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Aging disrupts brain function, leading to cognitive decline and neurodegenerative diseases. Senescent astrocytes, a hallmark of aging, contribute to this process through unknown mechanisms. This study investigates how senescence impacts astrocytic mitochondrial dynamics, which are critical for brain health. Our research, conducted using aged mouse brains, represents the first evidence of morphologically damaged mitochondria in astrocytes, along with functional alterations in mitochondrial respiration. In vitro experiments revealed that senescent astrocytes exhibit an increase in mitochondrial fragmentation and impaired mitophagy. Concurrently, there was an upregulation of mitochondrial biogenesis, indicating a compensatory response to mitochondrial damage. Importantly, these senescent astrocytes were more susceptible to mitochondrial stress, a vulnerability reversed by rapamycin treatment. These findings suggest a potential link between senescence, impaired mitochondrial quality control, and increased susceptibility to mitochondrial stress in astrocytes. Overall, our study highlights the importance of addressing mitochondrial dysfunction and senescence-related changes in astrocytes as a promising approach for developing therapies to counter age-related neurodegeneration and improve brain health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dengue virus (DENV) infection is known to affect host cell metabolism, but the molecular players involved are still poorly known. Using a proteomics approach, we identified six DENV proteins associated with mitochondria isolated from infected hepatocytes, and most of the peptides identified were from NS3. We also found an at least twofold decrease of several electron transport system (ETS) host proteins. Thus, we investigated whether NS3 could modulate the ETS function by incubating recombinant DENV NS3 constructs in mitochondria isolated from mouse liver. We found that NS3pro (NS3 protease domain), but not the correspondent catalytically inactive mutant (NS3proS135A), impairs complex I (CI)-dependent NADH:ubiquinone oxidoreductase activity, but not the activities of complexes II, III, IV, or V. Accordingly, using high-resolution respirometry, we found that both NS3pro and full-length NS3 decrease the respiratory rates associated with malate/pyruvate oxidation in mitochondria. The NS3-induced impairment in mitochondrial respiration occurs without altering either leak respiration or mitochondria's capacity to maintain membrane potential, suggesting that NS3 does not deeply affect mitochondrial integrity. Remarkably, CI activity is also inhibited in DENV-infected cells, supporting that the NS3 effects observed in isolated mitochondria may be relevant in the context of the infection. Finally, in silico analyses revealed the presence of potential NS3 cleavage sites in 17 subunits of mouse CI and 16 subunits of human CI, most of them located on the CI surface, suggesting that CI is prone to undergo proteolysis by NS3. Our findings suggest that DENV NS3 can modulate mitochondrial bioenergetics by directly affecting CI function., Importance: Dengue virus (DENV) infection is a major public health problem worldwide, affecting about 400 million people yearly. Despite its importance, many molecular aspects of dengue pathogenesis remain poorly known. For several years, our group has been investigating DENV-induced metabolic alterations in the host cells, focusing on the bioenergetics of mitochondrial respiration. The results of the present study reveal that the DENV non-structural protein 3 (NS3) is found in the mitochondria of infected cells, impairing mitochondrial respiration by directly targeting one of the components of the electron transport system, the respiratory complex I (CI). NS3 acts as the viral protease during the DENV replication cycle, and its proteolytic activity seems necessary for inhibiting CI function. Our findings uncover new nuances of DENV-induced metabolic alterations, highlighting NS3 as an important player in the modulation of mitochondria function during infection., Competing Interests: The authors declare no conflict of interest.

The extent to which evolution is repeatable remains debated. Here, we study changes over time in the frequency of cryptic color-pattern morphs in 10 replicate long-term field studies of a stick insect, each spanning at least a decade (across 30 years of total data). We find predictable "up-and-down" fluctuations in stripe frequency in all populations, representing repeatable evolutionary dynamics based on standing genetic variation. A field experiment demonstrates that these fluctuations involve negative frequency-dependent natural selection (NFDS). These fluctuations rely on demographic and selective variability that pushes populations away from equilibrium, such that they can reliably move back toward it via NFDS. Last, we show that the origin of new cryptic forms is associated with multiple structural genomic variants such that which mutations arise affects evolution at larger temporal scales. Thus, evolution from existing variation is predictable and repeatable, but mutation adds complexity even for traits evolving deterministically under natural selection.

Herein, we present a novel esterase enzyme, Ade1, isolated from a metagenomic library of Amazonian dark earths soils, demonstrating its broad substrate promiscuity by hydrolyzing ester bonds linked to aliphatic groups. The three-dimensional structure of the enzyme was solved in the presence and absence of substrate (tributyrin), revealing its classification within the α/β-hydrolase superfamily. Despite being a monomeric enzyme, enzymatic assays reveal a cooperative behavior with a sigmoidal profile (initial velocities vs substrate concentrations). Our investigation brings to light the allokairy/hysteresis behavior of Ade1, as evidenced by a transient burst profile during the hydrolysis of substrates such as p -nitrophenyl butyrate and p -nitrophenyl octanoate. Crystal structures of Ade1, coupled with molecular dynamics simulations, unveil the existence of multiple conformational structures within a single molecular state (E̅ 1 ). Notably, substrate binding induces a loop closure that traps the substrate in the catalytic site. Upon product release, the cap domain opens simultaneously with structural changes, transitioning the enzyme to a new molecular state (E̅ 2 ). This study advances our understanding of hysteresis/allokairy mechanisms, a temporal regulation that appears more pervasive than previously acknowledged and extends its presence to metabolic enzymes. These findings also hold potential implications for addressing human diseases associated with metabolic dysregulation.

