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Abstract Background Low Magnesium (Mg) dietary intake has been associated with increased risk of type 2 diabetes mellitus (T2DM). Furthermore, in patients with T2DM, hypomagnesemia is associated with worst glycaemic control. Bariatric surgery (BS) remains the most effective treatment in severe obesity and also provides resolution/improvement of T2DM. Our aim is to evaluate the association between Mg supplementation post-BS and Mg serum levels with diabetes status after BS. Methods We performed an observational study on patients with obesity and T2DM who underwent BS. Data was assessed pre-BS and one-year post-BS. Results We included a total of 403 patients with T2DM. At baseline, 43.4% of the patients had Mg deficiency. Pre-BS, patients with Mg deficiency had poorer glycaemic control – HbA1c 7.2 ± 1.6% vs 6.4 ± 1.0% (p

Yugo A Martins,1 Maria JV Fonseca,1 Theo Z Pavan,2 Renata FV Lopez1 1School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, São Paulo, 14040-903, Brazil; 2School of Philosophy, Sciences and Letters of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, 14090-900, BrazilCorrespondence: Renata FV LopezUniversity of São Paulo, School of Pharmaceutical Sciences of Ribeirao Preto, Av. Do Café s/n, Ribeirao Preto, SP 14040-903, BrazilTel +55(16)3315-4202Email rvianna@fcfrp.usp.brPurpose: Sonodynamic therapy (SDT) is a new therapeutic modality for the noninvasive cancer treatment based on the association of ultrasound and sonosensitizer drugs. Topical SDT requires the development of delivery systems to properly transport the sonosensitizer, such as zinc phthalocyanine (ZnPc), to the skin. In addition, the delivery system itself can participate in sonodynamic events and influence the therapeutic response. This study aimed to develop ZnPc-loaded micelle to evaluate its potential as a topical delivery system and as a cavitational agent for low-frequency ultrasound (LFU) application with the dual purpose of promoting ZnPc skin penetration and generating reactive oxygen species (ROS) for SDT.Methods: ZnPc-loaded micelles were developed by the thin-film hydration method and optimized using the Quality by Design approach. Micelles’ influence on LFU-induced cavitation activity was measured by potassium iodide dosimeter and aluminum foil pits experiments. In vitro skin penetration of ZnPc was assessed after pretreatment of the skin with LFU and simultaneous LFU treatment using ZnPc-loaded micelles as coupling media followed by 6 h of passive permeation of ZnPc-loaded micelles. The singlet oxygen generation by LFU irradiation of the micelles was evaluated using two different hydrophilic probes. The lipid peroxidation of the skin was estimated using the malondialdehyde assay after skin treatment with simultaneous LFU using ZnPc-loaded micelles. The viability of the B16F10 melanoma cell line was evaluated using resazurin after treatment with different concentrations of ZnPc-loaded micelles irradiated or not with LFU.Results: The micelles increased the solubility of ZnPc and augmented the LFU-induced cavitation activity in two times compared to water. After 6 h ZnPc-loaded micelles skin permeation, simultaneous LFU treatment increased the amount of ZnPc in the dermis by more than 40 times, when compared to non-LFU-mediated treatment, and by almost 5 times, when compared to LFU pretreatment protocol. The LFU irradiation of micelles induced the generation of singlet oxygen, and the lipoperoxidation of the skin treated with the simultaneous LFU was enhanced in three times in comparison to the non-LFU-treated skin. A significant reduction in cell viability following treatment with ZnPc-loaded micelles and LFU was observed compared to blank micelles and non-LFU-treated control groups.Conclusion: LFU-irradiated mice can be a potential approach to skin cancer treatment by combining the functions of increasing drug penetration and ROS generation required for SDT.Keywords: sonodynamic therapy, nanocarrier, topical delivery, reactive oxygen species, skin cancer

Brazilian savanna constitutes a valuable ecoregion that contributes to the supply of fruit known worldwide for its nutritional value and peculiar flavors. Among them, the Marolo (Annona crassiflora Mart.) fruit is known for its use in folk medicine. In order to establish the safety of Marolo for human consumption, this study evaluated the following: the chemical composition of Marolo pulp; its mutagenic and antimutagenic activities using micronucleus test; and the oxidative stress induced in the livers of mice fed a diet containing 1%, 10% or 20% pulp. It was observed that the chemical composition of marolo pulp was similar to that of common fruit; nevertheless, its lipidic content and energetic values were higher. In the mice fed experimental diets, the biochemical parameters of the blood serum showed normal levels of glucose, triglycerides, and cholesterol. The micronucleus test indicated neither mutagenic nor antimutagenic effects of Marolo consumption on bone marrow cells but showed potentialization of cyclophosphamide (CP). The oxidative stress levels observed indicated that CP was not exerting a great influence on the induction of reactive oxygen species. As the whole fruit is a complex matrix, the interactions between its components could be responsible for its negative and positive biological effects. [ABSTRACT FROM AUTHOR]

