Is Routine Post-operative Biological Laboratory Assessment Necessary After Sleeve Gastrectomy?

BACKGROUND: Incidence of post-operative complications after sleeve gastrectomy (SG) is low. However, the early identification of these complications remains crucial. Here, we report the impact of routine laboratory monitoring for the early diagnosis of complications after SG. MATERIAL AND METHODS: From January 2018 to December 2019, all consecutive patients who underwent primary SG (n = 457) were included. This was a comparative study of patients undergoing primary SG. Patients were divided into two groups: one group with routine laboratory monitoring performed at postoperative day (POD) 1 and 3 (LAB group) and another group without routine laboratory monitoring (control group). The study's primary endpoint was the overall impact of routine laboratory monitoring. The secondary endpoints were evaluation of patients with complications. RESULTS: The population in the two groups were similar in term of demographic and intra-operative data. There was a statistical difference between the two groups in term of length of stay (5.7 days in the LAB group and 3.5 days in the control group (p < 0.001)). There were 19 complications (6.0%) in the LAB group and 5 complications in the control group (3.5%) (p = 0.25). A cut-off C-reactive protein level of 46.3 mg/l was found to be significant (p = 0.006). In the LAB group, 9 patients (2.9%) required readmission vs. three patients (2.0%) in the control group (p = 0.62). CONCLUSION: The interest of routine laboratory monitoring after SG seems limited. Routine laboratory monitoring alone is not associated with earlier diagnosis of complications. This routine monitoring is associated with an increase of stay in hospital.

The association of dietary antioxidants and the inflammatory potential of the diet with poor physical function and disability in older Australian men: the Concord Health and Ageing in Men Project.

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed tests, and activities of daily living (ADL) and instrumental activities of daily living (IADL) questionnaires, at baseline and 3-year follow-up (n 616). Logistic regression analysis was used to identify associations between diet and incident poor physical function and disability. Both poor antioxidant intake and high E-DII scores at baseline were significantly associated with poor grip strength and ADL disability at 3-year follow-up. No significant associations with walking speed or IADL disability were observed. Individual micronutrient analysis revealed a significant association between the lowest two quartiles of vitamin C intake and poor grip strength. The lowest quartiles of intake for vitamins A, C, E and Zn were significantly associated with incident ADL disability. The study observed that poor antioxidant and anti-inflammatory food intake were associated with odds of developing disability and declining muscle strength in older men. Further interventional research is necessary to clarify the causality of these associations.

HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis - data from the ReumaCov-Brasil Registry.

BACKGROUND: Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. AIM: To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. METHODS: The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. RESULTS: From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. CONCLUSIONS: No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. TRIAL REGISTRATION: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Exploring the use of the GLIM criteria to diagnose malnutrition in cancer inpatients.

OBJECTIVES: The Global Leadership Initiative on Malnutrition (GLIM) criteria establish a diagnosis of malnutrition based on the presence of at least one phenotypic and one etiologic criterion. This study aimed to assess the concurrent and predictive validity of the GLIM criteria in hospitalized cancer patients. METHODS: This is an observational retrospective study, including 885 cancer patients, ages >18 y, admitted to a medical oncology inpatient unit between 2019 and 2020. All patients at risk for malnutrition according to the Nutritional Risk Screening 2002 score were assessed by the subjective global assessment (SGA) and 14 different combinations of the GLIM criteria. The SGA was considered the gold standard for assessing the concurrent validity of the GLIM combinations. For a subsample of patients with data available on inflammatory markers (n = 198), the serum albumin and C-reactive protein were included in the combinations as etiologic criteria. The predictive validity of the different combinations was tested using the occurrence of surgical complications as the clinical outcome. The sensitivity and specificity values were calculated to assess the concurrent validity, univariate and multivariate logistic regression models were used to test predictive validity. Adequate concurrent and predictive validity were determined as sensitivity and specificity values >80% and odds ratio values ≥2.0, respectively. RESULTS: The median age of the patients was 61.0 y (interquartile range = 51.0-70.0). Head and neck cancer was the prevailing diagnosis and 375 patients were at nutritional risk. According to the SGA, 173 (26.1%) patients were malnourished (SGA categories B or C) and the prevalence of malnutrition ranged from 3.9% to 30.0%, according to the GLIM combinations. None of the tested combinations reached adequate concurrent validity; however, the presence of malnutrition according to four combinations independently predicted surgical complications. CONCLUSIONS: The predictive validity of the GLIM was satisfactory in surgical cancer patients.

