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Marta Imamura,1 Rosa Alves Targino,1 Wu Tu Hsing,2,3 Satiko Imamura,1 Raymundo Soares Azevedo,3 Lucy Santos Villas Boas,4 Tania Regina Tozetto-Mendoza,5 Fábio Marcon Alfieri,1,6 Thais Raquel Filippo,1 Linamara Rizzo Battistella1,71Clinical Research Center, Institute of Physical Medicine and Rehabilitation, University of São Paulo Medical School, São Paulo, 2Division of Physical Medicine, Center for Acupuncture, Institute of Orthopedics and Traumatology, University of São Paulo, São Paulo, 3Department of Pathology, University of São Paulo, São Paulo, 4Laboratory of Medical Investigation LIM-52-HCFMUSP, Institute of Tropical Medicine, University of São Paulo, São Paulo, 5Tropical Laboratory of Hematology/Medical Research Laboratory-LIM 52, Institute of Tropical Medicine, University of São Paulo, São Paulo, 6Program of Master in Health Promotion, São Paulo Adventist University Center, São Paulo, 7Department of Legal Medicine, Medical Ethics, Social and Labor Medicine – Medicine School, University of São Paulo, São Paulo, BrazilIntroduction: Fibromyalgia and osteoarthritis may present a relationship with the concentration of cytokines. The aim of this study was to compare the serum concentrations of IL-12p70, tumor necrosis factor, IL-10, IL-6, IL-1ß, and IL-8 in patients with knee osteoarthritis and fibromyalgia.Materials and methods: The study included 53 women (71.2±7.6 years old) diagnosed with knee osteoarthritis with moderate-to-severe pain (visual analog scale >4) for at least 3 months. Sixty women (54.1±8.1 years old) diagnosed with fibromyalgia according to the American College of Rheumatology criteria and with moderate-to-severe pain (visual analog scale >4) also participated in this study. For the dosage of cytokines, blood was collected in the morning: 5 mL from the cubital vein. The material was centrifuged at 4°C, separated into 100 µL aliquots and stored at -80°C until processing. Serum concentrations of the studied cytokines were assessed using the BD Cytometric Bead Array method. Data were analyzed with Student’s t-test and the Mann–Whitney U test.Results: We found higher levels of IL-6, IL-10, and IL-1ß in fibromyalgia patients. After adjustment of age as a covariate, there was no statistically significant difference in the concentration of any cytokine between fibromyalgia and knee osteoarthritis patients.Conclusion: Patients with knee osteoarthritis and fibromyalgia with the same duration and intensity of pain demonstrate similar concentrations of cytokines. Aging may play a role in cytokine profile, a finding not so extensively addressed in the literature and one that should be further investigated.Keywords: cytokines, osteoarthritis, fibromyalgia, aging

INTRODUCTION: After the era of rubella vaccine, cytomegalovirus (CMV) infection is one of the most frequently causes of mental retardation and congenital deafness. Seroepidemiological studies are necessary to understand the transmission dynamics of the disease. The purpose of the study was to quantify the transmission rate of CMV disease in a community in the state of São Paulo, Brazil. METHODS: Using ELISA test (IgG), a retrospective serological survey looking for CMV antibodies was performed in an non-immunized community. Frozen sera from 443 individuals, randomly selected by cluster sampling technique in the town of Caieiras, São Paulo, were collected from November 1990 to January 1991. Seroprevalence was stratified by age (0-40 years). Mathematical techniques were applied to determine the age-dependent decay function of maternal antibodies during the first year of life, the age-dependent seroprevalence function and the force of infection for CMV in this community. RESULTS: It was observed a descending phase of seropositivity in the first 9 months, but changes in antibody titration were observed between 8 months old and one year of age. The average age of the first infection was 5.02 months of age and 19.84 years, when the age-dependent seroprevalence and the force of infection were analyzed between 10 months of age and 10 years of age and from 10 to 40 years old, respectively. CONCLUSION: CMV infection is highly prevalent among the population studied and infection occurs in the first year of life. This study shows that most women at reproductive age are vulnerable to the first infection, increasing the risk for congenital infection.

OBJECTIVE: It is an accepted fact that confinement conditions increase the risk of some infections related to sexual and/or injecting drugs practices. Mathematical techniques were applied to estimate time-dependent incidence densities of HIV infection among inmates. METHODS: A total of 631 prisoners from a Brazilian prison with 4,900 inmates at that time were interviewed and their blood drawn. Risky behavior for HIV infection was analyzed, and serological tests for HIV, hepatitis C and syphilis were performed, intended as surrogates for parenteral and sexual HIV transmission, respectively. Mathematical techniques were used to estimate the incidence density ratio, as related to the time of imprisonment. RESULTS: Prevalence were: HIV -- 16%; HCV -- 34%; and syphilis -- 18%. The main risk behaviors related to HIV infection were HCV prevalence (OR=10.49) and the acknowledged use of injecting drugs (OR=3.36). Incidence density ratio derivation showed that the risk of acquiring HIV infection increases with the time of imprisonment, peaking around three years after incarceration. CONCLUSIONS: The correlation between HIV and HCV seroprevalence and the results of the mathematical analysis suggest that HIV transmission in this population is predominantly due to parenteral exposure by injecting drug, and that it increases with time of imprisonment.