Background and Aims: Utilising real-world data, we quantified the burden of cardiovascular risk factors and long-term residual risk of atherothrombotic events among routine care cohorts with coronary (CAD) or peripheral (PAD) artery disease or ischemic stroke (IS) on guideline-recommended antiplatelet monotherapy (APMT)., Methods: Retrospective cohort study using data (2010-2020) from the United Kingdom Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics, including adults with CAD, PAD or IS who were first prescribed APMT (CAD/IS: aspirin; PAD: clopidogrel). Primary outcomes (recurrent events): major adverse cardiovascular events (MACE) for CAD/PAD/IS cohorts, major adverse limb events (MALE) for PAD., Results: 266,478 CAD, 13,162 PAD, and 14,788 IS patients were included (mean age: 71 years; women 37.7%-47.5 %). Risk factor burden was high and attainment of recommended goals was low. There were 73,691, 3,121 and 7,137 MACE among CAD, PAD and IS patients, respectively (median follow-up: 89.9, 42.4 and 75.9 months, respectively), and 4,767 MALE among PAD patients. MACE incidence rate per 1000 person-years was higher in IS (268.7; 95%CI 265.3-272.0) than CAD (92.9; 95%CI 92.5-93.4) or PAD cohorts (97.2; 95%CI 94.6-99.8). MALE incidence rate was 195.9 (95%CI 192.2-199.6) per 1000 person-years. IS patients presented a lower rate of hospitalisations and longer time-to-first hospitalisation, but once hospitalised, they had a longer length-of-stay. PAD patients had the highest hospitalisation rate., Conclusions: Among a contemporary cohort with cardiovascular disease on APMT, long-term residual atherothrombotic risk remains high despite being on APMT. Greater attention to risk factor control and use of appropriate evidence-based therapy is required to reduce residual risk among this very high-risk population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AJVV: personal fees for consulting from Bayer, during the conduct of the study; current or past participation in research grants to Imperial College London from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron, outside the submitted work; and personal fees for consulting from Regeneron and honoraria for lectures from Amgen, Mylan, Akcea, and Ferrer, outside the submitted work. KID: personal fees for consulting from Bayer, during the conduct of the study; grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron, outside the submitted study; and personal fees from Regeneron, outside the submitted work. NN,CCand STF:Bayer plc employees. MJF,ETand CL: none to report. KKR: personal fees for consulting from Bayer, during the conduct of the study; grants and personal fees from Aegerion, Amgen, Daiichi Sankyo, MSD, Pfizer, and Sanofi/Regeneron, and personal fees from Abbvie, Akcea, Algorithm, Astra Zeneca, Bayer, Boehringer Ingelheim, Cerenis Therapeutcics, Cipla, Dr Reddy's Laboratories, Esperion, Kowa, Lilly, Novartis, Silence Therapeutics, Takeda, and Zuellig Pharma, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to evaluate the disparity of the expectations and basic knowledge of prenatal ultrasound (US) screening among pregnant women and make a comparison with the current scientific knowledge and national recommendations. We hypothesize that sociodemographic factors, including age, education, and professional occupation, may be associated with different levels of knowledge., Methods: This was a cross-sectional study performed in 2021 of 336 women aged 18 to 46 years in a maternity facility in a tertiary hospital in Portugal. The main outcome measures were questionnaire data from questions divided into four categories (sociodemographic, expectations, knowledge, and final considerations/suggestions). The data were grouped according to the sociodemographic factors (age, educational level, and professional occupation) and analyzed and compared as a function of the social groups as well as overall tendencies., Results: Our data confirmed a significant discrepancy between the expectations and general knowledge of pregnant women regarding prenatal US when compared with the current scientific knowledge. Importantly, we found that both depended greatly on sociodemographic factors, particularly educational level. This reiterated the importance of conducting effective dissemination actions of current scientific knowledge, focusing on the main objectives of US screening as well as the limitations of the existing technology., Conclusion: This study will help in defining strategies for future dissemination actions aiming to improve current practice and lead to a higher synchrony of expectations towards US between couples and practitioners., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: A granular understanding of respiratory syncytial virus (RSV) burden in England is needed to prepare for new RSV prevention strategies. We estimated the rates of RSV hospital admissions before the age of 2 years in England and described baseline characteristics., Methods: A birth cohort of all infants born between March 1, 2015, and February 28, 2017 (n = 449,591) was established using Clinical Practice Research Datalink-Hospital Episode Statistics. Case cohorts included infants with admission for (1) RSV, (2) bronchiolitis, (3) any respiratory tract infection (RTI) <24 months and (4) RSV predicted by an algorithm <12 months. Baseline characteristics were described in the case and comparative cohorts (infants without corresponding admission). Cumulative incidence and admission rates were calculated. Multiple linear regression was used to estimate the proportion of RTI healthcare visits attributable to RSV., Results: The RSV-coded/RSV-predicted case cohorts were composed of 4813/12,694 infants (cumulative incidence: 1.1%/2.8%). Case cohort infants were more likely to have low birth weight, comorbidities and to be born during RSV season than comparative cohort infants, yet >77% were term-healthy infants and >54% were born before the RSV season. During the first year of life, 11.6 RSV-coded and 34.4 RSV-predicted hospitalizations occurred per 1000 person-years. Overall, >25% of unspecified lower RTI admissions were estimated to be due to RSV., Conclusions: In England, 1 in 91 infants had an RSV-coded admission, likely underestimated by ~3-fold. Most infants were term-healthy infants born before the RSV season. To decrease the total burden of RSV at the population level, immunization programs need to protect all infants., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To determine the prevalence of body image accuracy/distortion in Brazilian men and women and to investigate sociodemographic and lifestyle-related factors, and the presence of chronic diseases associated with body image distortion., Methods: Data from 6,357 men and 7,657 women participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were collected using a multidimensional questionnaire covering sociodemographic characteristics, health behaviors, heath conditions and body image perception., Results: Most participants (53.5% of the women and 54.7% of the men) were found to have an accurate self-perception of their body. When the factors associated with the perception of being heavier than reality were investigated, adopting weight loss measures and not being hypertensive proved protective against this distortion, both in women and men. Conversely, the perception of being lighter than reality was associated, in both women and men, with better education, being black or of mixed race, adopting weight loss measures and not being hypertensive or diabetic. Additional factors associated with underestimating weight were not consuming alcohol (only in women) and belonging to a lower social class (only in men)., Conclusion: These findings may contribute to the implementation of public health policies and interventions to promote health and well-being in the Brazilian population., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Video games have become increasingly popular worldwide, attracting billions of gamers across diverse demographics. While studies have highlighted their potential benefits, concerns about problematic gaming behaviors have also emerged. Conditions such as Internet Gaming Disorder (IGD) have been recognized by major health organizations, necessitating accurate diagnostic tools. However, existing methods, primarily reliant on self-report questionnaires, face challenges in accuracy and consistency. This paper proposes a novel technological approach to provide gaming behavior indicators, aiming to offer precise insights into gamer behavior and emotion regulation., Methods: To attain this objective, we investigate quantifiable gaming behavior metrics using automated, unobtrusive, and easily accessible methods. Our approach encompasses the analysis of behavioral telemetry data collected from online gaming platforms and incorporates automated extraction of gamer emotional states from face video recordings during gameplay. To illustrate the metrics and visualizations and demonstrate our method's application we collected data from two amateur and two professional gamers, all of whom played Counter-Strike2 on PC. Our approach offers objective insights into in-game gamer behavior, helping health professionals in the identification of patterns that may be difficult to discern through traditional assessment methods., Results: Preliminary assessments of the proposed methodology demonstrate its potential usefulness in providing valuable insights about gaming behavior and emotion regulation. By leveraging automated data collection and visualization analysis techniques, our approach offers a more comprehensive understanding of gamer behavior, which could enhance diagnostic accuracy and inform interventions for individuals at risk of problematic gaming behaviors., Conclusion: Our findings demonstrate the valuable insights obtainable from a tool that collects telemetry data, emotion regulation metrics, and gaming patterns. This tool, utilizing specific indicators, can support healthcare professionals in diagnosing IGD and tracking therapeutic progress, potentially addressing challenges linked to conventional IGD assessment methods. Furthermore, this initial data can provide therapists with detailed information on each player's problematic behaviors and gaming habits, enabling the development of personalized treatments tailored to individual needs. Future research endeavors will focus on refining the methodology and extending its application in clinical settings to facilitate more comprehensive diagnostic practices and tailored interventions for individuals at risk of problematic gaming behaviors., 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., (© 2024 Afonso, Fonseca, Cardoso and Vasquez.)

