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Background: Pediatric hypertension is linked to environmental factors like neighborhood noise disrupting sleep, which is crucial for health. The specific interaction between noise and sleep health in causing hypertension still needs to be explored., Methods and Results: We analyzed data from 3320 participants of the ABCD (Adolescent Brain Cognitive Development) study, recruited across 21 US cities and monitored from 2018 to 2020 through 2020 to 2022. Participants with complete data on Fitbit-tracked sleep, blood pressure, height, neighborhood noise, and covariates (biological sex, race and ethnicity, pubertal stage, waist circumference) were included. Hypertension was defined as average blood pressure ≥95th percentile for age, sex, and height. Sleep health was categorized on the basis of daily duration: healthy (9-12 hours), moderately healthy (±1 hour from optimal), and low (≥1 hour deviation). Noise exposure was measured as median nighttime anthropogenic noise levels by zip code. The incidence of hypertension increased from 1.7% (95% CI, 1.4-2.1) in 2018 to 2020 to 2.9% (95% CI, 2.4-3.6) in 2020 to 2022. Adolescents with healthier sleep had a lower risk of developing hypertension (relative risk, 0.63 [95% CI, 0.25-0.82]), while no significant effects were found for neighborhood noise alone or in combination with sleep health., Conclusions: Adequate sleep significantly reduces the risk of hypertension in adolescents, independent of environmental noise exposure. These findings underscore the importance of promoting good sleep hygiene among youth to mitigate hypertension risk.

This study investigated the biofilm-forming capabilities of Enterococcus isolates from Portuguese traditional cheeses with protected designation of origin (PDO) status, specifically Azeitão and Nisa . Given the absence of added starter cultures in the cheesemaking process, the characteristics of these cheeses are intrinsically linked to the autochthonous microbiota present in the raw materials and the production environment. Our findings demonstrate that all isolates possess biofilm production abilities, which are crucial for their colonization and persistence within cheese factories, thereby maintaining factory-specific microbial heritage. Through an integrated analysis utilizing principal component analysis (PCA), a direct correlation between biofilm formation and cell viability was established. Notably, these results underscore the adaptive capacity of enterococci to survive environmental fluctuations and their role in the unique characteristics of Portuguese traditional cheeses. Overall, this research enhances our understanding of the microbial dynamics in cheese production and highlights the importance of enterococci in preserving cheese quality and heritage.

Background: Severe malaria can cause respiratory symptoms, which may lead to malaria-acute lung injury (MA-ALI) due to inflammation and damage to the blood-gas barrier. Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by Plasmodium berghei NK65 (PbNK65)., Methods: C57BL/6 mice were randomly divided into control (C) and PbNK65 infected groups and were inoculated with uninfected or 10 4 infected erythrocytes, respectively. Then, the animals were treated with DHA (3 mg/kg) or vehicle (DMSO) at the 8-day post-infection (dpi) for 7 days and with ASA (100 mg/kg, single dose), and analyses were performed at 9 or 15 dpi. Lung mechanics were performed, and lungs were collected for oedema evaluation and histological analyses., Results: PbNK65 infection led to lung oedema, as well as increased lung static elastance (Est, L), resistive (ΔP1, L) and viscoelastic (ΔP2, L) pressures, percentage of mononuclear cells, inflammatory infiltrate, hemorrhage, alveolar oedema, and alveolar thickening septum at 9 dpi. Mice that received DHA or DHA + ASA had an increase in Est, L, and CD36 expression on inflammatory monocytes and higher protein content on bronchoalveolar fluid (BALF). However, only the DHA-treated group presented a percentage of inflammatory monocytes similar to the control group and a decrease in ΔP1, L and ΔP2, L compared to Pb + DMSO. Also, combined treatment with DHA + ASA led to an impairment in diffuse alveolar damage score and lung function at 9 dpi., Conclusions: Therapy with ASA maintained lung morpho-functional impairment triggered by PbNK65 infection, leading to a large influx of inflammatory monocytes to the lung tissue. Based on its deleterious effects in experimental MA-ALI, ASA administration or its treatment maintenance might be carefully reconsidered and further investigated in human malaria cases., (© 2024. The Author(s).)