Jorge Rodrigues de Sousa,1,2 Raimunda do Socorro da Silva Azevedo,1 Juarez Antônio Simões Quaresma,2–4 Pedro Fernando da Costa Vasconcelos1,4 1Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil; 2Núcleo de Medicina Tropical Belém, Universidade Federal do Pará, Belém, Pará, Brazil; 3Departamento de Patologia, Instituto Evandro Chagas, Ananindeua, Pará, Brazil; 4Universidade do Estado do Pará, Belém, Pará, BrazilCorrespondence: Pedro Fernando da Costa VasconcelosEvandro Chagas Institute, Rodovia BR-316, km-07, s/n, Ananindeua 67030-000, BrazilEmail pedrovasconcelos@iec.gov.brAbstract: Zika virus (ZIKV) is an arbovirus that is transmitted by Aedes mosquitos. Its prototype was isolated in 1947 from serum of a sentinel Rhesus monkey (Macaca mulatta) in the Zika forest of Uganda. As a member of the genus Flavivirus, family Flaviviridae, ZIKV is enveloped and icosahedral and possesses a single-stranded, positive-sense RNA genome of approximately 10.7 kb. Epidemiologically, infection by ZIKV has become a global health concern in recent years because of the occurrence of epidemics, its speed of dissemination, routes of transmission, and the sequelae it can cause especially in newborns. At the neural level, there are still many gaps in our understanding of the mechanisms that induce ZIKV infection-associated microcephaly. However, some studies already demonstrated that underlying cell death is determinant to induce the congenital malformation. In this report, we reviewed the various mechanisms of cell injury involved in the immunopathogenesis of ZIKV infection and discussed its relationship with the death of neuronal and glial cells development and microcephaly.Keywords: ZIKV, microcephaly, neuroinflammatory response, cell death

SUMMARYIn order to analyse the impact of vaccination against cytomegalovirus (CMV) on congenital infection incidence using current vaccines tested in phase II clinical trials, we simulated different scenarios by mathematical modelling, departing from the current vaccine characteristics, varying age at vaccination, immunity waning, vaccine efficacy and mixing patterns. Our results indicated that the optimal age for a single vaccination interval is from 2 to 6 months if there is no immunity waning. Congenital infection may increase if vaccine-induced immunity wanes before 20 years. Congenital disease should increase further when the mixing pattern includes transmission among children with a short duration of protection vaccine. Thus, the best vaccination strategy is a combined schedule: before age 1 year plus a second dose at 10-11 years. For CMV vaccines with low efficacy, such as the current ones, universal vaccination against CMV should be considered for infants and teenagers. [ABSTRACT FROM AUTHOR]

Background: To assess the impact of water sanitation and sewage disposal, part of a major environmental control programme in Rio de Janeiro, we carried out sero-prevalence studies for Hepatitis A virus (HAV) in three micro-regions in Rio de Janeiro. Each region varied with regard to level of sanitation. We are interested in assessing the discriminating power of age-specific prevalence curves for HAV as a proxy for improvement in sanitation. These curves will serve as baseline information to future planned surveys as the sanitation programme progresses.Methods: Incidence rate curves from prevalence data are estimated parametrically via a Weibull-like survival function, and non-parametrically via maximum likelihood and monotonic splines. Sera collected from children and adults in the three areas are used to detect antibodies against HAV through ELISA.Results: We compare baseline incidence curves at the three sites estimated by the three methods. We observe a strong negative correlation between level of sanitation and incidence rates for HAV infection. Incidence estimates yielded by the parametric and non-parametric approaches tend to agree at early ages in the microregion showing the best level of sanitation and to increasingly disagree in the other two.Conclusion: Our results support the choice of HAV as a sentinel disease that is associated with level of sanitation. We also introduce monotonic splines as a novel non-parametric approach to estimate incidence from prevalence data. This approach outperforms current estimating procedures. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic has disproportionately affected individuals residing in Long-Term Care Facilities (LTCFs), necessitating tailored strategies to manage outbreaks. This study examines the outcomes of the ILPI BH project, a collaborative effort between the Municipal Health Department and the Hospital das Clínicas of the Federal University of Minas Gerais, designed to mitigate COVID-19 spread within LTCFs., Methods: Prospective cohort of secondary data: 1,794 old residents in 99 long-term care facilities of Belo Horizonte, Brazil, were followed from May 2020 to January 2021. The study analyzed the prevention strategies, residents' clinical data, and the characteristics of the long-term care facilities, correlating these variables with the number of infections, hospitalizations, and deaths from COVID-19. It checked absolute numbers and rates of incidence, hospitalization, mortality, and lethality., Results: There have been 58 COVID-19 outbreaks in long-term care facilities. There were 399 cases among residents, 96 hospitalizations for COVID-19 and 48 deaths from COVID-19 (2.7 % of the cohort), with a case fatality rate of 12 %. After multivariate analysis, the intrinsic variables to residents associated with higher mortality risk were higher degree of frailty (OR=1.08; p = 0.004) and the fact of living in a long-term care facility with a considerable proportion of residents' coverage by health plans (OR = 1.01; p = 0.028). Early geriatric follow-up showed an association with a reduction in the number of hospitalizations due to COVID-19., Conclusion: The correct classification of the degree of frailty of institutionalized older people seems to have been relevant for predicting mortality from COVID-19. The extensive assistance by private health plans, contrary to what is supposed, did not result in better health protection. Early geriatric follow-up was beneficial and may be an attractive strategy in the face of health emergencies that affect long-term care facilities to reduce hospital admissions., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