Crotalaria juncea L. enhances the bioremediation of sulfentrazone-contaminated soil and promotes changes in the soil bacterial community.

Sulfentrazone (STZ) is an efficient tool for the pre- and post-emergence control of monocotyledonous and dicotyledonous weeds in fields of crops such as pineapple, coffee, sugarcane, citrus, eucalyptus, tobacco, and soybean. However, this herbicide persists in the soil, causing phytotoxicity in the subsequent crop. Therefore, it is important to use efficient strategies for the remediation of STZ-contaminated areas. The aim of this study was to evaluate the effects of Crotalaria juncea L. on the remediation of STZ-contaminated soil and on the microbial activity and bacterial community structure therein. The study was conducted in three stages: (i) cultivation of C. juncea in soil contaminated with 200, 400, and 800 g ha-1 STZ; (ii) determination of the soil microbial activity (basal respiration, microbial biomass carbon, and bacterial community structure); and (iii) cultivation of a bioindicator species and determination of the residual fraction of STZ. The soil microbial activity was impacted by the soil type and STZ dose. Soil previously cultivated with C. juncea (rhizospheric soil) displayed higher CO2 and lower qCO2 values than non-rhizospheric soil (no previous C. juncea cultivation). Increasing doses of STZ reduced the activity and lowered the diversity indices of the soil microorganisms. The bacterial community structure was segregated between the rhizospheric and non-rhizospheric soils. Regardless of soil type, the bioindicator of remediation (Pennisetum glaucum R.Br.) grew only at the STZ dose of 200 g ha-1, and the plant intoxication level was also lower in rhizospheric soil treated with this herbicide dose. All P. glaucum plants died in the soils treated with 400 and 800 g ha-1 STZ. Previous cultivation of C. juncea in soils contaminated with 200, 400, and 800 g ha-1 STZ reduced the residual fraction of the herbicide by 4.8%, 12.5%, and 17.4%, respectively, compared with that in the non-rhizospheric soils. In conclusion, previous cultivation with C. juncea promoted increases in the soil bacterial activity and diversity indices, mitigated the deleterious effects of STZ on the bioindicator crop, and reduced the residual fraction of the herbicide in the soil.

Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors.

The association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naïve BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.

A Novel Strategy Based on Zn(II) Porphyrins and Silver Nanoparticles to Photoinactivate Candida albicans.