The Anaplasmataceae family includes obligate, arthropod-transmitted intracellular bacteria that can be zoonotic and potentially fatal. Studies focusing on the interaction between neotropical primates and the agents of this family are scarce. The present study aimed to identify agents of the Anaplasmataceae family in the whole blood of free-living and captive neotropical primates in the State of Mato Grosso, Central-West Brazil. Thirty-eight samples of six nonhuman primate (NHP) species were collected in seven municipalities and analysed through polymerase chain reaction (PCR), nucleotide sequencing, and phylogenetic analysis of the dsb, groEL, 16S rRNA, and gltA genes. DNA fragments similar to those of Ehrlichia canis were detected in Sapajus apella and Ehrlichia chaffeensis from Mico melanurus. The sequences generated in this study and homologous sequences retrieved from GenBank® were used for phylogenetic analyses to characterize the Ehrlichial agents detected in NHPs. The agents were then grouped into clades corresponding to different isolates from the NHP species. In addition, an Anaplasma sp. closely related to Anaplasma marginale was identified in two S. apella individuals. These findings shed light on the susceptibility of neotropical NHPs to Anaplasmataceae agents. These bacteria are known to be transmitted by ticks, which can also serve as possible sources of infection for other animals, including humans., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Agriculture and food science literature on waste-to-value applications that allow upcycling of by-product ingredients is increasing. However, this stream of research rarely takes an international trade and sustainability systems perspective. This focused review defines the term of waste-to-value and the sustainable development goals connected to it, and points to the tensions and questions arising when international trade is involved. Further, it exemplifies the challenges and opportunities of waste-to-value in tropical fruit trade through five cases of tropical fruit from South America: Green coconut, açaí, maracujá, cambuci, and jabuticaba. We present a model of the international supply chain that indicates where the opportunities of waste-to-value applications in international tropical fruit trade are situated, and discuss which future research questions need to be addressed to tackle the challenges of waste-to-value in global tropical fruit chains. Establishing the waste-to-value approach in the export of yet-underused tropical fruits can amongst others improve local employment, preserve natural resources, allow favorable use of side-streams in local energy production, environmentally friendly packaging material for transport, and add health functionalities to the end-consumer products, but challenges have to be solved in order to ensure these environmental and social benefits materialize.

One of the main challenges in CBIR systems is to choose discriminative and compact features, among dozens, to represent the images under comparison. Over the years, a great effort has been made to combine multiple features, mainly using early, late, and hierarchical fusion techniques. Unveiling the perfect combination of features is highly domain-specific and dependent on the type of image. Thus, the process of designing a CBIR system for new datasets or domains involves a huge experimentation overhead, leading to multiple fine-tuned CBIR systems. It would be desirable to dynamically find the best combination of CBIR systems without needing to go through such extensive experimentation and without requiring previous domain knowledge. In this paper, we propose ExpertosLF, a model-agnostic interpretable late fusion technique based on online learning with expert advice, which dynamically combines CBIR systems without knowing a priori which ones are the best for a given domain. At each query, ExpertosLF takes advantage of user's feedback to determine each CBIR contribution in the ensemble for the following queries. ExpertosLF produces an interpretable ensemble that is independent of the dataset and domain. Moreover, ExpertosLF is designed to be modular, and scalable. Experiments on 13 benchmark datasets from the Biomedical, Real, and Sketch domains revealed that: (i) ExpertosLF surpasses the performance of state of the art late-fusion techniques; (ii) it successfully and quickly converges to the performance of the best CBIR sets across domains without any previous domain knowledge (in most cases, fewer than 25 queries need to receive human feedback)., Competing Interests: Conflict of interestsThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Dental pathology is among the most ubiquitous diseases in cats of all ages. Dental pain is yet to be fully understood in cats and therefore its presence is often missed. To better understand feline dental disease as a pain trigger during routine examination and whether disease severity correlates to the degree of pain, a 6-month prospective study in a cats' only veterinary hospital in Portugal was conducted. Sixty-four cats that randomly presented for different clinical procedures were evaluated. Dental and periodontal abnormalities (primary dental parameters, PDP), as well as clinical signs related to dental pain (secondary dental parameters, SDP), were assessed. All cats underwent an oral cavity examination, upon which, the Feline Acute Pain Scale from Colorado State University Veterinary Teaching Hospital (CPS), was used in order to assess pain. Six PDP (periodontal disease, gingival index, calculus index, tooth resorption, tooth fracture and missing teeth) and five SDP (mouth discomfort, halitosis, hypersalivation, difficulty in holding food and several attempts at prehension of food), were compared with CPS pain scores. All SDP were significantly associated to higher CPS pain scores (p < 0.05). The number of missing teeth was significantly associated to higher CPS pain scores (p < 0.0001). A trend was observed between higher CPS pain scores and tooth resorption (p = 0.08). This study concluded that cats with dental disease feel pain during clinical examination and the pain increases as the severity of the disease progresses.

Cryptococcus neoformans is an opportunistic fungal pathogen known for its remarkable ability to infect and subvert phagocytes. This ability provides survival and persistence within the host and relies on phenotypic plasticity. The viable but nonculturable (VBNC) phenotype was recently described in C. neoformans, whose study is promising in understanding the pathophysiology of cryptococcosis. The use of fluorescent strains is improving host interaction research, but it is still underexploited. Here, we fused histone H3 or the poly(A) binding protein (Pab) to enhanced green fluorescent protein (eGFP) or mCherry, obtaining a set of C. neoformans transformants with different colors, patterns of fluorescence, and selective markers (hygromycin B resistance [Hyg r ] or neomycin resistance [Neo r ]). We validated their similarity to the parental strain in the stress response, the expression of virulence-related phenotypes, mating, virulence in Galleria mellonella, and survival within murine macrophages. PAB-GFP, the brightest transformant, was successfully applied for the analysis of phagocytosis by flow cytometry and fluorescence microscopy. Moreover, we demonstrated that an engineered fluorescent strain of C. neoformans was able to generate VBNC cells. GFP-tagged Pab1, a key regulator of the stress response, evidenced nuclear retention of Pab1 and the assembly of cytoplasmic stress granules, unveiling posttranscriptional mechanisms associated with dormant C. neoformans cells. Our results support that the PAB-GFP strain is a useful tool for research on C. neoformans. IMPORTANCE Cryptococcus neoformans is a human-pathogenic yeast that can undergo a dormant state and is responsible for over 180,000 deaths annually worldwide. We engineered a set of fluorescent transformants to aid in research on C. neoformans. A mutant with GFP-tagged Pab1 improved fluorescence-based techniques used in host interaction studies. Moreover, this mutant induced a viable but nonculturable phenotype and uncovered posttranscriptional mechanisms associated with dormant C. neoformans. The experimental use of fluorescent mutants may shed light on C. neoformans-host interactions and fungal biology, including dormant phenotypes.