The cyanobacterium Synechococcus elongatus PCC 7942 holds significant potential as a biofactory for recombinant protein (RP) production due to its capacity to harness light energy and utilize CO 2 . This study aimed to enhance RP production by integration of native promoters and magnetic field application (MF) in S. elongatus PCC 7942. The psbA2 promoter, which responds to stress conditions, was chosen for the integration of the ZsGreen1 gene. Results indicated successful gene integration, affirming prior studies that showed no growth alterations in transgenic strains. Interestingly, exposure to 30 mT (MF30) demonstrated a increase in ZsGreen1 transcription under the psbA2 promoter, revealing the influence of MF on cyanobacterial photosynthetic machinery. This enhancement is likely attributed to stress-induced shifts in gene expression and enzyme activity. MF30 positively impacted photosystem II (PSII) without disrupting the electron transport chain, aligning with the "quantum-mechanical mechanism" theory. Notably, fluorescence levels and gene expression with application of 30 mT were significantly different from control conditions. This study showcases the efficacy of utilizing native promoters and MF for enhancing RP production in S. elongatus PCC 7942. Native promoters eliminate the need for costly exogenous inducers and potential cell stress. Moreover, the study expands the scope of optimizing RP production in photoautotrophic microorganisms, providing valuable insights for biotechnological applications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espírito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espírito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) ( p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) ( p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) ( p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present ( p < 0.001) or when only PC mutations were detected ( p = 0.047), reinforcing their role in viral replication.

Background: gingival/alveolar mucosal reactive hyperplastic lesions (GRHL), including fibrous hyperplasia (FH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF) and peripheral giant cell lesion (PGCL), are a common group of oral diseases. The aim of the present study was to access the frequency and distribution of the clinical and histological features of these disorders in a Brazilian population., Material and Methods: all specimens diagnosed as GRHL in three Oral Pathology laboratories were selected for the study. Clinical information was retrieved from the laboratory biopsy forms and hematoxylin and eosin stained histological slides were reviewed for analysis of the histological characteristics., Results: final sample was composed of 996 specimens, including 463 FH (47%), 280 PG (28%), 183 POF (18%) and 70 PGCL (7%). Females were more affected by FH, PG, and POF, and most cases affected adults with mean ages ranging from 40 to 53 years. FH, PG, and POF were more common in the upper gingiva/alveolar mucosa. Most PG, POF and PGCL were pedunculated, in contrast with FH (p<0.001). PG, FH and POF were mostly red or normal mucosal in color, while PGCL were mostly red/purple (p<0.001). PGCL were larger, followed by POF, FH and PG (p<0.001). Some histological features were characteristically found in some conditions, but they were also encountered in other lesions with variable frequencies., Conclusions: Oral medicine specialists, oral pathologists and periodontists are usually the professionals in contact with patients presenting GRHL and it is of upmost relevance that they should be familiarized with their clinical and histological profile.

