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Childhood obesity rates in Latin America are among the highest in the world. This paper examines and evaluates the many efforts underway in the region to reduce and prevent further increases in obesity, identifies and discusses unique research challenges and opportunities in Latin America, and proposes a research agenda in Latin America for the prevention of childhood obesity and concomitant non-communicable diseases. Identified research gaps include biological challenges to healthy growth across the life cycle, diet and physical activity dynamics, community interventions promoting healthy child growth, and rigorous evaluation of national food and activity programs and regulatory actions. Addressing these research gaps is critical to advance the evidence-based policy and practice in childhood obesity tailored to the Latin American context that will be effective in addressing obesity.

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OBJECTIVE: To describe the worldwide prevalence of physical inactivity and to analyze its association with development level of each country. METHODS: Pooled analysis of three multicenter studies, conducted between 2002 and 2004, which investigated the prevalence of physical inactivity in 76 countries, and comprised almost 300,000 individuals aged 15years or older. Each study used the International Physical Activity Questionnaire to assess physical inactivity. The level of development of each country was analyzed by the Human Development Index (HDI). RESULTS: The crude worldwide prevalence of physical inactivity was 21.4% (95%CI 18.4-24.3), being higher among women (mean=23.7%, 95%CI 20.4-27.1) than men (mean=18.9%, 95%CI 16.2-21.7). It ranged from 2.6% (in Comoros) to 62.3% (in Mauritania), with a median equal to 18%. After weighting for the total population of each country, the worldwide prevalence of physical inactivity was 17.4% (95%CI 15.1-19.7). There was a positive association between HDI and prevalence of physical inactivity (rho=0.27). Less developed countries showed the lowest prevalence of physical inactivity (18.7%), while physical inactivity was more prevalent among the most developed countries (27.8%). CONCLUSIONS: One out of five adults around the world is physically inactive. Physical inactivity was more prevalent among wealthier and urban countries, and among women and elderly individuals. [ABSTRACT FROM AUTHOR]

Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Alternative transcription start sites (TSS) are widespread in eukaryotes and can alter the 5' UTR length and coding potential of transcripts. Here we show that inorganic phosphate (Pi) availability regulates the usage of several alternative TSS in Arabidopsis (Arabidopsis thaliana). In comparison to phytohormone treatment, Pi had a pronounced and specific effect on the usage of many alternative TSS. By combining short-read RNA sequencing with long-read sequencing of full-length mRNAs, we identified a set of 45 genes showing alternative TSS under Pi deficiency. Alternative TSS affected several processes, such as translation via the exclusion of upstream open reading frames present in the 5' UTR of RETICULAN LIKE PROTEIN B1 mRNA, and subcellular localization via removal of the plastid transit peptide coding region from the mRNAs of HEME OXYGENASE 1 and SULFOQUINOVOSYLDIACYLGLYCEROL 2. Several alternative TSS also generated shorter transcripts lacking the coding potential for important domains. For example, the EVOLUTIONARILY CONSERVED C-TERMINAL REGION 4 (ECT4) locus, which encodes an N 6 -methyladenosine (m 6 A) reader, strongly expressed under Pi deficiency a short noncoding transcript (named ALT ECT4 ) ~550 nt long with a TSS in the penultimate intron. The specific and robust induction of ALT ECT4 production by Pi deficiency led to the identification of a role for m 6 A readers in primary root growth in response to low phosphate that is dependent on iron and is involved in modulating cell division in the root meristem. Our results identify alternative TSS usage as an important process in the plant response to Pi deficiency., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Infection of astrocytes by Human Immunodeficiency Virus (HIV-1) remains a topic of debate, with conflicting data, yet instances of astrocytes containing viral DNA have been observed in vivo . In this study, we aimed to elucidate potential routes through which astrocytes could be infected and their ability to produce infectious particles using primary human astrocytes., Methods: We infected primary astrocytes derived from either neuroprogenitor cells (NPCs) or induced pluripotent stem cells (iPSCs) that express both C-X-C chemokine receptor type 4 (CXCR4) and the C-C chemokine receptor type 5 (CCR5) coreceptors, using either cell-free HIV-1 virus directly or cell-associated virus indirectly through infected macrophages and microglia., Results: Low-level infectivity by cell-free viruses was primarily attributed to a defect in the entry process. Bypassing HIV-specific receptor-mediated entry using pseudotyped viruses resulted in productive infection and the release of infectious particles., Conclusions: These findings suggest that astrocytes may be one of the potential sources of neurotoxicity in HIV-associated neurocognitive disorders (HAND) and could possibly act as reservoirs for HIV in the central nervous system (CNS)., (© 2024 The Author(s). Published by IMR Press.)

By providing spaces for recreation, physical activity, social gatherings, and time in nature, urban parks offer physical, mental, and social benefits to users. However, many urban residents face barriers to park use. The COVID-19 pandemic introduced new potential barriers to urban park access and use, including changes to daily life and employment, closure of park amenities and restrictions to public movement, and risk from the coronavirus itself. The mixed-methods PARCS study measured use and perceptions of a large urban park in St. Louis, Missouri before, during, and after local COVID-19 contingency measures and restrictions. We examine data from 1,157 direct observation assessments of park usership, an online survey of park users (n=561), interviews with key stakeholders (n=27), four focus groups (n=30), and a community-based participatory research sub-study (n=66) to comprehensively characterize the effects of the COVID-19 pandemic on park use. Park users who felt unsafe from the coronavirus experienced 2.65 higher odds of reducing park use. However, estimated park visits during COVID-19 contingency measures (n=5,023,759) were twice as high as post-contingency (n=2,277,496). Participants reported using the park for physical activity, recreation, time in nature, and socializing during the contingency period. Black, Hispanic/Latino, and young people were less likely to visit the park than others, suggesting an additional, disproportionate impact of the pandemic on minoritized and socioeconomically disadvantaged communities. This study highlights the role of public spaces like parks as resources for health and sites where urban health inequities can be alleviated in times of public crisis., (© 2024. The New York Academy of Medicine.)