Background: Multimorbidity is a worldwide concern related to greater disability, worse quality of life, and mortality. The early prediction is crucial for preventive strategies design and integrative medical practice. However, knowledge about how to predict multimorbidity is limited, possibly due to the complexity involved in predicting multiple chronic diseases., Methods: In this study, we present the use of a machine learning approach to build cost-effective multimorbidity prediction models. Based on predictors easily obtainable in clinical practice (sociodemographic, clinical, family disease history and lifestyle), we build and compared the performance of seven multilabel classifiers (multivariate random forest, and classifier chain, binary relevance and binary dependence, with random forest and support vector machine as base classifiers), using a sample of 15105 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We developed a web application for the building and use of prediction models., Results: Classifier chain with random forest as base classifier performed better (accuracy = 0.34, subset accuracy = 0.15, and Hamming Loss = 0.16). For different feature sets, random forest based classifiers outperformed those based on support vector machine. BMI, blood pressure, sex, and age were the features most relevant to multimorbidity prediction., Conclusions: Our results support the choice of random forest based classifiers for multimorbidity prediction., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Literature has demonstrated an inverse relation between magnesium (Mg) consumption and development of type 2 diabetes mellitus (T2DM), hypertension (HT), and dyslipidemia. After bariatric surgery (BS), micronutrients deficiencies are common, it being important to ensure appropriate supplementation. There is no recommendation about Mg supplementation and to our knowledge, its effect has not been studied to date. Our aim was to evaluate the effect of Mg supplementation in cardio-metabolic risk factors on post-bariatric patients., Materials and Methods: A retrospective observational study of patients with obesity who underwent BS was performed. Data was assessed preoperatively and yearly (4-year follow-up)., Results: A total of 3363 patients were included. In the first year of follow-up, 79.8% (n = 2123) of the patients were supplemented with Mg, with evidence of slightly decreased percentages in the following years. Mg deficiency (serum Mg < 1.52 mEq/L) was more common among patients who were not supplemented during each year of follow-up (p < 0.05). Among those who underwent Mg supplementation, the percentage of T2DM, HT, or low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL was significantly lower. In the first year post-surgery, the supplementation group had a lower risk of T2DM (OR = 0.545, p < 0.0001), LDL-C > 130 mg/dL (OR = 0.612, p < 0.0001), and HT (OR = 0.584, p < 0.0001). The OR for having these metabolic comorbidities persisted lower during the 4 years' follow-up. Patients who had Mg deficiency had higher prevalence of T2DM and HT., Conclusion: Mg supplementation seems to have a protective effect on the development of T2DM, HT, and LDL-C > 130 mg/dL in post-bariatric patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Chronic kidney disease (CKD) is a public health problem and it is associated with a high risk of mortality. Overweight and obesity are known as independent risk factors for CKD., Objective: To investigate the association between adiposity indexes and kidney disease., Methods: This study included 14,636 adults from ELSA-Brazil. Outcome variables: altered glomerular filtration rate (GFR), categorized as yes (GFR <60 mL/min/1.73 m 2 ) and no (GFR ≥60 mL/min/1.73 m 2 ), albuminuria, estimated by albumin-creatinine ratio and categorized as yes (≥30 mg/g) and no (<30 mg/g), and presence of chronic kidney disease (CKD) (altered GFR and/or albuminuria). Exposure variables: obesity and overweight (body mass index (BMI)≥30 and ≥25 kg/m 2 , respectively), high waist circumference (WC) (≥102 cm in men and ≥88 cm in women), high waist-to-hip ratio (WHR) (≥0.90 in men and ≥0.85 in women), and high waist-to-height ratio (WHtR) (≥0.5). To estimate the association between main exposures and outcomes, logistic regression analyses were performed using models adjusted for sociodemographic variables (age, gender, race/skin color, education), behavioral (smoking, physical activity, alcohol consumption), components of the metabolic syndrome (HDL cholesterol, triglycerides, hypertension, diabetes mellitus ) and history of cardiovascular disease (myocardial infarction, angina or heart failure)., Results: Individuals with obesity, high WC, WHR and WHtR were more prone to albuminuria when compared to individuals with normal values for these measures. It was also observed that these altered measures were positively associated with the presence of CKD., Conclusion: Adiposity indexes have a direct and significant association with albuminuria and CKD.

Cardiovascular diseases are the main cause of mortality worldwide, and childhood excess weight/obesity are strong correlators of accumulated risk in later life. A relationship between maternal preeclampsia and offspring's childhood obesity is recognized, but most studies fail to control for strong confounders. Our goal is to analyze the association between preeclampsia and childhood excess weight/obesity, after accounting for important confounders. We recruited 5133 women with singleton pregnancies during admission for delivery. Sixty-seven pregnancies were complicated by preeclampsia. Maternal and children outcomes were assessed at 10 years of age. We analyzed the association between preeclampsia and childhood excess weight/obesity by fitting a linear regression model (using offspring body mass index (BMI) z-score at 10 years of age) and a logistic regression model (using excess weight/obesity status). We then controlled both models for known confounders, namely maternal prepregnancy BMI, parity, and smoking during pregnancy. At 10 years of age, offspring of preeclamptic mothers had a higher BMI z-score and were more likely classified as overweight/obese, but these differences were not statistically significant. After controlling for maternal prepregnancy BMI, parity, and smoking during pregnancy, there was a high magnitude change in the beta coefficient of preeclampsia in the linear (0.175; -0.014) and the logistic regression models (1.48; 1.23) suggesting that the association between preeclampsia and childhood excess weigh/obesity is significantly confounded by these variables. These confounders also showed a significant association with childhood obesity. This finding suggests that in utero exposure to preeclampsia seems to have less impact in childhood obesity than the previously described confounders.

Objective: To estimate annual weight gain and the incidence of overweight and obesity, stratified according to gender and socioeconomic factors., Methods: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we included 13 625 women and men aged 35-74 (2008-2010) who attended a follow-up visit after a mean 3.8-years. Standardized questionnaires were used to record sociodemographic data, and height and weight were measured on all participants during in-person visits at research centers. The incidence rate to overweight was calculated among those not having excess weight at baseline, and incident obesity among those not having this condition at baseline. We evaluated the incidence of overweight and obesity in men and women, adjusted by age, through Poisson regression with robust variance. Large annual weight gain by gender was being defined as ≥90th percentile in the cohort., Results: A global incidence of 7.7% for overweight and 10.6% for obesity was observed, with higher levels seen among black woman (28.5%), young men (21.1%) and woman with low educational level (35.0%). The proportions of overweight and obesity increased with age at both time points, more commonly among those with the lowest levels of per capita income and fewer years of schooling. Large annual weight gain was greater among participants with an intermediate level of education and those who self-identified as black., Conclusions: A high overall risk of becoming overweight/obese was found, especially among women. The roles of race and education level are fundamental to understanding the effects produced by social inequalities in rates of excess weight., (© 2021 Wiley Periodicals LLC.)