Background: Photodynamic inactivation (PDI) is an attractive alternative to treat Candida albicans infections, especially considering the spread of resistant strains. The combination of the photophysical advantages of Zn(II) porphyrins (ZnPs) and the plasmonic effect of silver nanoparticles (AgNPs) has the potential to further improve PDI. Here, we propose the novel association of polyvinylpyrrolidone (PVP) coated AgNPs with the cationic ZnPs Zn(II) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin or Zn(II) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin to photoinactivate C. albicans. Methods: AgNPs stabilized with PVP were chosen to allow for (i) overlap between the NP extinction and absorption spectra of ZnPs and (ii) favor AgNPs-ZnPs interaction; prerequisites for exploring the plasmonic effect. Optical and zeta potential (ζ) characterizations were performed, and reactive oxygen species (ROS) generation was also evaluated. Yeasts were incubated with individual ZnPs or their respective AgNPs-ZnPs systems, at various ZnP concentrations and two proportions of AgNPs, then irradiated with a blue LED. Interactions between yeasts and the systems (ZnP alone or AgNPs-ZnPs) were evaluated by fluorescence microscopy. Results: Subtle spectroscopic changes were observed for ZnPs after association with AgNPs, and the ζ analyses confirmed AgNPs-ZnPs interaction. PDI using ZnP-hexyl (0.8 µM) and ZnP-ethyl (5.0 µM) promoted a 3 and 2 log10 reduction of yeasts, respectively. On the other hand, AgNPs-ZnP-hexyl (0.2 µM) and AgNPs-ZnP-ethyl (0.6 µM) systems led to complete fungal eradication under the same PDI parameters and lower porphyrin concentrations. Increased ROS levels and enhanced interaction of yeasts with AgNPs-ZnPs were observed, when compared with ZnPs alone. Conclusion: We applied a facile synthesis of AgNPs which boosted ZnP efficiency. We hypothesize that the plasmonic effect combined with the greater interaction between cells and AgNPs-ZnPs systems resulted in an efficient and improved fungal inactivation. This study provides insight into the application of AgNPs in PDI and helps diversify our antifungal arsenal, encouraging further developments toward inactivation of resistant Candida spp.

High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients.

BACKGROUND: Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19. METHODS: In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis. RESULTS: A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)-categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1ß, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1ß and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1ß, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals. CONCLUSION: We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination.

Clinical characteristics and outcomes of children with newly diagnosed acute myeloid leukemia and hyperleukocytosis managed with different cytoreductive methods.

BACKGROUND: Hyperleukocytosis in patients with acute myeloid leukemia (AML) has been associated with worse outcomes. For cytoreduction, leukapheresis has been used but its clinical utility is unknown, and low-dose cytarabine (LD-cytarabine) is used as an alternative method. METHODS: Children with newly diagnosed AML treated between 1997 and 2017 in institutional protocols were studied. Hyperleukocytosis was defined as a leukocyte count of ≥100 × 109 /L at diagnosis. Clinical characteristics, early complications, survival data, and effects of cytoreductive methods were reviewed. Among 324 children with newly diagnosed AML, 49 (15.1%) presented with hyperleukocytosis. Initial management of hyperleukocytosis included leukapheresis or exchange transfusion (n = 16, considered as one group), LD-cytarabine (n = 18), hydroxyurea (n = 1), and no leukoreduction (n = 14). RESULTS: Compared with patients who received leukapheresis, the percentage decrease in leukocyte counts following intervention was greater among those who received LD-cytarabine (48% vs. 75%; p = .02), with longer median time from diagnosis to initiation of protocol therapy (28.1 vs. 95.2 hours; p < .001). The incidence of infection was higher in patients (38%) who had leukapheresis than those who receive LD-cytarabine (0%) or leukoreduction with protocol therapy (14%) (p = .008). No differences were noted in the outcomes among the intervention groups. Although patients with hyperleukocytosis had higher incidences of pulmonary and metabolic complications than did those without, no early deaths occurred, and the complete remission, event-free survival, overall survival rates, and outcomes of both groups were similar. CONCLUSION: LD-cytarabine treatment appears to be a safe and effective means of cytoreduction for children with AML and hyperleukocytosis.

A case-control study of Clostridioides difficile symptomatic infections in a pediatric cancer hospital.

OBJECTIVE: The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer. METHODS: This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016-2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors. RESULTS: We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3-12.5); for meropenem, 4.41 (95%CI 2.1-9.2); and for cefepime, 2.6 (95%CI 1.3-5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2-6.2), melphalan 9.04 (95%CI 1.9-42.3), busulfan 16.7 (95%CI 2.1-134.9), and asparaginase 8.97 (95%CI 1.9-42.9). CONCLUSIONS: C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors.

Diversity of HLA-A2-Restricted and Immunodominant Epitope Repertoire of Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Protein: Novel Insights among N-Terminal, Central and C-Terminal Regions.

