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BackgroundDespite the great progress made over the last decades, stronger structural interventions are needed to end the HIV/AIDS pandemic in Low and Middle-Income Countries (LMIC). Brazil is one of the largest and data-richest LMIC, with rapidly changing socioeconomic characteristics and an important HIV/AIDS burden. Over the last two decades Brazil has also implemented the world's largest Conditional Cash Transfer programs, the Bolsa Familia Program (BFP), and one of the most consolidated Primary Health Care (PHC) interventions, the Family Health Strategy (FHS).ObjectiveWe will evaluate the effects of socioeconomic determinants, BFP exposure and FHS coverage on HIV/AIDS incidence, treatment adherence, hospitalizations, case fatality, and mortality using unprecedently large aggregate and individual-level longitudinal data. Moreover, we will integrate the retrospective datasets and estimated parameters with comprehensive forecasting models to project HIV/AIDS incidence, prevalence and mortality scenarios up to 2030 according to future socioeconomic conditions and alternative policy implementations.Methods and analysisWe will combine individual-level data from all national HIV/AIDS registries with large-scale databases, including the "100 Million Brazilian Cohort", over a 19-year period (2000-2018). Several approaches will be used for the retrospective quasi-experimental impact evaluations, such as Regression Discontinuity Design (RDD), Random Administrative Delays (RAD) and Propensity Score Matching (PSM), combined with multivariable Poisson regressions for cohort analyses. Moreover, we will explore in depth lagged and long-term effects of changes in living conditions and in exposures to BFP and FHS. We will also investigate the effects of the interventions in a wide range of subpopulations. Finally, we will integrate such retrospective analyses with microsimulation, compartmental and agent-based models to forecast future HIV/AIDS scenarios.ConclusionThe unprecedented datasets, analyzed through state-of-the-art quasi-experimental methods and innovative mathematical models will provide essential evidences to the understanding and control of HIV/AIDS epidemic in LMICs such as Brazil.

IntroductionThe thyroid cancer has the ninth larger incidence of cancer in the world. Investigations related to the exposure to metals have become important due to the sensibility of the thyroid gland to them. Studies reveal that carcinogenic progressions are associated to the deficiency of the essential trace elements. In this context, the zinc is highlighted, essential for the metabolism of the thyroidal hormone and has a potential relation with the pathogenesis of the thyroid cancer. The objective of this systematic review and meta-analysis is to evaluate the low serum zinc as a risk factor for thyroid cancer in adults.Methods and analysisPubMed/MEDLINE, Scopus, Embase and LILACS databases will be searched for observational studies investigating the low serum zinc as a risk factor for thyroid cancer in adults. No language or publication period restrictions will be imposed. The primary outcome will be that the low serum zinc is a risk factor for thyroid cancer. Three independent reviewers will select the studies and extract data from the original publications. The risk-of-bias will be assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data synthesis will be performed using the R software (V.4.3.1) and to assess heterogeneity, we will compute the I2 statistic and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence.Prospero registration numberInternational Prospective Register of Systematic Reviews (PROSPERO) CRD42023463747.

The aberrant activation of HER2 has a pivotal role in bone metastasis implantation and progression in several tumor types, including prostate cancer (PC). Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Although HER2 overexpression has been reported in PC, anti-HER2 therapy response has revealed conflicting results. We investigated the potential of lapatinib in inhibiting cell migration and inducing apoptosis in two human (LNCaP and PC3) and two canine PC cell lines (PC1 and PC2). Cell migration and apoptosis were evaluated by Annexin V/PI analysis after lapatinib treatment. The transcriptome analysis of all cell lines before and after treatment with lapatinib was also performed. We found increased apoptosis and migration inhibition in LNCaP cells (androgen-sensitive cell line), while PC1, PC2, and PC3 cells showed no alterations after the treatment. The transcriptome analysis of LNCaP and PC3 cell lines showed 158 dysregulated transcripts in common, while PC1 and PC2 cell lines presented 82. At the doses of lapatinib used, we observed transcriptional modifications in all cell lines. PI3K/AKT/mTOR pathway were enriched in human PC cells, while canine PC cells showed enrichment of tyrosine kinase antitumor response and HER2-related pathways. In canine PC cells, the apoptosis failed after lapatinib treatment, possibly due to the downregulation of MAPK genes. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective antitumor response and clinical benefits to PC patients.

IntroductionSeptic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients.MethodsProspective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA.Ethics and disseminationThe results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025.Trial registrationTrial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

PurposeThis paper reports a systematic review and meta-analysis protocol that will be used to evaluate the efficacy and safety of pembrolizumab, alone or combined with bevacizumab and other therapies, in adult women with cervical carcinoma from stage IB2 onwards.MethodsThe protocol follows PRISMA-P recommendations and was registered on PROSPERO (CRD42024531233). The search will be conducted without restrictions on language and year of publication in the following databases: Pubmed, Embase, Scopus, Web of Science, Cancerlit, The World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and Clinical Trials Registry Platform. Grey literature will be searched using the following sources: Clinicaltrials.gov, Google Scholar and Opengrey. Manual search will be carried out for the reference lists of eligible studies. The studies will be selected independently by two reviewers and all completed or ongoing randomized clinical trials that evaluated the efficacy and safety of pembrolizumab, used alone or combined with chemotherapy, radiotherapy, bevacizumab or surgery, in adult women diagnosed with cervical cancer, will be included. The data extraction will include population characteristics, type of treatment and main outcomes of studies. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias 2.0. The certainty of the evidence will be rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).ConclusionsThe findings will be presented in narrative summary tables and a quantitative synthesis will be conducted using the 'meta' package of R software, version 4.3.1. This future systematic review may contribute with quality evidence for clinical decision-making on the use of pembrolizumab in women with cervical cancer.

