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Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

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This work aimed to study the effect of trehalose in protecting cells against Sod1 proteinopathy associated with amyotrophic lateral sclerosis (ALS). Humanized yeast cells in which native Sod1 was replaced by wild-type human Sod1 or an ALS mutant (WT-A4V Sod1 heterodimer) were used as the experimental model. Cells were treated with 10% trehalose (p/v) before or after the appearance of hSod1 proteinopathy induced by oxidative stress. In both conditions, trehalose reduced the number of cells with Sod1 inclusions, increased Sod1 activity, and decreased the levels of intracellular oxidation, demonstrating that trehalose avoids Sod1 misfolding and loss of function in response to oxidative stress. The survival rates of ALS Sod1 cells stressed in the presence of trehalose were 60% higher than in their absence. Treatment with trehalose after the appearance of Sod1 inclusions in cells expressing WT Sod1 doubled longevity; after 5 days, non-treated cells did not survive, but 15% of cells treated with sugar were still alive. Altogether, our results emphasize the potential of trehalose as a novel therapy, which might be applied preventively in ALS patients with a family history of the disease or after diagnosis in ALS patients who discover the disease following the first symptoms.

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A cloud point method was developed and applied for the first time to extract and preconcentrate thiabendazole (TBZ) from commercial whole grape juice samples, with determination by high performance liquid chromatography coupled to electrochemical detection (HPLC/EC), using a cathodically pretreated boron-doped diamond electrode (BDD). The best conditions for extraction and preconcentration of TBZ by cloud point extraction (CPE) were performed at pH 6.0, by adding 1 mL of the surfactant Tergitol TMN-6 at 10% (mass-to-mass ratio), without heating (at 27 °C) and ultrasonic stirring time of (20 kHz) for 60 min. The HPLC/EC determination was duly validated in a C8 column, in mobile phase with a 69 : 31 ratio (V/V) of phosphate buffer (pH 7.0):ACN, at a flow rate of 1.2 mL min-1 and electrochemical detection with BDD electrode by applying 1.40 V × Ag/AgCl (3.0 mol L-1). Under these conditions, the procedure showed a preconcentration factor (FC) of 21.7, and limits of detection (LOD) and quantification (LOQ) of 6.64 × 10-9 mol L-1 (or 1.33 µg L-1) and 1.66 × 10-8 mol L-1 (or 3.34 µg L-1), respectively. The method provided a percent recovery of 81% to 98%, with a coefficient of variation between 3% and 15%.

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Under certain stress conditions, astrocytes operate in aerobic glycolysis, a process controlled by pyruvate dehydrogenase (PDH) inhibition through its E1 α subunit (Pda1) phosphorylation. This supplies lactate to neurons, which save glucose to obtain NADPH to, among other roles, counteract reactive oxygen species. A failure in this metabolic cooperation causes severe damage to neurons. In this work, using humanized Saccharomyces cerevisiae cells in which its endogenous Cu/Zn Superoxide Dismutase (SOD1) was replaced by human ortholog, we investigated the role of human SOD1 (hSOD1) in aerobic glycolysis regulation and its implications to amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. Yeast cells ferment glucose even in the presence of oxygen and switch to respiratory metabolism after glucose exhaustion. However, like cells of SOD1-knockout strain, cells expressing A4V mutant of hSOD1 growing on glucose showed a respiratory phenotype, i.e., low glucose and high oxygen consumptions and low intracellular oxidation levels in response to peroxide stress, contrary to cells expressing wild-type (WT) SOD1 (yeast or human). The A4V mutation in hSOD1 is linked to ALS. In contrast to WT SOD1 strains, PDH activity of both sod1Δ and A4V hSOD1 cells did not change in response to a metabolic shift toward oxidative metabolism, which was associated to lower Pda1 phosphorylation levels under growth on glucose. Taken together, our results suggest that A4V mutant cannot regulate aerobic glycolysis via Pda1 phosphorylation the same way WT hSOD1, which might be linked to problems observed in the motor neurons of ALS patients with the SOD1 A4V mutation.