Humicola grisea var. thermoidea is a thermophilic ascomycete and important enzyme producer that has an efficient enzymatic system with a broad spectrum of thermostable carbohydrate-active (CAZy) enzymes. These enzymes can be employed in lignocellulose biomass deconstruction and other industrial applications. In this work, the genome of H. grisea var. thermoidea was sequenced. The acquired sequence reads were assembled into a total length of 28.75 Mbp. Genome features correlate with what was expected for thermophilic Sordariomycetes. The transcriptomic data showed that sugarcane bagasse significantly upregulated genes related to primary metabolism and polysaccharide deconstruction, especially hydrolases, at both pH 5 and pH 8. However, a number of exclusive and shared genes between the pH values were found, especially at pH 8. H. grisea expresses an average of 211 CAZy enzymes (CAZymes), which are capable of acting in different substrates. The top upregulated genes at both pH values represent CAZyme-encoding genes from different classes, including acetylxylan esterase, endo-1,4-β-mannosidase, exoglucanase, and endoglucanase genes. For the first time, the arsenal that the thermophilic fungus H. grisea var. thermoidea possesses to degrade the lignocellulosic biomass is shown. Carbon source and pH are of pivotal importance in regulating gene expression in this organism, and alkaline pH is a key regulatory factor for sugarcane bagasse hydrolysis. This work paves the way for the genetic manipulation and robust biotechnological applications of this fungus. IMPORTANCE Most studies regarding the use of fungi as enzyme producers for biomass deconstruction have focused on mesophile species, whereas the potential of thermophiles has been evaluated less. This study revealed, through genome and transcriptome analyses, the genetic repertoire of the biotechnological relevant thermophile fungus Humicola grisea . Comparative genomics helped us to further understand the biology and biotechnological potential of H. grisea . The results demonstrate that this fungus possesses an arsenal of carbohydrate-active (CAZy) enzymes to degrade the lignocellulosic biomass. Indeed, it expresses more than 200 genes encoding CAZy enzymes when cultivated in sugarcane bagasse. Carbon source and pH are key factors for regulating the gene expression in this organism. This work shows, for the first time, the great potential of H. grisea as an enzyme producer and a gene donor for biotechnological applications and provides the base for the genetic manipulation and robust biotechnological applications of this fungus.

Background: We aimed to evaluate the association of adiposity rebound (AR) timing on cardiometabolic health in childhood., Methods: Participants were part of the Generation XXI birth cohort, enrolled in 2005/2006 in Porto. All measurements of the child's weight and height performed by health professionals as part of routine healthcare were collected. Individual body mass index (BMI) curves were fitted for 3372 children, using mixed-effects models with smooth spline functions for age and random effects. The AR was categorized into very early (<42 months), early (42-59 months), normal (60-83 months) and late (≥84 months). At age 10 years, cardiometabolic traits were assessed and age- and sex-specific z-scores were generated. Adjusted regression coefficients and 95% confidence intervals [β (95% CI)] were computed., Results: The mean age at AR was 61.9 months (standard deviations 15.7). Compared with children with normal AR, children with very early or early AR had higher z-scores for BMI [β = 0.40 (95% CI: 0.28; 0.53); β = 0.21 (95% CI: 0.12; 0.30)], waist circumference [β = 0.33 (95% CI: 0.23; 0.43); β = 0.18 (95% CI: 0.10; 0.25)], waist-height ratio [β = 0.34 (95% CI: 0.24; 0.44); β = 0.14 (95% CI: 0.07; 0.22)], fat mass index [β = 0.24 (95% CI: 0.15; 0.33); β = 0.14 (95% CI: 0.08; 0.21)], fat-free mass index [β = 0.25 (95% CI: 0.14; 0.35); β = 0.11 (95% CI: 0.03; 0.19)], systolic blood pressure [β = 0.10 (95% CI: 0.01; 0.20); β = 0.08 (95% CI: 0.01; 0.15)], insulin [β = 0.16 (95% CI: 0.04; 0.29); β = 0.10 (95% CI: 0.01; 0.19)], HOMA-IR [β = 0.17 (95% CI: 0.04; 0.29); β = 0.10 (95% CI: 0.03; 0.19)] and C-reactive protein [β = 0.14 (95% CI: 0.02; 0.26); β = 0.10 (95% CI: 0.01; 0.19)]. Children with very early AR also had worse levels of diastolic blood pressure [β = 0.09 (95% CI: 0.02; 0.16)], triglycerides [β = 0.21 (95% CI: 0.08; 0.34)] and high-density lipoprotein cholesterol [β=-0.18 (95% CI: -0.31; -0.04)]. When analysed continuously, each additional month of age at the AR was associated with healthier cardiometabolic traits., Conclusion: The earlier the AR, the worse the cardiometabolic health in late childhood, which was consistently shown across a wide range of outcomes and in the categorical and continuous approach., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Recognition of emotions from physiological signals, and in particular from electroencephalography (EEG), is a field within affective computing gaining increasing relevance. Although researchers have used these signals to recognize emotions, most of them only identify a limited set of emotional states (e.g., happiness, sadness, anger, etc.) and have not attempted to predict exact values for valence and arousal, which would provide a wider range of emotional states. This paper describes our proposed model for predicting the exact values of valence and arousal in a subject-independent scenario. To create it, we studied the best features, brain waves, and machine learning models that are currently in use for emotion classification. This systematic analysis revealed that the best prediction model uses a KNN regressor (K = 1) with Manhattan distance, features from the alpha, beta and gamma bands, and the differential asymmetry from the alpha band. Results, using the DEAP, AMIGOS and DREAMER datasets, show that our model can predict valence and arousal values with a low error (MAE < 0.06, RMSE < 0.16) and a strong correlation between predicted and expected values (PCC > 0.80), and can identify four emotional classes with an accuracy of 84.4%. The findings of this work show that the features, brain waves and machine learning models, typically used in emotion classification tasks, can be used in more challenging situations, such as the prediction of exact values for valence and arousal.