Heavy mineral deposits occur in several coastal areas of the world, formed over a long period due to variations in mean sea level, wave action, and winds. These are the main sources of ilmenite (FeTiO3), which in turn is the source of more than 80% of the TiO2 produced and applied in various industries, most recently in nanotechnology. The present study mapped heavy mineral deposits on the coast of Rio Grande do Sul in southern Brazil using integrated proximal and orbital thermal infrared (TIR) remote sensing techniques. Mineral groups, such as oxides and silicates, have spectral features in the TIR wavelengths. Using laboratory spectroscopy at TIR using Nicolet 6700 Thermo Scientific Spectrometer, we measured the spectral signature of the local sample of heavy minerals (between 8 and 14 μm) and identified a diagnostic spectral feature at 10.75 μm. The signature was resampled to be compatible with the Advanced Spaceborne Thermal Emission Radiometer (ASTER) sensor bandwidth values and used as a reference endmember for the Spectral Angle Mapper (SAM) and Linear Spectral Unmixing (LSU) digital image classification algorithms. Thus, we identified the presence of the reference endmember (heavy minerals) in the pixels of the ASTER scene. In pixels classified by SAM as the presence of heavy minerals, LSU was applied to estimate the surface concentration within the pixel. The results showed a concentration of up to 20% of heavy minerals, with the highest concentration on the beach and dune fields. Opaque minerals such as ilmenite do not have spectral reflectance features in visible, near-infrared, and short-wave infrared, which makes their identification by remote sensing difficult. The present study showed that the integration of proximal and orbital as well as hyperspectral and multispectral thermal data can be considered as an alternative for detecting and mapping heavy minerals in coastal areas.

ObjectiveThis study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) and the use of probiotics on the treatment of halitosis.MethodsFifty-two participants, aged from 18 to 25 years, exhaling sulfhydride (H2S) ≥ 112 ppb were selected. They were allocated into 4 groups (n = 13): Group 1: tongue scraper; Group 2: treated once with aPDT; Group 3: probiotic capsule containing Lactobacillus salivarius WB21 (6.7 x 108 CFU) and xylitol (280mg), 3 times a day after meals, for 14 days; Group 4: treated once with aPDT and with the probiotic capsule for 14 days. Halimetry with gas chromatography (clinical evaluation) and microbiological samples were collected from the dorsum of the tongue before and after aPDT, as well as after 7, 14, and 30 days. The clinical data failed to follow a normal distribution; therefore, comparisons were made using the Kruskal-Wallis test (independent measures) and Friedman ANOVA (dependent measures) followed by appropriate posthoc tests, when necessary. For the microbiological data, seeing as the data failed to follow a normal distribution, the Kruskal-Wallis rank sum test was performed with Dunn's post-test. The significance level was α = 0.05.ResultsClinical results (halimetry) showed an immediate significant reduction in halitosis with aPDT (p = 0.0008) and/or tongue scraper (p = 0.0006). Probiotics showed no difference in relation to the initial levels (p = 0.7530). No significant differences were found in the control appointments. The amount of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were not altered throughout the analysis (p = 0.1616, p = 0.2829 and p = 0.2882, respectively).ConclusionThere was an immediate clinical reduction of halitosis with aPDT and tongue scraping, but there was no reduction in the number of bacteria throughout the study, or differences in the control times, both in the clinical and microbiological results. New clinical trials are necessary to better assess the tested therapies.Trial registrationClinical Trials NCT03996044.

Violence against women or gender-based violence (GBV) is a significant public health issue facing women and girls in different settings. It is reported to have worsened globally during the COVID-19 pandemic. Despite the impact of the COVID-19 pandemic on increased violence against women in general, which has been reported in many settings globally, there is a paucity of evidence of its impact on violence against highly vulnerable women living with HIV or tuberculosis (TB). Using a qualitative design, this study aimed to explore the views and experiences of women living with HIV (n = 19) or TB (n = 23) in Timor Leste regarding the GBV they faced during the COVID-19 pandemic. They were recruited using the snowballing sampling technique. Data were collected using one-on-one, in-depth interviews and focus group discussions. The five steps of qualitative data analysis suggested in Ritchie and Spencer's analysis framework were employed to guide the analysis of the findings. Findings indicated that women in this study experienced intensified physical, verbal, sexual and psychological violence by their partners, spouses, in-laws, and parents or other family members during the COVID-19 pandemic. Several prominent risk factors that worsened violence against women during the pandemic were (i) HIV or TB-positive status, (ii) traditional gender roles or responsibilities and expectations, (iii) economic and financial difficulties reflected in the loss of jobs and incomes due to the pandemic, and (iv) individual factors such as jealousy and increased alcohol drinking developed during the lockdowns. The women's experience of GBV during the pandemic also led to various negative psychological impacts. The findings underscore the urgent need for multifaceted interventions to address GBV, which should encompass challenging traditional gender norms, addressing economic inequalities, and targeting individual-level risk factors. The findings also indicate the need for the development of robust monitoring and evaluation systems to assess the effectiveness of policies and interventions addressing GBV where the results can inform future improvement. The findings also indicate the need to include GBV in the protocol or guidelines for HIV and TB management. Future large-scale quantitative studies to capture the magnitude and specific drivers of GBV against women living with HIV and TB during the pandemic are recommended.

IntroductionSimilar to chronic pain conditions, individuals with endometriosis can be affected by central sensitization syndrome (CSS), which is characterized by a loss of analgesia and central amplification of pain. Transcranial direct current stimulation (tDCS) has shown potential as an effective intervention to improve pain generated by other chronic pain conditions impacted by CSS, such as fibromyalgia and chronic pelvic issues. This study aims to evaluate the effectiveness of tDCS on pain, fatigue, and quality of life among patients affected by endometriosis.MethodsThis is a single-center, parallel, double-blinded, randomized, controlled clinical trial protocol study. We aim to recruit 40 participants affected by endometriosis (active group, n = 20; sham group, n = 20). Anodal tDCS will be delivered at an intensity of 2mA, applied over the primary motor cortex for 20 minutes per day for 10 consecutive days. There will be four assessment times: 1 week before beginning the intervention; on the 10th day following the last tDCS session; and 1 and 2 months after the last tDCS session. Pain evaluated by the algometry will be the primary outcome. Pain intensity, quality of life, fatigue, and global perception of change will be the secondary outcomes. We will calculate the effects of the active versus sham stimulation on primary and secondary outcomes by using generalized estimated equations or mixed model analysis. The effect size calculation will represent the effect measure. We expect that only the active group show reductions in pain, fatigue, and quality of life. The results of this trial will produce an important first step in providing evidence on the effectiveness of neuromodulation for the management of pain and will provide data to support new studies on tDCS.RegistrationBrazilian Clinical Trials Registry (RBR-4q69573).