Aim: To test the association between sociodemographic and social characteristics with COVID-19 cases and deaths in small and large Brazilian cities., Methods: This ecological study included COVID-19 data available in State Health Secretaries (managed by brasil.io API) and three national databases (IBGE, DATASUS and Embrapa). Temporal spread of COVID-19 in Brazil during the first year considered as outcome: a) days until 1st case in each city since 1st in the country; b) days until 1,000 cases/100,000 inhabitants since 1st case in each city; c) days until 1st death until 50 deaths/100,000 inhabitants. Covariates included geographic region, city social and environmental characteristics, housing conditions, job characteristics, socioeconomic and inequalities characteristics, and health services and coverage. The analysis were stratified by city size into small (<100,000 inhabitants) and large cities (≥100,00 inhabitants). Multiple linear regressions were performed to test associations of all covariates to adjust to potential confounders., Results: In small cities, the first cases were reported after 82.2 days and 1,000 cases/100,000 were reported after 117.8 days, whereas in large cities these milestones were reported after 32.1 and 127.7 days, respectively. For first death, small and large cities took 121.6 and 36.0 days, respectively. However, small cities were associated with more vulnerability factors to first case arrival in 1,000 cases/100,000 inhabitants, first death and 50 deaths/100,000 inhabitants. North and Northeast regions positively associated with faster COVID-19 incidence, whereas South and Southeast were least., Conclusion: Social and built environment characteristics and inequalities were associated with COVID-19 cases spread and mortality incidence in Brazilian cities., Competing Interests: RSR: was supported by the Centene Charitable Foundation, founded by the Centene Corporation, for travel support by the funder and no salary or any compensation was provided by this agreement. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2024 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neuroinflammation and synaptodendritic damage represent the pathological hallmarks of HIV-1 associated cognitive disorders (HAND). The post-synaptic protein neurogranin (Nrgn) is significantly reduced in the frontal cortex of postmortem brains from people with HIV (PWH) and it is associated with inflammatory factors released by infected microglia/macrophages. However, the mechanism involved in synaptic loss have yet to be elucidated. In this study, we characterized a newly identified long non-coding RNA (lncRNA) transcript (RP11-677M14.2), which is antisense to the NRGN locus and is highly expressed in the frontal cortex of HIV-1 individuals. Further analysis indicates an inverse correlation between the expression of RP11-677M14.2 RNA and Nrgn mRNA. Additionally, the Nrgn-lncRNA axis is dysregulated in neurons exposed to HIV-1 infected microglia conditioned medium enriched with IL-1β. Moreover, in vitro overexpression of this lncRNA impacts Nrgn expression at both mRNA and protein levels. Finally, we modeled the Nrgn-lncRNA dysregulation within an HIV-1-induced inflammatory environment using brain organoids, thereby corroborating our in vivo and in vitro findings. Together, our study implicates a plausible role for lncRNA RP11-677M14.2 in modulating Nrgn expression that might serve as the mechanistic link between Nrgn loss and cognitive dysfunction in HAND, thus shedding new light on the mechanisms underlying synaptodendritic damage., (© 2024. The Author(s).)

This study scrutinizes structural racism's influence on the training and work of Black professionals in primary health care (PHC) in Rio de Janeiro, particularly focusing on the experiences of Black female physicians. Employing a qualitative approach via a Focus Group, conducted in November 2022, we adopted symbolic interactionism to interpret racism-related experiences. Our findings encompass two primary dimensions: the manifestation of structural and institutional racism within the Unified Health System (SUS), and how racism permeates health work processes and consequences. Results highlight enduring impacts, spanning education to PHC roles, hindering healthcare process recalibration. Participants identify institutional and structural racism, from managerial neglect to territorial violence and physician scarcity, constraining comprehensive care. It is crucial to unveil and grasp racism's structural essence within healthcare, aligned with the vision of health as a fundamental right.

The development of 3D-organoid models has revolutionized the way diseases are studied. Recently, our brain organoid model has been shown to recapitulate in in vitro the human brain cytoarchitecture originally encountered in HIV-1 neuropathogenesis, allowing downstream applications. Infected monocytes, macrophages, and microglia are critically important immune cells for infection and dissemination of HIV-1 throughout brain during acute and chronic phase of the disease. Once in the brain parenchyma, long-lived infected monocytes/macrophages along with resident microglia contribute to the establishment of CNS latency in people with HIV (PWH). Hence, it is important to better understand how HIV-1 enters and establishes infection and latency in CNS to further develop cure strategies. Here we detailed an accessible protocol to incorporate monocytes (infected and/or labeled) as a model of transmigration of peripheral monocytes into brain organoids that can be applied to characterize HIV-1 neuroinvasion and virus dissemination., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