Cryptococcus is a globally distributed fungal pathogen that primarily afflicts immunocompromised individuals. The therapeutic options are limited and include mostly amphotericin B or fluconazole, alone or in combination. The extensive usage of antifungals allowed the selection of resistant pathogens posing threats to global public health. Histone deacetylase genes are involved in Cryptococcus virulence, and in pathogenicity and resistance to azoles in Candida albicans. Aiming to assess whether histone deacetylase genes are involved in antifungal response and in synergistic drug interactions, we evaluated the activity of amphotericin B, fluconazole, sulfamethoxazole, sodium butyrate or trichostatin A (histone deacetylase inhibitors), and hydralazine or 5- aza-2'-deoxycytidine (DNA methyl-transferase inhibitors) against different Cryptococcus neoformans strains, C. neoformans histone deacetylase null mutants and Cryptococcus gattii NIH198. The drugs were employed alone or in different combinations. Fungal growth after photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion, alone or in combination with the aforementioned drugs, was assessed for the C. neoformans HDAC null mutant strains. Our results showed that fluconazole was synergistic with sodium butyrate or with trichostatin A for the hda1Δ/hos2Δ double mutant strain. Sulfamethoxazole was synergistic with sodium butyrate or with hydralazine also for hda1Δ/hos2Δ. These results clearly indicate a link between HDAC impairment and drug sensitivity. Photodynamic therapy efficacy on controlling the growth of the HDAC mutant strains was increased by amphotericin B, fluconazole, sodium butyrate or hydralazine. This is the first study in Cryptococcus highlighting the combined effects of antifungal drugs, histone deacetylase or DNA methyltransferase inhibitors and photodynamic therapy in vitro., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pathogenic microbes are exposed to a number of potential DNA-damaging stimuli during interaction with the host immune system. Microbial survival in this situation depends on a fine balance between the maintenance of DNA integrity and the adaptability provided by mutations. In this study, we investigated the association of the DNA repair response with the virulence of Cryptococcus neoformans , a basidiomycete that causes life-threatening meningoencephalitis in immunocompromised individuals. We focused on the characterization of C. neoformans APN1 and APN2 putative genes, aiming to evaluate a possible role of the predicted Apurinic/apyrimidinic (AP) endonucleases 1 and 2 of the base excision repair (BER) pathway on C. neoformans response to stress conditions and virulence. Our results demonstrated the involvement of the putative AP-endonucleases Apn1 and Apn2 in the cellular response to DNA damage induced by alkylation and by UV radiation, in melanin production, in tolerance to drugs and in virulence of C. neoformans in vivo. We also pointed out the potential use of DNA repair inhibitor methoxy-amine in combination with conventional antifungal drugs, for the development of new therapeutic approaches against this human fungal pathogen. This work provides new information about the DNA damage response of the highly important pathogenic fungus C. neoformans .

Metagenomics is an exciting alternative to seek carbohydrate-active enzymes from a range of sources. Typically, metagenomics reveals dozens of putative catalysts that require functional characterization for further application in industrial processes. High-throughput screening methods compatible with adequate natural substrates are crucial for an accurate functional elucidation of substrate preferences. Based on DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) analysis of enzymatic-reaction products, we generated product profiles to consequently infer substrate cleavage positions, resulting in the generation of enzymatic-degradation maps. Product profiles were produced in high throughput for arabinoxylan (AX)-active enzymes belonging to the glycoside hydrolase families GH43 (subfamilies 2 [MG43 2 ], 7 [MG43 7 ], and 28 [MG43 28 ]) and GH8 (MG8) starting from 12 (arabino)xylo-oligosaccharides. These enzymes were discovered through functional metagenomic studies of feces from the North American beaver ( Castor canadensis ). This work shows how enzyme loading alters the product profiles of all enzymes studied and gives insight into AX degradation patterns, revealing sequential substrate preferences of AX-active enzymes. IMPORTANCE Arabinoxylan is mainly found in the hemicellulosic fractions of rice straw, corn cobs, and rice husk. Converting arabinoxylan into (arabino)xylo-oligosaccharides as added-value products that can be applied in food, feed, and cosmetics presents a sustainable and economic alternative for the biorefinery industries. Efficient and profitable AX degradation requires a set of enzymes with particular characteristics. Therefore, enzyme discovery and the study of substrate preferences are of utmost importance. Beavers, as consumers of woody biomass, are a promising source of a repertoire of enzymes able to deconstruct hemicelluloses into soluble oligosaccharides. High-throughput analysis of the oligosaccharide profiles produced by these enzymes will assist in the selection of the most appropriate enzymes for the biorefinery., (Copyright © 2020 American Society for Microbiology.)

The key role of bioinformatics in explaining biological phenomena calls for the need to rethink didactic approaches at high school aligned with a new scientific reality. Despite several initiatives to introduce bioinformatics in the classroom, there is still a lack of knowledge on their impact on students' learning gains, engagement, and motivation. In this study, we detail the effects of four bioinformatics laboratories tailored for high school biology classes named "Mining the Genome: Using Bioinformatics Tools in the Classroom to Support Student Discovery of Genes" on literacy, interest, and attitudes on 387 high school students. By exploring these laboratories, students get acquainted with bioinformatics and acknowledge that many bioinformatics tools can be intuitive for beginners. Furthermore, introducing comparative genomics in their learning practices contributed for a better understanding of curricular contents regarding the identification of genes, their regulation, and how to make evolutionary assumptions. Following the intervention, students were able to pinpoint bioinformatics tools required to identify genes in a genomics sequence, and most importantly, they were able to solve genomics-related misconceptions. Overall, students revealed a positive attitude regarding the integration of bioinformatics-based approaches in their learning practices, reinforcing their added value in educational approaches., (Copyright © 2020 Martins, Fonseca, Lemos, Lencastre and Tavares.)