The present study sought to search for the immunodominance related to the N-terminal, Central and C-terminal regions of HTLV-1 Tax using novel, cutting-edge peptide microarray analysis. In addition, in silico predictions were performed to verify the presence of nine amino acid peptides present along Tax restricted to the human leukocyte antigen (HLA)-A2.02*01 haplotype, as well as to verify the ability to induce pro-inflammatory and regulatory cytokines, such as IFN-γ and IL-4, respectively. Our results indicated abundant dose-dependent reactivity for HLA-A*02:01 in all regions (N-terminal, Central and C-terminal), but with specific hotspots. Furthermore, the results of fold-change over the Tax11-19 reactivity obtained at lower concentrations of HLA-A*02:01 reveal that peptides from the three regions contain sequences that react 100 times more than Tax11-19. On the other hand, Tax11-19 has similar or superior HLA-A*02:01 reactivity at higher concentrations of this haplotype. The in silico analysis showed a higher frequency of IFN-γ-inducing peptides in the N-terminal portion, while the C-terminal portion showed a higher frequency of IL-4 inducers. Taken together, these results shed light on the search for new Tax immunodominant epitopes, in addition to the canonic Tax11-19, for the rational design of immunomodulatory strategies for HTLV-1 chronic diseases.

Improvement of Color and Oxidative Stabilities in Nellore Bull Dark Meat in High-Oxygen Package by Lactate and Rosemary Oil Extract.

This study aimed to improve the color and oxidative stabilities of dark Nellore bull steaks with greater-than-normal ultimate pH (pHu) by the injection (8% raw wet weight basis) of a solution with L-lactate (2.5%), phosphate (0.3%) and rosemary extract (0.06%), with further packaging in high oxygen atmosphere (HiOx MAP). Longissimus lumborum muscles from pasture-fed Nellore bulls were divided into three pHu ranges: normal (<5.80), intermediate (5.81-6.19), and high (≥6.2). Muscles were then halved, with sections were randomly assigned to non-enhanced (C, n = 6/pHu range) or injected (E, n = 6/pHu range) groups, at 72 h postmortem. Each section was cut into 2 cm-slices, which were HiOx-packed and then stored for 5 days (dark) and displayed for 9 days (fluorescent lighting) at 2 °C. Higher pHu steaks exhibited greater a*, b*, h*, C* and surface oxymyoglobin and lower surface deoxymyoglobin and oxygen consumption compared to those of normal pHu between days 0 and 5 (p < 0.05). Over the time, normal-pHu muscles showed oxidative protection (lower TBARS and greater metmyoglobin reducing ability values, p < 0.05) in enhanced-steaks. Therefore, enhancement and HiOx MAP seem to produce greater-than-normal pHu Nellore bull steaks with a preferable color and quality, even after display time.

Inflammasome genes polymorphisms are associated with progression to mechanical ventilation and death in a cohort of hospitalized COVID-19 patients in a reference hospital in Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1ßrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.

Precursors of insulin resistance underlying periodontitis in adolescents aged 17-18 years.

OBJECTIVE: To investigate the association between insulin resistance markers and periodontitis in adolescents, analyzing confounder variables and the adiposity as a mediator. METHODS: This is population-based study is representative of adolescents aged 17-18 years from public schools in São Luís, Brazil (n = 405). Insulin resistance was assessed using the Model of Assessment of the Homeostasis of the Insulin Resistance Index (HOMA-IR) and its percussor triglycerides/HDL-cholesterol ratio (TG/HDL-c). The outcome was Initial Periodontitis, a latent variable estimated by the common variance shared among bleeding on probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 4 mm. The association between insulin resistance and Initial Periodontitis was modeled via pathways triggered by socioeconomic status, smoking, alcohol, and Adiposity, using structural equation modeling. RESULTS: Higher TG/HDL-c was directly associated with higher Initial Periodontitis (standardized coefficient [SC] = 0.130, p < 0.001). HOMA-IR was not associated with periodontal outcome (SC = 0.023, p = 0.075), but it was with Adiposity (SC = 0.495, p < 0.001). Higher TG/HDL-c was associated with Adiposity (SC = 0.202, p < 0.001). CONCLUSION: The insulin resistance markers were associated with early signs of periodontal breakdown among adolescents, suggesting a possible relationship between diabetes and periodontitis commences early in life.