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The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0-10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.

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Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

RESUMO

Importance: Bothrops venom acts almost immediately at the bite site and causes tissue damage. Objective: To investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations. Design, Setting, and Participants: This was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022. Intervention: The intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point. Main Outcomes and Measures: Feasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients' acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients' discharge. P values for outcomes were adjusted with Bonferroni correction. Results: A total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P < .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed. Conclusions and Relevance: The data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-4qw4vf.

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The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants’ lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0–10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron’s sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.

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Objetivo: Descrever a utilização das boas práticas de atenção ao parto e nascimento e o grau de satisfação e experiência de puérperas com o parto. Métodos: Estudo transversal, realizado no período de julho de 2017 a janeiro de 2018, em uma maternidade de referência em Fortaleza, Ceará. Para coleta de dados utilizou-se o Questionário de Experiência e Satisfação com o Parto e questionário para avaliação dos dados sociodemográficos e obstétricos. Os dados foram analisados no softwareStatistical Package for the Social Science. O estudo foi aprovado pelo Comitê de Ética em Pesquisa. Resultados: Participaram 237 puérperas com média de idade de 26 anos. 168 (70,9%) mulheres estiveram bastante satisfeitas com a estrutura da instituição, 119 (50,2%) com os cuidados profissionais prestados e 160 (67,5%) com o trabalho de parto e parto. Dentre os fatores que estiveram associados à experiência positiva com o parto, destaca-se a realização do contato pele a pele, o estímulo ao aleitamento materno e a utilização dos métodos não farmacológicos de alívio da dor. Conclusão: Para uma experiência mais positiva de parto, ressalta-se a importância de abordagens mais humanizadas que incentivem práticas como contato pele a pele e início precoce do aleitamento materno, além de garantir que profissionais de saúde forneçam cuidados holísticos. Descritores: Satisfação do Paciente; Enfermagem Obstétrica; Trabalho de Parto; PartoNormal; PartoHumanizado.

Objective:To describe the use of good practices in delivery and childbirth care and the satisfaction levels and experiences of puerperal women with their deliveries.Methods:A cross-sectional study conducted from July 2017 to January 2018 in a reference maternity hospital from Fortaleza, Ceará. The Childbirth Experience and Satisfaction Questionnaire and another one to assess the sociodemographic and obstetric data were used for data collection. The data were analyzed in the Statistical Package for the Social Science. The study was approved by the Research Ethics Committee. Results:The participants were 237 puerperal women with a mean age of 26 years old. 168 (70.9%) women were quite satisfied with the institution's structure, 119 (50.2%) with the professional care provided, and 160 (67.5%) with labor and delivery. Among the factors that were associated with positive experiences with delivery, the most important are skin-to-skin contact, stimulating breastfeeding, and using non-pharmacological pain relief methods. Conclusion: For a more positive experience with delivery, it is worth emphasizing the importance of more humanized approaches that encourage practices such as skin-to-skin contact and early breastfeeding initiation, as well as ensuring that health professionals provide holistic care. Descriptors:Patient Satisfaction; Obstetric Nursing; Labor. Normal Delivery; Humanized Delivery.