This study aimed to analyze the effect of magnetic field (MF) application on the metabolism of Synechococcus elongatus PCC 7942. Concentrations of biomass, carbohydrate, protein, lipid, and photosynthetic pigments (chlorophyll-a, C-phycocyanin, allophycocyanin and phycoerythrin) were determined. In cultures with MF application (30 mT for 24 h d -1 ), there were increases of 47.5% in total protein content, 87.4% in C-phycocyanin, and 332.8% in allophycocyanin contents, by comparison with the control. Allophycocyanin is the most affected pigment by MF application. Therefore, its biosynthetic route was investigated, and four genes related to its synthesis were found. However, the analysis of the gene expression showed no statistical differences from the control culture, which suggests that induction of such genes may occur soon after MF application with consequent stabilization over time. MF application may be a cost-effective alternative to increase production of compounds of commercial interest by cyanobacteria., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: An outbreak of febrile illness was reported from January to February 2018 in the Expedito Ribeiro Settlement, ​​Santa Bárbara do Pará municipality, Pará State, Brazil., Objective: This study aimed to investigate the pathogenic agent responsible for the outbreak and the circulation of arboviruses in the region., Study Design: We analyzed 94 individuals through laboratory tests for arboviruses. Forty out of 94 individuals were asymptomatic but were living with or near febrile cases, and 55 participants were symptomatic., Results: Our results showed that 51.1% of the investigated individuals were positive for arboviruses (Oropouche, Mayaro, and Chikungunya), of which 77.8% were symptomatic. We detected 93.7% of positive cases for Oropouche infection, 2.1% for Mayaro fever, and 4.2% were positive for both Oropouche and Chikungunya infection., Conclusion: Oropouche virus was mainly responsible for the outbreak; however, we also detected a few Chikungunya and Mayaro fever cases. Serologic assays showed evidence of arboviruses circulation of different genera in the area., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Breast cancer is the most prevalent malignant neoplasm in women. Optimal treatment frequently includes a hormonal-blockage phase maintained for 5-10 years. Pharmacologic agents used for this blockage induce many climacteric-like symptoms, which often exact a heavy toll on patients' quality of life. Acupuncture has had promising results for treating climacteric-like symptoms induced by hormonal blockage, but there is no evidence of efficacy for controlling hot flashes. Materials and Methods: This trial used acupuncture to treat the climacteric-like symptoms of patients with breast cancer, focusing on the mental, physical, and genitourinary symptoms and sleep disturbances, to determine the influence of acupuncture treatment. The randomized placebo-controlled trial, at a university-based cancer center, with blinded data collectors, compared an Acupuncture group (A), a Sham-Acupuncture group (S), and a Wait-List Control group (C). The patients were receiving tamoxifen. Group A had 10 weekly sessions of manual Acupuncture; Group S had 10 weekly sessions of Sham Acupuncture; and Group C spent 10 weeks on a Wait-List. The main outcome measures were the Beck Depression Inventory-II (BDI-II), the Pittsburgh Sleep Quality Index (PSQI), and the Menopause Rating Scale (MRS). Results: Primary analysis revealed differences among the groups' improvements in scores for the 3 questionnaires ( P  < 0.001), The A group had significant improvements on the BDI-II ( P  < 0.001), PSQI ( P  < 0.002), and MRS ( P  < 0.004) compared to the S group in a post hoc analysis. Conclusions: Acupuncture improved sleep, and mental and emotional distress symptoms induced by hormonal blockage in patients with breast cancer. Clinical Trial: This trial was registered at CAAE as trial #: 37758414.8.0000.0065., Competing Interests: No financial conflicts of interest exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Introduction and Objectives: Espírito Santo state is considered a region with a higher frequency of hepatitis B virus infection. This study characterized demographic, epidemiological, laboratory, virological and clinical aspects of 587 chronic HBV carriers followed up at the University of Espírito Santo Hospital., Materials and Methods: Demographic, epidemiological, laboratory and clinical data were extracted from medical records during the entire follow-up period. Classification of the evolutionary phases of chronic hepatitis B was defined as immunotolerant; inactive carrier; chronic active hepatitis HBeAg (+)  and HBeAg (-). Characterization of HBV genotypes/subgenotypes was performed by sequencing of overlapping surface antigens and HBV DNA polymerase genes. Phylogenetic relationships were determined using BEAST 1.8.3 software., Results: and Conclusions: Genotypes found were A (132/65.3%) [A1 = 129 (63.9%) and A2 = 3 (1.5%)], D (66/32.7%) [D3 = 56 (27.7%), D4 = 8 (4.0%) and D2 = 2 (1.0%)] and F (4/2.0%) - all F2a. Subgenotypes A1 or D3 were not associated with age, sex, HIV/HCV co-infection, viral load, antiviral usage, HBeAg status or clinical stages of chronic hepatitis B. Mother -to-child-transmission (MTCT) was associated with the subgenotype A1 and intrafamilial transmission with subgenotype D3. Subgenotype A1 was more frequent than D3 among individuals born outside ES compared to those born in ES., Conclusions: The most predominant clinical phases were HBeAg (-), inactive carrier and chronic active hepatitis HBeAg (-). Subgenotypes A1 and D3 were most frequent and were associated were MTCT and intrafamilial transmission of HBV, respectively., Competing Interests: Conflicts of interest The authors declare that they do not have any conflict of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The aim of this study was to evaluate the preventive effect of ozonated oil on the development of MRONJ-like lesions at tooth extraction sites in rats submitted to zoledronic acid treatment., Materials and Methods: Twelve rats were divided into two groups. Each rat received an injection of zoledronic acid solution once a week for 5 weeks before having its upper first molar extracted. In group 1, the clotted socket was maintained, while in the group 2, the socket was treated with ozonated oil for 10 min/day during 3 days. After euthanasia, block resection was performed for histological analysis. Necrotic bone was defined as the area of the bone with empty osteocyte lacunae and vital bone as the area with osteocyte-occupied lacunae., Results: There was no statistically significant difference between the groups in the average area of vital bone (p = 0.2248) and the average area of necrotic bone (p = 0.1208). However, the average area of vital bone in group 1 was smaller (24.1 ± 2.9 cells/cm 2 ) than in group 2 (26.8 ± 4.2 cells/cm 2 ), and the average area of necrotic bone in group 1 was higher (7.0 ± 2.5 cells/cm 2 ) than in group 2 (4.0 ± 1.1 cells/cm 2 ), indicating that ozonated oil may reduce the development of osteonecrosis., Conclusions: Our findings suggest that ozonated oil might prevent MRONJ-like lesions at tooth extraction sites in rats submitted to a disease induction protocol. Further research should be conducted to confirm this hypothesis., Clinical Relevance: MRONJ has been reported as a complication of surgical dental procedures, and there are currently no predictable preventive therapies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the necessity of developing protocols for diagnosing infections and training medical personnel to recognize the pathogenicity of Oropouche virus in neurological infections., (© 2021. The Author(s).)

Background: At the moment we have more than 177 million cases and 3.8 million deaths (as of June 2021) around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far., Methods: We propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus disease (COVID-19) on the number of cases and deaths due to the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations., Results: The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths will occur by the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, for each month of delay the number of deaths increases monotonically in a logarithmic fashion, for both the State of Sao Paulo and Brazil as a whole., Conclusions: Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time., (© 2021. The Author(s).)

