Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein.

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses regarding SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear B-cell epitopes in its spike glycoprotein with an SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. The bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), which was confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA for anti-SARS-CoV-2 antibodies. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infections of monocytes was observed in vitro with pre-pandemic Dengue-positive sera. A significant increase in viral load was measured compared to that of the controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. Cross-reactivity against peptides from spike proteins was observed for the pre-pandemic sera. This study highlights the importance of identifying specific epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future infections on diseases and their impact on vaccinations and immunodiagnostics.

Tailoring Endometrial Cancer Treatment Based on Molecular Pathology: Current Status and Possible Impacts on Systemic and Local Treatment.

Endometrial cancer (EC) is a heterogeneous disease with a rising incidence worldwide. The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). More recently, the International Federation of Gynecology and Obstetrics (FIGO) updated their staging classification to include information about POLE mutation and p53 status, as the prognosis differs according to these characteristics. Other biomarkers are being identified and their prognostic and predictive role in response to therapies are being evaluated. However, the incorporation of molecular aspects into treatment decision-making is challenging. This review explores the available data and future directions on tailoring treatment based on molecular subtypes, alongside the challenges associated with their testing.

Humoral Immune Response to SARS-CoV-2 Spike Protein Receptor-Binding Motif Linear Epitopes.

The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, apprehension remains regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is due to the specific amino acid residues of the receptor-binding motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we evaluated serum immunogenicity from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and a mutated linear RBM. Despite a modest antibody response to wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, and F486V) that result in even lower antibody titers. The primary immune responses observed were directed toward IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. An evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, targeting not only SARS-CoV-2 but also anticipating potential future coronaviruses.

Cardiovascular risk in women with nonclassical congenital adrenal hyperplasia.

CONTEXT: The outcomes related to cardiovascular risk (CVR) in patients with nonclassical form of congenital adrenal hyperplasia (NCAH) are unknown, especially those related to therapeutic options, including low doses of glucocorticoids (GCs) or oral contraceptive pills. OBJECTIVES: to analyze CVR by markers of atherosclerosis in females with nonclassical form according to therapeutic options. DESIGN AND SETTING: a cross-sectional study at a tertiary center. PATIENTS AND METHODS: Forty-seven females with NCAH (33.4 ± 10 years) were subdivided into: G1 (n = 28) treated with dexamethasone (0.14 ± 0.05 mg/m2/day); G2 (n = 19) with oral contraceptive pills; and G3 (30 matched controls). CVR was analyzed through serum lipids, HOMA-IR, inflammatory cytokines levels and quantitative image evaluations (pulse wave velocity-PWV, endothelial function by flow mediated dilatation-FMD, carotid intima media thickness-CIMT and visceral fat-VAT by abdominal tomography. RESULTS: There were no statistically significant differences in BMI, HOMA-IR, HDL-cholesterol, or triglyceride levels among groups (p > 0.05). Serum interleukin-6 levels ​​were higher in G1 than in G2 (p = 0.048), and interleukin-8 levels were higher in G1 than in G2/3 (p = 0.008). There were no statistically significant differences in VAT, PWV, FMD or CIMT among groups (p > 0.05). In multivariable regression analysis, there was no statistically significant association between glucocorticoid dose and evaluated outcomes. CONCLUSION: Adult females with NCAH did not show increased CVR using methodologies for detection of precocious atherosclerosis. Although patients receiving dexamethasone therapy had increased IL-6 and 8 levels, these data were not associated with radiological markers of atherosclerosis. Our cohort was composed of young adults and should be reevaluated in a long-term follow-up.

Validade preditiva da escala de EVARUCI para pacientes de terapia intensiva / Predictive validity of the EVARUCI scale for intensive care patients

Objetivo:Avaliar a validade preditiva da escala de EVARUCI para pacientes de terapia intensiva. Métodos:Estudo longitudinal retrospectivo, com dados secundários, realizado em UTI referência em neurologia e traumato-ortopedia. A população do estudo foi composta por todos os usuários que deram entrada na UTI entre janeiro e dezembro de 2020, sendo excluídos aqueles com tempo de internação menor que 48 horas e os que tiveram óbito como desfecho. Coletaram-se dados referentes à admissão, às primeiras 48 horas de internamento e à alta. Resultados:O perfil encontrado foi de homens jovens, vítimas de causas externas. A incidência de LPP foi de 18,9%, maiores scores da EVARUCI foram registrados na admissão. A sensibilidade do teste foi de 90,9% e 72,73%, a especificidade de 16,9% e 48,9%, a validade preditiva positiva de 20,27% e 24,74% e a negativa de 88,89% e 88,46% na admissão e primeiras 48 horas, respectivamente. Conclusão: A escala não conseguiu predizer de forma satisfatória o alto risco. No entanto, apresentou-se satisfatória para predizer o baixo risco para LPP. Os pacientes que apresentaram pontuação menor que 10 na escala apresentaram menor probabilidade de desenvolver as lesões.

