A, 5 m.kg-1, administered five minutes before renal reperfusion in rats with acute-induced hyperglycemia under either isoflurano or propofol anesthesia, attenuated early apoptosis and preserved viability in renal tubular cells, regardless of the anesthetic used.

Dermatophytosis is one of the most common human infections affecting both immunocompetent individuals and immunocompromised patients, in whom the disease is more aggressive and can reach deep tissues. Over the last decades, cases of deep dermatophytosis have increased and the dermatophyte-host interplay remains poorly investigated. Pattern recognition molecules, such as Toll-like receptors (TLR), play a crucial role against infectious diseases. However, there has been very little research reported on dermatophytosis. In the present study, we investigated the role of TLR2 during the development of experimental deep dermatophytosis in normal mice and mice with alloxan-induced diabetes mellitus, an experimental model of diabetes that exhibits a delay in the clearance of the dermatophyte, Trichophyton mentagrophytes (Tm). Our results demonstrated that inoculation of Tm into the footpads of normal mice increases the expression of TLR2 in CD115 + Ly6C high blood monocytes and, in hypoinsulinemic-hyperglycemic (HH) mice infected with Tm, the increased expression of TLR2 was exacerbated. To understand the role of TLR2 during the development of murine experimental deep dermatophytosis, we employed TLR2 knockout mice. Tm-infected TLR2 -/- and TLR2 +/+ wild-type mice exhibited similar control of deep dermatophytic infection and macrophage activity; however, TLR2 -/- mice showed a noteworthy increase in production of IFN-γ, IL-10, and IL-17, and an increased percentage of splenic CD25 + Foxp3 + Treg cells. Interestingly, TLR2 -/- HH-Tm mice exhibited a lower fungal load and superior organization of tissue inflammatory responses, with high levels of production of hydrogen peroxide by macrophages, alongside low TNF-α and IL-10; high production of IL-10 by spleen cells; and increased expansion of Tregs. In conclusion, we demonstrate that TLR2 diminishes the development of adaptive immune responses during experimental deep dermatophytosis and, in a diabetic scenario, acts to intensify a non-protective inflammatory response.