In 1998, Bill Gray and colleagues showed that warm temperatures trigger arabidopsis hypocotyl elongation in an auxin-dependent manner. This laid the foundation for a vibrant research discipline. With several active members of the 'thermomorphogenesis' community, we here reflect on 25 years of elevated ambient temperature research and look to the future., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Plants exposed to mildly elevated temperatures display morphological and developmental changes collectively termed thermomorphogenesis. This adaptative process has several undesirable consequences for food production, including yield reduction and increased vulnerability to pathogens. Understanding thermomorphogenesis is, thus, critical for understanding how plants will respond to conditions of increasingly warmer temperature, such as those caused by climate change. Recently, major advances in that direction have been made, and it has become apparent that plants resort to a broad range of molecules and molecular mechanisms to perceive and respond to increases in environmental temperature. However, most effort has been focused on regulation of transcription and protein abundance and activity, with an important gap encompassing nearly all processes involving RNA (i.e. post-transcriptional regulation). Here, current knowledge of thermomorphogenesis involving transcriptional, post-transcriptional, and post-translational regulation is summarized, focusing on opportunities and challenges in understanding post-transcriptional regulation-a fertile field for exciting new discoveries., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Arginine is the main amino acid that constitutes the sperm protamine of roosters, named galline, which complexes with sperm DNA, allowing high compaction of its chromatin. Arginine supplementation has positive effects on semen quality in aged roosters, but this supplementation is not known to limit the progressive worsening of sperm chromatin compaction. This work aimed to verify whether L-arginine supplementation in the feed improve or maintain sperm chromatin quality since aging in roosters is usually accompanied by worsening chromatin quality. Four groups of 52-wk-old Ross AP95 lineage roosters were used, of which 6 semen samples per group were evaluated, totaling 24 samples. Another 24 samples, 6 per group, were evaluated after 6 wk of supplementation when one group was not supplemented (control) and the other 3 were supplemented with 1.15 kg (treatment 1), 2.17 kg (treatment 2), and 3.18 kg (treatment 3) of L-arginine/ton of feed. Computer image analysis of semen smears stained with toluidine blue pH 4.0 was used for sperm chromatin evaluation. Sperm chromatin was evaluated for compaction heterogeneity and compaction intensity by percentage decompaction relative to standard heads and by integrated optical density (IOD), which was used for the first time to identify sperm chromatin changes. Sperm head morphology was also evaluated by means of area and length. The IOD proved to be more efficient in identifying changes in rooster sperm chromatin compaction than the percentual decompaction. In general, chromatin compaction was positively influenced by the supplementation with L-arginine, being better in the supplementation with the highest levels tested. This was corroborated by the smaller average of the variables referring to the size of the spermatozoa heads of the animals that received feed with a higher content of L-arginine, since better compacted heads naturally tend to be smaller. Finally, arginine supplementation was able to limit or even improve sperm chromatin decompaction during the experimental period., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Phytates are a type of organophosphorus compound produced in terrestrial ecosystems by plants. In plant feeds, phytic acid and its salt form, phytate, account for 60%-80% of total phosphorus. Because phytate is a polyanionic molecule, it can chelate positively charged cations such as calcium, iron, and zinc. Due to its prevalence in vegetal tissues and the fact that people consume plants, phytate was first considered a potential health benefit. This updated review aims to summarize the current data on the results of clinical trials of phytates on human health, highlighting both beneficial and undesirable effects. To obtain these updated data, published papers in electronic databases such as PubMed/MedLine, TRIP database, Wiley, Google Scholar, Baidu, and Scopus were searched. Study results have shown that phytate can have beneficial health effects such as antioxidant, anticancer potential and reduction of pathological calcifications in blood vessels and organs; but also, negative effects by reducing the absorption of minerals important for maintaining the homeostasis of the human body. According to these recent results derived from recent clinical studies, phytates may be a potential natural source for health benefits. To improve clinical efficacy and human health benefits, further dose-response studies are needed to determine effective therapeutic doses and potential interactions with conventional drugs., 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 © 2023 Pires, Reis, Cardoso, Pezzani, Paredes-Osses, Seilkhan, Ydyrys, Martorell, Sönmez Gürer, Setzer, Abdull Razis, Modu, Calina and Sharifi-Rad.)

Given its origins in high-income countries, the field of physical activity and public health research and promotion has broadly followed a choice-based model. However, a substantial amount of the physical activity occurring routinely in many settings, particularly in low- and middle-income countries (LMICs), is the result of economic necessity and is not due to true, free choices. We propose the "necessity- versus choice-based physical activity models" framework as a conceptual tool to ground physical activity and public health research and promotion efforts in LMICs, helping ensurethat these efforts are relevant, ethical, responsive, and respectful to local contexts. Identifying ways to ensure that LMIC populations can maintain high levels of active transport while increasing opportunities for active leisure must be prioritized. To promote equity, physical activity research, programs, and policies in LMICs must focus on improving the conditions under which necessity-driven physical activity occurs for a vast majority of the population.

Purpose: To summarize the existing treatment options regarding central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), arteritic anterior ischemic optic neuropathy (AAION), non-arteritic anterior ischemic optic neuropathy (NAION), and ocular ischemic syndrome (OIS), proposing an approach to manage and treat these patients., Methods: A systematic literature search of articles published since 1st January 2010 until 31st December 2020 was conducted using MEDLINE (PubMed), Scopus, and Web of Science. Exclusion criteria included case reports, non-English references, articles not conducted in humans, and articles not including diagnostic or therapeutic options. Further references were gathered through citation tracking, by hand search of the reference lists of included studies, as well as topic-related European society guidelines., Results: Acute ocular ischemia, with consequent visual loss, has a variety of causes and clinical presentations, with prognosis depending on an accurate diagnosis and timely therapeutic implementation. Unfortunately, most of the addressed entities do not have a standardized management, especially regarding their treatment, which often lacks good quality evidence on whether it should or not be used to treat patients., Conclusion: Ophthalmologic signs and symptoms may be a warning sign of cardiovascular or cerebrovascular events, namely stroke. Most causes of acute ocular ischemia do not have a standardized management, especially regarding their treatment. Timely intervention is essential to improve the visual, and possibly vital, prognosis. Awareness must be raised among non-ophthalmologist clinicians that might encounter these patients. Further research should focus on assessing the benefit of the management strategies already being employed ., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Studying neurological diseases have long been hampered by the lack of physiologically relevant models to resemble the complex human brain and the associated pathologies. Three-dimensional brain organoids have emerged as cutting-edge technology providing an alternative in vitro model to study healthy neural development and function as well as pathogenesis of neurological disorders and neuropathologies induced by pathogens. Nonetheless,  the absence of immune cells in current models poses a barrier to fully recapitulate brain microenvironment during the onset of HIV-1-associated neuropathogenesis. To address this and to further the brain organoid technology, we have incorporated HIV-target microglia into brain organoids, generating a complex multicellular interaction, which mimics the HIV-1-infected brain environment. Here we describe the method to generate a brain organoid consisting on neurons, astrocytes, and microglia (with and without HIV infection) that recapitulate the HIV-associated neuropathology. This model has tremendous potential to expand our knowledge on neuronal dysfunction associated with HIV-1 infection of glia., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

We report an unusual case of cerebral venous thrombosis (CVT temporally associated with an otherwise asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While coronavirus disease 2019 (COVID-19) has been associated with thrombotic events at different sites, most published cases report on symptomatic SARS-CoV-2 infection. We are confident this was an otherwise asymptomatic infection as the patient reported no symptoms and molecular and serological testing was consistent with infection more than 3weeks in the past. We believe this is an important report as it adds to the existing literature on thrombotic events in patients with COVID. It may even inform discussion of COVID vaccines and CVT since our patient, as those reported in association with vaccines, also had thrombocytopenia on admission., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society. All rights reserved.)