Objective:To evaluate the predictive validity of the EVARUCI scale for intensive care patients. Methods:This is a retrospective longitudinal study with secondary data carried out in a reference ICU in neurology and trauma-orthopedics. The study population consisted of all users who were admitted to the ICU between January and December 2020, excluding those with a length of stay of less than 48 hours, and those who died as an outcome. Data were collected regarding admission, the first 48 hours of hospitalization and discharge. Results:The profile found was of young men, victims of external causes. The incidence of PI was 18.9%, higher EVARUCI scores were recorded on admission. The sensitivity of the test was 90.9% and 72.73%, the specificity was 16.9% and 48.9%, the positive predictive validity was 20.27% and 24.74%, and the negative validity was 88.89% and 88.46% at admission and first 48 hours, respectively. Conclusion:The scale was unable to satisfactorily predict high risk. However, it was satisfactory to predict the low risk for PI, patients who scored less than 10 on the scale were less likely to develop the lesions.

Phenotypic and molecular reanalysis of a cohort of patients with monogenic diabetes reveals a case of partial lipodystrophy due to the A8344G mutation in the mitochondrial DNA

SUMMARY Familial partial lipodystrophy (FPLD) is a very rare genetic disease characterized by insulin resistance due to a loss of subcutaneous fat from the extremities together with a progressive storage of fat around the face and neck and inside the abdomen. In over 50% of cases, molecular genetic testing reveals pathogenic variants in two nuclear genes, LMNA and PPARG. The case reported here refers to a woman phenotypically diagnosed with FPLD, who presented with diabetes and multiple cervical lipomatosis and in whom no variant had been found in the nuclear genes classically associated with this syndrome that could explain her phenotype. Genetic sequencing using a target panel containing 48 nuclear genes related to monogenic diabetes plus the whole mitochondrial genome revealed the mitochondrial variant m.A8344G in 84.1% heteroplasmy. Following molecular diagnosis, her phenotype was expanded with the recognition of additional clinical characteristics: mild sensorineural hearing loss, proximal myopathy, fatigue, cognitive impairment, sensory ataxia, cardiac abnormalities and, finally, muscle biopsy findings compatible with mitochondrial disease. Therefore, careful and detailed phenotypic and genotypic reanalysis proved crucial in improving molecular diagnosis in FPLD.

Epidemiology of monkeypox notifications in the state of Minas Gerais, Brazil.

OBJECTIVES: to describe the epidemiological profile of suspected, confirmed, and probable cases of monkeypox in the state of Minas Gerais, Brazil. METHODS: a descriptive, retrospective study of reported suspected, confirmed, and probable cases of monkeypox infection in the state of Minas Gerais, Brazil. The study period was from the first notification, on June 11, to September 7, 2022. RESULTS: a total of 759 suspected, confirmed, and probable cases of monkeypox infection were reported, with 35.44% suspected, 53.75% confirmed, and 10.81% probable cases, respectively. As for the coexisting diseases within confirmed cases, 38.79% were related to people living with human immunodeficiency virus, and 13.74% had some active sexually transmitted infection. Regarding the evolution of confirmed cases, 47.43% were cured. CONCLUSIONS: the results contribute to greater knowledge and control of the infection by allowing better disease management and care offered in health services.

The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients.

IMPORTANCE: The study provides valuable insights into the sociodemographic characteristics, clinical outcomes, and humoral immune response of those affected by the virus that has devastated every field of human life since 2019; the COVID-19 patients. Firstly, the association among clinical manifestations, comorbidities, and the production of neutralizing antibodies (Nabs) against SARS-CoV-2 is explored. Secondly, varying levels of Nabs among patients are revealed, and a significant correlation between the presence of Nabs and a shorter duration of hospitalization is identified, which highlights the potential role of Nabs in predicting clinical outcomes. Lastly, a follow-up conducted 7 months later demonstrates the progression and persistence of Nabs production in recovered unvaccinated individuals. The study contributes essential knowledge regarding the characteristics of the study population, the early humoral immune response, and the dynamics of Nabs production over time. These findings have significant implications for understanding the immune response to COVID-19 and informing clinical management approaches.

