Oswaldo Cruz Foundation

An unprecedented global outbreak caused by the monkeypox virus (MPXV) prompted the World Health Organization to declare a public health emergency of international concern on July 23, 2022. Therapeutics and vaccines for MPXV are not widely available, necessitating further studies, particularly in drug repurposing area. To this end, the standardization of in vitro infection systems is essential. The most robust in vitro studies on poxviruses concern the Vaccinia virus, and there are significant gaps in understanding the replicative cycle of MPXV. Herein, we conducted ultrastructural studies using transmission and scanning electron microscopies and 3D reconstruction to describe and elucidate the step‐by‐step morphogenesis of MPXV. Vero cells, derived from the kidney lineage of Cercopithecus aethiops monkeys, were infected with a strain isolated from an oropharyngeal swab of a patient with suspected Mpox, collected during an observational cohort study conducted between June 12 and August 19, 2022, in Rio de Janeiro, Brazil. Infected Vero cells exhibited several morphological alterations, including cell lysis plaque formation, nuclei with altered chromatin profiles, thickening of the rough endoplasmic reticulum (RER), presence of myelin figures, disorganization of mitochondrial cristae, and the formation of a granular and fibrous matrix (viral factory) surrounded by mitochondria and RER cisternae in a perinuclear space. Viral entry into cells occurred via endocytosis MPXV particles were observed adhering to cytoskeletal filaments, and viral progeny extrusion occurred through exocytosis. This article presents novel data on the morphogenesis of MPXV that have not been previously documented in the literature.

Background For a long time, the penalty of imprisonment has been studied and criticized as ineffective in achieving the goals of resocialization and rehabilitation of offenders, and studies have associated incarceration with increased prevalence of disease. In response to the COVID-19 pandemic, the World Health Organization recommended decarceration as a prevention measure. The aim of this review was to analyze the effectiveness of non-exposure to incarceration in preventing COVID-19 and mitigating associated events. Methods We conducted a systematic review and meta-analysis of observational studies comparing the adult general population (GP) and incarcerated population (IP). Results We identified 1,334 publications without duplicates and extracted data from 22 studies. We found that COVID-19 incidence was 61% lower in the GP (RR = 0.39 [0.34, 0.45], p < 0.0001). Non-exposure to incarceration was associated with lower age- and sex-adjusted mortality (RR = 0.36, [0.27, 0.49], p < 0.0001). We did not find standardized data on age-adjusted case fatality. The hospitalized GP was older and showed a higher rate of obesity than the hospitalized IP; however, no statistically significant differences were found between the populations for admission to intensive care (RR = 0,91 [0.74, 1.13], p = 0.41) and hospital mortality (RR = 0.81 [0.54, 1.23], p = 0.32). Prevalence of the use of invasive mechanical ventilation was 23% lower in the GP (RR = 0.77 [0.70, 0.84, p < 0.0001). Conclusion Non-exposure to incarceration can be a strategy for preventing the spread of COVID-19 and reduces COVID-19 mortality in younger populations. Despite differences in age distribution and presence of comorbidities among the hospitalized GP and IP, we did not find any statistically significant differences between the two populations across most of the hospital-related outcomes. These findings should be interpreted with caution because it was not possible to determine a cause-and-effect relationship between the COVID-19 outcomes and exposure to incarceration. Registration PROSPERO CRD42023446610.