Validation of a food frequency questionnaire for assessing the intake of food groups and nutrients in adults / Validação de um questionário de frequência alimentar para avaliação do consumo de grupos de alimentos e nutrientes em adultos

ABSTRACT Objective: To validate a food frequency questionnaire used to assess food consumption among adults in a Brazilian cohort. Methods: Cross-sectional study conducted on 100 adults. Food intake was assessed by the food frequency questionnaire and by two 24-hour recalls. Validation was performed for nutrients (n=19) and food groups (n=21). Results: Moderate deattenuated Pearson's correlation coefficients (>0.4) were observed for the consumption of dairy products, breads and crackers, rice, pasta and tubers, leafy vegetables, other vegetables, fats, sweetened drinks, sandwiches and savory snacks, and nuts, and for the following nutrients (deattenuated and adjusted for energy intake): fiber, calcium, and vitamins A, B2, and C. Based on almost all food groups and nutrients assessed, ≥70% of the individuals were classified into the same or adjacent quartile for both methods, except for red and pork meat, snacks, nuts, phosphorus, potassium, and vitamin B3. The food groups and nutrients with fair kappa agreement (>0.2) were: dairy products, other vegetables, sweetened drinks, breakfast cereals, energy, carbohydrate, iron, and vitamin A. Conclusion: The food frequency questionnaire has proven useful for estimating the intake of some nutrients and food groups of the subjects evaluated. Only the intake of red and pork meat, snacks, nuts, vitamin B3, phosphorus and potassium were estimated with less accuracy.

RESUMO Objetivo: Validar um questionário de frequência alimentar para avaliar o consumo alimentar de adultos em uma coorte brasileira. Métodos: Estudo transversal realizado com 100 adultos. A ingestão alimentar foi avaliada pelo questionário de frequência alimentar e por dois recordatórios de 24 horas. A validação foi realizada para nutrientes (n=19) e grupos de alimentos (n=21). Resultados: Coeficientes de correlação de Pearson deatenuados moderados (>0,4) foram observados para o consumo de laticínios, pães e biscoitos, arroz, macarrão e tubérculos, vegetais folhosos, outros vegetais, gorduras, bebidas adoçadas, sanduíches e salgadinhos, e nozes, e para os seguintes nutrientes (deatenuados e ajustados para ingestão de energia): fibra, cálcio e vitaminas A, B2 e C. Com base em quase todos os grupos de alimentos e nutrientes avaliados, ≥70% dos indivíduos foram classificados no mesmo quartil ou quartil adjacente para ambos os métodos, exceto para carnes vermelhas e suínas, salgadinhos, nozes, fósforo, potássio e vitamina B3. Os grupos de alimentos e nutrientes com concordância kappa justa (>0,2) foram: laticínios, outras verduras, bebidas açucaradas, cereais matinais, energia, carboidratos, ferro e vitamina A. Conclusão: O questionário de frequência alimentar mostrou-se útil para estimar a ingestão de alguns nutrientes e grupos de alimentos dos sujeitos avaliados. Apenas o consumo de carnes vermelhas e suínas, salgadinhos, nozes, vitamina B3, fósforo e potássio foi estimado com menor precisão.

Suplementação de vitamina C: o que mostram as revisões sistemáticas Cochrane? / Vitamin C supplementation: what do Cochrane systematic reviews show?

