Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings.

Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.

Anxiety in the pandemic: a study about the impacts on mental health during the COVID-19 contagion in Brazil / Ansiedade na pandemia: um estudo sobre os impactos na saúde mental durante o contágio de Covid-19 no Brazil

The aim of this study was to investigate the symptoms of anxiety resulting from social distancing and its impacts on the Brazilian population during the COVID-19 pandemic. The study consisted of a cross-sectional survey, with data constructed through an online questionnaire that included sociodemographic information and information about anxiety symptoms. The questions were constructed considering the concept of "mental health waves", as being the mental health demands presented at the respective moment of the pandemic. The sample consisted of 632 participants, and the prevalence of anxiety identified was 81%, with no statistically significant differences between genders. The main factors related to anxiety were loneliness (OR=2.18, 95% CI=1.16-4.09), sleeping difficulties (OR=2.59, 95% CI=1.57-4.28), irritability (OR= 1.85, 95% CI=1.11-3.09), financial difficulties (OR=1.85, 95% CI=1.01-3.40), and problems related to emotional isolation (OR=2.43, 95% CI=1.47- 4.01). In the context of the challenges for mental health, the results obtained contribute to deeper understanding of the changes related to anxiety that emerged with the advent of social distancing policies and the context of the pandemic.

O objetivo deste estudo foi investigar os sintomas de ansiedade decorrentes do distanciamento social e seus impactos sobre a população brasileira durante a pandemia COVID-19. O estudo consistiu em uma pesquisa transversal, com dados construídos por meio de questionário online que incluía informações sociodemográficas e informações sobre sintomas de ansiedade. As questões foram construídas considerando o conceito de "ondas de saúde mental", como sendo as demandas de saúde mental apresentadas no respectivo momento da pandemia. A amostra foi composta por 632 participantes, e a prevalência de ansiedade identificada foi de 81%, sem diferenças estatisticamente significativas entre os sexos. Os principais fatores relacionados à ansiedade foram solidão (OR=2,18, 95% IC =1,16-4,09), dificuldades para dormir (OR=2,59, 95% IC =1,57-4,28), irritabilidade (OR= 1,85, 95% IC =1,11%-3,09), dificuldades financeiras (OR=1,85, 95% IC =1,01-3,40) e problemas relacionados ao isolamento emocional (OR=2,43, 95% IC =1,47-4,01). No contexto dos desafios para a saúde mental, os resultados obtidos contribuem para uma compreensão mais profunda das mudanças relacionadas à ansiedade que surgiram com o advento das políticas de distanciamento social e o contexto da pandemia.

Kidney function and daily emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis against HIV: results from the real-life multicentric demonstrative project PrEP Brazil.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. METHODS: Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. RESULTS: Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = - 0.005; p < 0.01) and 48 (r = - 0.006; p < 0.01). CONCLUSIONS: These results suggest that the renal function profile in individuals on TDF/FTC may be assessed on week 4 and then only annually, allowing a more flexible medical follow-up in primary care centers.

Effect of weekly versus daily primaquine on Plasmodium vivax malaria recurrences: A real-life cohort study

ABSTRACT Background: Although primaquine (PQ) is indicated for G6PD-deficient patients, data on weekly PQ use in Brazil are limited. Methods: We aimed to investigate malaria recurrences among participants receiving daily and weekly PQ treatments in a real-life setting of two municipalities in the Amazon between 2019 and 2020. Results: Patients receiving weekly PQ treatment had a lower risk of recurrence than those receiving daily PQ treatment (risk ratio: 0.62, 95% confidence interval: 0.41-0.94), using a model adjusted for study site. Conclusions: Weekly PQ use did not increase the risk of malaria recurrence. Further studies with larger populations are warranted.

Prevalence and force of Plasmodium vivax blood-stage infection and associated clinical malaria burden in the Brazilian Amazon

BACKGROUND Understanding the epidemiology of malaria through the molecular force of the blood-stage infection of Plasmodium vivax (molFOB) may provide a detailed assessment of malaria transmission. OBJECTIVES In this study, we investigated risk factors and spatial-temporal patterns of incidence of Plasmodium infection and clinical malaria episodes in three peri-urban communities of Manaus, Western Brazilian Amazon. METHODS Monthly samples were collected in a cohort of 1,274 individuals between April 2013 and March 2014. DNA samples were subject to Plasmodium species. molFOB was calculated by counting the number of genotypes observed on each visit, which had not been present in the preceding two visits and adjusting these counts by the respective times-at-risk. FINDINGS Respectively, 77.8% and 97.2% of the population remained free of P. vivax and P. falciparum infection. Expected heterozygosity for P. vivax was 0.69 for MSP1_F3 and 0.86 for MS2. Multiplicity of infection in P. vivax was close to the value of 1. The season was associated with P. vivax positivity [adjusted hazard ratio (aHR) 2.6 (1.9-5.7)] and clinical disease [aHR 10.6 (2.4-47.2)]. P. falciparum infection was associated with previous malarial episodes [HR 9.7 (4.5-20.9)]. Subjects who reported possession of a bed net [incidence rate ratio (IRR) 1.6 (1.2-2.2)] or previous malaria episodes [IRR 3.0 (2.0-4.5)] were found to have significantly higher P. vivax molFOB. MAIN CONCLUSIONS Overall, P. vivax infection prevailed in the area and infections were mostly observed as monoclonal. Previous malaria episodes were associated with significantly higher P. vivax molFOB.