Determining environmental risk levels posed to different urban lagoon can provide an important overview regarding the relative severity of the environmental degradation of these ecosystems, increasing the risks visibility, which can be used as an important decision-making tool to prioritize investments. Jacarepaguá Lagoon (JPAL) is part of a coastal lagoon system comprising four interconnected lagoons in Rio de Janeiro city, Southeastern Brazil. Real estate speculation and insufficient sanitation infrastructure resulted in untreated sewage discharge into this ecologically sensitive lagoon system. An Environmental Risk Assessment for Jacarepaguá lagoon was carried out integrating three Lines of Evidence (LoE): (i) Water Quality LoE; (ii) Ecotoxicological LoE; (iii) Ecological LoE to estimate an Environmental Risk Index (EnvRI) for this area. Surface water samples were collected during four bimonthly campaigns at five JPAL sampling points as well as an upstream reference area. The Water Quality LoE based on physicochemical parameters was used to estimate the Water Quality Risk Index (WQRI); the Ecotoxicological LoE based on two chronic ecotoxicity bioassays was used to estimate the Ecotoxicological Risk Index (EcotoxRI); and the Ecological LoE based on the richness and the abundance of phytoplankton taxa was used to estimate the Ecological Risk Index (EcoRI). The final EnvRI was then estimated by integrating these three Risk Indices. The WQRI (0.79 ± 0.07), as well as the EcotoxRI (0.80 ± 0.21), and the EcoRI (0.78 ± 0.13), were all in the range classified as very high. The EnvRI for JPAL was consequently also very high (0.81 ± 0.12), which indicates urgent intervention. EnvRI combined with high concentrations of organic compounds directly affected the diversity of phytoplankton species; however, it was observed that the high content of phytoplankton biomass also represents a part of the organic matter in question. The final goal was achieved: a feasible risk assessment tool available for comparison of different aquatic ecosystems, to facilitate decision making establishing priorities of investments under a limited resources scenario.

Introduction Childhood obesity is a major global public health issue globally and in Brazil. The impacts of childhood obesity include higher risk of disease during childhood and of obesity and non-communicable diseases in adulthood and represent an important epidemiological and economic burden to countries. This study aims to analyze the trends and to estimate the direct healthcare costs of childhood and adolescent obesity to the National Health System from 2013 to 2022. Methods We used Prais-Winsten regressions for determining the trends in the prevalence of obesity and modeled the attributable to childhood and adolescent obesity in the Brazilian National Health System using previous meta-analysis of studies. Results The hospitalizations of children and adolescents with obesity as a primary cause totaled Int$2.6 million to the Brazilian National Health System from 2013 to 2022, demonstrating that obesity is rarely considered as a cause of hospitalization especially among children and adolescents. The additional costs of hospitalizations attributable to childhood obesity totaled Int$101.5 million during the same period. The additional non-hospital, outpatient and medication cost attributable to childhood obesity in Brazil were estimated at Int$6.0 million, so the total estimated healthcare costs were of approximately Int$107.5 million in the last decade. Conclusion This study highlights that childhood and adolescent obesity are increasing for most age-groups and that its costs are not limited to the economic impacts on adult health and represent a relevant economic burden to the Brazilian National Health System and to families because of additional costs during childhood and adolescence. Therefore, the prevention and control of childhood and adolescent obesity must be public health priorities.

Feline leishmaniasis is increasingly recognized as a disease affecting cats worldwide, with notable prevalence in regions surrounding the Mediterranean Basin and in Brazil. An approximately one-year-old domestic shorthair cat was presented with small papules and nodules (2 mm) on the nasal planum. Physical examination and routine blood analyses were normal. The cat tested negative for FIV and FeLV. Skin biopsies of the lesions were conducted, removing the nodules entirely due to their small size. The samples were submitted for histopathological and molecular analysis. Histopathology confirmed the presence of Leishmania amastigotes, while PCR-RFLP and Sanger sequencing of the hsp70 gene identified the infecting species as Leishmania guyanensis. The patient has since been under continuous clinical monitoring every six months, with no recurrence observed to date. This is the first documented case of L. guyanensis infection in a domestic cat, underscoring the need for improved diagnostic accuracy and a broader understanding of feline leishmaniasis.

