Search Results (26)

Kala-azar is a protracted disease caused by the protozoan Leishmania infantum (zoonotic) or L. donovani (anthroponotic), transmitted by sandflies. Patients present with fever, anemia, and hepatosplenomegaly, potentially progressing to hemorrhaging, secondary infections, and death. Its pathogenesis is linked to an exaggerated cytokine response. We studied 72 hospitalized patients, analyzing clinical data and outcomes in relation to L. infantum DNA loads in blood and bone marrow, and plasma concentrations of IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α, and TGF-β. Cytokine levels were found to be elevated. L. infantum kDNA loads in blood and bone marrow were strongly correlated and increased with disease duration. Higher parasite loads were observed in men, adults, and HIV-infected patients, and they were significantly associated with mortality. IL-6 was independently linked to sepsis. In multivariate analysis, IL-12 was the only cytokine inversely associated with blood parasite load. Parasite load, but not cytokine levels, correlated with disease severity, suggesting additional mechanisms drive progression. IL-12 appears to limit parasitemia, indicating a weak, persistent adaptive immune response that is ultimately overwhelmed by a progressive, inefficient, and inflammatory innate response. Full article

The Oropouche virus (OROV) is an arbovirus (Peribunyaviridae: Orthobunyavirus) that traditionally causes febrile outbreaks in Latin America’s Amazon region. Previously, OROV was not associated with severe pregnancy outcomes. During the 2022–2024 outbreak in Brazil, OROV expanded geographically, revealing links to adverse pregnancy outcomes. This study describes six cases with varied fetal outcomes, including miscarriage, antepartum, intrauterine fetal demise (IFD), and normal development, correlating with maternal symptoms but not symptom severity. Vertical transmission was confirmed by detecting OROV through RT-qPCR, ELISA, and immunohistochemistry in fetal tissues. Genome sequencing from an IFD case identified a novel reassortment pattern reported in the 2022–2024 outbreak. Severe encephalomalacia, meningoencephalitis, vascular compromise, and multi-organ damage were evident, underscoring the significant risk OROV poses to fetal development and emphasizing the need for further investigation. Full article

This study aimed to explore the RNA viruses affecting Passiflora species in Brazil. Our results enhance the understanding of the viruses that infect Passiflora plants by identifying and characterizing three previously unrecognized viruses: Passiflora cytorhabdovirus (PFCV), Passiflora nucleorhabdovirus 1 (PaNV1), and Passiflora nucleorhabdovirus 2 (PaNV2). These rhabdoviruses were identified through high-throughput sequencing and validated by reverse transcription-polymerase chain reaction (RT-PCR) in various Passiflora species. PFCV has a genome organization 3′-N-P-P3-P4-M-G-P7-L-5′ and was classified as a novel member of the Gammacytorhabdovirus genus. A particularly noteworthy feature of PFCV is its glycoprotein, as the genomes of other gammarhabdoviruses do not contain this gene. PFCV has a high incidence across multiple locations and was identified in plants from Northeastern, Central, and Southeastern Brazil. PaNV1 with genome structure 3′-N-P-P3-M-G-L-5′ and PaNV2 with genome organization 3′-N-X-P-Y-M-G-L-5′ are new members of the Alphanucleorhabdovirus genus and have a more restricted occurrence. Importantly, all three viruses were found in mixed infections alongside at least one other virus. In situ observations confirmed mixed infections, with PaNV2 particles co-located in tissues with a potyvirus and a carlavirus. Phylogenetic and glycoprotein sequence similarity network analysis provided insights into their evolutionary placement and potential vector associations. These findings expand the known diversity of rhabdoviruses in Passiflora and contribute to the understanding of their evolution and epidemiology. Full article

In the history of yellow fever (YF) outbreaks in Brazil, howler monkeys (Alouatta sp.) and marmosets (Callithrix sp.) have been among the most affected genera, exhibiting significant hepatic injuries similar to those seen in humans. However, limited information exists regarding yellow fever virus (YFV) infection in their central nervous system (CNS). To address this gap, an epidemiological study was conducted to assess tissue changes, viral detection, and cytokine profiles in the brains of both neotropical primate species when they are naturally infected with YFV. A total of 22 brain samples from these species (8 from Alouatta sp. and 14 from Callithrix sp.) showing infection with YFV in the liver via immunohistochemistry (IHC) were selected. From them, YFV antigen detection occurred in 35.7% (5/14) of Callithrix sp. brain samples and 87.5% (7/8) of Alouatta sp. samples, with a higher frequency of viral antigen quantification in Callithrix sp. Both species exhibited similar CNS lesions, characterized by congestion, low hemorrhage, limited inflammatory infiltration interstitial and perivascular edema associated with neuronal degeneration, neurophagy, and higher cell death (necrosis and apoptosis) quantification. Pro- and anti-inflammatory cytokine profiles were balanced, with TNF-α and IL-1β playing a key role in inflammation, while IL-10 and IL-13 exhibited a prominent role in immunomodulation, suggesting an anti-inflammatory modulation typical of flaviviruses occurs. This study demonstrates that YFV can induce CNS lesions in neotropical primates, establishing it as a secondary target of viral tropism. These findings highlight the importance of collecting nervous tissue during epizootics, particularly in Callithrix sp., as such tissue is often overlooked despite its critical role in disease monitoring. Full article

