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Rita Chelly Felix Tavares,1 Ana Cristina de Castro Amaral Feldner,1 João Renato Rebello Pinho,2,3 Fernanda de Mello Malta,3 Roberto José Carvalho-Filho,1 Rúbia Anita Ferraz Santana,2 Vanessa Fusco Duarte de Castro,2 Gregório Tadeu Fernando Dastoli,2 Juliana Custódio Lima,1 Maria Lucia Cardoso Gomes Ferraz1 1Gastroenterology Division, Federal University of Sao Paulo, São Paulo, SP, Brazil; 2Albert Einstein Diagnostic Medicine, Albert Einstein Hospital São Paulo, SP, Brazil; 3Laboratory of Tropical Gastroenterology and Hepatology “João Alves de Queiroz and Castorina Bittencourt Alves,” Institute of Tropical Medicine, Department of Gastroenterology, University of São Paulo, São Paulo, SP, Brazil Background: Direct-acting antiviral agents (DAAs) permit the use of interferon (IFN)-free regimens to treat hepatitis C (HCV) in patients with chronic kidney disease (CKD) on hemodialysis (HD) or renal transplant (RTx) recipients, with excellent response rates and safety. However, the occurrence of basal or therapy-induced resistance-associated substitutions (RASs) to DAAs can result in treatment failure. The aim of this study was to estimate the prevalence of RASs to NS3A, NS5A and NS5B inhibitors, and particularly the Q80K polymorphism, in CKD patients on HD and RTx recipients infected with HCV. Patients and methods: HD and RTx patients infected with HCV-genotype 1 (GT1) were subjected to sequencing of the NS3, NS5A and NS5B regions. Results: Direct sequencing of NS3 protease, NS5A and NS5B was performed in 76 patients (HD, n=37; RTx, n=39). The overall prevalence of RASs was 38.2%, but only 5.3% of the patients had mutations in more than one region. Substitutions were detected in NS3A (17.8%), NS5A (21.9%) and NS5B (8.4%). Q80K was detected in 1.5 % of the patients. Highly inhibitory RASs were uncommon (L31M, 2.6%; L159F+C316N, 2.6%). RASs were more prevalent in HCV-GT1a (42.9%) than in HCV-GT1b (32.4%), P=0.35. RASs were detected in 52.4% of treatment-naive patients and 27.8% of peg-IFN/ribavirin-experienced patients (P=0.12). The presence of RASs was associated with time of RTx (P=0.01). Conclusion: The Q80K polymorphism was uncommon in our sample of HD and RTx patients. Despite the high prevalence of naturally occurring RASs, most of the substitutions detected were associated with a low level of resistance to DAAs. Keywords: HCV, treatment, DAA resistance, hepatitis

Background. Overweight and obesity are global health issues, impacting a significant portion of young adults. Obesity is a complex condition influenced by genetics and environmental factors, leading to increased susceptibility to cardiovascular diseases (CVDs), hypertension, dyslipidemia, and insulin resistance. Irisin, a protein derived from the cleavage of fibronectin type III domain-containing protein 5, may have relationship with these cardiometabolic diseases. Objective. This systematic review aims to examine the relationship between serum irisin levels and obesity, particularly in individuals predisposed to cardiovascular risk factors. Methods. A thorough literature search was conducted in multiple databases, including “Science Direct,” “Scopus,” “PubMed,” and “Lilacs,” from July 2020. Inclusion criteria encompassed subjects with metabolic disorders (with or without obesity, BMI ≥30 kg/m2), clinical trials, and observational studies published between 2010 and June 2020. Exclusion criteria were animal studies, meta-analyses, systematic reviews, studies evaluating only healthy subjects, and those investigating disorders beyond cardiometabolic diseases. Results. Out of 151 identified articles, 30 met the inclusion criteria. These studies, published between 2013 and 2020, assessed adults (≥21 years) and included 26 observational studies and 4 clinical trials (n = 7585 subjects). All studies examined irisin’s role in obesity and CVDs, often including associated diseases such as type 2 diabetes and hypertension. Despite varying sample sizes, the samples within the articles were homogeneous. Observational studies exhibited a low risk of bias in at least 60% of the evaluated domains. Clinical trials demonstrated a low risk of bias in at least 50% of the domains. Limitations. Although the systematic review provides valuable insights, it is limited by the available literature and the varying methodologies used across studies. Conclusion. The review suggests that irisin plays a significant role as both a preventive measure and a biomarker for comorbidities linked to obesity and cardiometabolic disorders. Future research should focus on standardized irisin measurement methods and diverse populations to further elucidate its mechanisms of action.