Introduction: Acute viral hepatitis is a disease of great clinical importance. This study proposes actions to better characterise cases of acute hepatitis in Brazil and to provide relevant information to institutionalised health policies within the Unified Health System. Available data on acute hepatitis in Brazil need to be re-evaluated regarding the different hepatotropic agent (hepatitis A to E virus) frequencies, as well as other agents that can cause similar clinical conditions, such as Herpes Simplex Virus 1 and 2(HSV1, HSV2), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Human Herpes Virus 6 and 7 (HHV6, HHV7), arbovirus (yellow fever, dengue, chikungunya, Zika), parvovirus B19, adenovirus, parechovirus, enterovirus, HIV, leptospirosis, toxoplasmosis and syphilis, in addition to autoimmune hepatitis. In this context, the primary aim of this study is the clinical-epidemiological and molecular characterisation of acute viral hepatitis in Brazilian health services from all geographical regions of the country. The present article describes the study protocol., Methods and Analysis: This study will evaluate 2280 patients with symptoms and/or signs suggestive of acute liver disease in Brazilian health institutions in all five geographic Brazilian regions. Demographic, epidemiological and clinical data will be collected, as well as blood samples to be analysed at Hospital Israelita Albert Einstein Clinical Laboratory., Ethics and Dissemination: Ethics approval was obtained at the national research ethics committee (Conselho Nacional de Ética em Pesquisa- CONEP-CAAE 00952818.4.1001.0071) and at all participating sites. Results will be published in journals and presented at scientific meetings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This cross-sectional study aimed to evaluate the prevalence and factors potentially associated with the development of actinic cheilitis (AC) in Brazilian rural workers., Subjects and Methods: A professional performed all physical examinations and evaluations using semi-structured questionnaires in 240 rural workers., Results: Eighty-three participants were diagnosed with AC (34.6%). It was more prevalent among workers older than 45 years (3.29-10.96 95% IC; OR = 3.30; p = .0018), Caucasians (phototypes I and II) (4.78-16.12 95% IC; OR = 10.81; p < .0001), illiterate individuals (2.16-21.59 95% IC; OR = 10.43; p = .0037), those with 6 or fewer years of formal schooling (2.03-7.89 95% IC; OR = 4.63; p = .0013), those regularly using pesticides (1.58-6.64 95% IC; OR = 2.79; p = .0260) and those who used the private health service in their last appointment (1.17-3.54 95% IC; OR = 2.72; p = .0083)., Conclusion: There was a substantial prevalence of AC among rural workers with advanced age, white skin, and illiteracy, those with lower levels of education, those who regularly use pesticides, and those who utilised private health services in their last appointment. Thus, healthcare strategies that include rural workers are required for the control and prevention of AC in both public and private health services., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objectives: With the declining numbers of coronavirus disease 2019 (COVID-19) cases in the state of São Paulo, Brazil, social distancing measures have gradually been lifted. However, the risk of a surge in the number of cases cannot be overlooked. Even with the adoption of nonpharmaceutical interventions, such as restrictions on mass gatherings, wearing of masks, and complete or partial closure of schools, other public health measures may help control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing., Methods: We developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the state of São Paulo., Results: For a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact-tracing strategy is implemented., Conclusion: Contact tracing of symptomatic individuals may potentially be an alternative strategy when the number of diagnostic tests available is not sufficient for massive testing.

In a hepatitis C virus (HCV)/HIV-positive Brazilian cohort, evaluate the safety and efficacy of HCV DAAs, the frequency of resistance substitutions in the HCV NS5A and NS5B genes and identify predictors of treatment failure.Retrospective multicenter study of HCV/HIV patients treated with sofosbuvir (SOF)-based regimens at 10 reference centers in Brazil.Clinical and virological data were collected. Genetic diversity in the NS5A and NS5B genes was assessed by direct nucleotide sequencing. The primary outcome was sustained virological response (SVR) 12 weeks after DAA completion.Of 643 HCV/HIV patients analyzed, 74.7% were male, median CD4+ T cell count was 617 cells/mm, 90% had an undetectable HIV viral load. HCV genotype 1 was detected in 80.2%, and 60% were taking at least 1 medication other than antiretroviral drugs during their DAA therapy. Cirrhosis was present in 42%. An SOF/daclatasvir (DCV) regimen was used in most patients (98%). The frequency of NS5A polymorphisms associated with clinically relevant resistance to DCV was 2%; no relevant NS5B variants were identified. The SVR12 rate was 92.8% in an intention to treat (ITT) analysis and 96% in a modified ITT (m-ITT) analysis. AE occurred in 1.6% of patients. By multivariate analysis, therapeutic failure was associated, in the m-ITT analysis, with concomitant use of anticonvulsant drugs (P = .001), age (P = .04), and female gender (P = .04).SOF/DCV regimens were associated with a high SVR rate in an HCV/HIV population. The use of concurrent anticonvulsant drugs and DAAs decreases the chances of achieving an SVR.

Anaplastic large cell lymphomas (ALCL) encompass several subgroups that differ in their clinical presentation, genetic features, and prognosis. We characterized the genetic subgroups of 74 patients with ALCL and correlated programmed death ligand 1 (PD-L1) protein expression and compared the densities and ratios of FOXP3+ T regulatory cells and CD8+ tumor-infiltrating lymphocytes (TILs) in tumor cells and the immune microenvironment. The subgroups included anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and ALK-negative (ALK-) ALCL and DUSP22-rearranged and nonrearranged ALK- ALCL. None of our cases represented the TP63-rearrangement ALK- ALCL subgroup. Our results showed that ALK+ ALCL had a higher expression of PD-L1 in the tumor cells, in contrast to ALK- ALCL, which expressed high PD-L1 in tumor-associated macrophages (TAMs). DUSP22-rearranged ALK- ALCL lacked PD-L1 expression in the tumor cells and instead expressed PD-L1 only in TAMs. There was a significant positive correlation of PD-L1 expression between tumor and TAMs in ALK+ ALCL with a negative correlation in ALK- ALCL. Systemic ALCL subgroups had similar densities of CD8+ tumor-infiltrating lymphocytes and FOXP3 T regulatory cells, but differences were observed in the ratio of CD8/FOXP3. Our results suggest that alterations in tumor microenvironment and immune responses exist among systemic ALCL subgroups and these features may account for different clinical behavior and prognosis.