Acute gastroenteritis (AGE) is a common pediatric infection that remains a significant cause of childhood morbidity and mortality worldwide, especially in low-income regions. Thus, the objective of this study was to detect human adenovirus (HAdV) and non-polio enterovirus (NPEV) in fecal samples from the Gastroenteritis Surveillance Network, and to identify circulating strains by nucleotide sequencing. A total of 801 fecal samples were tested using qPCR/RT-qPCR, and 657 (82.0%) were inoculated into HEp-2C and RD cell lines. The HAdV and NPEV positivity rates obtained using qPCR/RT-qPCR were 31.7% (254/801) and 10.5% (84/801), respectively, with 5.4% (43/801) co-detection. Cytopathic effect was observed in 9.6% (63/657) of patients, 2.7% (18/657) associated with HAdV, and 6.2% (41/657) associated with NPEV after testing by ICC-PCR. A comparison of the two methodologies demonstrated an agreement of 93.5% for EVNP and 64.4% for HAdV. These two viruses were detected throughout the study period, with HAdV positivity rates ranging from 41% in Amapá to 18% in Pará. The NEPV varied from 18% in Pará/Rondônia to 3% in Acre. The most affected age group was over 60 months for both HAdV and NPEV. Samples previously positive for rotavirus and norovirus, which did not show a major difference in the presence or absence of diarrhea, fever, and vomiting, were excluded from the clinical analyses of these two viruses. These viruses circulated over five years, with a few months of absence, mainly during the months corresponding to the waves of SARS-CoV-2 infection in Brazil. Five HAdV species were identified (A, B, C, D, and F), with a greater predominance of HAdV-F41 (56.5%) followed by HAdV-C (15.2%). Three NPEV species (A, B, and C) were detected, with serotypes E14 (19.3%) and CVA-24 (16.1%) being the most prevalent. The present study revealed a high diversity of NPEV and HAdV types circulating in children with AGE symptoms in the northern region of Brazil.

IntroductionPeople with Amyotrophic Lateral Sclerosis (ALS) can present initially muscle weakness, which is a debilitating symptom that may be improved by engaging in muscle strengthening activities. Currently, the effects of motor interventions for muscle strengthening in people with ALS are unclear. This review intends to analyze the effects of motor interventions for muscle strengthening in individuals with ALS.Methods and analysisRandomized, non-randomized, and quasi-experimental clinical trials assessing individuals with ALS of both sexes, aged 18 years or older, who have received motor interventions for muscle strengthening considering all practices that can lead to increased strength, endurance, power and muscular hypertrophy will be included. No restriction on language, location, or publication date will be applied. MEDLINE, EMBASE, Cochrane Library (CENTRAL), SPORTDiscus, and Physiotherapy Evidence Database (PEDro) databases will be searched. The US National Institutes of Health Ongoing, ClinicalTrials.gov, and the reference lists of included studies will also be searched. Two reviewers will independently screen titles and abstracts and extract data from included studies. The methodological quality of the included studies will be assessed by the PEDro scale and the certainty of the evidence by the GRADE approach. Disagreements will be resolved by a third researcher. Findings will be presented in text and table formats. A meta-analysis will compare the effects of motor interventions for muscle strengthening versus placebo or other interventions.

The present study compares the ability of distinct immunological assays (chemiluminescence immunoassay-CLIA, western blot-WB and flow cytometry-FC-Simplex and Duplex) to detect anti-HTLV (human T-lymphotropic virus) antibodies in candidates for blood donations at the Amazonas State Blood Center (Brazil) between January 2018 and December 2022. Overall, 257,942 samples from candidates for blood donations were screened using CLIA, which led to 0.15% seropositivity for HTLV (409 samples). A total of 151 candidates for blood donations were enrolled for retesting with CLIA followed by additional testing using WB and FC-Simplex and Duplex analysis. Our results demonstrated that 62% (93/151), 20% (30/151) and 17% (26/151) of the samples presented positive results with retesting using CLIA, WB and FC-Simplex analysis, respectively. Additional analysis of the CLIA, WB and FC-Simplex results revealed an overall agreement of 56% for CLIA and WB (22 co-negative; 30 co-positive samples), 48% for CLIA and FC-Simplex (21 co-negative; 24 co-positive samples) and 80% for WB and FC-Simplex (51 co-negative; 23 co-positive samples). Considering the WB as the reference standard for the diagnosis of infection with HTLV-1/2, we observed that the CLIA results of ≤3.0 RLU and >10.0 RLU in the retest can be used define a negative or positive result, respectively, and could be used as new specific cut-off values. The overall agreement between WB and FC-Duplex for accomplishing the differential diagnosis was evaluated and demonstrated 100% correspondence for the diagnosis of HTLV-1 (15/15) and HTLV-2 (7/7). Our findings demonstrate that gaps in the diagnosis of infection with HTLV-1/2 could be overcome by the simultaneous use of distinct immunological assays during retesting of candidates for blood donations.