Ana Paula de Torres Santos,1,2 Vanessa Cristina Martins Silva,1 Maria Cássia Mendes-Corrêa,3 Marcilio Figueiredo Lemos,1 Fernanda de Mello Malta,4 Rúbia Anita Ferraz Santana,5 Gregório Tadeu Fernando Dastoli,5 Vanessa Fusco Duarte de Castro,5 João Renato Rebello Pinho,2,4,5 Regina Célia Moreira1 1Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, São Paulo, SP, Brazil; 2Divisão de Laboratório Central, Laboratório de Imunologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil; 3LIM-52-Institute of Tropical Medicine, Department of Infectious Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil; 4Laboratory of Tropical Gastroenterology and Hepatology “João de Queiroz and Castorina Bettencourt Alves”‑LIM 07‑Institute of Tropical Medicine Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil; 5Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, BrazilCorrespondence: Regina Célia MoreiraInstituto Adolfo Lutz, Centro de Virologia, Av: Dr Arnaldo, 355 Pacaembu, SP, Cep 01246-000, BrazilTel +55 11 30682911Email regina.moreira@ial.sp.gov.brPurpose: Globally, it is estimated that 71 million people are chronically infected with hepatitis C, and 10– 20% of these will develop cirrhosis and hepatocellular carcinoma. The development of new direct-acting antiviral (DAA) drugs has contributed to sustained virological response (SVR), eliminating the infection and achieving cure of chronic hepatitis C. However, treated patients can develop HCV resistance to DAAs, which can contribute to the failure of treatment. Here, we aimed to evaluate the prevalence and specific pattern of NS5A and NS5B resistance-associated substitutions (RAS) in samples from patients chronically infected with HCV genotype 3a at a public health laboratory, Instituto Adolfo Lutz, São Paulo, Brazil.Patients and Methods: Serum samples from the enrolled individuals were submitted to “in-house” polymerase chain reaction amplification of NS5A and NS5B non-structural protein genes, which were then sequenced by Sanger method.Results: A total of 170 and 190 samples were amplified and analyzed for NS5A and NS5B, respectively. For NS5A, 20 (12.0%) samples showed some important RAS; 16 (9.0%) showed some type of substitution and 134 (79.0%) showed no polymorphism. No sample showed any RAS for NS5B.Conclusion: This study found important RAS in samples from naïve chronic HCV patients in some areas from São Paulo. The most prevalent were A62S, A30K, and Y93H, which could indicate an increase in resistance to some DAAs used in HCV treatment.Keywords: HCV, nonstructural NS5A/NS5B, resistance, polymorphism, RAS

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Copyright of Revista Odonto Ciencia is the property of EDIPUCRS - Editora Universitaria da PUCRS and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A 68-year-old Brazilian woman had 3 months of progressive fatigue, difficulty walking and 18 kg weight loss. On examination, there was gait apraxia and executive dysfunction. MR scan of brain showed communicating hydrocephalus and a cerebrospinal fluid showed 105 white cells/µL (≤5), predominantly lymphocytes, protein of 1.35 g/L (0.15-0.45) and the glucose content of 0.06 mmol/L (3.3-4.4). We suspected an infective cause and used of metagenomic next-generation sequencing to diagnose neurocysticercosis. This case highlights the challenge of diagnosing chronic meningitis and the relevance of genetic approaches in diagnosing neurological infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations., Methods: This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger's sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool., Results: Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L ( n =2) and rt180M+rt204V+rt202G ( n =1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18)., Conclusions: The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

At over 0.6% of the population, Peru has one of the highest SARS-CoV-2 mortality rate in the world. Much effort to sequence genomes has been done in this country since mid-2020. However, an adequate analysis of the dynamics of the variants of concern and interest (VOCIs) is missing. We investigated the dynamics of the COVID-19 pandemic in Peru with a focus on the second wave, which had the greatest case fatality rate. The second wave in Peru was dominated by Lambda and Gamma. Analysis of the origin of Lambda shows that it most likely emerged in Peru before the second wave (June-November, 2020). After its emergence it reached Argentina and Chile from Peru where it was locally transmitted. During the second wave in Peru, we identify the coexistence of two Lambda and three Gamma sublineages. Lambda sublineages emerged in the center of Peru whereas the Gamma sublineages more likely originated in the north-east and mid-east. Importantly, it is observed that the center of Peru played a prominent role in transmitting SARS-CoV-2 to other regions within Peru., (© 2023. The Author(s).)