A worm in the toilet bowl! What does it tell us about the challenges in the identification of supposed human parasites in practical parasitology?

Non-parasitic vermiform organisms can circumstantially be associated with humans and their identification can be challenging for medical professionals. The present report describes the finding of a worm in the toilet bowl by a patient from Brazil, who thought he had expelled it in his feces. The gross analyses in a clinical laboratory reveal the worm was different from other macroscopic organisms routinely identified, and the laboratory staff requested assistance in an academic laboratory specialized in helminthology. After preliminary analysis in a stereomicroscope, the supposed human worm was identified as an oligochaete annelid (earthworm). The patient was contacted to investigate a possible case of pseudoparasitism. However, we were informed that the organism had been collected in a toilet bowl from a rural environment where the untreated water comes from a cistern indicating our finding was circumstantial. The methodology revisited herein allowed a quick microscopic analysis of easy-to-view morphological structures, which are useful to separate oligochaete annelids from helminths and can prevent misdiagnosis in similar situations. We discuss the overly restricted view on human parasites by health professionals in collecting clinical history and laboratory analysis, providing some epistemological insights on the necessary interdisciplinarity between parasitology and other basic knowledge with health practice.

Rare variants in the MECP2 gene in girls with central precocious puberty: a translational cohort study.

BACKGROUND: Identification of genetic causes of central precocious puberty have revealed epigenetic mechanisms as regulators of human pubertal timing. MECP2, an X-linked gene, encodes a chromatin-associated protein with a role in gene transcription. MECP2 loss-of-function mutations usually cause Rett syndrome, a severe neurodevelopmental disorder. Early pubertal development has been shown in several patients with Rett syndrome. The aim of this study was to explore whether MECP2 variants are associated with an idiopathic central precocious puberty phenotype. METHODS: In this translational cohort study, participants were recruited from seven tertiary centres from five countries (Brazil, Spain, France, the USA, and the UK). Patients with idiopathic central precocious puberty were investigated for rare potentially damaging variants in the MECP2 gene, to assess whether MECP2 might contribute to the cause of central precocious puberty. Inclusion criteria were the development of progressive pubertal signs (Tanner stage 2) before the age of 8 years in girls and 9 years in boys and basal or GnRH-stimulated LH pubertal concentrations. Exclusion criteria were the diagnosis of peripheral precocious puberty and the presence of any recognised cause of central precocious puberty (CNS lesions, known monogenic causes, genetic syndromes, or early exposure to sex steroids). All patients included were followed up at the outpatient clinics of participating academic centres. We used high-throughput sequencing in 133 patients and Sanger sequencing of MECP2 in an additional 271 patients. Hypothalamic expression of Mecp2 and colocalisation with GnRH neurons were determined in mice to show expression of Mecp2 in key nuclei related to pubertal timing regulation. FINDINGS: Between Jun 15, 2020, and Jun 15, 2022, 404 patients with idiopathic central precocious puberty (383 [95%] girls and 21 [5%] boys; 261 [65%] sporadic cases and 143 [35%] familial cases from 134 unrelated families) were enrolled and assessed. We identified three rare heterozygous likely damaging coding variants in MECP2 in five girls: a de novo missense variant (Arg97Cys) in two monozygotic twin sisters with central precocious puberty and microcephaly; a de novo missense variant (Ser176Arg) in one girl with sporadic central precocious puberty, obesity, and autism; and an insertion (Ala6_Ala8dup) in two unrelated girls with sporadic central precocious puberty. Additionally, we identified one rare heterozygous 3'UTR MECP2 insertion (36_37insT) in two unrelated girls with sporadic central precocious puberty. None of them manifested Rett syndrome. Mecp2 protein colocalised with GnRH expression in hypothalamic nuclei responsible for GnRH regulation in mice. INTERPRETATION: We identified rare MECP2 variants in girls with central precocious puberty, with or without mild neurodevelopmental abnormalities. MECP2 might have a role in the hypothalamic control of human pubertal timing, adding to the evidence of involvement of epigenetic and genetic mechanisms in this crucial biological process. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and the Wellcome Trust.