Objective: The aim of this study was to evaluate gynecological cancer and metabolic screening of Brazilian women aged 65 years or older., Methods: This retrospective descriptive study was conducted by including 1,001 Brazilian patients of the gynecological geriatric outpatient office of our institution to evaluate the influence of age on gynecological cancer and metabolic screening parameters at the first clinical visit. All patients were divided into three groups: a) 65 to 69 years; b) 70 to 74 years; c) ≥ 75 years. We considered clinical, laboratorial, and image data as variables of this study. The Chi-square test was used to assess the proportion of differences among the age groups, and Kruskal-Wallis was used for quantitative variables., Results: The values of BMI and height in the group over 75 years was lower than that of the 65 to 69 years (p = 0.001). Regardless of the age group, high arterial blood pressure levels were found in 85.45% of participants. Also, many patients had glucose intolerance in the blood. The pelvic ultrasonography showed abnormal endometrial echo thickness (> 5 mm) in 6.14% of patients, but with no significant statistical difference between the age groups. A total of 4.04% of patients had ovaries with high volume values ( > 6.1 mL). Abnormal mammography (BI-RADS 3 or 4) was observed in 12.21%., Conclusions: our data suggest that a great reduction in BMI and stature is more frequent in the group over 75 years. Also, systemic arterial hypertension and carbohydrate disturbance are frequent morbidities in women over 65 years.

Background: Primary cutaneous CD30+ lymphoproliferative disorders (pc-CD30-LPD) are a group of clonal T cell lymphoproliferative disorders that despite very similar tumor histology follow different and characteristic clinical courses, suggesting a homeostatic role of the tumor microenvironment. Little is known about tumor microenvironment and there is almost no literature about PD-L1 expression in pc-CD30-LPD., Methods: This retrospective study presents a fully clinicopathologically characterized series of pc-CD30-LPDs from an academic medical center in Brazil, including 8 lymphomatoid papulomatosis (LyP), 9 primary cutaneous anaplastic large cell lymphoma (pcALCL) and 4 borderline lesions. All the cases were scored for FOXP3+ regulatory T-cells (Treg) and CD8+ cytotoxic tumor infiltrating lymphocytes (TIL) densities, as well as PD-L1 expression in tumor cells and tissue associated macrophages. The CD8+/FOXP3+ ratio was also evaluated., Results: Among the 21 cases of pc-CD30-LPD, PD-L1 expression is frequent in both tumor cells and tissue associated macrophages in pc-CD30-LPD across categories, suggesting that the PD-L1 axis may be a common feature of pc-CD30-LPDs. While reactive T cell infiltrates vary widely from case to case, a common feature across pc-CD30-LPDs is higher density of CD8 than FOXP3 + T cells. The distribution of T cells within the lesions however differed between LyP and pcALCL: we found that LyP lesions tend to be permeated by CD8+ and FOXP3+ T cells, whereas pcALCL tend to be surrounded by a rim of CD8+ TIL and FOXP3+ Tregs with relatively lower density infiltrates in the center of the lesion., Conclusions: LyP has a trend to have denser immune cells throughout the lesion, with higher FOXP3+ Treg and CD8+ TIL in the center than the edge comparing with pcALCL. PD-L1+ is frequent in tumor cells and tissue associated macrophages in pc-CD30-LPD. The differential distribution of CD8+ and FOXP3+ TILs in LyP as compared to pcALCL could provide a clue to the relapsing/remitting course of LyP as compared to the less frequent spontaneous regression of pcALCL.

Periodontal disease is one of the most common causes of tooth loss in the world. Ligature-induced is the most used method to study periodontitis. Here, we describe a alternative, easy and accessible experimental technique of ligation in mice. Twenty C57BL/6 female mice were divided in two groups, control and ligation. Ligature group (n = 10) was immobilized in a well described stabilization board and ligature was performed at the first molar using a new procedure here described in detail. Eight weeks later animals were euthanized, and periodontitis hallmarks were evaluated. Ligatures remained attached to the teeth in all animal during the hole experiment. The procedure induced a temporary loss of weight but no causalities or tooth loss. The animals affected by ligation in their molar teeth presented all periodontitis hallmarks, including alveolar bone loss, gingival retraction and inflammatory infiltrate in the studied region both macro and microscopically. The alternative method is low cost, easily reproducible, and induces all periodontitis hallmarks that are sustained until 8 weeks after placement. •Ligature-induced periodontitis in mouse is a powerful tool of research.•Methods describing the procedure in literature are difficult to reproduce.•A alternative stabilization and ligation procedure in mice is completely described here., (© 2019 The Author(s).)

Because of its ecological characteristics, the Caxiuanã National Forest (FLONA) is a potential area of arbovirus circulation. The present study aimed to investigate the occurrence of arbovirus transmission cycles at FLONA de Caxiuanã. Five field trips were performed to capture mosquitoes and sylvatic vertebrates. For these vertebrates, we attempted viral isolation by cell monolayer inoculation from blood, and hemagglutination inhibition and further seroneutralization assays from sera. For mosquitoes, we performed tests of viral genome detection. A total of 338 vertebrates were captured, and the greatest representative was birds (251/74.26%). A total of 16,725 mosquitoes were captured, distributed among 56 species. There were no viruses isolated by newborn mouse inoculation. Among birds, antibodies against Ilheus virus were the most prevalent. Catu virus , Caraparu virus , and Mucambo virus were the most prevalent among mammals and reptiles. Fragments of Mucambo virus , Ilheus virus , Bussuquara virus , and Rocio virus genome were detected in a pool of mosquito samples. These results of the study suggest the occurrence of arbovirus transmission cycles in the FLONA of Caxiuanã. The proximity of human populations with elements, involved in transmission cycles, makes surveillance necessary in this population to avoid dispersion of arboviruses to naïve locations.