Hearing loss (HL) is a common sensory deficit in humans and represents an important clinical and social burden. We studied whole-genome sequencing data of a cohort of 2,097 individuals from the Brazilian Rare Genomes Project who were unaffected by hearing loss to investigate pathogenic and likely pathogenic variants associated with nonsyndromic hearing loss (NSHL). We found relevant frequencies of individuals harboring these alterations: 222 heterozygotes (10.59%) for sequence variants, 54 heterozygotes (2.58%) for copy-number variants (CNV), and four homozygotes (0.19%) for sequence variants. The top five most frequent genes and their corresponding combined allelic frequencies (AF) were GJB2 (AF = 1.57%), STRC (AF = 1%), OTOA (AF = 0.69%), TMPRSS3 (AF = 0.41%), and OTOF (AF = 0.29%). The most frequent sequence variant was GJB2 :c.35del (AF = 0.72%), followed by OTOA :p. (Glu787Ter) (AF = 0.61%), while the most recurrent CNV was a microdeletion of 57.9 kb involving the STRC gene (AF = 0.91%). An important fraction of these individuals (n = 104; 4.96%) presented variants associated with autosomal dominant forms of NSHL, which may imply the development of some hearing impairment in the future. Using data from the heterozygous individuals for recessive forms and the Hardy-Weinberg equation, we estimated the population frequency of affected individuals with autosomal recessive NSHL to be 1:2,222. Considering that the overall prevalence of HL in adults ranges from 4-15% worldwide, our data indicate that an important fraction of this condition may be associated with a monogenic origin and dominant inheritance., Competing Interests: The following authors are employees (received salary and other bonuses) of Hospital Israelita Albert Einstein: CQ; AC; LM; RG; KC; JC; RM; MC; RD; BA; MN; AT; ML; TM; MM; GC; AR; AF; GC; EP; LV; CM; JP; MD; MC; TA; and JO., (Copyright © 2022 Quaio, Coelho, Moura, Guedes, Chen, Ceroni, Minillo, Caraciolo, Reis, Mascaro, Nobrega, Teixeira, Martinelli, Mota, Matta, Colichio, Roncalho, Ferreira, Campilongo, Perrone, Virmond, Moreno, Prota, França, Cervato, Almeida and Oliveira.)

Mitochondria are the major organelles of energy production; however, active mitochondria can decline their energetic role and show a dysfunctional status. Mitochondrial dysfunction was induced by high non-physiological level of L-galactone-1,4-lactone (L-GalL), the precursor of ascorbate (AsA), in plant mitochondria. The dysfunction induced by L-GalL was associated with the fault in the mitochondrial electron partition and reactive oxygen species (ROS) over-production. Using mitochondria from RNAi-plant lines harbouring silenced L-galactone-1,4-lactone dehydrogenase (L-GalLDH) activity, it was demonstrated that such dysfunction is dependent on this enzyme activity. The capacity of alternative respiration was strongly decreased by L-GalL, probably mediated by redox-inactivation of the alternative oxidase (AOX) enzyme. Although, alternative respiration was shown to be the key factor that helps support AsA synthesis in dysfunctional mitochondria. Experiments with respiratory inhibitors showed that ROS formation and mitochondrial dysfunction were more associated with the decline in the activities of COX (cytochrome oxidase) and particularly AOX than with the lower activities of respiratory complexes I and III. The application of high L-GalL concentrations induced proteomic changes that indicated alterations in proteins related to oxidative stress and energetic status. However, supra-optimal L-GalL concentration was not deleterious for plants. Instead, the L-GalLDH activity could be positive. Indeed, it was found that wild type plants performed better growth than L-GalLDH-RNAi plants in response to high non-physiological L-GalL concentrations., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Evidence exists on the health impacts of the current COVID-19 pandemic on health workers, but less is known about its impact on their work dynamics and livelihoods. This matters, as health workers-and physicians in particular-are a scarce and expensive resource in low- and middle-income countries (LMICs). Our cross-sectional survey set out to explore changes in working hours and earnings during the second year of the pandemic in a representative sample of 1183 physicians in Brazil's São Paulo (SP) and Maranhão (MA) states. Descriptive analysis and inferential statistics were employed to explore differences in working hours and earnings among public and private sector physicians across the two locations. The workloads and earnings of doctors working exclusively in the public sector increased the most in the second year of the epidemic, particularly in MA. Conversely, the largest proportion of private-only doctors in our sample saw a decrease in their working hours (48.4%, 95% CI 41.8-55.0), whereas the largest proportion of public-only doctors in MA saw an increase in their working hours (44.4%, 95% CI 38.0-50.8). Although earnings remained broadly stable in the public sector, a third of public sector-only physicians in MA saw an increase in their earnings (95% CI 24.4-36.2). More than half of private-only doctors across both states saw a decrease in their earnings (52.2%, 95% CI 45.6-58.8). The largest proportion of dual practitioners (the majority in Brazil and in our sample) maintained their pre-pandemic levels of income (38.8%, 95% CI 35.3-42.3). As public-sector doctors have been key in the fight against the pandemic, it is critical to invest in these cadres in order to develop epidemic preparedness in LMICs, and to find new ways to harness for-profit actors to deliver social benefits.

Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS)., Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data., Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples., Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases., 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 © 2022 Dalle Molle, de Mendonça Filho, Minuzzi, Machado, Reis, Rodrigues, Mucellini, Franco, Buchweitz, Toazza, Bortoluzzi, Salum, Boscenco, Meaney, Levitan, Manfro and Silveira.)

Rare diseases affect up to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the validation results of a whole genome sequencing (WGS) procedure for implementation in clinical laboratories. In addition, we report data quality for the first 1,200 real-world patients sequenced. We sequenced a well-characterized group of 76 samples, including seven gold standard genomes, using a PCR-free WGS protocol on Illumina Novaseq 6,000 equipment. We compared the observed variant calls with their expected calls, observing good concordance for single nucleotide variants (SNVs; mean F-measure = 99.82%) and indels (mean F-measure = 99.57%). Copy number variants and structural variants events detection performances were as expected (F-measures 96.6% and 90.3%, respectively). Our WGS protocol presented excellent intra-assay reproducibility (coefficients of variation ranging between 0.03% and 0.20%) and inter-assay reproducibility (coefficients of variation ranging between 0.02% and 0.09%). Limitations of the WGS protocol include the inability to confidently detect variants such as uniparental disomy, balanced translocations, repeat expansion variants, and low-level mosaicism. In summary, the observed performance of the WGS protocol was in accordance with that seen in the best centers worldwide. The Rare Genomes Project is an important initiative to bring pivotal improvements to the quality of life of the affected individuals., 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 © 2022 Coelho, Mascaro-Cordeiro, Lucon, Nóbrega, Reis, de Alexandre, Moura, Oliveira, Guedes, Caraciolo, Zurro, Cervato and Oliveira.)