Plasmodium falciparum Chloroquine-pfcrt Resistant Haplotypes in Brazilian Endemic Areas Four Decades after CQ Withdrawn.

(1) Background: Malaria is a public health problem worldwide. Despite global efforts to control it, antimalarial drug resistance remains a great challenge. In 2009, our team identified, for the first time in Brazil, chloroquine (CQ)-susceptible Plasmodium falciparum parasites in isolates from the Brazilian Amazon. The present study extends those observations to include survey samples from 2010 to 2018 from the Amazonas and Acre states for the purpose of tracking pfcrt molecular changes in P. falciparum parasites. (2) Objective: to investigate SNPs in the P. falciparum gene associated with chemoresistance to CQ (pfcrt). (3) Methods: Sixty-six P. falciparum samples from the Amazonas and Acre states were collected from 2010 to 2018 in patients diagnosed at the Reference Research Center for Treatment and Diagnosis of Malaria (CPD-Mal/Fiocruz), FMT-HVD and Acre Health Units. These samples were subjected to PCR and DNA Sanger sequencing to identify mutations in pfcrt (C72S, M74I, N75E, and K76T). (4) Results: Of the 66 P. falciparum samples genotyped for pfcrt, 94% carried CQ-resistant genotypes and only 4 showed a CQ pfcrt sensitive-wild type genotype, i.e., 1 from Barcelos and 3 from Manaus. (5) Conclusion: CQ-resistant P. falciparum populations are fixed, and thus, CQ cannot be reintroduced in malaria falciparum therapy.

High-Throughput IgG Epitope Mapping of Tetanus Neurotoxin: Implications for Immunotherapy and Vaccine Design.

Tetanus is an acute, fatal disease caused by exotoxins released from Clostridium tetani during infections. A protective humoral immune response can be induced by vaccinations with pediatric and booster combinatorial vaccines that contain inactivated tetanus neurotoxin (TeNT) as a major antigen. Although some epitopes in TeNT have been described using various approaches, a comprehensive list of its antigenic determinants that are involved with immunity has not been elucidated. To this end, a high-resolution analysis of the linear B-cell epitopes in TeNT was performed using antibodies generated in vaccinated children. Two hundred sixty-four peptides that cover the entire coding sequence of the TeNT protein were prepared in situ on a cellulose membrane through SPOT synthesis and probed with sera from children vaccinated (ChVS) with a triple DTP-vaccine to map continuous B-cell epitopes, which were further characterized and validated using immunoassays. Forty-four IgG epitopes were identified. Four (TT-215-218) were chemically synthesized as multiple antigen peptides (MAPs) and used in peptide ELISAs to screen post-pandemic DTP vaccinations. The assay displayed a high performance with high sensitivity (99.99%) and specificity (100%). The complete map of linear IgG epitopes induced by vaccination with inactivated TeNT highlights three key epitopes involved in the efficacy of the vaccine. Antibodies against epitope TT-8/G can block enzymatic activity, and those against epitopes TT-41/G and TT-43/G can interfere with TeNT binding to neuronal cell receptors. We further show that four of the epitopes identified can be employed in peptide ELISAs to assess vaccine coverage. Overall, the data suggest a set of select epitopes to engineer new, directed vaccines.

Management of patients with recurrent/metastatic endometrial cancer: Consensus recommendations from an expert panel from Brazil.

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.

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

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

Influência da escolaridade de famílias de crianças e adolescentes com deficiência auditiva em suas necessidades de informação: estudo descritivo / Influence of educational level of families of hard of hearing children and adolescents on their informational needs: descriptive study

RESUMO Objetivo avaliar a influência da escolaridade de responsáveis por crianças com deficiência auditiva com níveis de educação formal do ensino fundamental ao ensino médio, em relação às suas necessidades de informação no contexto de um serviço de reabilitação auditiva do Sistema Único de Saúde. Métodos estudo transversal, observacional, com amostra de conveniência de 58 responsáveis por crianças com deficiência auditiva. Aplicou-se o Inventário de Necessidades Familiares traduzido e adaptado para o português brasileiro e foram coletados os dados de escolaridade dos responsáveis e as variáveis idade da criança e idade no diagnóstico. Foi realizada análise descritiva e inferencial. Resultados todas as famílias apresentaram necessidades de informação, sendo que, para as famílias com menor escolaridade, a necessidade de informações sobre a audição e os dispositivos auditivos foi mais frequente. Na análise de regressão, não se observou influência da escolaridade na quantidade de necessidades de informação, mesmo considerando no modelo a idade cronológica da criança e a idade no seu diagnóstico. Conclusão famílias de todas as escolaridades analisadas apresentaram necessidades de informação, sendo que a escolaridade não influenciou a quantidade de informações requeridas. Foi possível observar diferença qualitativa nos tópicos de necessidades de informação, o que alerta para a importância de investigações sobre as necessidades das famílias em programas de reabilitação auditiva infantil, de modo a se efetivar abordagens mais centradas nas famílias.