Hepatitis B virus (HBV) spreads efficiently among all human populations worldwide. HBV is classified into ten genotypes (A to J) with their geographic distribution and clinical features. In Mexico, HBV genotype H is the leading cause of hepatitis B and has been detected in indigenous populations, suggesting that HBV genotype H may be native to Mexico. However, little is known about the evolutionary history of HBV genotype H. Thus, we aimed to determine the age of HBV genotype H in Mexico using molecular dating techniques. Ninety-two HBV sequences of the reverse transcriptase (RT) domain of the polymerase gene (~1,251 bp) were analyzed; 48 were genotype H, 43 were genotype F, and the oldest HBV sequence from America was included as the root. All sequences were aligned, and the most recent common ancestor (TMRCA) time was calculated using the Bayesian Skyline Evolutionary Analysis. Our results estimate a TMRCA for the genotype H in Mexico of 2070.9 (667.5-4489.2) years before the present (YBP). We identified four major diversification events in genotype H, named H1, H2, H3, and H4. The TMRCA of H1 was 1213.0 (253.3-2638.3) YBP, followed by H2 1175.5 (557.5-2424.2) YBP, H3 949.6 (279.3-2105.0) YBP, and H4 1230.5 (336.3, 2756.7) YBP. We estimated that genotype H diverged from its sister genotype F around 8140.8 (1867.5-18012.8) YBP. In conclusion, this study found that genotype H in Mexico has an estimated age of 2070.9 (667.5-4489.2) YBP and has experienced at least four major diversification events since then., 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 © 2023 Jose-Abrego, Roman, Laguna-Meraz, Rebello-Pinho, Justo Arevalo and Panduro.)

Background: Little is currently known about vaccine effectiveness (VE) for either 2 doses of Oxford-AstraZeneca (ChAdOx1) viral vector vaccine or CoronaVac (Instituto Butantan) inactivated viral vaccine followed by a third dose of mRNA vaccine (Pfizer/BioNTech) among healthcare workers (HCWs)., Methods: We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil from January to December 2021. VE was defined as 1 - incidence rate ratio (IRR), with IRR determined using Poisson models with the occurrence of laboratory-confirmed coronavirus disease 2019 (COVID-19) infection as the outcome, adjusting for age, sex, and job type. We compared those receiving viral vector or inactivated viral primary series (2 doses) with those who received an mRNA booster., Results: A total of 11 427 HCWs met the inclusion criteria. COVID-19 was confirmed in 31.5% of HCWs receiving 2 doses of CoronaVac vaccine versus 0.9% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001) and 9.8% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 1% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). In the adjusted analyses, the estimated VE was 92.0% for 2 CoronaVac vaccines plus mRNA booster and 60.2% for 2 ChAdOx1 vaccines plus mRNA booster, when compared with those with no mRNA booster. Of 246 samples screened for mutations, 191 (77.6%) were Delta variants., Conclusions: While 2 doses of ChAdOx1 or CoronaVac vaccines prevent COVID-19, the addition of a Pfizer/BioNTech booster provided significantly more protection., Competing Interests: Potential conflicts of interest. A. L. B. reports the following contracts or grants unrelated to this work: MCTIC/CNPq/FNDCT/MS/SCTIE/Decit 07/2020, Brazil. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19., Methods: We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed., Findings: Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production., Interpretation: Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments., Funding: CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart & Lung Foundation., Competing Interests: Declaration of interests J.E. is the founder of Medetect AB, Lund, Sweden. J.J., C.S. and C.L. are employees at Medetect AB. M.A.S. and J.O. are employees and shareholders at Regeneron Pharmaceuticals. All other co-authors have no conflict of interest to declare with the subject of the manuscript., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Only two naturally occurring human Sabiá virus (SABV) infections have been reported, and those occurred over 20 years ago., Methods: We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings., Results: We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte "pinewood knot" lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing., Conclusions: Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To evaluate clinical predictors of poor sleep quality in COPD patients with and without obstructive sleep apnea (OSA)., Methods: Consecutive stable patients with COPD were evaluated for OSA by means of overnight polysomnography; for sleep quality by means of the Pittsburgh Sleep Quality Index (PSQI); and for disease impact by means of the COPD Assessment Test. COPD severity was graded in accordance with the 2020 GOLD guidelines. Predictors of poor sleep quality were evaluated by multivariate logistic regression analysis., Results: We studied 51 patients with COPD alone and 51 patients with COPD and OSA. Both groups had similar age (66.2 ± 9.2 years vs. 69.6 ± 10.7, p = 0.09) and airflow limitation (p = 0.37). Poor sleep quality was present in 74.8% of the study participants, with no significant difference between COPD patients with and without OSA regarding PSQI scores (p = 0.73). Polysomnography showed increased stage 1 non-rapid eye movement sleep and arousal index, as well as reduced sleep efficiency and stage 3 non-rapid eye movement sleep, in the group of patients with COPD and OSA (p < 0.05). Independent predictors of poor sleep quality were GOLD grade C/D COPD (OR = 6.4; 95% CI, 1.79-23.3; p < 0.01), a COPD Assessment Test score ≥ 10 (OR = 12.3; 95% CI, 4.1-36.5; p < 0.01), and lowest SaO2 < 80% (p < 0.0001)., Conclusions: Poor sleep quality is quite common in patients with COPD and is associated with severe COPD and poor health status, having a negative impact on overall quality of life. Despite changes in polysomnography, OSA appears to have no impact on subjective sleep quality in COPD patients.