Introduction: Although pharmacological treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) has demonstrated efficacy, several individuals persist in experiencing social and academic impairment. Additionally, the occurrence of significant side effects may render the use of psychotropic medications untenable. However, Transcranial Direct Current Stimulation (tDCS), a non-invasive brain stimulation technique, shows promising results in treating ADHD., Objectives: To investigate the efficacy and safety of tDCS on the performance of children and adolescents with ADHD in neuropsychological tests involving visual attention, visual and verbal working memory, and inhibitory control., Methodology: This study was a triple-blind, randomized, sham-controlled, crossover clinical trial. The intervention consisted of a daily session of tDCS (2 mA) or sham targeting the left dorsolateral prefrontal cortex (L-DLPFC), for 30 min, on five consecutive days. The primary outcome was change in the Visual Attention Test, Fourth Edition (TAVIS-4) before and after each intervention. Subjects were also evaluated pre and post-tDCS using the Digit Span subtest of the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V), the Developmental Neuropsychological Assessment, Second Edition (NEPSY-II) Inhibiting Response (IR) subtest, and the Corsi Block-Tapping Task., Results: Fifteen individuals were included, and no statistically significant difference was observed when comparing the results of the TAVIS-4, the IR of NEPSY-II, and the intragroup Digit Span subtest of WISC-V undertaken before and after the procedure. Adverse events were mainly self-limiting and transient. The participants did not perceive any benefit from tDCS when measured on the Patient Global Impression of Improvement (PGI-I) Scale., Conclusion: This study did not meet its primary endpoint and found no performance enhancement in any investigated neuropsychological outcomes relating to the intervention group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guimarães, Bandeira, Barretto, Wanke, Alves, Baretto, Carvalho, Dorea-Bandeira, Tolentino, Lins-Silva, Lucena and Lucena.)

Aim: To outline the demographic and clinical features, treatment approaches and clinical outcomes of patients treated with palbociclib as the initial therapy for HR+/HER2- advanced or metastatic breast cancer (aBC/mBC) in private healthcare facilities in Brazil. Materials & methods: This study involved a retrospective review conducted from June 2022 to May 2023. Results: The study included 121 patients, with an average age of 54.4 years, and 82 (67.7%) were menopausal at the time of diagnosis. Of these, 51 patients (42.1%) were treated with palbociclib and fulvestrant, while 67 patients (55.8%) received palbociclib and aromatase inhibitors. Most patients (65.3%) did not need to adjust their doses. The progression-free survival rates were 78% at 6 months and 60% at 12 months. Overall survival rates were 86% at 6 months and 70% at 12 months. Conclusion: Palbociclib combinations show promising effectiveness in managing HR+/HER2- advanced or metastatic breast cancer.

Epigenetic mechanisms, such as DNA methylation, can influence gene regulation and affect phenotypic variation, raising the possibility that they contribute to ecological adaptation. Beginning to address this issue requires high-resolution sequencing studies of natural populations to pinpoint epigenetic regions of potential ecological and evolutionary significance. However, such studies are still relatively uncommon, especially in insects, and are mainly restricted to a few model organisms. Here, we characterize patterns of DNA methylation for natural populations of Timema cristinae adapted to two host plant species (i.e. ecotypes). By integrating results from sequencing of whole transcriptomes, genomes and methylomes, we investigate whether environmental, host and genetic differences of these stick insects are associated with methylation levels of cytosine nucleotides in the CpG context. We report an overall genome-wide methylation level for T. cristinae of ~14%, with methylation being enriched in gene bodies and impoverished in repetitive elements. Genome-wide DNA methylation variation was strongly positively correlated with genetic distance (relatedness), but also exhibited significant host-plant effects. Using methylome-environment association analysis, we pinpointed specific genomic regions that are differentially methylated between ecotypes, with these regions being enriched for genes with functions in membrane processes. The observed association between methylation variation and genetic relatedness, and with the ecologically important variable of host plant, suggests a potential role for epigenetic modification in T. cristinae adaptation. To substantiate such adaptive significance, future studies could test whether methylation can be transmitted across generations and the extent to which it responds to experimental manipulation in field and laboratory studies., (© 2023 John Wiley & Sons Ltd.)

The aim of this study was to characterize the normality of the fetal circulatory system through the time between ventricular systoles of the ductus venosus in the three gestational trimesters in healthy fetuses using nonlinear methods of the complexity of the signal. A prospective cohort study was conducted at the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) from December 2019 to May 2020. Pregnant women between 11 and 14 weeks, with intrauterine pregnancy and healthy fetus were included. Patients with multiple gestation, positive screening for congenital malformation, including heart disease, and under 18 years of age were excluded. Doppler velocimetry ultrasonography of the ductus venosus was performed between the 11th and 14th weeks, 20th and 24th weeks, and 28th and 32nd weeks of gestation, and then the sound signal was extracted and segmented from the videos. To compare the means between the gestational trimesters of the approximate entropy (ApEn) and Lempel-Ziv complexity (CLZ) of the time between ventricular systoles, the Friedman test was used, with a significance level of 5%. No statistically significant difference was found between the 1st, 2nd, and 3rd trimesters regarding the mean ApEn (P=0.281) and CLZ (P=0.595) of the time between ventricular systoles of the ductus venosus. Ductus venosus systolic time was not sensitive to differentiate fetal cardiovascular dynamics between gestational trimesters. This study pioneered the characterization of cardiovascular normality by nonlinear parameters of the fetal ductus venosus in all three trimesters.