The study investigates the efficacy of a bioinspired Particle Swarm Optimization (PSO) approach for PID controller tuning in Radiofrequency Ablation (RFA) for liver tumors. Ex-vivo experiments were conducted, yielding a 9th order continuous-time transfer function. PSO was applied to optimize PID parameters, achieving outstanding simulation results: 0.605% overshoot, 0.314 seconds rise time, and 2.87 seconds settling time for a unit step input. Statistical analysis of 19 simulations revealed PID gains: Kp (mean: 5.86, variance: 4.22, standard deviation: 2.05), Ki (mean: 9.89, variance: 0.048, standard deviation: 0.22), Kd (mean: 0.57, variance: 0.021, standard deviation: 0.14) and ANOVA analysis for the 19 experiments yielded a p-value ≪ 0.05. The bioinspired PSO-based PID controller demonstrated remarkable potential in mitigating roll-off effects during RFA, reducing the risk of incomplete tumor ablation. These findings have significant implications for improving clinical outcomes in hepatocellular carcinoma management, including reduced recurrence rates and minimized collateral damage. The PSO-based PID tuning strategy offers a practical solution to enhance RFA effectiveness, contributing to the advancement of radiofrequency ablation techniques.

Zika (ZIKV) and chikungunya (CHIKV) are arboviruses that cause infections in humans and can cause clinical complications, representing a worldwide public health problem. Aedes aegypti is the primary vector of these pathogens and Culex quinquefasciatus may be a potential ZIKV vector. This study aimed to evaluate fecundity, fertility, survival, longevity, and blood feeding activity in Ae. aegypti after exposure to ZIKV and CHIKV and, in Cx. quinquefasciatus exposed to ZIKV. Three colonies were evaluated: AeCamp (Ae. aegypti-field), RecL (Ae. aegypti-laboratory) and CqSLab (Cx. quinquefasciatus-laboratory). Seven to 10 days-old females from these colonies were exposed to artificial blood feeding with CHIKV or ZIKV. CHIKV caused reduction in fecundity and fertility in AeCamp and reduction in survival and fertility in RecL. ZIKV impacted survival in RecL, fertility in AeCamp and, fecundity and fertility in CqSLab. Both viruses had no effect on blood feeding activity. These results show that CHIKV produces a higher biological cost in Ae. aegypti, compared to ZIKV, and ZIKV differently alters the biological performance in colonies of Ae. aegypti and Cx. quinquefasciatus. These results provide a better understanding over the processes of virus-vector interaction and can shed light on the complexity of arbovirus transmission.

[This corrects the article DOI: 10.1371/journal.pone.0261734.].

BackgroundThere are few data reporting the needs and priorities of older adults in Brazil. This hampers the development and/or implementation of policies aimed at older adults to help them age well. The aim of this study was to understand areas of importance, priorities, enablers and obstacles to healthy ageing as identified by older adults and key stakeholders in both urban and rural environments.MethodsTwo locations were selected, one urban and one rural in the municipality of Santo André, in the metropolitan region of São Paulo (SP). Workshops for older adults (>60 y) and stakeholders were conducted separately in each location. The workshops incorporated an iterative process of discussion, prioritisation and ranking of responses, in roundtable groups and in plenary. Areas of commonality and differences between older adult and stakeholder responses were identified by comparing responses between groups as well as mapping obstacles and enablers to healthy ageing identified by older adults, to the priorities identified by stakeholder groups. The socio-ecologic model was used to categorise responses.ResultsThere were few shared responses between stakeholders and older adults and little overlap between the top ranked responses of urban and rural groups. With respect to areas of importance, both stakeholder groups ranked policies for older people within their top five reponses. Both older adult groups ranked keeping physically and mentally active, and nurturing spirituality. There was a marked lack of congruence between older adults' obstacles and enablers to healthy ageing and stakeholder priorities, in both urban and rural settings. Most responses were located within the Society domain of the socio-ecologic model, although older adults also responded within the Individual/ Relationships domains, particularly in ranking areas of most importance for healthy ageing.ConclusionsOur results highlight substantial differences between older adults and stakeholders with respect to areas of importance, priorities, enablers and obstacles to healthy ageing, and point to the need for more engagement between those in advocacy and policymaking roles and the older people whose needs they serve.

In this study, an extensive analysis of microsatellite markers (Single Tandem Repeats-STRs) in Penaeus vannamei was conducted at an advanced level. The markers were thoroughly examined, characterized, and specific markers located within coding regions were identified. Out of a total of 306 STRs, 117 were classified as perfect markers based on their single repeat motif. Among these perfect markers, 62 were found to be associated with predicted coding genes (mRNA), which were involved in various functions such as binding, catalytic activity, ATP-dependent activity, transcription, structural and molecular regulation. To validate the accuracy of the findings, a sample of nine markers was subjected to in vitro testing, which confirmed the presence of polymorphisms within the population. These results suggest the existence of different protein isoforms within the population, indicating the potential of these markers for application in both population and phenotype-genotype association studies. This innovative approach opens up new possibilities for investigating the impact of genomic plasticity in populations of P. vannamei.

Burnout is most commonly defined as a syndrome characterized by emotional exhaustion, cynicism, and ineffectiveness, which occurs in response to chronic stressors at work. It can adversely affect health workers' physical and mental health, and the quality of care provided. The COVID-19 pandemic increased stressors and could impact burnout prevalence in this group. There is a lack of information regarding the prevalence of burnout among hospital health workers in Brazil. A newer definition of burnout has been proposed that considers three different clinical profiles: the frenetic, underchallenged and worn-out subtypes. This differentiation could lead to interventions tailored for each subtype. The present study aimed to estimate the prevalence of burnout, its subtypes, and associated factors in workers of a public hospital network in Brazil, during the pandemic. A total of 143 randomly selected participants answered an online form that included sociodemographic and occupational items, and the Burnout Clinical Subtypes Questionnaire, a summarized version. This questionnaire evaluates three burnout dimensions (overload, lack of development, neglect) that can be used to discriminate the three burnout subtypes (frenetic, underchallenged, worn-out, respectively); higher scores indicate higher burnout levels. The prevalence of burnout was high (53.85%), similar to other studies during the pandemic. The most common subtypes were 'frenetic' (34.97%), characterized by increased efforts to meet work demands, to the point of neglecting personal needs, and 'lack of development' (23.78%), characterized by a sense that work is uninteresting and does not contribute to personal development, and a perfunctory behavior towards tasks. Age was associated with burnout: workers with less than 51 years presented higher levels of burnout. These findings indicate the need for effective interventions to prevent and/or treat burnout. The assessment of burnout subtypes can allow managers to better understand the processes affecting employees, and inform actions to improve workforce health.