ABSTRACT Purpose To evaluate the influence of education of guardians of hard of hearing children with formal education levels from elementary to high school, in relation to their information needs in the context of an auditory rehabilitation service. Methods Cross-sectional, observational study, with a convenience sample of 58 guardians of children with hearing loss. The Family Needs Inventory (INF) was applied, translated, and adapted into Brazilian Portuguese, and parents' education was collected, in addition to the variables age of the child and age at diagnosis. Results In the quantitative analysis of the "yes" responses from the INF, all the families presented need for information , and for families with less education, the need for information about hearing and hearing devices was greater. In the regression analysis, there was no influence of schooling on the amount of information needed, even considering the chronological age and diagnosis of the child in the model. As limitations of this study, we highlight the absence of sufficient number of families with higher education for the analysis of the final model, as well as the impossibility of including other variables in the analysis. Conclusion The analyzed families with different levels of schooling showed need for information , and schooling did not influence the amount of information required by them. It was possible to observe a qualitative difference in the topics of needed information, which alerts to the importance of investigation about the needs of families in child auditory rehabilitation programs, to implement more family-centered approaches.

Epidemiology of monkeypox notifications in the state of Minas Gerais, Brazil / Epidemiología de las notificaciones de viruela del mono en el estado de Minas Gerais, Brasil / Epidemiologia das notificações de monkeypox no estado de Minas Gerais, Brasil

ABSTRACT Objectives: to describe the epidemiological profile of suspected, confirmed, and probable cases of monkeypox in the state of Minas Gerais, Brazil. Methods: a descriptive, retrospective study of reported suspected, confirmed, and probable cases of monkeypox infection in the state of Minas Gerais, Brazil. The study period was from the first notification, on June 11, to September 7, 2022. Results: a total of 759 suspected, confirmed, and probable cases of monkeypox infection were reported, with 35.44% suspected, 53.75% confirmed, and 10.81% probable cases, respectively. As for the coexisting diseases within confirmed cases, 38.79% were related to people living with human immunodeficiency virus, and 13.74% had some active sexually transmitted infection. Regarding the evolution of confirmed cases, 47.43% were cured. Conclusions: the results contribute to greater knowledge and control of the infection by allowing better disease management and care offered in health services.

RESUMEN Objetivos: describir perfil epidemiológico de casos sospechosos, confirmados y probables por viruela símica en Minas Gerais, Brasil. Métodos: estudio descriptivo, retrospectivo, con casos notificados sospechosos, confirmados y probables de infección por viruela símica en el estado de Minas Gerais, Brasil. El período del estudio fue desde la primera notificación, en 11 de junio, hasta 7 de septiembre de 2022. Resultados: fueron notificados 759 casos sospechosos, confirmados y probables de infección por viruela símica, siendo, respectivamente, 35,44% sospechosos, 53,75% confirmados y 10,81% probables. Cuanto a las enfermedades coexistentes en los casos confirmados, 38,79% referidos a personas viviendo con virus de la inmunodeficiencia humana, y 13,74% poseían alguna infección sexualmente transmisible activa. Sobre la evolución de casos confirmados, 47,43% evolucionaron para la cura. Conclusiones: los resultados contribuyen para mayor conocimiento y control de la infección, auxiliando en la mejor gestión de la enfermedad y cuidado ofrecidos en los servicios de salud.