The recent outbreak of yellow fever (YF) in São Paulo during 2016-2019 has been one of the most severe in the last decades, spreading to areas with low vaccine coverage. The aim of this study was to assess the genetic diversity of the yellow fever virus (YFV) from São Paulo 2016-2019 outbreak, integrating the available genomic data with new genomes from patients from the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Using phylodynamics, we proposed the existence of new IE subclades, described their sequence signatures, and determined their locations and time of origin. Plasma or urine samples from acute severe YF cases ( n = 56) with polymerase chain reaction (PCR) positive to YFV were submitted to viral genome amplification using 12 sets of primers. Thirty-nine amplified genomes were subsequently sequenced using next-generation sequencing (NGS). These 39 sequences, together with all the complete genomes publicly available, were aligned and used to determine nucleotide/amino acids substitutions and perform phylogenetic and phylodynamic analysis. All YFV genomes generated in this study belonged to the genotype South American I subgroup E. Twenty-one non-synonymous substitutions were identified among the new generated genomes. We analyzed two major clades of the genotypes IE, IE1, and IE2 and proposed the existence of subclades based on their sequence signatures. Also, we described the location and time of origin of these subclades. Overall, our findings provide an overview of YFV genomic characterization and phylodynamics of the 2016-2019 outbreak contributing to future virological and epidemiological studies., 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 Moreira Salles, de Seixas Santos Nastri, Ho, Vilas Boas Casadio, Emanuel Amgarten, Justo Arévalo, Soares Gomes-Gouvea, Jose Carrilho, de Mello Malta and Rebello Pinho.)

Content available: Author Interview and Audio Recording., (© 2021 by the American Association for the Study of Liver Diseases.)

Objectives: Co-infection with hepatitis A or B viruses may aggravate liver injury in patients infected with hepatitis C virus (HCV). However, few studies have assessed co-infection with hepatitis E virus (HEV) and HCV. Therefore, this study aimed to assess the prevalence and impact of HEV infection among Brazilian patients with chronic HCV infection., Methods: This observational study included adult patients with chronic HCV infection who were naive to antiviral therapy from January 2013 to March 2016. A total of 181 patients were enrolled, and HEV serology and PCR were performed for all patients., Results: Seropositivity for anti-HEV IgG was detected in 22 (12.0%) patients and anti-HEV immunoglobulin M in 3 (1.6%). HEV RNA showed inconclusive results in nine (4.9%) patients and was undetectable in the remaining patients. HEV serology positive patients had more severe liver disease, characterized by liver fibrosis ≥3 versus ≤2 (p<0.001), Aspartate Aminotransferase-to-Platelet Ratio Index of ≥1.45 (p=0.003), and Fibrosis-4 score of ≥3.25 (p=0.001). Additionally, the odds of HEV-positive patients developing diabetes mellitus were 3.65 (95% CI 1.40-9.52) times the corresponding odds of HEV-negative patients. A case-control-based histological analysis (n=11 HEV-HCV-positive patients and n=22 HCV-positive patients) showed no significant differences between the groups., Conclusions: This prevalence is higher than that reported in previous studies of the general population in Brazil. Thus, HEV infection may influence the severity of liver disease and may represent an additional risk of developing diabetes mellitus in patients with HCV infection.