Carbonized polymer dots (CPDs) were obtained by using microwave irradiation under the same conditions. However, different carbogenic precursors were used, such as aromatic diamine molecules, ortho -phenylenediamine ( o -OPDA), and 3,4-diaminobenzoic acid (3,4-DABA). Both carbon nanoparticles showed different structural results based on Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, and atomic force microscopy analyses. However, there are similar spectroscopic (UV-visible and fluorescence emission) profiles. The photophysical results, like quantum yield (QY) and fluorescence lifetime, were not identical; CPDs-OPDA has a higher QY and fluorescence lifetime than CPDs-3,4-DABA. CPDs-3,4-DABA presents a more hydrophobic character than CPDs-OPDA and has a more negative superficial charge. Cell viability studies in both standard and tumor lines demonstrated higher cytotoxicity from CPDs-OPDA than that from CPDs-3,4-DABA. The oxidative stress identified in cells treated with CPDs-OPDA was based on reactive oxygen species and associated with nitric oxide production. CPDs-3,4-DABA showed more DPHH inhibition than CPDs-OPDA, indicating the antioxidant activity of CPDs., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Metabolic syndrome increases the risk of heart disease and diabetes. Early identification and management are crucial, especially in economically challenged regions with limited healthcare access., Aims: To develop nomograms for individualized risk estimation for metabolic syndrome in young people from low-income regions., Methods: We assessed 496 college students from two Brazilian cities with Gini indices ≤0.56. Of these, 69.9% were female, 65.1% were younger than 20 years, 71.8% were non-white, and 64.3% were enrolled in health-related courses. For external validity, we assessed metabolic syndrome in a subset of 375 students., Results: We found 10 variables associated with abdominal obesity by logistic regression: age, biological sex, physical education facilities, enrollment in sports competitions during elementary school, grade retention, physical education as the preferred subject, physical education classes per week, and enrollment in sports training in secondary school (score A); adherence to 24 h movement behaviors (B score); and body weight (score C). We designed three nomograms (for scores A, B, and C), all of which showed acceptable performance according to the area under the receiver operating characteristic curve (≥0.70) and calibration (Hosmer-Lemeshow test, p > 0.05). In the external validation, we observed higher predictive capability for the A and B scores, while the C score had lower but still acceptable predictive ability., Conclusions: User-friendly self-reported data accurately predict metabolic syndrome among youths from economically challenging areas.

Food fraud, a pervasive issue in the global food industry, poses significant challenges to consumer health, trust, and economic stability, costing an estimated $10-15 billion annually. Therefore, there is a rising demand for developing portable and miniature sensors that facilitate food authentication throughout the supply chain. This review explores the recent advancements and applications of portable and miniature sensors, including portable/miniature near-infrared (NIR) spectroscopy, e-nose and colorimetric sensors based on nanozyme for food authentication within the supply chain. After briefly presenting the architecture and mechanism, this review discusses the application of these portable and miniature sensors in food authentication, addressing the challenges and opportunities in integrating and deploying these sensors to ensure authenticity. This review reveals the enhanced utility of portable/miniature NIR spectroscopy, e-nose, and nanozyme-based colorimetric sensors in ensuring food authenticity and enabling informed decision-making throughout the food supply chain.

Objectives: We aimed to test the reliability and structural validity (also called dimensionality) of the online Pittsburgh Sleep Quality Index among college students from low-income regions., Methods: We assessed 195 Brazilian college students from a low-income region (Gini index of 0.56), of whom 117 were reassessed to evaluate the reliability. We collected all data in a self-reported online twice, 2-week apart. We evaluated reliability and structural validity., Results: All questionnaire components showed reliability, correlation coefficient ≥0.49. In the structural validity, the confirmatory analysis showed better global model adjustment for the one-factor (RMSEA = 0.019; SRMR = 0.041; CFI = 0.992; TLI = 0.986) solution compared with two-factor (RMSEA = 0.099; SRMR = 0.070; CFI = 0.764; TLI = 0.619) and three-factor (RMSEA = 0.108; SRMR = 0.066; CFI = 0.763; TLI = 0.548) solutions, respectively., Discussion: The online questionnaire presents acceptable reliability and structural validity in Brazilian low-income regions., 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 De Moraes, Conceição da Silva, Lima, Marin, Hunt and Nascimento-Ferreira.)