Cryptococcus gattii is a saprophytic basidiomycete that grows in the environment and can cause systemic cryptococcosis. Ocular cryptococcosis causes blindness and is commonly associated with central nervous system (CNS) infection. Toll-like receptor 9 (TLR9) can control cryptococcosis and another mycosis. Here, using C57BL/6 TLR9 knockout mice (TLR9-/-), we evaluated the role of TLR9 signaling in ocular involvement during systemic C. gattii-infection. We observed ocular impairment and found a high fungal burden in the retina, vitreous humor (VH), and optic nerve (ON) of TLR9-/- mice three weeks after infection. Capsular polysaccharide glucuronoxylomannan (GXM) deposition, astrogliosis and morphological alterations in retina lead to progressive blindness of TLR9-/- mice. The phenomenon observed in our work has not yet been explored in a murine model. These results contribute to the understanding of the role of TLR9 during ocular cryptococcosis. Therapies using TLR9 agonists may be important for the treatment of ocular cryptococcosis.

Background Nurses provide essential care for symptomatic chronic Chagas disease carriers, caused by Trypanosoma cruzi, offering crucial support, symptom management, medication administration, and monitoring to enhance their health-related quality of life. Objective To increase healthcare professionals’ awareness of the critical role played by high-quality care in the management of patients with chronic Chagas disease. Methods This scoping review employed the PRISMA-ScR method as a framework for article selection. A comprehensive search was conducted in the Scielo Brazil, PubMed, and LILACS databases, using the keywords “Chagas disease,” “nursing,” “nursing care”, and “nursing assistance” in Portuguese, English, and Spanish. The search covered the period from 1980 to 2022. The initial review identified a total of 633 studies, from which 17 studies were ultimately selected for analysis. These included two observational studies, two case series, and seven literature reviews. Results These studies underscored the crucial role of nurses in supporting patients with chronic Chagas disease, particularly those with cardiac and/or digestive manifestations. Additionally, interventions pertaining to neonates with the infection and users of pacemakers/implantable cardioverter defibrillators were examined. Conclusion Nurses play a critical role within a multidisciplinary care team in improving the health-related quality of life for individuals living with chronic Chagas disease, irrespective of the cardiac or digestive form of the disease. Therefore, it is essential to assess both the subjective and objective needs of infected individuals in order to develop tailored nursing care plans that address their individualized needs and clinical conditions.

Due to their biological characteristics, elasmobranchs are highly vulnerable to overfishing and habitat degradation. Environmental pollution has also been shown to increasingly affect elasmobranch microbiota composition, yet studies in this area remain scarce. This study aimed to provide a baseline assessment of enteric bacterial species detected in various shark and ray species from the Brazilian Amazon Coast. Enterobacteria samples were collected through cloacal smears from elasmobranchs, cultured, isolated, and biochemically identified (e.g., Vibrio, Aeromonas, Enterobacterales). Polymerase chain reaction (PCR) assays were conducted to identify Aeromonas spp. pathotypes. The most frequently detected enteric bacteria were Klebsiella pneumoniae (47%), Pseudomonas aeruginosa (38%), Citrobacter freundii (22%), and Serratia sp. (13%). Less commonly detected species included Plesiomonas shigelloides, Vibrio gazogenes, and Yersinia pseudotuberculosis (≤ 25%), categorized as rare among the assessed elasmobranchs. Notably, several bacterial species identified in this study (e.g., Acinetobacter baumannii, Klebsiella ozaenae, Klebsiella rhinoscleromatis, Pseudomonas luteola, Salmonella choleraesuis, Vibrio gazogenes, and Yersinia pseudotuberculosis) are reported for the first time in Brazilian elasmobranchs. Many of these bacteria are opportunistic pathogens to both animals and humans, posing potential risks of disease to colonized elasmobranchs and to humans who consume their meat. These findings underscore ecological and public health concerns within a One Health framework, highlighting the need for further research and monitoring.