People with mental illness tend to present low levels of physical activity and high levels of sedentary behavior. The study aims to compare these levels in mental illness patients, exploring the role of socioeconomic development and treatment setting. This cross-sectional study used accelerometers and the Simple Physical Activity Questionnaire (SIMPAQ) to assess physical activity and sedentary behavior in mental illness individuals living in 23 countries. Two-way ANOVAs were used to evaluate the interaction between socioeconomic development and the treatment settings on physical activity and sedentary behavior. A total of 884 (men = 55.3%) participants, mean age of 39.3 (SD = 12.8), were evaluated. A significant interaction between socioeconomic development and treatment settings was found in sedentary behavior (F = 5.525; p = 0.019; η2p = 0.009; small effect size). Main effects were observed on socioeconomic development (F = 43.004; p < 0.001; η2p = 0.066; medium effect size) and treatment setting (F = 23.001; p < 0.001; η2p = 0.036; small effect size) for sedentary behavior and physical activity: socioeconomic development (F = 20.888; p < 0.001; η2p = 0.033; small effect size) and treatment setting (F = 30.358; p < 0.001; η2p = 0.047; small effect size), showing that HIC patients were more active, while MIC patients were more sedentary. Moreover, despite of inpatients had presented higher levels of physical activity than outpatients, they also spent more time sitting. Socioeconomic development plays an important role in sedentary behavior in patients with mental disorders, warning the need to develop new strategies to reduce these levels in this population.

Genomic regions related to tropical adaptability are of paramount importance for animal breeding nowadays, especially in the context of global climate change. Moreover, understanding the genomic architecture of these regions may be very relevant for aiding breeding programs in choosing the best selection scheme for tropical adaptation and/or implementing a crossbreeding scheme. The composite MONTANA TROPICAL® population was developed by crossing cattle of four different biological types to improve production in harsh environments. Pedigree and genotype data (51962 SNPs) from 3215 MONTANA TROPICAL® cattle were used to i) characterize the population structure; ii) identify signatures of selection with complementary approaches, i.e. Integrated Haplotype Score (iHS) and Runs of Homozygosity (ROH); and iii) understand genes and traits related to each selected region. The population structure based on principal components had a weak relationship with the genetic contribution of the different biological types. Clustering analyses (ADMIXTURE) showed different clusters according to the number of generations within the composite population. Considering results of both selection signatures approaches, we identified only one consensus region on chromosome 20 (35399405-40329703 bp). Genes in this region are related to immune function, regulation of epithelial cell differentiation, and cell response to ionizing radiation. This region harbors the slick locus which is related to slick hair and epidermis anatomy, both of which are related to heat stress adaptation. Also, QTLs in this region were related to feed intake, milk yield, mastitis, reproduction, and slick hair coat. The signatures of selection detected here arose in a few generations after crossbreeding between contrasting breeds. Therefore, it shows how important this genomic region may be for these animals to thrive in tropical conditions. Further investigations on sequencing this region can identify candidate genes for animal breeding and/or gene editing to tackle the challenges of climate change.

To identify markers of oocyte competence, we compared the biochemical characteristics of fluid and cells from follicles containing oocytes with different capacities to form an embryo. Follicles (5-6 mm) were dissected, and follicular fluid (FF), granulosa cells (GC), cumulus cells (CC) from immature and mature cumulus-oocyte-complexes (COC) were individually collected. The oocytes were matured, fertilized, and cultured individually until day 8 (D8) of development. On D8, the samples were grouped according to embryo production into those that gave rise to blastocysts (EMB) and those that did not reach the blastocyst stage (NEMB). In CCs from immature and mature COCs and GCs, expression of CASP3, SERPINE2, VCAN, LUM, FSHR, EGFR, PGR, and GHR genes was quantified. Cell-free DNA (cfDNA), progesterone, and estradiol concentrations in the FF were determined. Data were analyzed by Mann-Whitney U test (GraphPad Prism 9). GHR was highly expressed in immature CCs from the EMB group, whereas CASP3 was highly expressed in mature CCs from the NEMB group (P

BackgroundThe emergence of SARS-CoV-2 variants led to subsequent waves of COVID-19 worldwide. In many countries, the second wave of COVID-19 was marked by record deaths, raising the concern that variants associated with that wave might be more deadly. Our aim was to compare outcomes of critically-ill patients of the first two waves of COVID-19.MethodsThis retrospective cohort included critically-ill patients admitted between March-June 2020 and April-July 2021 in the largest academic hospital in Brazil, which has free-access universal health care system. We compared admission characteristics and hospital outcomes. The main outcome was 60-day survival and we built multivariable Cox model based on a conceptual causal diagram in the format of directed acyclic graph (DAG).ResultsWe included 1583 patients (1315 in the first and 268 in the second wave). Patients in the second wave were younger, had lower severity scores, used prone and non-invasive ventilatory support more often, and fewer patients required mechanical ventilation (70% vs 80%, pConclusionsIn this cohort study, patients with COVID-19 admitted to the ICU in the second wave were younger and had better prognostic scores. Adjusted survival was similar in the two waves, contrasting with record number of hospitalizations, daily deaths and health system collapse seen across the country in the second wave. Our findings suggest that the combination of the burden of severe cases and factors such as resource allocation and health disparities may have had an impact in the excess mortality found in many countries in the second wave.