The saliva of patients with COVID-19 has a high SARS-CoV-2 viral load. The risk of spreading the virus is high, and procedures for viral load reduction in the oral cavity are important. Little research to date has been performed on the effect of mouthwashes on the salivary SARS-CoV-2 viral load. This pilot randomized single-center clinical trial investigated whether three types of mouthwash with solutions containing either 0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC + Zn), 1.5% hydrogen peroxide (HP), or 0.12% chlorhexidine gluconate (CHX) reduce the SARS-CoV-2 viral load in saliva at different time points. Sixty SARS-CoV-2-positive patients were recruited and randomly partitioned into a placebo (oral rinsing with distilled water) group and other groups according to the type of mouthwash. Saliva samples were collected from the participants before rinsing (T0), immediately after rinsing (T1), 30 min after rinsing (T2), and 60 min after rinsing (T3). The salivary SARS-CoV-2 viral load was measured by qRT-PCR assays. Rinsing with HP and CPC + Zn resulted in better reductions in viral load, with 15.8 ± 0.08- and 20.4 ± 3.7-fold reductions at T1, respectively. Although the CPC + Zn group maintained a 2.6 ± 0.1-fold reduction at T3, this trend was not observed for HP. HP mouthwash resulted in a significant reduction in the SARS-CoV-2 viral load up to 30 min after rinsing (6.5 ± 3.4). The CHX mouthwash significantly reduced the viral load at T1, T2, and T3 (2.1 ± 1.5-, 6.2 ± 3.8-, and 4.2 ± 2.4-fold reductions, respectively). In conclusion, mouthwash with CPC + Zinc and CHX resulted in significant reductions of the SARS-CoV-2 viral load in saliva up to 60 mins after rinsing, while HP mouthwash resulted in a significant reduction up to 30 mins after rinsing. Despite this transitory effect, these results encourage further studies and suggest that these products could be considered as risk-mitigation strategies for patients infected with SARS-CoV-2., Competing Interests: The authors declare the following conflict of interests: Zilson Malheiros, Bernal Stewart, Carlo Amorin Daep and Maria Ryan are currently employed by Colgate-Palmolive Company., (© 2021 Published by Elsevier Ltd.)

Hepatitis B virus (HBV) co-infection is possible in patients who are positive for human immunodeficiency virus (HIV) since both share similar transmission routes. Furthermore, through the continuous risk of exposure, they potentially can be infected by mixtures of distinct HBV genotypes which can result in the presence of two or more genotypes in a single patient. This study aimed to specify the frequency of mixtures of HBV genotypes and their potential clinic importance in HIV-infected Mexican patients. HBV infection was assessed by serological testing and molecular diagnostics. HBV mixtures were detected by multiplex PCR and DNA sequencing. Liver fibrosis was evaluated using transitional elastography, the Aspartate aminotransferase to Platelets Ratio Index score, and Fibrosis-4 score. Among 228 HIV-infected patients, 67 were positive for HBsAg. In 25 HBV/HIV co-infected patients, 44 HBV genotypes were found: H (50.0%, 22/44), G (22.7%, 10/44), D (15.9%, 6/44), A (9.1%, 4/44), and F (2.3%, 1/44). Among these, 44.0% (11/25) were single genotype, 36.0% (9/25) were dual and 20.0% (5/25) were triple genotype. The most frequent dual combination was G/H (44.4%, 4/9), while triple-mixtures were H/G/D (60.0%, 3/5). The increase in the number of genotypes correlated positively with age (Spearman's Rho = 0.53, p = 0.0069) and negatively with platelet levels (Spearman's Rho = - 0.416, p = 0.039). HBV viral load was higher in triply-infected than dually infected (31623.0 IU/mL vs. 1479.0 IU/mL, p = 0.029) patients. Triple-mixed infection was associated with significant liver fibrosis (OR = 15.0 95%CI = 1.29 - 174.38, p = 0.027). In conclusion, infection with mixtures of HBV genotypes is frequent in HIV patients causing significant hepatic fibrosis related to high viral load, especially in triple genotype mixtures., 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 Jose-Abrego, Roman, Rebello Pinho, de Castro and Panduro.)