This study explores the predictability of monthly asthma notifications using models built from different machine learning techniques in Maceió, a municipality with a tropical climate located in the northeast of Brazil. Two sets of predictors were combined and tested, the first containing meteorological variables and pollutants, called exp1, and the second only meteorological variables, called exp2. For both experiments, tests were also carried out incorporating lagged information from the time series of asthma records. The models were trained on 80% of the data and validated on the remaining 20%. Among the five methods evaluated—random forest (RF), eXtreme Gradient Boosting (XGBoost), Multiple Linear Regression (MLR), support vector machine (SVM), and K-nearest neighbors (KNN)—the RF models showed superior performance, notably those of exp1 when incorporating lagged asthma notifications as an additional predictor. Minimum temperature and sulfur dioxide emerged as key variables, probably due to their associations with respiratory health and pollution levels, emphasizing their role in asthma exacerbation. The autocorrelation of the residuals was assessed due to the inclusion of lagged variables in some experiments. The results highlight the importance of pollutant and meteorological factors in predicting asthma cases, with implications for public health monitoring. Despite the limitations presented and discussed, this study demonstrates that forecast accuracy improves when a wider range of lagged variables are used, and indicates the suitability of RF for health datasets with complex time series. Full article

Necroptosis is a regulated form of cell death implicated in several pathological conditions, including viral infections. In this study, we investigated the expression and correlation of necroptosis markers MLKL, RIP1 and RIP3 in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). The liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases underwent histopathological analysis, followed by tissue immunostaining with the immunohistochemical method of streptavidin–biotin peroxidase. Using the in situ method, we evaluated the centrilobular zone (Z3), midzonal zone (Z2), periportal zone and portal tract (PT) of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. A quantitative analysis revealed a significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PTs) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. A Pearson correlation analysis demonstrated significant correlations among necroptosis markers, which indicates their coordinated regulation during YF-induced liver injury. Full article

In this study, the analysis of metals in the solubilized extract of the organic fraction of Urban Solid Waste (MSW) from the municipality of Belém do Pará was carried out. The waste used in this research was collected in residential areas, through door-to-door collection, with the points and neighborhoods served in the municipality of Belém determined by the sectorization of these locations, with family income as the main parameter. The MSW was collected and transported to the segregation area. Gravimetric analysis of MSW was carried out and the selected organic and paper fractions were subjected to drying, crushing and sieving pre-treatment. Next, the solubilized extract of the organic fraction of MSW was obtained following the method set out in NBR nº 10.006/2004 of the Brazilian Association of Technical Standards. The values obtained were compared with CONAMA Resolutions n° 357/2005, 396/2008 and 430/2011, in addition to being compared with results of bibliographical research. The results indicated that these wastes do not comply with environmental and health regulations. Although a highly significant association was found between chromium and boron through Pearson’s correlation, the remaining strong correlations between other elements did not reach statistical significance. Furthermore, a similarity was observed in the solubilization conditions of these wastes with those found in landfill leachate. Full article

This article aimed to evaluate, using statistical tools, the generation and composition of municipal solid waste (MSW) in the city of Belém, Pará, from nine urban collection sectors in the municipality and the average nominal income of the population. Approximately 900 kg of urban solid waste was collected from the municipality in the period from 2021 to 2022. Statistical tests were carried out on hypotheses with 5% significance in comparative evaluations and their respective average nominal incomes. The results indicated that the organic fraction corresponded to 55.57% of the waste generated in the municipality, 14.26% was inert waste (potentially contaminating), and 0.67% was miscellaneous waste. It was observed that the waste generated by families with high purchasing power tended to contain higher percentages of recyclables while in families with lower purchasing power, the highest percentages tended to be organic. Knowledge of the generation of MSW is fundamental for the choice and dimensioning of operations and processes involved in the management chain at the municipal level. The decentralization of services offered based on solid waste management would enable greater success in serving the population. Full article