COVID-19 disease has been a challenge for health systems worldwide due to its high transmissibility, morbidity, and mortality. Severe COVID-19 is associated with an imbalance in the immune response, resulting in a cytokine storm and a hyperinflammation state. While hematological parameters correlate with prognosis in COVID patients, their predictive value has not been evaluated specifically among those severely ill. Therefore, we aim to evaluate the role of hematological and immune response biomarkers as a prognostic factor in critically ill patients with COVID-19 admitted to the intensive care unit. From May 2020 to July 2021, a retrospective cohort study was conducted in a reference hospital in Manaus, which belongs to the Brazilian public health system. This study was carried out as single-center research. Clinical and laboratory parameters were analyzed to evaluate the association with mortality. We also evaluated the role of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-lymphocyte ratio (CLR). We gathered information from medical records, as well as from prescriptions and forms authorizing the use of antimicrobial medications. During the study period, 177 patients were included, with a mean age of 62.58 ± 14.39 years. The overall mortality rate was 61.6%. Age, mechanical ventilation (MV) requirement, leukocytosis, neutrophilia, high c-reactive protein level, NLR, and CLR showed a statistically significant association with mortality in the univariate analysis. In the multivariate logistic regression analysis, only MV (OR 35.687, 95% CI: 11.084-114.898, p< 0.001) and NLR (OR 1.026, 95% CI: 1.003-1.050, p = 0.028) remained statistically associated with the outcome of death (AUC = 0.8096). While the need for mechanical ventilation is a parameter observed throughout the hospital stay, the initial NLR can be a primary risk stratification tool to establish priorities and timely clinical intervention in patients with severe COVID-19 admitted to the ICU.

ObjectiveTo end the AIDS epidemic by 2030, despite the increasing poverty and inequalities, policies should be designed to deal with population heterogeneity and environmental changes. Bottom-up designs, such as the Agent-Based Model (ABM), can model these features, dealing with such complexity. HIV/AIDS has a complex dynamic of structural factors, risk behaviors, biomedical characteristics and interventions. All embedded in unequal, stigmatized and heterogeneous social structure. To understand how ABMs can model this complexity, we performed a scoping review of HIV applications, highlighting their potentialities.MethodsWe searched on PubMed, Web of Science, and Scopus repositories following the PRISMA extension for scoping reviews. Our inclusion criteria were HIV/AIDS studies with an ABM application. We identified the main articles using a local co-citation analysis and categorized the overall literature aims, (sub)populations, regions, and if the papers declared the use of ODD protocol and limitations.ResultsWe found 154 articles. We identified eleven main papers, and discussed them using the overall category results. Most studies model Transmission Dynamics (37/154), about Men who have sex with Men (MSM) (41/154), or individuals living in the US or South Africa (84/154). Recent studies applied ABM to model PrEP interventions (17/154) and Racial Disparities (12/154). Only six papers declared the use of ODD Protocol (6/154), and 34/154 didn't mention the study limitations.ConclusionsWhile ABM is among the most sophisticated techniques available to model HIV/AIDS complexity. Their applications are still restricted to some realities. However, researchers are challenged to think about social structure due model characteristics, the inclusion of these features is still restricted to case-specific. Data and computational power availability can enhance this feature providing insightful results.

INTRODUCTION: Aging and chronic HIV infection are clinical conditions that share the states of inflammation and hypercoagulability. The life expectancy of the world population has increased in the last decades, bringing as complications the occurrence of diseases that undergoing metabolic, bone, cardiological, vascular and neurological alterations. HIV-infected patients experience these changes early and are living longer due to the success of antiretroviral therapy. The objectives of this study was to evaluate some changes in the plasma hemostatic profile of 115 HIV-reactive elderly individuals over 60 years old in the chronic phase of infection, and compare with 88 healthy uninfected elderly individuals. Plasma determinations of D-dimers, Fibrinogen, von Willebrand Factor, Antithrombin, Prothrombin Time, Activated Partial Thromboplastin Time, and platelet count were performed. In the HIV-reactive group, these variables were analyzed according to viral load, protease inhibitor use and CD4+ T lymphocyte values. After adjusted values for age and sex, the results showed higher levels of Antithrombin (103%; 88%, p = 0.0001) and Prothrombin Time activities (92.4%; 88.2%, p = 0.019) in the HIV group compared to the control group. We observed higher values of Fibrinogen in protease inhibitor users in both the male (p = 0.043) and female (p = 0.004) groups, and in the female HIV group with detected viral load (p = 0.015). The male HIV group with a CD4+ count> 400 cells / mm3 presented higher von Willebrand Factor values (p = 0.036). D-Dimers had higher values in the older age groups (p = 0.003; p = 0.042, respectively). CONCLUSION: Our results suggest that the elderly with chronic HIV infection with few comorbidities had a better hemostatic profile than negative control group, reflecting the success of treatment. Protease inhibitor use and age punctually altered this profile.

[This corrects the article DOI: 10.1371/journal.pone.0227763.].

Abortion, particularly when illegal, highlights inequities in different populations. Although abortion-related mortality is lower compared to other obstetric causes, abortion complications tend to be more lethal. Delays in seeking and obtaining care are determinants of negative outcomes. This study, nested within the GravSus-NE, analyzed healthcare delays and their association with abortion-related complications in three cities of northeastern Brazil (Salvador, Recife and São Luís). Nineteen public maternity hospitals were involved. All eligible women ≥18 years old hospitalized between August and December 2010 were evaluated. Descriptive, stratified and multivariate analyses were performed. Youden's index was used to determine delay. One model was created with all the women and another with those admitted in good clinical conditions, thus determining complications that occurred during hospitalization and their associated factors. Of 2,371 women, most (62.3%) were ≤30 years old (median 27 years) and 89.6% reported being black or brown-skinned. Most (90.5%) were admitted in good condition, 4.0% in fair condition and 5.5% in poor/very poor condition. Median time between admission and uterine evacuation was 7.9 hours. After a cut-off time of 10 hours, the development of complications increased considerably. Black women and those admitted during nightshifts were more likely to experience a wait time ≥10 hours. Delays were associated with severe complications (OR 1.97; 95%CI: 1.55-2.51), including in the women admitted in good condition (OR 2,56; 95%CI: 1.85-3.55), and even following adjustment for gestational age and reported abortion type (spontaneous/induced). These findings corroborate the literature, highlighting the social vulnerability of women hospitalized within Brazil's public healthcare system in a situation of abortion. The study strongpoints include having objectively measured the time between admission and uterine evacuation and having established a cut-off time defining delay based on conceptual and epidemiological criteria. Further studies should evaluate other settings and new measurement tools for effectively preventing life-threatening complications.