Contextualização: A vitamina C (ácido ascórbico) é, sem dúvida, a mais popular dentre as vitaminas e a vedete de vendas na mídia, sobretudo no inverno, sob o slogan de que previne doenças. Objetivos: O estudo avaliou a efetividade da suplementação de vitamina C para tratamento e prevenção de sintomas e doenças, segundo as revisões sistemáticas da Colaboração Cochrane. Métodos: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca na Cochrane Library (2022), sendo utilizado o termo "Ascorbic Acid". O desfecho primário de análise foi a redução da incidência da doença ou a melhora clínica, mediante suplementação de vitamina C. Resultados: A estratégia de busca recuperou 26 revisões sistemáticas Cochrane, sendo oito estudos incluídos, seguindo critérios de inclusão. Foram avaliados 91 ensaios clínicos (n = 54.864 participantes). Condições/doenças fetais, pneumonia, resfriado comum, tétano, doença cardiovascular, asma e broncoconstrição por exercício, retinopatia diabética e Doença de Charcot-Marie-Tooth configuraram objetos de análise. Não foi evidenciada efetividade da vitamina C nas análises dessas condições. Discussão: Não há evidência de efetividade da vitamina C para as doenças analisadas. Embora a maioria dos estudos primários tenha limitações sérias e a evidência seja de baixa qualidade, não é possível recomendar a suplementação da vitamina C para essas condições nesse momento. Conclusão: Não há efetividade, nesse momento, da suplementação da vitamina C para prevenção e tratamento de doenças analisadas pela Cochrane, A evidência é bastante limitada e recomenda-se a realização de novos ensaios clínicos randomizados, utilizando-se o CONSORT (Consolidated Standards of Reporting Trials) Statement.

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes.

Background: Tuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1ß inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1ß, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset. Methods: The individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations. Results: A higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-ß rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed. Conclusions: Our results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection.

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease (WHO < 6; n = 76), and group 2 included patients with severe/critical COVID-19 (WHO ≥ 6; n = 357). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic - National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype (ORadj = 0.36; P = 0.032), allele A (ORadj = 0.93; P = 0.010), or carrier-A (ORadj = 0.45; P = 0.027) in the NLRP3 rs1539019 polymorphism; A/T genotype (ORadj = 0.5; P = 0.045), allele T (ORadj = 0.93; P = 0.018), or carrier-T (ORadj = 0.48; P = 0.029) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C (ORadj = 0.11; P = 0.018), A-C-G-C-G (ORadj = 0.23; P = 0.003), C-C-G-C-C (ORadj = 0.37; P = 0.021), and C-T-G-A-C (ORadj = 0.04; P = 0.0473) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

Mutant KRAS modulates colorectal cancer cells invasive response to fibroblast-secreted factors through the HGF/C-MET axis.

Genetic alterations influence the malignant potential of cancer cells, and so does the tumor microenvironment. Herein, we combined the study of KRAS oncogenic effects in colorectal cancer cells with the influence of fibroblast-derived factors. Results revealed that mutant KRAS regulates cell fate through both autonomous and nonautonomous signaling mechanisms. Specifically, processes such as proliferation and cell-cell aggregation were autonomously controlled by mutant KRAS independently of the stimulation with fibroblasts conditioned media. However, cancer cell invasion revealed to be a KRAS-dependent nonautonomous effect, resulting from the cooperation between fibroblast-derived HGF and mutant KRAS regulation of C-MET expression. C-MET downregulation upon KRAS silencing rendered cells less responsive to HGF and thus less invasive. Yet, in one cell line, KRAS inhibition triggered invasion upon stimulation with fibroblasts conditioned media. Inhibition of PIK3CA oncogene did not promote invasion, thus showing a KRAS-specific effect. Moreover, the invasive capacity also depended on the HGF-C-MET axis. Overall, our study awards oncogenic KRAS an important role in modulating the response to fibroblast-secreted factors either by promoting or impairing invasion, and depicts the HGF-C-MET axis as a putative therapeutic target to impair the invasive properties of mutant KRAS cancer cells.

Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro, Brazil.

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.