Understanding the mechanisms that endow a somatic cell with the ability to differentiate into a somatic embryo, which could result in numerous biotechnological applications, is still a challenge. The objective of this work was to identify some of the molecular and physiological mechanisms responsible for the acquisition of embryogenic competence during somatic embryogenesis in Carica papaya L. We performed a broad characterization of embryogenic (EC) and nonembryogenic calli (NEC) of using global and mitochondrial proteomic approaches, histomorphology, histochemistry, respiratory activity, and endogenous hormonal and hydrogen peroxide (H 2 O 2 ) contents. EC and NEC presented remarkable differences in anatomical and histochemical characteristics, with EC showing a higher reactivity for the presence of proteins and neutral polysaccharides. Our results demonstrate that mitochondrial metabolism affects the embryogenic competence of C. papaya callus. The EC presented higher participation of alternative oxidase (AOX) enzymes, higher total cell respiration and presented a stronger accumulation of mitochondrial stress response proteins. Differential accumulation of auxin-responsive Gretchen Hagen 3 (GH3) family proteins in EC was related to a decrease in the content of free 2,4-dichlorophenoxyacetic acid (2,4-D). EC also showed higher endogenous H 2 O 2 contents. H 2 O 2 is a promising molecule for further investigation in differentiation protocols for C. papaya somatic embryos. SIGNIFICANCE: To further advance the understanding of somatic embryogenesis, we performed a broad characterization of embryogenic and nonembryogenic callus, through global and mitochondrial proteomic approaches, histomorphology, histochemistry, respiratory activity, and endogenous hormonal and hydrogen peroxide contents. Based on these results, we propose a working model for the competence of papaya callus. This model suggests that GH3 proteins play an important role in the regulation of auxins. In addition, embryogenic callus showed a greater abundance of stress response proteins and folding proteins. Embryogenic callus respiration occurs predominantly via AOX, and the inhibition of its activity is capable of inhibiting callus differentiation. Although the embryogenic callus presented greater total respiration and a greater abundance of oxidative phosphorylation proteins, they had less COX participation and less coupling efficiency, indicating less ATP production., (Copyright © 2021 Elsevier B.V. All rights reserved.)

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts., Material and Methods: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture., Results: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity., Discussion: Overall endovascular treatment rates and procedural times in Portugal are comparable to other international registries. We found geographic heterogeneity, with lower endovascular treatment rates and longer onset-to-puncture time in southern and inner regions., Conclusion: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitals.

Cryptococcosis is a systemic fungal disease acquired from contaminated environments with propagules of the basidiomycetous yeasts of the Cryptococcus neoformans and C. gattii species complexes. The C. neoformans species complex classically comprises four major molecular types (VNI, VNII, VNIII, and VNIV), and the C. gattii species complex comprises another four (VGI, VGII, VGIII, and VGIV) and the newly identified molecular type VGV. These major molecular types differ in their epidemiological and ecological features, clinical presentations, and therapeutic outcomes. Generally, the most common isolated types are VNI, VGI, and VGII. The epidemiological profile of cryptococcosis in domestic cats is poorly studied and cats can be the sentinels for human infections. Therefore, the present study aimed to determine the molecular characterization of Cryptococcus spp. isolated from domestic cats and their dwellings in the metropolitan area of Rio de Janeiro, Brazil. A total of 36 Cryptococcus spp. strains, both clinical and environmental, from 19 cats were subtyped using multilocus sequence typing (MLST). The ploidy was identified using flow cytometry and the mating type was determined through amplification with specific pheromone primers. All strains were mating type alpha and 6/36 were diploid (all VNII). Most isolates (63.88%) were identified as VNII, a rare molecular type, leading to the consideration that this genotype is more likely related to skin lesions, since there was a high percentage (68.75%) of cats with skin lesions, which is also considered rare. Further studies regarding the molecular epidemiology of cryptococcosis in felines are still needed to clarify the reason for the large proportion of the rare molecular type VNII causing infections in cats.

In plants, thousands of genes are associated with antisense transcription, which often produces noncoding RNAs. Although widespread, sense-antisense pairs have been implicated in a limited variety of functions in plants and are often thought to form extensive dsRNA stretches triggering gene silencing. In this opinion, we show that evidence does not support gene silencing as a major role for antisense transcription. In fact, it is more likely that antisense transcripts play diverse functions in gene regulation. We propose a general framework for the initial functional dissection of antisense transcripts, suggesting testable hypotheses relying on an experiment-based decision tree. By moving beyond the gene silencing paradigm, we argue that a broad and diverse role for natural antisense transcription will emerge., Competing Interests: Declaration of interests The authors have no interests to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pre-Olympic Games predictions commonly include an increase in population-based physical activity in the host city, as often stated in the bid, but the post-Olympic Games effects on physical activity have not been summarised. In this Series paper, we aim to do the following: examine mentions of a physical activity legacy in pre-Olympic bid documentation; analyse existing physical activity surveillance data collected before, during, and after the Olympic Games in hosting areas around the world; and evaluate Google Trends data surrounding the London 2012 Olympic Games as a case study of community interest in the topic of exercise during the time of the Olympic Games. Before 2007, little mention of physical activity was made in pre-Olympic Games documentation, but, after that, most documents had targets for population physical activity or sports participation. The synthesis of available surveillance data indicates that there was no change in the prevalence of physical activity or sports participation, except for the 2008 Summer Olympics in Beijing and the 1998 Winter Olympics in Nagano; although, the increase in participation in Nagano might not be attributable to the Olympic Games since there was no change in participation in winter sports. The Google Trends data showed an acute spike in searches with the term "Olympic" immediately associated with the London Olympic Games period and showed a sustained peri-Olympic increase in searches with the term "exercise". By themselves, the Olympic Games have not improved population-wide physical activity but might be an important missed public health opportunity. Such a legacy will require strategic planning and partnerships across the International Olympic Committee and the Olympic, sport, and public health agencies and a thorough evaluation framework implemented throughout the pre-Olympic Games and post-Olympic Games period in the host country., Competing Interests: Declaration of interests DD is supported by a Future Leader Fellowship from Heart Foundation Australia (#101234). AEB, MK, RSR, KM, NM, RPT, and PCH declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Many of the known solutions to the physical inactivity pandemic operate across sectors relevant to the United Nations Sustainable Development Goals (SDGs)., Methods: The authors examined the contribution of physical activity promotion strategies toward achieving the SDGs through a conceptual linkage exercise, a scoping review, and an agent-based model., Results: Possible benefits of physical activity promotion were identified for 15 of the 17 SDGs, with more robust evidence supporting benefits for SDGs 3 (good health and well-being), 9 (industry, innovation, and infrastructure), 11 (sustainable cities and communities), 13 (climate action), and 16 (peace, justice, and strong institutions). Current evidence supports prioritizing at-scale physical activity-promoting transport and urban design strategies and community-based programs. Expected physical activity gains are greater for low-and middle-income countries. In high-income countries with high car dependency, physical activity promotion strategies may help reduce air pollution and traffic-related deaths, but shifts toward more active forms of travel and recreation, and climate change mitigation, may require complementary policies that disincentivize driving., Conclusions: The authors call for a synergistic approach to physical activity promotion and SDG achievement, involving multiple sectors beyond health around their goals and values, using physical activity promotion as a lever for a healthier planet.