Introduction: Introduction: resistant arterial hypertension (HAR) is associated with a high risk for cardiovascular events due to oxidative stress. Research has shown the beneficial effects of dietary antioxidants on cardiovascular health. Objective: to analyze and correlate the biochemical, anthropometric profile and intake of antioxidant micronutrients of patients with HAR. Material and methods: the patients underwent a biochemical assessment, and an anthropometric assessment to calculate body mass index (IMC), waist circumference (PCI), hip circumference (PCA), waist-to-hip ratio (ICC), and micronutrient intake assessment: vitamin A, vitamin C, vitamin E, selenium and zinc, estimated by a semi-quantitative food frequency questionnaire and 24-hour recall. The statistical analysis was performed using the SPSS Statistics 20 software. A p-value < 0.05 was considered significant. Results: sixty individuals with HAR were studied, with a mean age of 62.83 ± 10.73 years. Mean IMC was 31.01 ± 5.60 kg/m², PCI, 98.12 ± 15.04 cm, PCA, 110.55 ± 13.16 cm, and ICC, 0.879 ± 0.084. Regarding the biochemical profile, mean total colesterol was 187.65 ± 48.29 mg/dL, triglycerides, 136.38 ± 99.91 mg/dL; HDL-col, 49.00 ± 10.99 mg/dL; LDL-col, 112.01 ± 41.89 mg/dL; glucose, 105.37 ± 14.81 mg/dL, and glycated hemoglobin, 6.29 ± 1.76 %. The average daily intake of antioxidants was: vitamin A, 241.47 ± 191.87 µg/d; vitamin C, 147.02 ± 192.94 mg/d; vitamin E, 1.99 ± 1.82 mg/d; selenium, 36.80 ± 34.56 µg/d, and zinc, 99.91 ± 6.64 mg/d, where 91.38 %, 46.55 %, 93.10 %, 67.24 %, and 46.55 % of the sample were below the recommended intakes, respectively. Conclusion: inadequate antioxidant intake was observed in these patients with HAR, with a high prevalence of obesity, especially visceral adiposity and alterations in lipid profile, conditions that require a greater usage of these micronutrients. We suggest there is a need for dietary planning for these patients to improve their quality of life and their response to antihypertensive treatment.

Background: The ability of coronavirus SARS-CoV-2 to spread is one of the determinants of the COVID-19 pandemic status. Until June 2020, global COVID-19 cases surpassed 10 million. Asymptomatic patients, with no respiratory impairment, are believed to be responsible for more than 80% of the transmission. Other viruses have been consistently detected in periodontal tissues. Objective: The aim of this study was to investigate the presence of SARS-CoV-2 in periodontal tissue. Methods: We conducted video-endoscope minimally invasive post-mortem biopsy in seven fatal cases of COVID-19, using a regular endoscope video system associated with a smartphone to locate periodontal tissue. We analyzed the samples using RT-PCR, to identify the SARS-CoV-2 RNA and histopathological analysis. Results: The seven studied autopsies with positive laboratory tests for COVID-19 included 57.14% of female patients at the average age of 47.4 (range 8 to 74). In five cases, periodontal tissue was positive for SARS-CoV-2 (RT-PCR). Histopathologic analyses showed morphologic alterations in the keratinocytes of the junctional epithelium, a vacuolization of the cytoplasm and nucleus and nuclear pleomorphism. Conclusion: We presented a biomolecular analysis obtained from minimally invasive autopsies. This is the first study to demonstrate the presence of SARS-CoV-2 in periodontal tissue in COVID-19 positive patients., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction and Objectives: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs)., Materials and Methods: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use., Results: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution., Conclusions: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment., (Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