Objective: To determine decision limits for total cholesterol, LDL-cholesterol, non-HDL cholesterol, HDL-cholesterol, and triglycerides in healthy children and adolescents from Cuiabá, Brazil., Methods: This was a cross-sectional study of 1866 healthy children and adolescents randomly selected from daycare centers and public schools in Cuiabá. The desirable levels of serum lipids were defined using the classic criteria, i.e., total cholesterol, LDL-cholesterol, non-HDL cholesterol, and triglycerides levels below the P75 percentile, and HDL-c above the P10 percentile., Results: For CT, P75 was: 160mg/dL for the age range of 1 to <3 years, 170mg/dL for ≥3 to <9 years, and 176mg/dL for ≥9 to <13 years. For non-HDL cholesterol, it was 122mg/dL for the age range of 1 to <13 years. For LDL-c, it was 104mg/dL at the age range of 1 to <9 years and 106mg/dL from ≥9 to <13 years. For TG, it was 127mg/dL from 1 to <2 years; 98mg/dL from ≥2 to <6 years; and 92mg/dL from ≥6 to <13 years. As for HDL-cholesterol, P10 was 24mg/dL, 28mg/dL, 32mg/dL, and 36mg/dL, for the age ranges of 1 to <2 years, ≥2 to <3 years, ≥3 to <4 years, and ≥4 to <13 years, respectively., Conclusion: The decision limits for the serum lipid levels defined in this study differed from those observed in the current Brazilian and North-American guidelines, especially because it differentiates between the age ranges. Using these decision limits in clinical practice will certainly contribute to improve the diagnostic accuracy for dyslipidemia in this population group., (Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Acetylcholinesterase (AChE; EC 3.1.1.7) is a serine hydrolase, whose main function is to modulate neurotransmission at cholinergic synapses. It is, therefore, the primary target of some pesticides and heavy metals. Its inhibition in aquatic organisms has been used as an indicator of the presence of these pollutants in water bodies. The present study aimed to characterize physicochemical and kinetic parameters of brain AChE in the benthic fish Hoplosternum littorale and to analyze the in vitro effects of pesticides (dichlorvos, diazinon, chlorpyrifos, parathion-methyl, temephos, carbaryl, carbofuran, aldicarb, diflubenzuron, novaluron and pyriproxyfen) and metal ions (As 3+ , Cd 2+ , Cu 2+ , Fe 2+ , Mn 2+ , Mg 2+ , K + , Pb 2+ , Hg 2+ , Zn 2+ ) investigating the potential of this enzyme as environmental biomarker based on current regulations. Specific substrates and inhibitors have indicated AChE to be the predominant cholinesterase (ChE) in the brain of H. littorale. Peak activity was observed at pH 8.0 and 30 °C. The enzymatic activity is otherwise moderately thermostable (≈ 50% activity at 45 °C). The enzyme can reduce the activation energy of acetylthiocholine hydrolysis reaction to 8.34 kcal mol -1 while reaching a rate enhancement of 10 6 . Among the pesticides under study, dichlorvos presented an IC 50 value below the maximum concentrations allowed by legislation. This study presents the first report on the inhibition of brain AChE activity from Siluriformes by the pesticides novaluron and pyriproxyfen. Mercury ion also exerted a strong inhibitory effect on its enzymatic activity. The H. littorale enzyme thus has the potential to function as an in vitro biomarker for the presence of the pesticide dichlorvos as well as mercury in areas of mining and industrial discharge., (Copyright © 2018. Published by Elsevier B.V.)

Aim: To evaluate the association between the presence of selected bacterial species/groups in the apical root canal and expression of mediators of soft and bone tissue destruction in apical periodontitis lesions. Relationships between bacteria and some other features of apical periodontitis were also investigated., Methodology: Seventeen freshly extracted teeth with pulp necrosis and apical periodontitis were included. The apical root segment was sectioned and cryopulverized; DNA was extracted and evaluated for the presence of 9 bacterial species/groups using real-time polymerase chain reaction. Lesions were processed for histopathological and immunohistochemical analyses, which targeted matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), receptor activator of NFκB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Associations of the target bacteria with expression of these mediators, presence of symptoms, lesion size and histopathological diagnosis were evaluated. Data were analysed using the chi-square, Fisher's exact, Mann-Whitney and Pearson tests. P values lower than 0.05 were considered significant., Results: All pulverized apical root samples were positive for bacteria. The most prevalent taxa were Actinobacteria (53%), Streptococcus species (35%), Fusobacterium species and Parvimonas micra (18%). The target mediators exhibited a high mean expression in the lesions (MMP-2: 82%; MMP-9: 73%; RANK: 78%; RANKL; 81%; OPG; 83%). Mean RANKL:OPG ratio was significantly higher in granulomas than cysts (P < 0.05, Mann-Whitney test). Actinobacteria were associated with granulomas, higher MMP-2 expression, lower OPG expression, and higher RANKL:OPG ratio (P < 0.05 for all, Fisher's exact test or Mann-Whitney test). No other significant associations were found., Conclusion: Actinobacteria may play an important role in the active phase of soft and bone tissue destruction in apical periodontitis., (© 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

[This corrects the article on p. 4210 in vol. 7, PMID: 27867726.].