A growing body of literature reports the need for an integrated approach to study the effects of the physical environment on the neurodevelopment of children. Assessment of the true neurotoxicity of pollutants cannot be performed separately from the ecological and multidimensional contexts in which they act. In this study, from the perspective of the Bronfenbrenner's bioecological model, a conceptual model was developed that encompasses the social and biological characteristics of children from the gestational period to childhood, considering exposure to toxic metals. First, we present the toxicity of the main metals and some concept notions that we used in our framework, such as social and structural determinants of health, allostatic load, embodiment, and epigenetic concepts. Then, the main aspects of the Bronfenbrenner's bioecological model, which allow integration of the gene-social relationship in addition to the physical environment, where these metals act, are explained. Finally, we present and discuss the conceptual framework showing how, in real life, biological and social factors may together influence the neurodevelopment of children. Although this model is based on a group of contaminants, it opens new horizons on how environmental sciences, such as neurotoxicology and environmental epidemiology, can articulate with the theoretical models from human sciences to provide a broader approach to study the effects on human neurodevelopment.

Drill cuttings comprise a mixture of rocks generated during drilling activities of exploration and production of oil and gas. These residues' properties are variable, depending on several drilling parameters and drilled rock composition. Many scientific studies have been published regarding the characterization of these residues. Articles summarizing these residues' characteristics and toxicity data are poorly explored in the literature. This work reviews the principal methods used to characterize drill cuttings and data about these residues' properties. Some authors have reported the large content of Zn in drill cuttings. These cuttings can be associated with base fluids (as olefins, varying from C 11 to C 18 ), and some time crude oil (high range of TPH, unresolved complex mixtures, and PAH compounds). Acute and chronic toxicity tests have shown negative impacts of different types of fluids, the components of these fluids, and cuttings on other marine organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Genome re-arrangements such as chromosomal inversions are often involved in adaptation. As such, they experience natural selection, which can erode genetic variation. Thus, whether and how inversions can remain polymorphic for extended periods of time remains debated. Here we combine genomics, experiments, and evolutionary modeling to elucidate the processes maintaining an inversion polymorphism associated with the use of a challenging host plant (Redwood trees) in Timema stick insects. We show that the inversion is maintained by a combination of processes, finding roles for life-history trade-offs, heterozygote advantage, local adaptation to different hosts, and gene flow. We use models to show how such multi-layered regimes of balancing selection and gene flow provide resilience to help buffer populations against the loss of genetic variation, maintaining the potential for future evolution. We further show that the inversion polymorphism has persisted for millions of years and is not a result of recent introgression. We thus find that rather than being a nuisance, the complex interplay of evolutionary processes provides a mechanism for the long-term maintenance of genetic variation.

Climate change has been causing severe modifications to the environment that are predicted to aggravate in the future, which create critical challenges for insects to cope. Populations can respond to the changes depending on the standing genetic variation. Additionally, they could potentially rely on epigenetic mechanisms as a source of phenotypic variation. These mechanisms can influence gene regulation and can respond to the external environment, being implicated in phenotypic plasticity. Thus, epigenetic variation could be advantageous in changing, unpredictable environments. However, little is known about causal relationships between epigenetic marks and insects' phenotypes, and whether the effects are truly beneficial to the fitness. Empirical studies are now urgent to better understand whether epigenetic variation can help or hinder insect populations facing climate change., Competing Interests: Declaration of Competing Interest No interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Barriers to accessing health care result in advanced cervical cancer. In Sao Paulo, Brazil, the Index of Social Responsibility (ISR) synthesizes the situation of each town concerning wealth, education, and longevity. This study aimed to evaluate in 645 municipalities the relation of the ISR with stage, age, and morphology in cervical cancer diagnosis., Methods: An ecological study that used data from Sao Paulo, Brazil, from 2010 to 2017. The ISR was identified through government platforms and data on cancer through the Hospital Cancer Registry. The subjects were the 9,095 women aged 30 years or older. The ISR summarizes municipalities into five levels: dynamic (ISR5), unequal (ISR4), equitable (ISR3), in transition (ISR2), and vulnerable (ISR1). It was used the chi 2 tests and logistic regression., Results: The proportion of stage 1 increased significantly with ISR level, ranging from 24.9% in ISR1 to 30.0% in ISR5 (p = 0.040). To every increase in ISR level, the chance of a woman being diagnosed in stage I was at least 30% higher. Woman living where ISR2 had a 1.4 times higher chance of being diagnosed in stage 1 than those living in ISR1 (OR 1.40, 95% CI 1.07-1.84). Squamous tumors frequency decreased when ISR level increased (p = 0.117). A higher proportion of women under 50 years were observed when they lived in wealthier cities (ISR4 and ISR5) (42.2% vs. 44.6%, p = 0.016)., Conclusion: The ISR was a good health indicator for understanding and predicting the social determinants in cervical cancer diagnosis. The proportion of stage I increased significantly in more favorable social conditions., (© 2023. The Author(s).)

The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables., (© 2023. The Author(s).)