The sugarcane borer moth, Diatraea saccharalis, is one of the most important pests of sugarcane and maize crops in the Western Hemisphere. The pest is widespread throughout South and Central America, the Caribbean region and the southern United States. One of the most intriguing features of D. saccharalis population dynamics is the high rate of range expansion reported in recent years. To shed light on the history of colonization of D. saccharalis, we investigated the genetic structure and diversity in American populations using single nucleotide polymorphism (SNPs) markers throughout the genome and sequences of the mitochondrial gene cytochrome oxidase (COI). Our primary goal was to propose possible dispersal routes from the putative center of origin that can explain the spatial pattern of genetic diversity. Our findings showed a clear correspondence between genetic structure and the geographical distributions of this pest insect on the American continents. The clustering analyses indicated three distinct groups: one composed of Brazilian populations, a second group composed of populations from El Salvador, Mexico, Texas and Louisiana and a third group composed of the Florida population. The predicted time of divergence predates the agriculture expansion period, but the pattern of distribution of haplotype diversity suggests that human-mediated movement was most likely the factor responsible for the widespread distribution in the Americas. The study of the early history of D. saccharalis promotes a better understanding of range expansion, the history of invasion, and demographic patterns of pest populations in the Americas.

The relationship between N-antigen concentration and viral load within and across different specimens guides the clinical performance of rapid diagnostic tests (RDT) in different uses. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)-PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one RDT on saliva. Antigen concentration correlated well with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs with nasal samples. Given lower antigen concentrations in saliva, rapid testing using saliva is expected to require improved RDT analytical sensitivity to achieve clinical sensitivity similar to rapid testing of nasal samples.

This study assessed the seroprevalence of SARS-CoV-2 in 496 asymptomatic individuals from Mato Grosso do Sul, located in Dourados, the largest periurban indigenous area in Brazil, from January 25 to February 4, 2021. The volunteers participated before receiving their first dose of the CoronaVac inactivated vaccine. For screening, blood samples were collected and analyzed using SARS-CoV-2 rapid tests and the enzyme-linked immunosorbent assay (ELISA). We observed varying trends in total anti-SARS-CoV-2 antibodies across different variables. Seropositivity among the participants tested was 63.70% (316/496) using the rapid test and 52.82% (262/496) were positive using the ELISA method. The majority of participants identified with the Guarani-Kaiowá ethnic group, with 66.15% (217/328), and other ethnic groups with 58.84% (193/328). The median age of the subjects was 30.5 years, with 79.57% (261/328) being femaleThis research showed the elevated seroprevalence of SARS-CoV-2 antibodies in asymptomatic Brazilians. The findings indicate a high seropositivity rate among the asymptomatic indigenous population of Midwest Brazil. This underscores the overlooked status of these communities and underscores the need for targeted national initiatives that emphasize the protection of vulnerable ethnic groups in the fight against COVID-19.

A series of 38 thiosemicarbazone derivatives based on camphene and limonene were evaluated for their antiproliferative activity. Among them, 19 were synthesized and characterized using proton and carbon-13 nuclear magnetic resonance (1H and 13C NMR). For initial compound selection, human melanoma cells (SK-MEL-37) were exposed to a single concentration of a compound (100 μM) for 24, 48, and 72 hours, and cell detachment was visually observed. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Nineteen compounds (4, 6, 8, 11, 13, 14, 15, 16, 17, 18, 20, 22, 25, 26, 31, 3', 4', 6', and 9') yielded cell viability below 20%. Subsequently, IC50 values for these compounds were determined, ranging from 11.56 to 55.38 μM, after 72 hours of treatment. Compound 17 (o-hydroxybenzaldehyde (-)-camphene-based thiosemicarbazone) demonstrated the lowest IC50 value, followed by compound 4 (benzaldehyde (-) camphene-based thiosemicarbazone) at 12.84 μM. Regarding compound 4, we observed the induction of a characteristic ladder pattern of DNA fragmentation through gel electrophoresis. Furthermore, fluorescence, flow cytometry and scanning microscopy assays revealed morphological changes consistent with apoptosis induction. Additionally, the measurement of caspase 6 and 8 activity in cellular extracts after treatment for 2, 4, 6, and 24 hours suggested the potential involvement of the extrinsic apoptosis pathway in the mechanism of action of compound 4. Further investigations, including molecular docking studies, are required to fully explore the potential of compound 4 and the other selected compounds, highlighting their promising role in future melanoma therapy research.

Since angiotensin-converting enzyme 2, ACE2, was identified as the receptor for SARS-CoV-2 and considering the intense physiological interplay between the two angitensinases isoforms, ACE and ACE2, as counter-regulatory axis of the renin-angiotensin system, we proposed the evaluation of polymorphisms in these two key regulators in relation to COVID-19 severity. A genetic association study involving 621 COVID-19 hospitalized patients from Brazil was performed. All subjects had a confirmed diagnosis of COVID-19 via RT-PCR. Patients were categorized into two groups: the "mild" group (N = 296), composed of individuals hospitalized in ward beds who progressed to cure, and the "severe" group (N = 325), composed of individuals who required hospitalization in an intensive care unit (ICU), or who died. Blood samples were genotyped for ACE I/D polymorphism and ACE2 G8790A polymorphism by real-time PCR via TaqMan assay. The analysis of combined polymorphisms revealed a protective role for genotypic profile II/A_ (ORA = 0,26; p = 0,037) against the worsening of COVID-19 in women. The results indicate a protection profile to COVID-19 progression, in which the II/A_ carriers have almost four times less chance of a severe outcome. It is proposed that a decreased activity of ACE (deleterious effects) in conjunction with an increased ACE2 activity (protective effects), should be the underlying mechanism. The findings are unprecedented once other studies have not explored the genotypic combination analysis for ACE and ACE2 polymorphisms and bring perspectives and expectations for dealing with the COVID-19 pandemic based on definitions of genetically-based risk groups within the context of personalized medicine.