Background: Women of advanced maternal age, defined as ≥ 35 years at delivery, are at increased risk of multiple complications during pregnancy, with perinatal death being one of the most feared. For instance, the risk of stillbirth at term in this subgroup of women is higher than in younger women, and particularly high beyond 39 weeks of gestation. Induction of labor at 39-40 weeks might help prevent some cases of perinatal death, however, the fact that induction of labor has been historically associated with an increased risk of cesarean delivery and the knowledge that advanced maternal age is an independent risk factor for cesarean delivery are some of the major reasons why clinicians are reluctant to offer elective induction of labor in this particular group., Objective: The aim of the study was to assess if induction of labor in advanced maternal age was associated with increased rates of cesarean delivery when compared to expectant management., Material and Methods: We performed an electronic search limited to published articles available between January 2000 and March 2020. Randomized clinical trials and retrospective studies with large cohorts comparing induction of labor with expectant management in singleton pregnancies at term, of women aged ≥ 35 years were included. The primary outcome was the rate of cesarean delivery in induction of labor versus expectant management, and secondary outcomes were the occurrence of assisted vaginal delivery and postpartum hemorrhage., Results: Eight studies, including 81151 pregnancies (26,631 in the induction group and 54,520 expectantly managed), were included in the analysis. Six of the included studies were randomized clinical trials with the remaining two being observational and retrospective cohort studies. Induction of labor was not associated with a significant increased risk of cesarean delivery (OR 0.97, 95 % CI 0.86-1.1), assisted vaginal delivery (OR 1.12, 95 % CI 0.96-1.32) or postpartum hemorrhage (OR 1.11, 95 % CI 0.88-1.41)., Discussion: The belief that induction of labor is associated with an increased risk of cesarean delivery is based on the results of retrospective studies comparing induction with spontaneous labor at the same gestational age. However, at any point in a pregnancy, the comparison should be between induction of labor and expectant management, with the latter contributing to a pregnancy of greater gestation age and not always leading to spontaneous labor. When comparing induction to expectant management, our study shows no significant increase of cesarean section, assisted vaginal delivery or postpartum hemorrhage. Our study was not powered to assess neonatal outcomes, and additional research is needed to confirm whether induction of labor might have a positive effect in preventing stillbirth., Conclusion: Induction of labor at term in advanced maternal age has no significant impact on cesarean delivery rates, assisted vaginal delivery or postpartum hemorrhage, giving additional reassurance to obstetricians who would consider this intervention in this particular subgroup., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of this research project was to test the effects of lifetime night work exposure on type 2 diabetes (T2DM) risk. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective cohort study of chronic conditions, such as diabetes and cardiovascular disease. The participants (N = 15105) were recruited (2008-2010) at five public universities and one research institute in six cities in Brazil. Participants from the first wave (2008-2010) were followed up for a mean of 3.8 years. Current analyses comprise 4671 women and 3965 men. Hazard ratios (HR) were estimated using Cox regression models. Crude T2DM incidence rates were 2.26 and 1.44 per 100 person-years, respectively, for women and men who reported ≥ 10 years' working nights. In women, ≥ 10 years of night work was associated with a higher risk of T2DM (HR 1.46 [95% CI: 1.03; 2.08]), after adjusting for age, education, work hours, and BMI. The additional adjustment for physical activity attenuated the association (HR 1.36 [95% CI: 0.94; 1.96]). In men, the results were not statistically significant (HR = 0.65 [95% CI: 0.40; 1.07]). The findings indicate the effects of lifetime night work on T2DM incidence seem to be greater among women than men.

The study of the epigenetic regulation of gene function has reached pivotal importance in life sciences in the last decades. The mechanisms and effects of processes such as DNA methylation, histone posttranslational modifications and non-coding RNAs, as well as their impact on chromatin structure and dynamics, are clearly involved in physiology homeostasis in plants, animals and microorganisms. In the fungal kingdom, studies on the model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe contributed enormously to the elucidation of the eukaryote epigenetic landscape. Epigenetic regulation plays a central role in the expression of virulence attributes of human pathogens such as Candida albicans. In this article, we review the most recent studies on the effects of drugs capable of altering epigenetic states and on the impact of chromatin structure-related genes deletion in filamentous fungi. Emphasis is given on plant and insect pathogens, endophytes, secondary metabolites and cellulases/xylanases producing species.

Even though nanotechnology has revolutionized the biomedical research, a plethora of studies debate the nanoparticles safety. In order to contribute to these studies, we evaluated the cytotoxic and epigenetic effects of maghemite nanoparticles covered with citric acid on human submandibular gland cells. Objective: This work objective was to evaluate the cytotoxic effects and epigenetic alterations induced in human salivary gland cells after treatment with maghemite nanoparticles covered with citric acid. Methods: For that, human submandibular gland cells were cultured and treated with nanoparticles for 24 or 48 hours. To assess cytotoxicity we used lactate dehydrogenase, a general oxidative stress indicator assay and microscopy. Epigenetic status was detected by colorimetric assays and the results were confirmed by quantitative polymerase chain reaction. Results: No cytotoxic effects were detected on cells exposed to up 3.0 mgFemL -1 for 48 hours, although cytoplasmic vacuoles formation was detected by light microscopy analyses. An increased generation of reactive oxygen species in cells exposed to nanoparticles was evidenced and iron clusters accumulated in the cytoplasm of treated cells. Global DNA methylation and histones H3 and H4 acetylation were also altered in response to nanoparticles exposure, thus suggesting a reprogramming of the epigenome. Transcripts accumulation analyses showed that genes related to iron metabolism and oxidative stress were upregulated, while the gene related to epigenetic reprogramming presented reduced transcript accumulation after treatment. Conclusion: We concluded that maghemite nanoparticles covered with citric acid exposure provoked several biological responses without impairment of human submandibular gland cells viability. This is the first report on the epigenetic effects of maghemite nanoparticles on this cell lineage.

Cryptococcosis is a disseminated infection caused mainly by C. neoformans and C. gattii. Limitations for the treatment involve the selection of isolates resistant to conventional antifungal drugs, prolonged treatment time and drugs side effects. This study evaluated the combined effect of histone deacetylase inhibitors (HDACi) and photodynamic therapy (PDT) on the growth of C. neoformans and C. gattii in vitro. Results showed that PDT inhibited yeasts proliferation and enhanced the HDACi-mediated cell viability impairment in Cryptococcus spp., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Evidence of psychosocial stress at work as a risk factor for diabetes and prediabetes is restricted., Objectives: Analyze the independent and combined association of the models, demand-control and social support (DC-SS) and the effort-reward imbalance and overcommitment (ERI-OC), and the incidence of glycemic alterations (prediabetes and diabetes)., Methods: A prospective study was carried out with data from 7503 active workers from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study in the period 2008-2014. Work stress was measured by two stress models. Glycemic levels were evaluated by glycated hemoglobin (HbA1c) in two moments and classified in four groups: normal, maintenance of prediabetes, incident prediabetes, and incident diabetes. Multinomial logistic regression was analyzed with 5% significance levels stratified by sex, and multiplicative interactions were investigated., Results: Work stress and glycemic alterations were more frequent in women. Psychosocial stress at work was shown to be associated to the risk of prediabetes and diabetes only among women. For women, the combination of models enlarged the magnitude of the association: prediabetes (DC-ERI = OR 1.51, 95% CI 1.15-1.99) and diabetes (DC-ERI = OR 2.10, 95% CI 1.20-3.65). Highly-educated women exposed to ERI-OC were four times more likely to have diabetes., Conclusion: Both models may contribute to explaining the psychosocial stress load according to each pattern of glycemic alteration among women., Competing Interests: The authors declare no conflicts of interest.

Background: The present study's main aim was to determine the predictors of movie rewatchability and recommendations., Methods: Using a sample of 318 participants, we first tested the structure of a gratification scale from watching a movie. Then, we examined the role of age, need for cognition, need for affect, extraversion, and emotional gratifications, in predicting individuals' interest in rewatching the movie and in making recommendations., Results: As in the original proposal of the emotional gratification scale, the following dimensions were identified: fun, thrill, empathic sadness, release of emotions, social sharing, contemplative experiences, and character engagement, with acceptable model fit and reliability, convergent and divergent validity. Social sharing, contemplate experiences, need for affect and age were significant predictors of movie recommendation; whereas social sharing, thrill, extraversion, and age contributed most to explaining rewatching interest., Conclusion: This study highlights the importance of considering distinct gratifications and individual differences in predicting rewatching and movie recommendation.