A major unresolved issue in biology is why phenotypic and genetic variation is sometimes continuous, yet other times packaged into discrete units of diversity, such as morphs, ecotypes, and species. In theory, ecological discontinuities can impose strong disruptive selection that promotes the evolution of discrete forms, but direct tests of this hypothesis are lacking. Here, we show that Timema stick insects exhibit genetically determined color morphs that range from weakly to strongly discontinuous. Color data from nature and a manipulative field experiment demonstrate that greater morph differentiation is associated with shifts from host plants exhibiting more continuous color variation to those exhibiting greater coloration distance between green leaves and brown stems, the latter of which generates strong disruptive selection. Our results show how ecological factors can promote discrete variation, and we further present results on how this can have variable effects on the genetic differentiation that promotes speciation.

Objective: To evaluate the prognosis of endocervical adenocarcinomas after reclassification according to the morphologic type based on the 2020 World Health Organization Classification., Methods: A retrospective longitudinal study with cases admitted at the University of Campinas, Brazil, from 2013 to 2020. The sample included 140 cases morphologically reclassified: 100 cases as adenocarcinoma HPV-associated (HPVA), 17 as HPV-independent (HPVI), and 23 non-HPVA/HPVI. Clinic and pathologic variables were evaluated. Analyses were performed by χ 2 , Fisher exact, and Mann-Whitney U tests, Kaplan-Meier curves, Log-rank test, and Cox regression., Results: Compared with the HPVA group, advanced stage (FIGO Stage II+) was more frequent in the HPVI group (P = 0.009), which also showed older patients (P = 0.032), and a higher proportion of deaths (P = 0.006). The median overall survival (OS) differed between groups: 73.3 months in HPVA and 42.4 months in HPVI (P = 0.005). At the multivariate analysis, the risk of death was 6.7 (95% confidence interval 1.9-23.0) times higher in patients diagnosed in advanced stages., Conclusion: HPVI cases were more frequent in older patients, presenting at more advanced stages and with worse OS. The morphology-based approach of the new WHO classification appears to be prognostically valuable and applicable in lower- and middle-income settings., (© 2022 International Federation of Gynecology and Obstetrics.)

Objective: The aim of this study is to assess the outcomes of 610 excision types I and II in a referral facility as a function of transformation zone (TZ) types., Methods: This is a retrospective cohort study of women with cervical precursor lesions who underwent loop electrocautery excision procedure from 2017 to 2019 at the University of Campinas. The primary outcome was endocervical margin status, negative or positive. Other variables were excision type (I/II), TZ (1/2/3), age, menopausal status, hormonal contraceptives, smoking, and sexual debut. Tests used were chi-square or Fisher exact, Mann-Whitney, and simple and multiple logistic regression., Results: The most frequent was TZ 1 (62.5%). Excision II was the most frequent: 54.1% in TZ 1, 67.2% in TZ 2, and 82.1% in TZ 3. A negative margin was observed in TZ 1, 76.0% when excision I and 86.4% when excision II ( p = .009); TZ 2, 86.4% when excision I and 88.9% when excision II ( p = .672); and TZ 3, 76.5% when excision I and 78.9% when excision II ( p = .672). Multivariate analysis revealed in TZ 1 a 2.12 (1.23-3.65) higher risk of obtaining a negative margin in excision type II. In TZ 2 and 3, none of the variables predicted the chance of a negative margin., Conclusions: The endocervical margin was negative in 3 in every 4 women who underwent loop electrocautery excision procedure, regardless of excision type. Age, menopausal status, smoking, and hormonal contraception did not predict margin status., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Purpose: To describe the results of 610 patients who underwent LEEP and evaluate factors related to a negative margin., Methods: A retrospective study of patients treated by LEEP at a colposcopy referral service in Campinas, Brazil, 2017-2019. Patients were referred to treat high-grade squamous intraepithelial lesion or adenocarcinoma in situ suspected by cytology and colposcopy (screen-and-treat) or by biopsy. Descriptive analysis was performed by frequencies as a function of the status of the margins (negative or positive). Factors associated with margin status were assessed by regression., Results: The endocervical, ectocervical or both margins were negative in 82.4%, 75.7% and 65.9%, respectively. Age, sexual debut, parity, menopause status, smoking and hormonal contraception showed no difference in the proportion of negative margins. Both margins were negative in 66.1% of patients with transformation zone type(TZ) 1, 73.1% of TZ 2, and 54.7% of TZ 3 (p = 0.015). The endocervical negative margin was obtained in 78.0% of patients submitted to excision I (loop 10 mm) and 82.5% to excision II (loop 15 mm) (p = 0.016). Having the sexual debut at 18 years or older or being submitted to an excision type II doubled the chance of negative endocervical margin (1.98;1.04-3.77 and 1.95; 1.18-3.21, respectively)., Conclusion: The proportion of negative endocervical margin was 78% in excision I and 86% in excision II. Sexual onset and excision type II increased the chance of obtaining a negative endocervical margin., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Identifying the genetic basis of adaptation is a central goal of evolutionary biology. However, identifying genes and mutations affecting fitness remains challenging because a large number of traits and variants can influence fitness. Selected phenotypes can also be difficult to know a priori , complicating top-down genetic approaches for trait mapping that involve crosses or genome-wide association studies. In such cases, experimental genetic approaches, where one maps fitness directly and attempts to infer the traits involved afterwards, can be valuable. Here, we re-analyse data from a transplant experiment involving Timema stick insects, where five physically clustered single-nucleotide polymorphisms associated with cryptic body coloration were shown to interact to affect survival. Our analysis covers a larger genomic region than past work and revealed a locus previously not identified as associated with survival. This locus resides near a gene, Punch ( Pu ) , involved in pteridine pigments production, implying that it could be associated with an unmeasured coloration trait. However, by combining previous and newly obtained phenotypic data, we show that this trait is not eye or body coloration. We discuss the implications of our results for the discovery of traits, genes and mutations associated with fitness in other systems, as well as for supergene evolution. This article is part of the theme issue 'Genetic basis of adaptation and speciation: from loci to causative mutations'.