A large portion of eukaryotic genes are associated with noncoding, natural antisense transcripts (NATs). Despite sharing extensive sequence complementarity with their sense mRNAs, mRNA-NAT pairs elusively often evade dsRNA-cleavage and siRNA-triggered silencing. More surprisingly, some NATs enhance translation of their sense mRNAs by yet unknown mechanism(s). Here, we show that translation enhancement of the rice (Oryza sativa) PHOSPHATE1.2 (PHO1.2) mRNA is enabled by specific structural rearrangements guided by its noncoding antisense RNA (cis-NATpho1.2). Their interaction in vitro revealed no evidence of widespread intermolecular dsRNA formation, but rather specific local changes in nucleotide base pairing, leading to higher flexibility of PHO1.2 mRNA at a key high guanine-cytosine�(GC) regulatory region inhibiting translation, ∼350-nt downstream of the start codon. Sense-antisense RNA interaction increased formation of the 80S complex in PHO1.2, possibly by inducing structural rearrangement within this inhibitory region, thus making this mRNA more accessible to 60S. This work presents a framework for nucleotide resolution studies of functional mRNA-antisense pairs., (� The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: To compare the maxillary dentoalveolar changes of patients treated with three distalization force systems: Jones Jig, Distal Jet and First Class appliances, using digitized models., Material and Methods: The retrospective sample comprised 118 digitized models of 59 patients with Class II malocclusion divided into three groups: Group 1 consisted of 22 patients treated with the Jones Jig appliance; Group 2 consisted of 20 patients treated with the Distal Jet, and Group 3 comprised 17 patients treated with the First Class appliance. Pretreatment and post-distalization plaster models of all patients were digitized and evaluated with OrthoAnalyzerTM software. The pretreatment and post-distalization variables regarding sagittal, rotational and transverse changes were compared by the One-way Analysis of Variance (ANOVA) and Kruskal-Wallis tests, depending on normality., Results: All appliances presented similar amounts of distalization. The Distal Jet appliance promoted significantly smaller mesial displacement of premolars and greater expansion of posterior teeth. The First Class presented the smallest rotation of the maxillary molars and treatment time., Conclusions: The distalizers were effective in correcting Class II molar relationship, however, a palatal force seems to provide fewer undesirable effects. Additionally, the degree of rotation and expansion was associated with the side of force application. Key words: Malocclusion, Angle Class II, Orthodontics, Corrective, Distalizers., Competing Interests: Conflicts of interest The authors declare that no conflict of interest exist., (Copyright: © 2021 Medicina Oral S.L.)

In this study, we propose a broad conceptual model that incorporates social capital dimensions and problem-solving routines to understand the determinants behind hotel managements' perception of and ability to cope with the COVID-19 pandemic-and thus, to innovate their service offering. We provide empirical support for the notion that, due to uncertainty about reopening after lockdown, the hospitality sector has found existing problem-solving routines to be of little use. Although the local community has been unable to form a shared vision around the pandemic, hoteliers have nevertheless relied on their network of relationships to sense the crisis and find their own ways to adapt. Interestingly, we find that overreliance on trustworthy relationships can diminish the ability to sense a crisis objectively. Our results not only shed light on sensemaking in the hotel industry, but also grapple with the theoretical nature of sensemaking as a socially constructed process., (© 2020 Elsevier Ltd. All rights reserved.)

Somatic embryogenesis is an important biotechnological technique for large-scale propagation of elite genotypes. Identifying stage-specific compounds associated with somatic embryo development can help elucidate the ontogenesis of Carica papaya L. somatic embryos and improve tissue culture protocols. To identify the stage-specific proteins that are present during the differentiation of C. papaya somatic embryos, proteomic analyses of embryos at the globular, heart, torpedo and cotyledonary developmental stages were performed. Mass spectrometry data have been deposited in the ProteomeXchange with the dataset identifier PXD021107. Comparative proteomic analyses revealed a total of 801 proteins, with 392 classified as differentially accumulated proteins in at least one of the developmental stages. The globular-staged presented a higher number of unique proteins (16), and 7 were isoforms of 60S ribosomal proteins, suggesting high translational activity at the beginning of somatic embryogenesis. Proteins related to mitochondrial metabolism accumulated to a high degree at the early developmental stages and then decreased with increasing development, and they contributed to cell homeostasis in early somatic embryos. A progressive increase in the accumulation of vicilin, late embryogenesis abundant proteins and chloroplastic proteins that lead to somatic embryo maturation was also observed. The differential accumulation of acetylornithine deacetylase and S-adenosylmethionine synthase 2 proteins was correlated with increases in putrescine and spermidine contents, which suggests that both polyamines should be tested to determine whether they increase the conversion rates of globular- to cotyledonary-staged somatic embryos. Taken together, the results showed that somatic embryo development in C. papaya is regulated by the differential accumulation of proteins, with ribosomal and mitochondrial proteins more abundant during the early somatic embryo stages and seed maturation proteins more abundant during the late stages., (Copyright © 2020 Elsevier B.V. All rights reserved.)