Campomanesia adamantium O. Berg. is a fruit tree species native to the Brazilian Cerrado biome whose fruits are consumed raw by the population. The present study determined the chemical composition of the C. adamantium fruit pulp (FPCA) and investigated its in vitro antioxidant potential and its biological effects in a Caenorhabditis elegans model. The chemical profile obtained by LC-DAD-MS identified 27 compounds, including phenolic compounds, flavonoids, and organic carboxylic acids, in addition to antioxidant lipophilic pigments and ascorbic acid. The in vitro antioxidant activity was analysed by the radical scavenging method. In vivo, FPCA showed no acute reproductive or locomotor toxicity. It promoted protection against thermal and oxidative stress and increased the lifespan of C. elegans. It also upregulated the antioxidant enzymes superoxide dismutase and glutathione S-transferase and activated the transcription factor DAF-16. These results provide unprecedented in vitro and in vivo evidence for the potential functional use of FPCA in the prevention of oxidative stress and promotion of longevity.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems.

Monitoring of clinical trials is critical to the protection of human subjects and the conduct of high-quality research. Even though the adoption of risk-based monitoring (RBM) has been suggested for many years, the RBM approach has been less widespread than expected. Centralized monitoring is one of the RMB pillars, together with remote-site monitoring visits, reduced Source Data Verification (SDV) and Source Document Reviews (SDR). The COVID-19 pandemic promoted disruptions in the conduction of clinical trials, as on-site monitoring visits were adjourned. In this context, the transition to RBM by all actors involved in clinical trials has been encouraged. In order to ensure the highest quality of data within a COVID-19 clinical trial, a centralized monitoring tool alongside Case Report Forms (CRFs) and synchronous automated routines were developed at the clinical research platform, Fiocruz, Brazilian Ministry of Health. This paper describes how these tools were developed, their features, advantages, and limitations. The software codes, and the CRFs are available at the Fiocruz Data Repository for Research-Arca Dados, reaffirming Fiocruz's commitment to Open Science practices.

BackgroundNewborns with one-or-more adverse birth outcomes (ABOs) are at greater risk of mortality or long-term morbidity with health impacts into adulthood. Hence, identifying ABO-associated factors is crucial for devising relevant interventions. For this study, ABOs were defined as prematurity (PTB) for gestational age 4 kg, asphyxia for a 5-minute Apgar score MethodsA hospital-based unmatched case‒control study was conducted among newborns from randomly selected mothers. Newborns with one-or-more ABO were the cases (ABO group), while healthy newborns were the controls (no-ABO group). Data were collected by a face-to-face interview and abstracted from antenatal care (ANC) pregnancy cards and medical records. Multivariable logistic regression analysis was performed to identify ABO-associated factors considering a level of significance of α = 0.05.ResultsA total of 519 newborns (176 with ABO and 343 no-ABO) were enrolled. The mean gestational age and birthweight of cases and controls were 36 (SD = 3.7) weeks with 2659 (SD = 881.44) g and 39.6 (SD = 1.0) weeks with 3256 (SD = 345.83) g, respectively. In the multivariable analysis, twin pregnancy [aOR 4.92, 95% CI 2.25-10.74], prolonged rupture of membranes [aOR 3.43, 95% CI 1.69-6.95], and meconium- fluid [aOR 1.59, 95% CI 0.97-2.62] were significantly associated with ABOs. Eight or more ANC contacts were found to be protective [aOR 0.33, 95% CI 0.18-0.60, pConclusionModifiable factors were associated with ABOs in this study and should be considered in cost-effective interventions. The provision of high-quality ANC should be a priority. Twin pregnancies and intrapartum factors such as prolonged rupture of membranes and meconium-stained amniotic fluid are red flags for ABOs that should receive prompt intervention and follow-up.

IntroductionDriving under the influence of alcohol is one of the main factors for morbidity and mortality from traffic accidents. In 2010 and 2013, the Program Life in Traffic was implemented in Brazil, including the international initiative "Road Safety in Ten Countries", which established actions to reduce one of the main risk factors for road traffic injuries, the driving under the influence of alcohol. In 2012, a new zero-tolerance drinking and driving law (new dry law) was implemented, establishing a zero-tolerance limit for the drivers' blood alcohol concentration, and increasing punitive measures. This study aimed at analyzing the impact of these measures on the prevalence of driving under the influence of alcohol abuse in Brazilian capitals.MethodsAn interrupted time series study was conducted using the models of autoregressive integrated moving average or seasonal autoregressive integrated moving average. The main outcome was the prevalence of driving after alcohol abuse in the adult population (≥ 18 years). The model's predictors were the interventions "Program Life in Traffic" and "New Dry Law". The former was implemented in the first quarter of 2011, initially in five capitals: Belo Horizonte, Campo Grande, Palmas, Teresina, and Curitiba, being expanded to the other capitals in the first quarter of 2013. The latter was implemented in the country on the first quarter of 2013. Data source for the study was the records of the surveillance system for risk and protection factors of chronic diseases through telephone survey (Vigitel) from 2007 to 2016.ResultsThe time intervals considered in the study were the quarters. Thirty-eight units were considered in the analysis, corresponding to time series points. It was found that after the implementation of the Program Life in Traffic, in the first quarter of 2011, there was a reduction in the prevalence in Belo Horizonte and Curitiba. Because the introduction of the New Dry Law and the Program Life in Traffic took place in similar periods in the other cities, there was a significant reduction in the outcome prevalence in the cities of Aracaju, Belo Horizonte, Boa Vista, Fortaleza, João Pessoa, Maceió, Manaus, Palmas, Porto Alegre, Recife, Teresina, Rio Branco, and Vitória following the law application.ConclusionThe present study identified an immediate impact of the Program Life in Traffic in two capitals (Belo Horizonte and Curitiba) and a joint impact of the New Dry Law in 13 capitals. The results of this study have implications for strengthening interventions aimed at reducing the burden of morbidity and mortality from traffic accidents in Brazil.

[This corrects the article DOI: 10.1371/journal.pone.0287224.].