RESUMO Objetivos: descrever o perfil epidemiológico dos casos suspeitos, confirmados e prováveis por monkeypox no estado de Minas Gerais, Brasil. Métodos: estudo descritivo, retrospectivo, com os casos notificados suspeitos, confirmados e prováveis de infecção pelo monkeypox no estado de Minas Gerais, Brasil. O período do estudo foi desde a primeira notificação, em 11 de junho, até 7 de setembro de 2022. Resultados: foram notificados 759 casos suspeitos, confirmados e prováveis de infecção pelo monkeypox, sendo, respectivamente, 35,44% suspeitos, 53,75% confirmados e 10,81% prováveis. Quanto às doenças coexistentes nos casos confirmados, 38,79% referiam-se a pessoas vivendo com vírus da imunodeficiência humana, e 13,74% possuíam alguma infecção sexualmente transmissível ativa. Sobre a evolução dos casos confirmados, 47,43% evoluíram para a cura. Conclusões: os resultados contribuem para maior conhecimento e controle da infecção, de modo a auxiliar no melhor gerenciamento da doença e cuidado ofertados nos serviços de saúde.

NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features.

Background: The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. Methods: This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. Results: The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance ≥ 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values ≥ 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. Conclusions: In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.

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

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

High-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohort.

Context: Polycystic ovary syndrome (PCOS) etiology remains to be elucidated, but familial clustering and twin studies have shown a strong heritable component. Objective: The purpose of this study was to identify rare genetic variants that are associated with the etiology of PCOS in a preselected cohort. Methods: This prospective study was conducted among a selected group of women with PCOS. The study's inclusion criteria were patients with PCOS diagnosed by the Rotterdam criteria with the following phenotypes: severe insulin resistance (IR), normoandrogenic-normometabolic phenotype, adrenal hyperandrogenism, primary amenorrhea, and familial PCOS. Forty-five patients were studied by target sequencing, while 8 familial cases were studied by whole exome sequencing. Results: Patients were grouped according to the inclusion criteria with the following distribution: 22 (41.5%) with severe IR, 13 (24.5%) with adrenal hyperandrogenism, 7 (13.2%) with normoandrogenic phenotype, 3 (5.7%) with primary amenorrhea, and 8 (15.1%) familial cases. DNA sequencing analysis identified 1 pathogenic variant in LMNA, 3 likely pathogenic variants in INSR, PIK3R1, and DLK1, and 6 variants of uncertain significance level with interesting biologic rationale in 5 genes (LMNA, GATA4, NR5A1, BMP15, and FSHR). LMNA was the most prevalent affected gene in this cohort (3 variants). Conclusion: Several rare variants in genes related to IR were identified in women with PCOS. Although IR is a common feature of PCOS, patients with extreme or atypical phenotype should be carefully evaluated to rule out monogenic conditions.

Patterns, appropriateness and outcomes of peripherally inserted central catheter use in Brazil: a multicentre study of 12 725 catheters.

BACKGROUND: Little is known about peripherally inserted central catheter (PICC) use, appropriateness and device outcomes in Brazil. METHODS: We conducted an observational, prospective, cohort study spanning 16 Brazilian hospitals from October 2018 to August 2020. Patients ≥18 years receiving a PICC were included. PICC placement variables were abstracted from medical records. PICC-related major (deep vein thrombosis (DVT), central line-associated bloodstream infection (CLABSI) and catheter occlusion) and minor complications were collected. Appropriateness was evaluated using the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC). Devices were considered inappropriate if they were in place for <5 days, were multi-lumen, and/or were placed in patients with a creatinine >2.0 mg/dL. PICCs considered appropriate met none of these criteria. Mixed-effects logistic regression models adjusting for patient-level and hospital-level characteristics assessed the association between appropriateness and major complications. RESULTS: Data from 12 725 PICCs were included. Mean patient age was 66.4±19 years and 51.0% were female. The most common indications for PICCs were intravenous antibiotics (81.1%) and difficult access (62.7%). Most PICCs (72.2%) were placed under ultrasound guidance. The prevalence of complications was low: CLABSI (0.9%); catheter-related DVT (1.0%) and reversible occlusion (2.5%). Of the 12 725 devices included, a total of 7935 (62.3%) PICCs were inappropriate according to MAGIC. With respect to individual metrics for appropriateness, 17.0% were placed for <5 days, 60.8% were multi-lumen and 11.3% were in patients with creatinine >2.0 mg/dL. After adjusting for patient and hospital-level characteristics, multi-lumen PICCs considered inappropriate were associated with greater odds of major complications (OR 2.54, 95% CI 1.61 to 4.02). CONCLUSIONS: Use of PICCs in Brazilian hospitals appears to be safe and comparable with North America. However, opportunities to improve appropriateness remain. Future studies examining barriers and facilitators to improving device use in Brazil would be welcomed.