The present study examined the efficacy of the topical 15d‑PGJ2‑poloxamer 407 hydrogel in an atopic dermatitis (AD) animal model. The 15d‑PGJ2 hydrogel was prepared and characterized. The examined rats possessed AD‑Like cutaneous lesions, which were induced using 2,4‑dinitrochlorobenzene, the rats were then treated with a hydrogel vehicle, 15d‑PGJ2 hydrogel or tacrolimus for 14 days. The rats were sacrificed and blood samples were collected to quantify the IgE levels. Subsequently, skin biopsies were stained with toluidine blue to identify mast cells and immunohistochemistry was performed for ROR‑γt and TNF‑α. Histological analyses demonstrated that 15d‑PGJ2 hydrogel significantly decreased mast cell infiltration (P<0.05) when compared with the AD‑group. Tacrolimus at 0.1% exhibited decreased mast cell infiltration; however, this difference was not statistically significant from the AD‑group. Topical 15d‑PGJ2 hydrogel and Tacrolimus 0.1% significantly reduced the serum levels of IgE (P<0.05) compared with the AD‑group. Immunohistochemistry revealed a significant decrease in ROR‑γt and TNF‑α positive cell expression (P<0.05) in the 15d‑PGJ2 hydrogel group compared with the AD‑group. In summary, topical administration of 15d‑PGJ2 hydrogel had a beneficial effect on AD symptoms, suggesting that this formulation may be a useful strategy for the treatment of AD.

Background & Aims: All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear., Methods: We analysed sera from 124 Brazilian monkeys collected during 2012-2016 for hepadnaviruses using molecular and serological tools, and conducted evolutionary analyses., Results: We identified a novel orthohepadnavirus species in capuchin monkeys (capuchin monkey hepatitis B virus [CMHBV]). We found CMHBV-specific antibodies in five animals and high CMHBV concentrations in one animal. Non-inflammatory, probably chronic infection was consistent with an intact preCore domain, low genetic variability, core deletions in deep sequencing, and no elevated liver enzymes. Cross-reactivity of antisera against surface antigens suggested antigenic relatedness of HBV, CMHBV, and WMHBV. Infection-determining CMHBV surface peptides bound to the human HBV receptor (human sodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected human hepatoma cells via the human sodium taurocholate co-transporting polypeptide, and were poorly neutralised by HBV vaccine-derived antibodies, suggesting that cross-species infections may be possible. Ancestral state reconstructions and sequence distance comparisons associated HBV with humans, whereas primate hepadnaviruses as a whole were projected to NHP ancestors. Co-phylogenetic analyses yielded evidence for co-speciation of hepadnaviruses and New World NHP. Bayesian hypothesis testing yielded strong support for an association of the HBV stem lineage with hominoid ancestors. Neither CMHBV nor WMHBV was likely the ancestor of the divergent human HBV genotypes F/H found in American natives., Conclusions: Our data suggest ancestral co-speciation of hepadnaviruses and NHP, and an Old World origin of the divergent HBV genotypes F/H. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B., Lay Summary: The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: Hepatitis B virus (HBV) infection leads to a chronic liver disease that is distributed worldwide. The characterization of HBV into genotypes/subgenotypes is not only a mere procedure for distinguishing different HBV strains around the world because determining their geographic distribution is crucial to understanding their spread across the world., Material and Methods: We characterized different HBV genotypes and subgenotypes in five municipalities located in northeastern Maranhão, in the Brazilian north Atlantic coast. 92 HBsAg-positive individuals were submitted to PCR (polymerase chain reaction). Fifty samples were sequenced using automated Sanger sequencing and classified by phylogenetic methods., Results: Subgenotypes D4 and A1 were found in 42 (84%) and eight (16%) samples, respectively. To our knowledge, this is the first study to describe a high frequency of subgenotype D4 in any population. Subgenotype A1 is frequently found across Brazil, but D4 has been rarely detected and only in a few Brazilian states. This study shows the characterization of HBV subgenotypes from a population based study in the state of Maranhão, particularly in populations that do not have frequent contact with populations from other regions of the world., Conclusion: Our findings showed a HBV subgenotype profile that probably reflect the viruses that were brought with the slave trade from Africa to Maranhão. This study also reinforces the need to evaluate the status of HBV dispersion not only in large urban centers, but also in the hinterland, to enable the implementation of effective control and treatment measures.