HIV-1 associated neurocognitive disorder (HAND) is characterized by neuroinflammation and glial activation that, together with the release of viral proteins, trigger a pathogenic cascade resulting in synaptodendritic damage and neurodegeneration that lead to cognitive impairment. However, the molecular events underlying HIV neuropathogenesis remain elusive, mainly due to lack of brain-representative experimental systems to study HIV-CNS pathology. To fill this gap, we developed a three-dimensional (3D) human brain organoid (hBORG) model containing major cell types important for HIV-1 neuropathogenesis; neurons and astrocytes along with incorporation of HIV-infected microglia. Both infected and uninfected microglia infiltrated into hBORGs resulting in a triculture system (MG-hBORG) that mirrors the multicellular network observed in HIV-infected human brain. Moreover, the MG-hBORG model supported productive viral infection and exhibited increased inflammatory response by HIV-infected MG-hBORGs, releasing tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) and thereby mimicking the chronic neuroinflammatory environment observed in HIV-infected individuals. This model offers great promise for basic understanding of how HIV-1 infection alters the CNS compartment and induces pathological changes, paving the way for discovery of biomarkers and new therapeutic targets.

Introduction: This retrospective study aimed to assess the stability of Class II malocclusion treatment with the distal jet, followed by fixed appliances., Methods: Seventy-five cephalograms of 30 subjects were divided into 2 groups. The treated group consisted of 15 patients who were evaluated at the pretreatment, posttreatment, and long-term posttreatment stages. The control group consisted of 15 subjects with normal occlusion, comparable to the experimental group at the long-term posttreatment period. Intergroup comparison of posttreatment changes was evaluated with t tests., Results: In the long-term posttreatment period, there was no significant change in the anteroposterior position of the maxilla and mandible to the cranial base. The lower anterior face height had a significantly smaller increase in the treated than in the control group. The maxillary molars in the treated group had significantly smaller vertical development, and the mandibular incisors had significantly greater labial tipping and protrusion than the control group. The treatment produced significant improvement in molar relationship and reduction of overbite and overjet, which remained stable in the long-term posttreatment period. There was greater upper lip protrusion in the experimental than in the control group in the long-term posttreatment period., Conclusions: Treatment of Class II malocclusions with the distal jet, followed by fixed appliances, showed good long-term stability in molar relationship, overbite, and overjet., (Copyright © 2020 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Inorganic orthophosphate (Pi) is an essential nutrient for plant growth, and its availability strongly impacts crop yield. PHOSPHATE1 (PHO1) transfers Pi from root to shoot via Pi export into root xylem vessels. In this work, we demonstrate that an upstream open reading frame (uORF) present in the 5' untranslated region of the Arabidopsis ( Arabidopsis thaliana ) PHO1 inhibits its translation and influences Pi homeostasis. The presence of the uORF strongly inhibited the translation of a PHO1 5'UTR-luciferase construct in protoplasts. A point mutation removing the PHO1 uORF (ΔuORF) in transgenic Arabidopsis resulted in increased association of its mRNA with polysomes and led to higher PHO1 protein levels, independent of Pi availability. Interestingly, deletion of the uORF led to higher shoot Pi content and was associated with improved shoot growth under low external Pi supply and no deleterious effects under Pi-sufficient conditions. We further show that natural accessions lacking the PHO1 uORF exhibit higher PHO1 protein levels and shoot Pi content. Increased shoot Pi content was linked to the absence of the PHO1 uORF in a population of F2 segregants. We identified the PHO1 uORF in genomes of crops such as rice ( Oryza sativa ), maize ( Zea mays ), barley ( Hordeum vulgare ), and wheat ( Triticum aesativum ), and we verified the inhibitory effect of the rice PHO1 uORF on translation in protoplasts. Our work suggests that regulation of PHO1 expression via its uORF might be a genetic resource useful-both in natural populations and in the context of genome editing-toward improving plant growth under Pi-deficient conditions., (© 2020 American Society of Plant Biologists. All Rights Reserved.)

Transcription termination has important regulatory functions, impacting mRNA stability, localization and translation potential. Failure to appropriately terminate transcription can also lead to read-through transcription and the synthesis of antisense RNAs which can have profound impact on gene expression. The Transcription-Export (THO/TREX) protein complex plays an important role in coupling transcription with splicing and export of mRNA. However, little is known about the role of the THO/TREX complex in the control of transcription termination. In this work, we show that two proteins of the THO/TREX complex, namely TREX COMPONENT 1 (TEX1 or THO3) and HYPER RECOMBINATION1 (HPR1 or THO1) contribute to the correct transcription termination at several loci in Arabidopsis thaliana. We first demonstrate this by showing defective termination in tex1 and hpr1 mutants at the nopaline synthase (NOS) terminator present in a T-DNA inserted between exon 1 and 3 of the PHO1 locus in the pho1-7 mutant. Read-through transcription beyond the NOS terminator and splicing-out of the T-DNA resulted in the generation of a near full-length PHO1 mRNA (minus exon 2) in the tex1 pho1-7 and hpr1 pho1-7 double mutants, with enhanced production of a truncated PHO1 protein that retained phosphate export activity. Consequently, the strong reduction of shoot growth associated with the severe phosphate deficiency of the pho1-7 mutant was alleviated in the tex1 pho1-7 and hpr1 pho1-7 double mutants. Additionally, we show that RNA termination defects in tex1 and hpr1 mutants leads to 3'UTR extensions in several endogenous genes. These results demonstrate that THO/TREX complex contributes to the regulation of transcription termination., Competing Interests: The authors have declared that no competing interests exist.

Objective: Children with renal tumors included in clinical trials have significantly better outcomes. In Brasil, the enrollment of patients in clinical trials remains challenging. Here we aimed to describe participation accrual in the Brazilian Wilms Tumor Study Group (BWTSG) and to identify barriers to trial registration of children with renal tumors., Methods: We determined the numbers of renal tumor diagnoses in 105 hospital-based cancer registries from 2001-2009. We then compared these totals with the numbers of renal tumor cases registered in the BWTSG from the same hospitals during the same time period. We also invited members of the Brazilian Pediatric Oncology Society to complete a 5-point Likert-type scale questionnaire regarding their opinions of the importance of participation in cooperative group trials., Results: The accrual rate of patient participation per hospital varied from 25% to 76%, and was highest in the South region. The accrual rate of hospital participation also varied according to the region (20-31%) and was highest in the Southeast region. For the questionnaire regarding the importance of participation in cooperative groups, the responses showed an agreement of >75% on 10 of the 13 statements., Conclusion: Our results demonstrated low accrual of participation in a cooperative group trial in Brasil. We identified variations in registration rates according to geographic region and hospital, which may help targeted efforts to increase registration rates. The survey responses demonstrated that colleagues understand the importance of trial participation.