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 ( N  = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution-individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

Neuropsychological alterations have been identified in populations heavily exposed to metals with neurotoxic potential, such as manganese (Mn). This study examined the associations between Mn environmental exposure in school-aged children and executive functions, using structural equation modeling. Children, aged between 7 and 12 years (N = 181), were recruited from four elementary schools located in a region that is under the influence of atmospheric emissions from a ferro-manganese alloy plant in the municipality of Simões Filho, Bahia, Brazil. The following cognitive functions were evaluated: Intelligence, Inhibitory Control, Cognitive Flexibility, Verbal and Design Fluency, Verbal and Visual Working Memory and Attention. We performed structural equation modeling to identify the following executive functions latent variables: working memory, inhibitory control and cognitive flexibility. We further analyzed the relations between executive functions and Mn measured in hair (MnH) and toenails (MnTn) with linear mixed models, after controlling for co-variables. A positive effect at the individual level on working memory, inhibition control and cognitive flexibility was observed with MnTn after controlling for co-variables, but no association was found with MnH levels. However, children attending school most environmentally exposed to Mn emissions, which had the highest rate of Mn dust deposition, had the poorest scores on working memory. These findings suggest both benefits and risk of Mn on children's cognitive development., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present update is a reassessment of the 2018 'Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil' (Zeferino et al.)9, according to the changes observed in new international guidelines and knowledge updates. The most relevant and recent guidelines were assessed. Questions regarding the clinical practice were formulated, and the answers considered the perspective of the public and private sectors of the Brazilian health system. The review addressed risk-based strategies regarding age to start and stop screening, the use of cytology and colposcopy to support management decisions, treatment, follow-up strategies, and screening in specific groups, including vaccinated women. The update aims to improve the prevention of cervical cancer and to reduce overtreatment and the misuse of HPV testing., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Delta-aminolevulinic acid dehydratase (ALAD) enzyme catalyzes the second phase of the heme biosynthesis and is involved in lead toxicokinetics. This research aimed to evaluate its influence on the relationship between blood lead (PbB) levels and intellectual performance in Afro-Brazilian children. PbB, hemoglobin concentration, ALAD activity, and polymorphism were determined in whole blood. Anthropometric, socioeconomic, and family environment stimuli data were collected with appropriate instruments. The non-verbal intelligence of children and their mothers or guardians was assessed using the correspondent Raven's Progressive Matrix versions. The medians (range) of PbB levels and ALAD activity were 1.0 μg/dL (0.1-21.3) and, 71 U/L (31-113), respectively. ALAD G177C was distributed as follows: 97.9% for ALAD1/1 and 2.1% for ALAD1/2 genotypes. The mean of Raven raw score was 19.3 (± 5.6) points and there were no differences according to sex or environmental Pb exposure. No statistically significant association was observed between PbB level and children's IQ. However, ALAD activity presented an inverse significant association with PbB levels, children's percentile IQ, and children's IQ/Age ratio, suggesting a neuroprotective role of ALAD1 genotype in those with low PbB level., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics., (© 2022. The Author(s).)

Background Infertility is associated with increased anxiety, depressive symptoms and mood disorders. Unfortunately, mental health is not often addressed in infertility treatment and infertile patients could be at higher risk of self-administration of not prescribed drugs or/and be exposed to alternative emotional treatments. Therefore, the aim of the present study is to investigate the use of psychotropic medication and to evaluate the frequency of psychiatric diagnosis among infertile women seeking assisted reproductive technology (ART) therapy. Methods All infertile women starting treatment at an ART clinic who agreed to participate in the study were included. Patients were submitted to a structured psychiatric interview, the Mini International Neuropsychiatric Interview (M.I.N.I.). Current and lifetime use of psychotropic medication were assessed. Results Ninety patients who agreed to participate completed the research protocol.  A total of 12/90  were on current use of psychotropic medication.Thirty-six out of ninety patients  had at least one psychiatric disorder. Mood disorders were detected in 19 of the 90. Anxiety disorders were highly frequent, reaching 27/90 of the patients, as agoraphobia the most common diagnosis (12/90). Limitations The study has several limitations, such as the absence of a control group of fertile patients and strict inclusion criteria, in which only subjects that spontaneously agreed to participate were enrolled. Conclusion Women suffering from infertility seeking ART treatment are at high risk for depression and anxiety disorders and a considerable number of them are in use of medication. Its implications on infertility treatments and offspring are uncertain., (Copyright © 2021. Published by Elsevier B.V.)