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Objetivo:avaliar o conhecimento, a atitude e a prática (CAP) de gestantes sobre incontinência urinária (IU), identificar a prevalência de IU durante a gestação, avaliar seu impacto na qualidade de vida (QV) e identificar os fatores associados ao CAP inadequados em relação à IU. Metodologia: Estudo observacional realizado de maio a novembro de 2019 na cidade de Fortaleza, Ceará. Utilizaram-se dois instrumentos para coleta de dados: um para avaliação sociodemográfica, obstétrica e de perdas urinárias e outro para avaliação do CAP sobre IU. Resultados: Participaram 237 gestantes. A prevalência de IU foi de 49,3% e observou-se baixo impacto na QV. A maioria apresentou conhecimento (89,6%) e prática inadequados tanto para prevenir (89,2%) quanto para tratar (78,8%) a IU. Identificaram-se baixos percentuais de acerto relacionados ao conhecimento sobre fatores de risco (46,8%), prevenção (43,8%) e tratamento da IU (42,8%). Apesar disso, a atitude foi considerada adequada para a maioria das mulheres (98,5%). Ausência de orientação sobre o preparo do períneo para o parto durante o pré-natal (p = 0,019), baixa escolaridade (p < 0,001), casos mais leves de IU (p = 0,027) e gestação de alto risco (p = 0,004) associaram-se a prática inadequada. Conclusão: o conhecimento sobre causas, prevenção e tratamento da IU é insuficiente e interfere no manejo dessa condição.perineum for childbirth during prenatal care (p = 0.019), low education (p < 0.001), milder cases of UI (p = 0.027) and high-risk pregnancy (p = 0.004) were associated with inappropriate practice. Conclusions: knowledge about the causes, prevention and treatment of UI is insufficient and interferes with the management of this condition.

Objectives:To assess the knowledge, attitude and practice (KAP) of pregnant women about urinary incontinence (UI), identify the prevalence of UI, assess its impact on quality of life (QoL) and identify factors associated with inadequate KAP in relation to UI. Methodology: Observational study carried out from May to November 2019 in the city of Fortaleza, Ceará, Brazil. Two instruments were used for data collection: one for sociodemographic, obstetric and urinary loss assessment and another for KAP assessment on UI. Results: 237 pregnant women participated. The prevalence of UI was 49.3% and a low impact on QoL was observed. Most had knowledge (89.6%) and inadequate practice both to prevent (89.2%) and to treat (78.8%). Low percentages of correct answers were identified related to knowledge about risk factors (46.8%), prevention (43.8%) and treatment of UI (42.8%). Despite this, the attitude was considered adequate for most women (98.5%). Absence of guidance on preparation of the perineum for childbirth during prenatal care (p = 0.019), low education (p < 0.001), milder cases of UI (p = 0.027) and high-risk pregnancy (p = 0.004) were associated with inappropriate practice. Conclusions: knowledge about the causes, prevention and treatment of UI is insufficient and interferes with the management of this condition.

Objetivos:evaluar el conocimiento, la actitud y la práctica (CAP) de las gestantes sobre la incontinencia urinaria (IU), identificar la prevalencia de la IU, evaluar su impacto en la calidad de vida (CV) e identificar los factores asociados a una PAC inadecuada en relación con la IU. Metodología: estudio observacional realizado de mayo a noviembre de 2019 en la ciudad de Fortaleza/CE. Se utilizaron dos instrumentos para la recolección de datos: uno para la evaluación sociodemográfica, obstétrica y de pérdidas urinarias y otro para la evaluación del CAP en la IU. Resultados: Participaron 237 gestantes. La prevalencia de IU fue del 49,3% y se observó un bajo impacto en la CV. La mayoría tenía conocimiento (89,6%) y práctica inadecuada tanto para prevenir (89,2%) como para tratar (78,8%). Se identificaron bajos porcentajes de aciertos relacionados con el conocimiento sobre factores de riesgo (46,8%), prevención (43,8%) y tratamiento de la IU (42,8%). A pesar de ello, la actitud fue considerada adecuada por la mayoría de las mujeres (98,5%). La ausencia de orientación sobre la preparación del perineo para el parto durante el control prenatal (p = 0,019), la baja escolaridad (p < 0,001), los casos más leves de IU (p = 0,027) y el embarazo de alto riesgo (p = 0,004) se asociaron con una atención inadecuada. práctica. Conclusión: el conocimiento sobre las causas, la prevención y el tratamiento de la IU es insuficiente e interfiere con el manejo de esta condición.

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