Spontaneously occurring resistance may impair the success of protease inhibitors based regimens in HCV treatment. This study aimed to evaluate associations between amino acid substitutions in NS3/NS4A domain and clinical features of 247 HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at least one resistance-associated substitution (RAS). The following RASs were detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A amino acid substitutions., (© 2017 Wiley Periodicals, Inc.)

Dietary proteins/essential amino acids (EAAs) are nutrients with anabolic properties that may increase muscle mass or attenuate muscle loss during immobilization and aging via the stimulation of muscle protein synthesis (MPS). An EAA's anabolic threshold, capable to maximize the stimulation of MPS has been hypothesized, but during certain conditions associated with muscle loss, this anabolic threshold seems to increase which reduces the efficacy of dietary EAAs to stimulate MPS. Preliminary studies have demonstrated that acute ingestion of dietary proteins/EAA (with a sufficient amount of leucine) was capable to restore the postprandial MPS during bed rest, immobilization or aging; however, whether these improvements translate into chronic increases (or attenuates loss) of muscle mass is equivocal. For example, although free leucine supplementation acutely increases MPS and muscle mass in some chronic studies, other studies have reported no increases in muscle mass following chronic leucine supplementation. In contrast, chronically increasing leucine intake via the consumption of an overall increase in dietary protein appears to be the most effective dietary intervention toward increasing or attenuating lean mass during aging; however, more research investigating the optimal dose and timing of protein ingestion is necessary. Several studies have demonstrated that decreases in postprandial MPS as a result of increased circulating oxidative and inflammatory are more responsible than muscle protein breakdown for the decreases in muscle mass during disuse and health aging. Therefore, nutritional interventions that reduce oxidation or inflammation in conjunction with higher protein intakes that overcome the anabolic resistance may enhance the MPS response to feeding and either increase muscle mass or attenuate loss. In preliminary studies, antioxidant vitamins and amino acids with antioxidant or anti-inflammatory properties show potential to restore the anabolic response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

Mutations in the a determinant of S gene may develop co-existence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in the serum of infected hepatitis B virus (HBV) individuals. Mutations in this region may change the antigenicity of HBsAg, which in turn, lead to escape of neutralizing action of anti-HBs antibodies. This study identified individuals with concomitant HBsAg and anti-HBs serological markers in individuals of Maranhão, Northeastern Brazil. Samples from a population-based study were evaluated for HBsAg, anti-HBs, and anti-HBc, and those that tested positive for simultaneous HBsAg and anti-HBs were submitted to HBV DNA quantification and S gene characterization by Sanger sequencing. Mutations were investigated in the a determinant located in major hydrophilic region (MHR) of the S gene. Among 3,984 samples analyzed, 92 (2.3%) were positive for HBsAg and three had the atypical HBsAg and anti-HBs-positive profile (3.26%). The frequency of HBsAg and anti-HBs co-existence was similar to previous studies. Only one individual harbored mutation in the S gene a determinant associated with this profile. Little is known about this phenomenon; however, studies as ours may contribute for future enlightenment of this important issue. J. Med. Virol. 89:458-462, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Strongyloidiasis is a potentially serious infection in immunocompromised patients. Thus, the availability of sensitive and specific diagnostic methods is desirable, especially in the context of immunosuppressed patients in whom the diagnosis and treatment of strongyloidiasis is of utmost importance. In this study, serological and molecular tools were used to diagnose Strongyloides stercoralis infections in immunosuppressed patients. Serum and stool samples were obtained from 52 patients. Stool samples were first analyzed by Lutz, Rugai, and Agar plate culture methods, and then by a quantitative real time polymerase chain reaction (qPCR). Serum samples were evaluated by an enzyme-linked immunosorbent assay (ELISA) using a soluble (AS) or a membrane fractions antigen (AM) obtained from alkaline solutions of the filariform larvae of Strongyloides venezuelensis. Of the 52 immunosuppressed patients, three (5.8%) were positive for S. stercoralis by parasitological methods, compared to two patients (3.8%) and one patient (1.9%) who were detected by ELISA using the AS and the AM antigens, respectively. S. stercoralis DNA was amplified in seven (13.5%) stool samples by qPCR. These results suggest the utility of qPCR as an alternative diagnostic tool for the diagnosis of S. stercoralis infection in immunocompromised patients, considering the possible severity of this helminthiasis in this group of patients.