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) from patients with chronic obstructive pulmonary disease (COPD) appear to be phenotypically and functionally similar to BM-MSCs from healthy sources in vitro , the impact of COPD on MSC metabolism and mitochondrial function has not been evaluated. In this study, we aimed to comparatively characterize MSCs from healthy and emphysematous donors (H-MSCs and E-MSCs) in vitro and to assess the therapeutic potential of these MSCs and their extracellular vesicles (H-EVs and E-EVs) in an in vivo model of severe emphysema. For this purpose, C57BL/6 mice received intratracheal porcine pancreatic elastase once weekly for 4 weeks to induce emphysema; control animals received saline under the same protocol. Twenty-four hours after the last instillation, animals received saline, H-MSCs, E-MSCs, H-EVs, or E-EVs intravenously. In vitro characterization demonstrated that E-MSCs present downregulation of anti-inflammatory (TSG-6, VEGF, TGF-β, and HGF) and anti-oxidant (CAT, SOD, Nrf2, and GSH) genes, and their EVs had larger median diameter and lower average concentration. Compared with H-MSC, E-MSC mitochondria also exhibited a higher respiration rate, were morphologically elongated, expressed less dynamin-related protein-1, and produced more superoxide. When co-cultured with alveolar macrophages, both H-MSCs and E-MSCs induced an increase in iNOS and arginase-1 levels, but only H-MSCs and their EVs were able to enhance IL-10 levels. In vivo , emphysematous mice treated with E-MSCs or E-EVs demonstrated no amelioration in cardiorespiratory dysfunction. On the other hand, H-EVs, but not H-MSCs, were able to reduce the neutrophil count, the mean linear intercept, and IL-1β and TGF-β levels in lung tissue, as well as reduce pulmonary arterial hypertension and increase the right ventricular area in a murine model of elastase-induced severe emphysema. In conclusion, E-MSCs and E-EVs were unable to reverse cardiorespiratory dysfunction, whereas H-EVs administration was associated with a reduction in cardiovascular and respiratory damage in experimental severe emphysema., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Antunes, Braga, Oliveira, Kitoko, Castro, Xisto, Coelho, Rocha, Silva-Aguiar, Caruso-Neves, Martins, Carvalho, Galina, Weiss, Lapa e Silva, Lopes-Pacheco, Cruz and Rocco.)

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is characterized by a persistent pattern of inattention and hyperactivity/impulsivity. Despite the proven efficacy of pharmacological treatment, many individuals continue to suffer socially and academically and some experience significant side effects that negate the use psychotropic drugs. Transcranial direct current stimulation (tDCS) is a cortical neuromodulation feature that has shown positive results in the treatment of various neuropsychiatric conditions., Objectives: To investigate the effect of tDCS on the performance of children and adolescents with ADHD in the neuropsychological tests of visual attention, verbal, and inhibitory control., Methodology: Triple blind, randomized, sham-controlled, cross-over trial involving tDCS in children and adolescents with ADHD. Initial screening will be performed using Swanson, Nolan, and Pelham - IVand Wechsler intelligence scale for children fourth edition vocabulary and cube subtests. Individuals will be evaluated pre-tDCS and post-tDCS with the Wechsler intelligence scale for children fourth edition Digitus subtest, neuropsychological assessment battery second edition inhibiting responses subtest, Corsi cubes, and visual attention test-4., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Genetic interactions such as epistasis are widespread in nature and can shape evolutionary dynamics. Epistasis occurs due to nonlinearity in biological systems, which can arise via cellular processes that convert genotype to phenotype and via selective processes that connect phenotype to fitness. Few studies in nature have connected genotype to phenotype to fitness for multiple potentially interacting genetic variants. Thus, the causes of epistasis in the wild remain poorly understood. Here, we show that epistasis for fitness is an emergent and predictable property of nonlinear selective processes. We do so by measuring the genetic basis of cryptic colouration and survival in a field experiment with stick insects. We find that colouration shows a largely additive genetic basis but with some effects of epistasis that enhance differentiation between colour morphs. In terms of fitness, different combinations of loci affecting colouration confer high survival in one host-plant treatment. Specifically, nonlinear correlational selection for specific combinations of colour traits in this treatment drives the emergence of pairwise and higher-order epistasis for fitness at loci underlying colour. In turn, this results in a rugged fitness landscape for genotypes. In contrast, fitness epistasis was dampened in another treatment, where selection was weaker. Patterns of epistasis that are shaped by ecologically based selection could be common and central to understanding fitness landscapes, the dynamics of evolution and potentially other complex systems.