This work aimed to predict the physical–chemical characteristics of leachate according to the analysis of the solubilized extract from urban household solid waste (UHSW), on a laboratory scale, in the city of Belém/PA, Brazil. The neighborhoods where the waste was collected were sectorized based on geographic and socioeconomic data, with family income as the main parameter. After collection, the material was sent to the segregation area, where a gravimetric analysis of the UHSW was performed and fractions (paper, cardboard, Tetra Pak, rigid plastic, malleable plastic, metals, glass, organic matter, sanitary waste, fabrics and rejects) were segregated. After the gravimetric characterization, it was found that the highest average proportions were 55.57% organic matter, 14.26% sanitary waste and 9.97% malleable plastic. The organic fraction was selected and subjected to drying, crushing, sieving and packaging pretreatment, and then the solubilized extract of this fraction was obtained according to NBR No. 10.006/2004 of the Brazilian Association of Technical Standards. In the analyses of the solubilized extract, values for total nitrogen (201.80 to 359.90 mg·L⁻¹), ammonia nitrogen (161 to 289 mg·L⁻¹), nitrate (10 to 40 mg·L⁻¹) and chemical oxygen demand were obtained (28,701 mg·L⁻¹ to 38,608 mg·L⁻¹), indicating the similarity of the waste solubilization conditions to those of leachate from landfills, in addition to being in noncompliance with environmental and health legislation, thus making it necessary to have an efficient waste management system, which avoids the release of waste into the environment that would result in environmental impacts similar to those of leachate contact with the environment. Full article

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy. Full article

An oil palm (Elaeis guineensis Jacq.) bud rod disorder of unknown etiology, named Fatal Yellowing (FY) disease, is regarded as one of the top constraints with respect to the growth of the palm oil industry in Brazil. FY etiology has been a challenge embraced by several research groups in plant pathology throughout the last 50 years in Brazil, with no success in completing Koch’s postulates. Most recently, the hypothesis of having an abiotic stressor as the initial cause of FY has gained ground, and oxygen deficiency (hypoxia) damaging the root system has become a candidate for stress. Here, a comprehensive, large-scale, single- and multi-omics integration analysis of the metabolome and transcriptome profiles on the leaves of oil palm plants contrasting in terms of FY symptomatology—asymptomatic and symptomatic—and collected in two distinct seasons—dry and rainy—is reported. The changes observed in the physicochemical attributes of the soil and the chemical attributes and metabolome profiles of the leaves did not allow the discrimination of plants which were asymptomatic or symptomatic for this disease, not even in the rainy season, when the soil became waterlogged. However, the multi-omics integration analysis of enzymes and metabolites differentially expressed in asymptomatic and/or symptomatic plants in the rainy season compared to the dry season allowed the identification of the metabolic pathways most affected by the changes in the environment, opening an opportunity for additional characterization of the role of hypoxia in FY symptom intensification. Finally, the initial analysis of a set of 56 proteins/genes differentially expressed in symptomatic plants compared to the asymptomatic ones, independent of the season, has presented pieces of evidence suggesting that breaks in the non-host resistance to non-adapted pathogens and the basal immunity to adapted pathogens, caused by the anaerobic conditions experienced by the plants, might be linked to the onset of this disease. This set of genes might offer the opportunity to develop biomarkers for selecting oil palm plants resistant to this disease and to help pave the way to employing strategies to keep the safety barriers raised and strong. Full article

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies. Full article

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense. Full article

Osteoarthritis (OA) is a chronic degenerative disease that has a significant global impact. It is associated with aging and characterized by widespread joint destruction. Cuminaldehyde is a biologically active component of essential oils that has shown promise in the treatment of nociceptive and inflammatory diseases. This study investigated the effects of cuminaldehyde on an experimental model of osteoarthritis induced in rat knees. Cuminaldehyde was found to be as effective as indomethacin in reducing pain in all evaluated tests, including forced walking, functional disability of weight distribution on the legs, and spontaneous pain in animals with osteoarthritis. The knees of animals treated with cuminaldehyde had significantly higher radiographic and histopathological scores than those of animals that did not receive the treatment. Cuminaldehyde also modulated the production of pro-inflammatory cytokines. In vitro assays showed that cuminaldehyde preferentially inhibits COX-2 enzyme activity. In silico studies demonstrated that cuminaldehyde has satisfactory energy affinity parameters with opioid receptors and COX-2. These findings suggest that cuminaldehyde’s anti-inflammatory activity is multifactorial, acting through multiple pathways. Its nociceptive activity occurs via central and peripheral mechanisms. Cuminaldehyde modulates the immune response of the inflammatory process and may be considered a leading compound for the development of new anti-inflammatory and analgesic drugs. Full article

The scientific literature mentions the existence of factors associated with fear of falling in older adults. However, the direct and indirect paths of its predictors have not yet been fully explored. This study aimed to analyze the socioeconomic, clinical, and health factors directly and indirectly associated with fear of falling in community-dwelling older adults. This is a cross-sectional study conducted in older adults (n = 410 – 70.11 ± 7.22 years). Clinical and health-condition data were collected, as were data on fear of falling using the Falls Efficacy Scale International—Brazil (FES-I Brazil). It was found that being female and having a higher number of self-reported morbidities, worse physical performance, and a higher number of depressive symptoms were directly associated with greater fear of falling. Regarding indirect associations, physical inactivity, mediated by a greater number of morbidities, worse physical performance, and a greater number of depressive symptoms, was associated with greater fear of falling. In addition, worse self-rated health, mediated by a greater number of depressive symptoms, as well as older age, mediated by worse physical performance, were associated with the outcome. This study provides information on the predictors directly and indirectly associated with fear of falling, expanding current understanding of this relationship. Full article