Background: Different directions of the association of birthweight with cardio-metabolic health have been found, especially in children, which may be explained by the mediating effect of attained adiposity. We aimed to untangle direct and BMI-mediated associations of birthweight with childhood cardio-metabolic indicators., Methods: Children from Generation XXI birth cohort were included (n = 4881). Birthweight was abstracted from clinical files. At age 4 and 7, children were re-evaluated. Glucose, triglycerides, LDL-cholesterol, systolic (SBP) and diastolic blood pressure (DBP) z-scores were the cardio-metabolic traits analyzed. Regression coefficients and respective 95% confidence intervals [β (95%CI)] were computed using path analysis., Results: Birthweight had inverse total effect on SBP at age 4 [-0.005 (-0.010; -0.001)] and 7 [-0.011 (-0.017; -0.006)] and DBP at 7 [-0.008 (-0.012; -0.004)]. Direct effects were found for SBP at 4 [-0.013 (-0.018; -0.009)] and 7 [-0.014 (-0.019; -0.009)], and DBP at 7 [-0.010 (-0.015; -0.006)], explaining the inverse total effects. Positive BMI-mediated indirect effects were found for all cardio-metabolic traits: higher birthweight was associated with higher childhood BMI, which in turn was associated with higher levels of cardio-metabolic traits., Conclusions: Positive BMI-mediated effect of birthweight on all cardio-metabolic traits was found. However, direct effects were in the opposite direction, significant for blood pressure, which may explain the diversity of results observed in the literature. Combining the direct and BMI-mediated effects, higher birthweight was associated with lower blood pressure at age 7 and have no effect on other cardio-metabolic traits.

Purpose: Early timing of pubertal development is associated with worse cardiometabolic health in adulthood. We aimed to evaluate this association in 10-year-old girls and boys and clarify if it is independent of previous body mass index (BMI)., Methods: Pubertal development was evaluated through the Tanner scale in 4,548 children from the birth cohort Generation XXI. Data on anthropometrics, body composition, blood pressure, lipid profile, fasting plasma glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein were collected. Bonferroni correction was applied, using an alpha of .004 for statistical significance. Regression coefficients and 99.6% confidence intervals were computed using linear regression models., Results: Girls with a Tanner stage ≥2 presented statistically significant higher values of BMI, waist circumference (WC), waist-to-height ratio, fat mass index, blood pressure, glucose, insulin, HOMA-IR, triglycerides, and high-sensitivity C-reactive protein and lower values of high-density lipoprotein cholesterol. Boys with a Tanner stage ≥2 presented statistically significant higher values of BMI, WC, systolic blood pressure, and HOMA-IR and lower values of high-density lipoprotein cholesterol. After adjustment, including previous BMI, a Tanner stage ≥2 remained associated with BMI z-score (girls β = .41 [.32, .50]; boys β = .10 [.01, .19]) and WC (girls β = 2.64 cm [1.86, 3.43]; boys β = .81 cm [.11, 1.51]), and only in girls with waist-to-height ratio (β = .01 [.00, .01]), fat mass index (β = .31 kg/m 2 [.08; .54]), glucose (β = 1.59 mg/dL [.85, 2.33]), insulin (β = 1.73 μU/mL [.68, 2.78]), and HOMA-IR (β = .40 [.16, .64])., Conclusions: Independently of previous BMI, preteens with early puberty already had more adiposity at age 10 years. In addition, girls had higher glucose, insulin, and HOMA-IR, which may predict a worse glucose metabolism. These preteens should be a target for public health interventions., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: To identify sensitive periods for the effect of early life growth on childhood bone mass we compared the associations between weight and length/height velocities from birth to age six and bone mineral content (BMC) and areal density (aBMD) at 7 years of age., Methods: We analyzed data from 1853 participants from the Generation XXI birth cohort scanned with a whole body dual-energy X-ray absorptiometry system. Velocities of growth in weight and length/height were obtained through linear spline multilevel models on the basis of data collected during routine health examinations. Using linear regression we computed associations of birth weight, birth length, five weight velocities ("early neonatal": 0-10 days, "early infancy": 10 days-3 months, "late infancy": 3-12 months, "early childhood": 1-3 years, and "later childhood": 3-6 years) and four length/height velocities ("early infancy": 0-3 months, "late infancy": 3-12 months, "early childhood": 1-3 years, and "later childhood": 3-6 years) with outcomes BMC, aBMD, height and height-adjusted BMC at age seven. Confounding by maternal and child characteristics was addressed and effects of growth velocities were adjusted to preceding growth., Results: Weight and length/height velocities up to the age of six were associated with increased bone mass, areal density and height at 7 years with the strongest associations observed for growth in early childhood. In this age period, after concurrent height and confounder adjustment, one standard deviation (SD) increase in weight velocity was associated with higher BMC z-scores: 0.27 (95%CI: 0.22, 0.32) in girls and 0.24 (95%CI: 0.19, 0.29) in boys. Height velocity was also associated with greater height-adjusted BMC z-score: 0.12 (95%CI: 0.07, 0.17) per SD in girls and 0.11 (95%CI: 0.06, 0.16) in boys. The pattern of associations was similar, albeit attenuated, after adjusting for preceding growth., Conclusion: Growth in second and third years of life may represent a sensitive period for the effect of growth on childhood bone mass, partly through their effect on concurrent body size., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: We aimed to compare cardiometabolic indicators in singletons and multiples at age 7 and explore the birthweight mediation effect., Methods: We studied 5431 singletons and 103 sets of multiples from Generation XXI birth cohort. Anthropometric measurements, body composition, and fasting blood samples were obtained. Age- and sex-specific z-scores were calculated (additionally height-specific for blood pressure). Adjusted regression coefficients and respective 95% confidence intervals [β (95%CI)] were computed using path analysis., Results: Multiples had lower weight [- 0.419 (- 0.616;-0.223)], height [- 0.404 (- 0.594;-0.213)], BMI [- 0.470 (- 0.705;-0.234)], fat mass index [- 0.359 (- 0.565;-0.152)], waist circumference [- 0.342 (- 0.537;-0.147)], and waist-to-height ratio [- 0.165 (- 0.326;-0.003)] z-scores. These results were explained by the indirect effect via birthweight, which was also negative and significant for all the aforementioned cardiometabolic indicators, while no direct effect was present. There were also significant indirect effects regarding fat-free mass index, glucose, insulin, and blood pressure, though the total effects were not significant, due to the balance between direct and indirect effects. The only significant direct effect was regarding diastolic blood pressure [- 0.165 (- 0.302;-0.028)]., Conclusions: At age 7, multiples presented better cardiometabolic indicators explained by lower weight at birth, except for the lower blood pressure which was independent of an effect via birthweight.