The types of mutations affecting adaptation in the wild are only beginning to be understood. In particular, whether structural changes shape adaptation by suppressing recombination or by creating new mutations is unresolved. Here, we show that multiple linked but recombining loci underlie cryptic color morphs of Timema chumash stick insects. In a related species, these loci are found in a region of suppressed recombination, forming a supergene. However, in seven species of Timema , we found that a megabase-size "supermutation" has deleted color loci in green morphs. Moreover, we found that balancing selection likely contributes more to maintaining this mutation than does introgression. Our results show how suppressed recombination and large-scale mutation can help to package gene complexes into discrete units of diversity such as morphs, ecotypes, or species., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Studies with children exposed to methylmercury (MeHg) through fish consumption in the Brazilian Amazon region report that the high levels of hair Hg are associated with significant decreases in intelligence, memory, attention, and visuospatial processing., Objective: To investigate the relationship between mercury exposure and neuropsychological functions in riverside communities of the Brazilian Amazon., Method: 263 participants aged 6 to 14 years old were assessed, from resettlement regions, near the Madeira river, Rondônia, Brazil. To assess the neuropsychological functions we used the following instruments: intelligence (WASI), working memory (Corsi Block-Tapping Task and Digit Span), verbal fluency (Word Generation - NEPSY II), inhibitory control (Inhibition Errors - NEPSY II), shifting (Trail Making Test) and manual motor dexterity (Grooved PegBoard Test). Socioeconomic status was obtained through household surveys. Total Hg levels were quantified hair samples (Total HgH) collected from the occipital region of the scalp and analyzed by Cold Vapor Atomic Absorption Spectrometry., Results: The group in the upper quartile of Total HgH levels presented lower scores on the tasks that assessed estimated IQ, visuospatial working memory, semantic knowledge and phonological verbal fluency, when compared to the group in the lower quartile level. A regression analysis controlled for age, sex, and maternal education showed that for each increase of 10 μg/g of Total HgH, there was a decrease around half standard deviation in Verbal IQ, estimated IQ scores, semantic knowledge, phonological verbal fluency and for verbal and visuospatial working memory., Conclusions: High concentrations of Total Hg in hair were associated with a lower performance in neuropsychological functions tests. The results show that environmental exposure to Hg is associated to children and adolescents' lower neuropsychological performance in the riverine and resettled areas of the Brazilian Amazon region., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A chronic infection caused by Toxoplasma gondii was considered asymptomatic in immunologically healthy humans, but results from animal and epidemiological studies led to a reconsideration of this assumption. The objective of this study was to evaluate the seroprevalence of T. gondii infection and its possible effects on the behavior of school-aged children in Bahia, Brazil. Serum anti-body determinations were performed by Enzyme-linked Immunosorbent Assay (ELISA). Blood lead levels (BLL) were measured by graphite furnace atomic absorption spectrometry (GFAAS). The evaluation of a child's behavior was assessed using the Child Behavior Check List (CBCL). Multivariate models applying logistic regression were used to test the association of chronic T. gondii infection and BLL with behavioral outcomes in children. Seroprevalence for anti-T. gondii IgG antibody was 43.7 % (95 %-CI: 35.8-51.9). Significant associations between chronic T. gondii infection and total behavioral problems (OR = 2.50; 95 %-CI: 1.06-5.88), internalizing spectrum problems (OR = 4.35; 95 %-CI: 1.11-17.14) and rule breaking (OR = 2.61; 95 %-CI: 1.12-6.05) were observed. A possible interaction between toxoplasmosis prevalence and lead exposure was detected. Children with above the median BLL and positive for IgG anti-T. gondii showed a 5.51-fold increase (95 %-CI: 1.75-17.38) in the chance of displaying disobedient behavior. The results suggest that T. gondii infection may be contributing to the high indices of behavioral changes. Moreover, these findings are the first evidence for a possible interaction between chronic T. gondii infection and elevated blood lead levels on children's neurobehavior., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To analyze the knowledge about tuberculosis among nursing undergraduate students of a Federal Higher Education Institution., Method: Descriptive cross-sectional study, with quantitative approach. Data were collected through a questionnaire based on the WHO's guide to developing evaluation instruments on knowledge, attitudes and practices related to TB. Students were classified as "with knowledge" and "with little knowledge" based on the mean percentage of correct responses to the variables analyzed. Descriptive statistics techniques were used., Results: 60 nursing students were interviewed. "with little knowledge" was observed among students who were studying at the university for less time and who had no previous contact with the subject, and "with knowledge" was observed among those whose knowledge about tuberculosis was acquired in the health services., Conclusion: Knowledge gaps among undergraduate nursing students were identified, suggesting the need to rethink teaching-learning strategies on the subject.