Objective: To determine the self-perceived health status and clinical-functional vulnerability of the elderly attended at a Reference Center of Minas Gerais, Brazil and to evaluate the association between these variables through the Clinical-Functional Vulnerability Index (IVCF-20) instrument., Method: This is an epidemiological, retrospective study of 311 medical records. Statistical analyses were performed using the Stata program; the evaluations were by Pearson's Chi-square test and Poisson regression models., Results: The majority of the elderly presented negative self-perceived health status(70.10%); there was statistical significance between negative self-perceived health and the variables of mood and recent hospitalization., Conclusion: Perceived health status influences the morbidity and mortality of the elderly. Mood disorders and recent hospitalizations directly interfere with active aging.

Background: Histological grading typically reflects the biological behavior of solid tumors, thus providing valuable prognostic information. This is also expected in hepatocellular carcinoma (HCC), although limited access to biopsy samples and a lack of standardization might hinder its full predictive value in this cancer., Objectives: In order to better understand the current practices of histological grading in HCC, we examined the latest publications addressing its impact on the outcome of patients following surgical treatment., Methods: We searched the PubMed (MEDLINE) database under the headings "hepatocellular carcinoma," "grade OR grading," and "prognosis." Qualitative and quantitative assessment of publications was performed according to the reference they used to grade their tumors (e.g., Edmondson-Steiner, World Health Organization)., Results: We reviewed a total of 216 articles: 114 enclosed adequate information and were included herein. Among these, we found divergences and inaccuracies in the histological grade assessment of this cancer, which might have led to a non-standardized grade distribution, with further impact on data analysis. Nevertheless, in most of them, poor tumor differentiation correlated with worse prognosis, expressed by lower overall and/or disease-free survival., Conclusion: While histological grading of HCC has an important prognostic role, there is an unsatisfactory heterogeneity on the microscopic assessment of this tumor, urging for a movement toward standardization.

Purpose  The aim of this study was to evaluate the health aspects of Brazilian women older than 65 years of age. Design  This was a retrospective study that included 1,001 Brazilian women cared for in the gynecological geriatric outpatient office of our institution. We report a cross-sectional analysis of female adults aged over 65 years, including data on demographics, clinical symptoms such as vasomotor symptoms, associated morbidities, physical examination and sexual intercourse. We used the chi-squared test to assess the data. Results  The age of the patients on their first clinic visit ranged from 65 to 98 years, with a mean age of 68.56 ± 4.47 years; their mean age at the time of natural menopause was 48.76 ± 5.07 years. The most frequent clinical symptoms reported during the analyzed period were hot flashes ( n  = 188), followed by arthropathy, asthenia, and dry vagina. The most frequent associated morbidities after 65 years of age were systemic arterial hypertension, gastrointestinal disturbance, diabetes mellitus, and depression, among others. The assessment of the body mass index (BMI) found decreases in BMI with increased age. At the time of the visit, 78 patients reported sexual intercourse. The majority of women reporting sexual intercourse (89.75%, n  =  70) were between 65 and 69 years of age, 8.97% ( n  = 7) were between 70 and 74 years of age, and only 1.28% ( n  = 1) of those were aged older than 75 years. Conclusions  Our findings suggested that vasomotor symptoms can persist after 65 years of age. There was a significant decrease in sexual intercourse with increased age. The cardiovascular disturbances in our study are health concerns in these women., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Purpose: To evaluate the satisfaction and expectations of patients and physicians before and after the implementation of an electronic health record (EHR) in the outpatient clinic of a university hospital., Methods: We conducted 389 interviews with patients and 151 with physicians before and after the implementation of a commercial EHR at the internal medicine clinic of Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (HC-FMUSP), Brazil. The physicians were identified by their connection to the outpatient clinic and categorized by their years since graduation: residents and preceptors (with 10 years or less of graduation) or assistants (with more than 10 years of graduation). The answers to the questionnaire given by the physicians were classified as favorable or against the use of EHR, before and after the implementation of this system in this clinic, receiving 1 or 0 points, respectively. The sum of these points generated a multiple regression score to determine which factors contribute to the acceptance of EHR by physicians. We also did a third survey, after the EHR was routinely established in the outpatient clinic., Results: The degree of patient satisfaction was the same before and after implementation, with more than 90% positive evaluations. They noted the use of the computer during the consultation and valued such use. Resident (younger) physicians had more positive expectations than assistants (older physicians) before EHR implementation. This optimism was reduced after implementation. In the third evaluation the use of EHR was higher among resident physicians. Resident physicians perceived and valued the EHR more and used it more. In 28 of the 57 questions on performance of clinical tasks, resident physicians found it easier to use EHR than assistant physicians with significant differences (p<0.05). When questioned specifically about EHR satisfaction, resident physicians responded "good" and "excellent" to a greater extent than assistant physicians (p=0.002)., Conclusions: Our results reinforce the idea that the EHR introduction in a clinical setting should be preceded by careful planning to improve physician's adherence to the use of EHR. Patients do not seem to notice much difference to the quality of the consultation done using paper or EHR. It became clear after the third evaluation with the physicians that the younger (residents and some preceptors) perceived the advantages of the EHR more than the older physicians. Resident physicians use the EHR more and are more satisfied with it., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Here, we report the complete genome sequence of the BeAn 58058 virus (prototype) strain, isolated from a wild rodent Oryzomys sp. in the Utinga forest, Belém, state of Pará, Brazil in 1963. The genome of this virus showed similarity to the Poxviridae family, suggesting its inclusion in a possible new genus., (Copyright © 2017 Wanzeller et al.)