Athenaea velutina (Sendtn.) D’Arcy, a native plant of the Brazilian Atlantic Forest, has exhibited potential pharmacological effects due to the presence of withanolides with anti-cancer and anti-inflammatory activities. However, there is a lack of research on the safety and toxicity of this plant species. This study aimed to assess the safety of the ethanolic extract of A. velutina leaves (Av-E) through toxicity and phytochemical analysis. Acute [1000 mg kg−1 body weight (BW)] and subacute (250, 500, and 1000 mg kg−1 BW) toxicity tests were conducted on female Wistar rats, along with an evaluation of the toxic reversal effect. HPLC-HRMS revealed the presence of withanolide steroids in Av-E. Reduced alanine aminotransferase (ALT), bilirubin levels, and increased calcium concentrations were observed after the acute toxicity test. Subacute toxicity demonstrated lowered ALT (250 and 1000 mg kg−1 BW) and aspartate aminotransferase (AST) (250 and 500 mg kg−1 BW) levels and increased sodium concentration (250 mg kg−1 BW). No fatalities or clinical signs of toxicity occurred, and histological and biochemical analysis revealed no apparent liver or kidney toxicity. In conclusion, Av-E exhibited no toxicity in the experiments, encouraging further research to develop new herbal medicines.

Resumo: O artigo aponta a necessidade de se estimular a educação permanente em cuidados paliativos. Objetiva apresentar resultados da pesquisa exploratório-descritiva “Oficinas Itinerantes em Cuidados Paliativos”, fundamentada em Paulo Freire, conduzida em unidades de saúde, envolvendo profissionais e gestores. Foi utilizado um questionário on-line para a coleta de dados, contabilizando 62 participantes. Dentre os achados, destacou-se uma deficiência na capacitação profissional em cuidados paliativos.

Objective To describe the polio vaccination status in 26 state capitals, the Federal District, and 12 municipalities in Brazil, among children born between 2017 and 2018. Methods This was a population-based household survey conducted from 2020 to 2022, which assessed polio vaccination coverage in children, considering valid, administered, and timely doses by municipality. Results Data were collected from 37,801 children. Vaccination coverage for the complete valid dose schedule was 87.5% (95%CI 86.2;88.7), dropping to 79.6% (95%CI 78.1;81.0), when the booster dose was considered. The dropout rate was 4.5% for the complete schedule, and 11.7% for the first booster. There was no correlation between campaign implementation and high coverage. Conclusion Vaccination coverage for the complete valid dose schedule and the first booster did not meet the 95.0% target. Regional disparities and the association between vaccination coverage and social indicators should be taken into consideration in strategies to increase coverage.

Objective To analyse vaccination coverage and factors associated with incomplete polio vaccination in a cohort of children born in 2017-2018, in state capitals and interior region municipalities of Northeast Brazil. Methods Household survey of children aged ≤24 months conducted between 2020 and 2022. Vaccination coverage and dropout rates were estimated, as well as factors associated with incomplete vaccination, analyzed by calculating odds ratios (OR) and 95% confidence intervals (95%CI). Results : Among 12,137 children, vaccination coverage (4 doses) was 80.9% (95%CI 78.4;83.1); 8.4% were not vaccinated. Not having a vaccination card (OR=18.06; 95%CI 10.01;32.61) and use of private services (OR=1.46; 95%CI 1.23;1.74) were associated with incomplete vaccination. Higher dropout rates were found for the booster dose, especially in the highest stratum. Conclusion Low vaccination coverage, poor dose follow-up and high dropout rates were found for polio vaccines in the areas studied.

Goats are the one of the most susceptible domestic species to toxoplasmosis affecting animal health and production. The present study aimed to determine the seroprevalence of T. gondii infection in dairy goats from Rio de Janeiro, Brazil, as well as to evaluate associated risk factors, parasitic DNA detection in raw goat milk samples, and attempts to isolate the parasite from raw goat milk samples. Between October 2020 and December 2022, blood samples were collected from 460 goats, and 220 milk samples were taken from goats raised in the Rio de Janeiro state, Brazil. The serum samples were tested for anti-T. gondii IgG antibodies using IFAT. The milk samples were tested for parasitic DNA detection using nPCR, and attempts were made to isolate the protozoan in mice. For risk factor analysis, the farmers answered a semi-structured questionnaire covering various epidemiological variables. Overall, 24.1% tested positive for anti-T. gondii IgG in serum samples. Risk factors included farm location, age group, rearing system, presence of cats, grazing, and access of cats to water sources. In nPCR, 38.6% were positive, but none were positive in the bioassay. However, 3.2% of the mice inoculated with goat milk seroconverted. This study found that the exposure of dairy goats in Rio de Janeiro to T. gondii is driven by ineffective management practices in preventing and controlling the parasite in these animals. Moreover, despite the detection of parasitic DNA in raw goat milk, the shedding of viable parasites in milk from naturally exposed goats appears to be low.