Manganese (Mn) is an essential element, however high levels of Mn have been associated with lower neuropsychological performance and behavioral problems in children. We investigated the associations between hair Mn concentrations and neuropsychological and behavioral performances among children with long-term exposure to airborne Mn aged between 7 and 12 years. Neuropsychological performance included tests of: verbal memory, inhibitory control, cognitive flexibility, verbal fluency, and motor function. We used the Conners Abbreviated Rating Scale for teachers to assess students' behaviors of hyperactivity. Hair manganese (MnH) concentrations in children and exposure to airborne manganese from a ferro-manganese alloy plant were analyzed and correlated with tests scores. Multivariable linear models adjusting for potential confounders showed that elevated levels of MnH were associated with lower performance in verbal memory, as measured by the free recall after interference (β = - 1.8; 95% CI: - 3.4, - 0.2), which indicates susceptibility to interference, and Delayed Effect (β = -2.0; 95% CI: -3.7, - 0.2), representing a loss of information over time. Additionally, we found patterns of effect modification by sex in three subtests measuring verbal memory: the free recall after interference score, Interference Effect, and Delayed Effect (all at p < 0.10). Overall, the results suggest that long-term airborne Mn exposure may be associated with lower performance in verbal memory, and hyperactivity behaviors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Excessive exposure to Mn can lead to its accumulation in the brain with neurotoxic consequences. In children, elevated Mn has been associated with deficits in certain neuropsychological domains such as cognition, motor function, memory and attention, and in some instances, hyperactivity and behavioral problems. The aim of this study was to evaluate behavioral effects in school-aged children living near a ferro-manganese alloy plant and examine their association with Mn exposure. Occipital hair, toenails and blood samples were collected from 225 children (7-12 years old) enrolled in four elementary schools with different levels of exposure to Mn, based on dust Mn deposition rates. Full data set collection was completed and run from 165 children. Mn in hair (MnH), toenails (MnTn), blood (MnB) and blood lead levels (PbB) were determined by graphite furnace atomic absorption spectrometry. Children's behavior was assessed with the Child Behavior Check List (CBCL) reported by parents. Median levels and range of MnH, MnT and MnB were, respectively, 0.73 µg/g (0.16-8.79), 0.84 µg/g (0.15-9.29) and 8.98 μg/L (1.51-40.43). Median and range of PbB were 1.2 µg/dL (0.2-15.6). MnH and MnB were not associated with any scale of the CBCL behavior scores. We found a positive association between logMnTn and raw total CBCL score (β = 10.17, p = 0.034), adjusting for sex, age, maternal IQ and logPbB. Analyses using Generalized Additive Model showed non-linear associations between MnTn and externalizing behavior (p = 0.035), as well as with the related subscales: aggressive behavior (p = 0.045) and rule-breaking behavior (p = 0.024). Further positive associations were observed between MnTn and thought problems (p = 0.031) and social problems (p = 0.027). These findings corroborate previous studies showing an association between Mn exposures and externalizing behavior. Our results suggest that toenail Mn, as a biomarker of environmental exposure, is associated with disruptive behavior in children living near a ferro-manganese alloy plant., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mortality from collision with vehicles is the most visible impact of road traffic on wildlife. Mortality due to roads (hereafter road-kill) can affect the dynamic of populations of many species and can, therefore, increase the risk of local decline or extinction. This is especially true in Brazil, where plans for road network upgrading and expansion overlaps biodiversity hotspot areas, which are of high importance for global conservation. Researchers, conservationists and road planners face the challenge to define a national strategy for road mitigation and wildlife conservation. The main goal of this dataset is a compilation of geo-referenced road-kill data from published and unpublished road surveys. This is the first Data Paper in the BRAZIL series (see ATLANTIC, NEOTROPICAL, and BRAZIL collections of Data Papers published in Ecology), which aims make public road-kill data for species in the Brazilian Regions. The dataset encompasses road-kill records from 45 personal communications and 26 studies published in peer-reviewed journals, theses and reports. The road-kill dataset comprises 21,512 records, 83% of which are identified to the species level (n = 450 species). The dataset includes records of 31 amphibian species, 90 reptile species, 229 bird species, and 99 mammal species. One species is classified as Endangered, eight as Vulnerable and twelve as Near Threatened. The species with the highest number of records are: Didelphis albiventris (n = 1,549), Volatinia jacarina (n = 1,238), Cerdocyon thous (n = 1,135), Helicops infrataeniatus (n = 802), and Rhinella icterica (n = 692). Most of the records came from southern Brazil. However, observations of the road-kill incidence for non-Least Concern species are more spread across the country. This dataset can be used to identify which taxa seems to be vulnerable to traffic, analyze temporal and spatial patterns of road-kill at local, regional and national scales and also used to understand the effects of road-kill on population persistence. It may also contribute to studies that aims to understand the influence of landscape and environmental influences on road-kills, improve our knowledge on road-related strategies on biodiversity conservation and be used as complementary information on large-scale and macroecological studies. No copyright or proprietary restrictions are associated with the use of this data set other than citation of this Data Paper., (© 2018 The Authors. Ecology © 2018 The Ecological Society of America.)

Studies have demonstrated that, for urban children, dust represents the main exposure to sources of metals like lead (Pb) and manganese (Mn). We aimed to investigate the exposure to these metals and their association with intellectual deficit in children living in an industrial region. This cross-sectional study recruited volunteers from four elementary schools in the town of Simões Filho, Brazil. We evaluated 225 school-aged children (7⁻12 years) for blood lead (PbB) and manganese hair (MnH) and toenails (MnTn) by graphite furnace atomic absorption spectrometry. Child and maternal IQs were estimated using the Wechsler Abbreviated Scale for Intelligence (WASI). Median and range PbB were 1.2 (0.3⁻15.6) μg/dL. MnH and MnTn medians (ranges) were 0.74 (0.16⁻8.79) μg/g and 0.85 (0.15⁻13.30) μg/g, respectively. After adjusting for maternal IQ, age and Mn exposure, child IQ drops by 8.6 points for a 10-fold increase in PbB levels. Moreover, an effect modification of Mn co-exposure was observed. In children with low MnTn, association between Pb and child IQ was not significant (β = -6.780, p = 0.172). However, in those with high MnTn, the association was increased by 27.9% (β = -8.70, p = 0.036). Low Pb exposure is associated with intellectual deficit in children, especially in those with high MnTn.

Studies suggest that the protozoan Toxoplasma gondii can disturb human behavior. This study aimed to systematically review the scientific literature on the possible associations between Toxoplasma gondii infection and neurobehavioral abnormalities in humans. We reviewed and summarized the studies published since 1990. The descriptors used were related to T. gondii infection and behavioral outcomes in humans; the main databases of the medical literature were accessed. The results of eight original articles published between 1994 and 2016 were evaluated and described. The most common serological method was the enzyme immunoassay. Most of the researchers used validated instruments for behavioral evaluation. Seven studies reported some association between the prevalence of anti-T. gondii antibodies and some altered behavioral aspects in adult humans; these studies focused on adult population in Europe and the USA. The most reported behavioral deviations are related to greater impulsivity and aggressiveness. There are very few studies on this subject, which present some limitations for inference and conclusions: most were cross-sectional studies, with a small sample size and in similar populations. Investigations with a larger sample size of different population groups should be performed to evaluate multiple factors.