A convergent parallel mixed methods design was used to understand parenting practices for outdoor play, their influence on adolescent's physical activity and outdoor play and the role of the neighborhood and child's sex. Adolescents (n = 263) and their parents completed questionnaires and wore accelerometers. Parents (n = 30) participated in in-depth interviews. Parenting practices were examined by neighborhood disadvantage and child's sex in quantitative (Chi-square and T-tests) and qualitative (comparative thematic analysis) samples. Multi-level linear mixed models examined the associations between parenting practices and two adolescent outcomes: physical activity and outdoor play. Parents in high disadvantage neighborhoods and of female adolescents imposed more restrictions on outdoor play. Restrictive parenting practices were negatively associated with outdoor play, but not physical activity. Policy and environment change that improves neighborhood conditions may be necessary to reduce parents' fear and lessen restrictions on outdoor play., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Glyphosate (GLY) is a broad-spectrum, post-emergent, non-selective and synthetic universal herbicide, whose commercial formulations are referred to as glyphosate-based-herbicides (GBHs). These chemicals and their metabolites can be found in soil, air, water, as well as groundwater and food products. This review summarizes to summarize current in vitro and epidemiological studies investigating the effects of GLY exposure on human health. Recent human cell studies have reported several GLY and GBH toxicological effects and have contributed to a better understanding of the deleterious consequences associated with their exposure. However, these detrimental effects are dependent on the cell type, chemical composition, as well as magnitude and time of exposure, among other factors. Moreover, the deleterious effects of GLY exposure on human health were observed in epidemiological studies; however, most of these studies have not determined the GLY dosage to confirm a direct effect. While GLY toxicity is clear in human cells, epidemiological studies investigating individuals exposed to different levels of GLY have reported contradictory data. Therefore, based on currently available in vitro and epidemiological data, it is not possible to confirm the complete safety of GLY use, which will require additional comprehensive studies in animal models and humans., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk., Methods: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies., Results: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis., Conclusions: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.

Introduction: Active commuting to school could help increasing physical activity levels among adolescents. However, there is limited understanding on how the relationship between the environment in school surroundings, as well the distance to school, could affect this behavior., Aim: To analyze the characteristics of the environment and distance between house and school with objective measures and their association with active commuting between adolescents of Curitiba, Brazil., Methods: 493 adolescents were interviewed and 124 schools evaluated. The study variables included the schools' surroundings accessibility characteristics obtained through systematic observation, and the distance between home to school was determined through Geographic Information Systems (GIS) data., Results: The presence of "safety signs" was inversely associated with active commuting (PR = 0.78; 95%CI 0.67-0.91; p = 0.003), as well distance 1,501-3,000 m (PR = 0.53; 95%CI 0.40 - 0.71; p < 0.001) and ≥ 3,501 m (PR 0.29; 95%CI 0.18 - 0.45; p < 0.001). Overall, schools' surroundings showed walking friendly characteristics., Conclusion: Traffic safety and distance to school were associated with active commuting to school among the study participants. Policies aiming at integrating access to school and traffic safety could help to promoting active commuting among adolescents.

Objective Maxillary molar distalization with intraoral distalizer appliances is a non-extraction orthodontic treatment used to correct molar relationship in patients with Class II malocclusion presenting maxillary dentoalveolar protrusion and minor skeletal discrepancies. This study compares the changes caused by three distalizers with different force systems. Methodology 71 patients, divided into three groups, were included. The Jones jig group (JJG, n=30; 16 male, 14 female, 13.17 years mean age) was treated with the Jones jig for 0.8 years. The Distal jet group (DJG, n=25; 8 male, 17 female, 12.57 years mean age) was treated with the Distal jet for 1.06 years. The First Class group (FCG, n=16; 6 male, 10 female, 12.84 years mean age) was treated with the First Class for 0.69 years. Intergroup treatment changes were compared using one-way ANOVA, followed by post-hoc Tukey's tests. Results Intergroup comparisons showed significantly greater maxillary incisor protrusion in DJG than in FCG (2.56±2.24 mm vs. 0.74±1.39mm, p=0.015). The maxillary first premolars showed progressive and significantly smaller mesial angulation in JJG, FCG and DJG, respectively (14.65±6.31º, 8.43±3.99º, 0.97±3.16º; p<0.001). They also showed greater mesialization in JJG than FCG (3.76±1.46 mm vs. 2.27±1.47 mm, p=0.010), and greater extrusion in DJG compared to JJG (0.90±0.77 mm vs 0.11±0.60 mm, p=0.004). The maxillary second premolars showed progressive and significantly smaller mesial angulation and mesialization in JJG, FCG and DJG, respectively (12.77±5.78º, 3.20±3.94º, -2.12±3.71º and 3.87±1.34 mm, 2.25±1.40 mm, 1.24±1.26 mm, respectively; p<0.001). DJG showed smaller distal angulation of maxillary first molars (-2.14±5.09º vs. -7.73±4.28º and -6.05±3.76º, for the JJG and FCG, respectively; p<0.001) and greater maxillary second molars extrusion (1.17±1.41 mm vs -0.02±1.16 mm and 0.16±1.40 mm, for the JJG and FCG, respectively; p=0.003). Overjet change was significantly larger in DJG compared to FCG (1.79±1.67 mm vs 0.68±0.84; p=0.046). Treatment time was smaller in FCG (0.69±0.22 years vs 0.81±0.33 years and 1.06±0.42 years, comparing it with the JJG and DJG, respectively; p=0.005). Conclusion The three appliances corrected the Class II molar relationship by dentoalveolar changes. The Distal jet produced smaller molar distal angulation than the Jones jig and First Class. The First Class appliance showed less anchorage loss, greater percentage of distalization and shorter treatment time than the Jones jig and Distal jet.