Background Diabetes mellitus, a metabolic disease characterized by high blood glucose levels, has increased dramatically in recent years, prompting the need for more affordable diagnoses and treatments. Objective This study aimed to conduct a brief historical and theoretical review on the development of insulin. Methods Scientific and technological data have been retrieved and analyzed with a focus on the development of the active pharmaceutical ingredient insulin and insulin-based medicines. Data have been retrieved from the PubMed database available via the CAPES portal Results Diabetes is one of the oldest diseases in the world. The year 2021 marked the 100th anniversary of the discovery of insulin, which transformed diabetes from a fatal disease into a chronic disease. The extraction and purification of insulin from bovine or porcine pancreases from slaughterhouses has enabled the pharmaceutical industry to produce insulin on a large scale. The introduction of insulin analogs in 1996 expanded the options. Currently, commercial insulin consists of human insulin and/or human insulin analogs. Conclusion The state-of-the-art and technological development of insulin over the last 100 years has been presented in this work. The development of new pharmaceutical technologies has led to the obtainment of improved versions of insulin, as well as the emergence of different types of insulin. Alongside the innovations in the development of the active ingredient and related medicines, new formulations, methods, and routes of administration have emerged based on the pharmacodynamic, pharmacokinetic, and pharmacotechnical modulations of the drug.

Background Inflammation plays a key role in Alzheimer's disease (AD) progression. Interleukin 8 (CXCL8) has emerged as an important cytokine involved in neuroinflammation. It is known as an inflammatory factor that induces a chemotactic response to sites of injury, involving the infiltration of neutrophils. In AD, interactions between CXCL8, Aβ42, and Tau suggest that CXCL8 amplifies inflammatory reactivity induced by Aβ42 and increases Tau phosphorylation and subsequent NFT formation. Our main objective was to determine the CXCL8 profile and its relationship with AD biomarkers in clinical and biological groups in a cohort of Brazilian older adults. Method seventy‐four older adults were recruited and grouped based on different cognitive profile: Alzheimer’s dementia (n=33), Mild Cognitive Impairment (MCI) (n= 22) and normal cognition (NC) (n=19). CSF samples were collected by lumbar puncture and levels of Aβ42, p‐Tau, t‐Tau and, CXCL8 were assessed by the Luminex xMAP technique. Subsequently, based on biological criteria, the participants were classified in accordance with the AT(N) system into two groups AD continuum and non‐AD. Spearman correlation test and comparison between groups using the Mann‐Whitney U‐test and Kruskal‐Wallis's test were performed. Significant associations between CSF levels of Aβ42, p‐Tau, and p‐Tau/Aβ42 and CXCL8 were further explored in multiple linear regression analyses adjusted for age, sex, education, and APOE allele ε4 carrier status. Result A significant correlation was found between CSF IL‐8 levels and the pTau/Aβ42 ratio (r=‐.456; p=.009) only in individuals with AD. We observed decreased CSF CXCL8 levels in the AD continuum compared to the non‐AD group [U=450.0; p=.022]. Considering clinical groups, we also observed decreased CXCL8 levels in AD group compared to the MCI group [X2 (2): 8.2; p=.016]. A significant positive association adjusted by sex, age, formal education and allele Ɛ4 was found between CXCL8 and Aβ42 (ß=.316; p=.016) and a negative association with pTau/Aß42 ratio (ß=. ‐257; p=.036). Conclusion a decrease in CXCL8 levels was observed in the AD‐related groups and there was an increase in the MCI group, suggesting that IL‐8 may be more active in the prodromal stage of the disease and then its activity decreases as the disease progresses.