Accurate evaluation of the mitral valve (MV) apparatus is essential for understanding the mechanisms of MV disease across various clinical scenarios. The mitral annulus (MA) is a complex and crucial structure that supports MV function; however, conventional imaging techniques have limitations in fully capturing the entirety of the MA. Moreover, recognizing annular changes might aid in identifying patients who may benefit from advanced cardiac imaging and interventions. Multimodality cardiovascular imaging plays a major role in the diagnosis, prognosis, and management of MV disease. Transthoracic echocardiography is the first-line modality for evaluation of the MA, but it has limitations. Cardiac MRI (CMR) has emerged as a robust imaging modality for assessing annular changes, with distinct advantages over other imaging techniques, including accurate flow and volumetric quantification and assessment of variations in the measurements and shape of the MA during the cardiac cycle. Mitral annular disjunction (MAD) is defined as atrial displacement of the hinge point of the MV annulus away from the ventricular myocardium, a condition that is now more frequently diagnosed and studied owing to recent technical advances in cardiac imaging. However, several unresolved issues regarding MAD, such as the functional significance of pathologic disjunction and how this disjunction advances in the clinical course, require further investigation. The authors review the role of CMR in the assessment of MA disease, with a focus on MAD and its functional implications in MV prolapse and mitral regurgitation. © RSNA, 2024 Supplemental material is available for this article. See the invited commentary by Stojanovska and Fujikura in this issue.

The double burden of malnutrition (DBM) is a condition in which malnutrition coexists with overweight, reflecting a new layer of malnutrition. Our objectives were to assess prevalence; test associations between DBM and 24-hour movement behaviors; and investigate whether DBM is associated with clusters of social determinants. Methods: This multicenter cross-sectional study included 1152 adolescents (12 to 17 years old) from four Brazilian cities. Body mass index (BMI, kg/m 2 ) was used to estimate overweight, and the adopted cutoff points took into account the curves established for age and sex: Z-score > 1 and ≤2 (overweight) and Z-score > 2 (obesity). The serum concentration of 25-hydroxyvitamin D [25(OH)D] was stratified into three levels: vitamin D deficiency ≤ 20 ng/mL; vitamin D insufficiency = 21-29 ng/mL; optimal vitamin D ≥ 30 ng/mL. We used multilevel Poisson regression models to estimate prevalence ratios (PRs) and their respective 95% confidence intervals (95%CI) and to analyze the association between DBM and covariates. A significance level of p < 0.05 was considered. Cluster analyses were performed by applying a combination of hierarchical and non-hierarchical methods. Results: A population prevalence of DBM of 7.3% (95% CI: 5.9-8.9) was revealed. A percentage of 19.2% (95% CI: 17.0-21.6) of adolescents were overweight, and 8.3% (95% CI: 6.8-10.1) were obese. A total of 41.5% (95% CI: 38.7-44.4) had vitamin D deficiency, and 25.8% (95% CI: 23.4-28.4) had vitamin D insufficiency. However, 24-hour movement behaviors were not associated with DBM. Adolescents living in the southern region of the country, from public schools whose mothers have higher education, have a 1.94 [PR = 2.94 (95% CI: 1.20-7.23)] times greater chance of developing DBM. These results highlight the importance of specific factors to improve the nutritional health of adolescents, considering the specific social determinants identified in this study., Competing Interests: The authors declare no conflicts of interest.

Ralstonia solanacearum species complex (RSSC) is a phytopathogenic bacterial group that causes bacterial wilt in several crops, being potato ( Solanum tuberosum ) one of the most important hosts. The relationship between the potato plant ionome (mineral and trace elements composition) and the resistance levels to this pathogen has not been addressed until now. Mineral content of xylem sap, roots, stems and leaves of potato genotypes with different levels of resistance to bacterial wilt was assessed in this work, revealing a positive correlation between divalent calcium (Ca) cation concentrations and genotype resistance. The aim of this study was to investigate the effect of Ca on bacterial wilt resistance, and on the growth and virulence of RSSC. Ca supplementation significantly decreased the growth rate of Ralstonia pseudosolanacearum GMI1000 in minimal medium and affected several virulence traits such as biofilm formation and twitching motility. We also incorporate for the first time the use of microfluidic chambers to follow the pathogen growth and biofilm formation in conditions mimicking the plant vascular system. By using this approach, a reduction in biofilm formation was observed when both, rich and minimal media, were supplemented with Ca. Assessment of the effect of Ca amendments on bacterial wilt progress in potato genotypes revealed a significant delay in disease progress, or a complete absence of wilting symptoms in the case of partially resistant genotypes. This work contributes to the understanding of Ca effect on virulence of this important pathogen and provides new strategies for an integrated control of bacterial wilt on potato., Importance: Ralstonia solanacearum species complex (RSSC) includes a diverse group of bacterial strains that cause bacterial wilt. This disease is difficult to control due to pathogen aggressiveness, persistence, wide range of hosts, and wide geographic distribution in tropical, subtropical, and temperate regions. RSSC causes considerable losses depending on the pathogen strain, host, soil type, environmental conditions, and cultural practices. In potato, losses of $19 billion per year have been estimated for this pathogen worldwide. In this study, we report for the first time the mineral composition found in xylem sap and plant tissues of potato germplasm with different levels of resistance to bacterial wilt. This study underscores the crucial role of calcium (Ca) concentration in the xylem sap and stem in relation to the resistance of different genotypes. Our in vitro experiments provide evidence of Ca's inhibitory effect on the growth, biofilm formation, and twitching movement of the model RSSC strain R . pseudosolanacearum GMI1000. This study introduces a novel element, the Ca concentration, which should be included into the integrated disease control management strategies for bacterial wilt in potatoes., Competing Interests: The authors declare no conflict of interest.

Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Diagnosing MM presents considerable challenges, involving the identification of plasma cells in cytology examinations on hematological slides. At present, this is still a time-consuming manual task and has high labor costs. These challenges have adverse implications, which rely heavily on medical professionals' expertise and experience. To tackle these challenges, we present an investigation using Artificial Intelligence, specifically a Machine Learning analysis of hematological slides with a Deep Neural Network (DNN), to support specialists during the process of diagnosing MM. In this sense, the contribution of this study is twofold: in addition to the trained model to diagnose MM, we also make available to the community a fully-curated hematological slide dataset with thousands of images of plasma cells. Taken together, the setup we established here is a framework that researchers and hospitals with limited resources can promptly use. Our contributions provide practical results that have been directly applied in the public health system in Brazil. Given the open-source nature of the project, we anticipate it will be used and extended to diagnose other malignancies., (© 2024. The Author(s).)

Diabetes mellitus (DM) complications are a burden to health care systems due to the associated consequences of poor glycemic control and the side effects of insulin therapy. Recently. adjuvant therapies, such as vanadium compounds, have gained attention due to their potential to improve glucose homeostasis in patients with diabetes. In order to determine the anti-diabetic and antioxidant effects of the oxidovanadium(IV) complex (Et 3 NH) 2 [{VO(OH} 2 )(ox) 2 (µ-ox)] or Vox2), rats with streptozotocin (STZ)-induced diabetes were treated with 30 and 100 mg/kg of Vox2, orally administered for 12 days. Vox2 at 100 mg/kg in association with insulin caused a 3.4 times decrease in blood glucose in STZ rats (424 mg/dL), reaching concentrations similar to those in the normoglycemic animals (126 mg/dL). Compared to insulin alone, the association with Vox2 caused an additional decrease in blood glucose of 39% and 65% at 30 and 100 mg/kg, respectively, and an increased pancreatic GSH levels 2.5 times. Vox2 alone did not cause gastrointestinal discomfort, diarrhea, and hepatic or renal toxicity and was not associated with changes in blood glucose level, lipid profile, or kidney or liver function. Our results highlight the potential of Vox2 in association with insulin in treating diabetes.

Bovine bone is an animal-origin matrix rich in type I collagen (COL I) and it necessitates prior demineralization and makes COL I available. This study investigated the ossein-hydroxyapatite physicochemical properties evaluation as a result of processing and solubilization by acids and revealed the bone matrix demineralization and making COL I available. The tibia residue from bovine sources was processed, ground, and transformed into bone matrix powder. The bone matrix was solubilized in acetic acid followed by lactic acid. The bone matrix was evaluated as a result of processing and solubilization by acids: ossein and hydroxyapatite percentages by nitrogen and ash content, mineral content, particle size distribution, Fourier-transformation infrared spectroscopy, x-ray diffraction, and scanning electron microscope. For the obtained residual extracts, pH and mineral content were evaluated. The solubilization by acids affected the ossein-hydroxyapatite physicochemical properties, and the bone matrix solubilized by acetic and lactic acid showed the preservation of the ossein alongside the loss of hydroxyapatite. The processing and the solubilization by acids were revealed to be a  alternative to bone matrix demineralization and enabling the accessibility of bone COL I. PRACTICAL APPLICATION: Bovine bone is an abundant type I collagen source, but processing maneuvers and demineralization effect present limitations due to the rigidity of the structural components. Exploring methodologies to process and demineralize will allow type I collagen to be obtained from the bone source, and direct and amplify the potentialities in the chemical and food industries. The research focused on bone sources and collagen availability holds paramount significance, and promotes repurposing agribusiness residues and development of protein-base products., (© 2024 Institute of Food Technologists.)

Objective: This study evaluated Temporomandibular Disorder (TMD) in individuals with Spinal Cord Injuries (SCI) compared to individuals without physical disabilities., Design: Cross-sectional., Setting: International Fair of Technologies in Rehabilitation and Accessibility (REATECH) and School of Dentistry at the University of São Paulo (USP), Brazil., Participants: In total, 19 patients with SCI and 19 patients without SCI (36.9 ± 11.4 years old) were examined by a calibrated examiner., Methods: using the following parameters: cervical spine mobility, palpation of muscle groups of the head and neck, functional manipulation of the lateral and medial pterygoids, and joint palpation (Diagnostic Criteria). The pattern and amplitude of mandibular movements were determined during screening using the Helkimo index., Statistical Analyses: Student's t-test, chi-square, Fisher's exact and Shapiro-Wilk test were used., Results: The groups did not differ in the presence of noise, pain, temporomandibular joint palpation, locking, dislocation, jaw pain, muscle sensitivity, or in pain, mobility of the cervical spine and functional manipulation. With respect to the jaw mobility index, the groups differed in range of movement (P  = 0.020 ) and maximum right lateral movement (P  = 0.007 ), with the worst values in the SCI group. The groups also differed in relation to lateral flexion in cervical mobility , in which the group without SCI presented better results (P  = 0.046 )., Conclusion: The Spinal Cord Injuries group showed higher levels of TMD in terms of range of movement, lateral flexion, and maximum right lateral movement, than the individuals without physical disabilities, demonstrating a clinical significance between cervical and mandibular disability in this group.

Individuals with low levels of vitamin D are associated with cardiovascular risks, such as elevated blood pressure (BP), and are; therefore, more likely to develop hypertension. Patients with vitamin D deficiency may face an increased risk of cardiovascular events. In this study, a multicenter, cross-sectional, and school-based investigation was conducted as part of the ERICA project. The sample comprised 1152 adolescents aged 12-17 years from 4 Brazilian cities. Anthropometric variables, BP measurements, and hydroxyvitamin D concentrations were assessed. A 2-level linear regression was fitted to examine the relationship between each level of BP and independent variables. Our findings indicate that movement behaviors were not associated with BP levels, with the exception of sleep time, which demonstrated a positive association. However, after adjustment, this association was found to be nonsignificant. Our study's mediation analysis revealed that vitamin D mediates up to 12.9% of the association between physical activity and systolic BP. Vitamin D is inversely associated with BP in adolescents. In addition to mediating the physical activity and systolic BP association, engaging in physical activity, particularly outdoors, can provide a dual benefit for adolescents by increasing serum vitamin D levels and assisting in the control of BP levels.

Introduction: Introduction: to reduce the prevalence of overweight and obesity, lifestyle interventions, particularly in nutritional education programs, should be prioritized among university students. Monitoring sedentary behavior is an important step toward preventing and controlling obesity. Therefore, we assessed the reliability and validity of an online questionnaire on sedentary behavior among university students from low-income regions. Methods: this cross-sectional methodological feasibility study evaluated the psychometric properties of the South American Youth/Child Cardiovascular and Environmental (SAYCARE) questionnaire. We administered this questionnaire in an online format to 195 and 117 university students (aged between 17 and 53 years) to assess its validity and reliability, respectively. The questionnaire measures the daily time spent watching TV, playing electronic games, using a computer, studying and passive commuting on weekdays and weekends. The questionnaire involved two stages (Q1 and Q2) separated by an interval of 2 weeks. Reliability was assessed using Spearman's correlation analysis. The structural validity of the construct was evaluated by exploratory factor analysis. Results: all variables showed acceptable reliability (Spearman's rho > 0.30 and p < 0.05). Regarding construct structural validity, the exploratory factor analysis identified 4 factors (variance explained: 71.4 %) and did not exclude any items. Conclusion: the online SAYCARE questionnaire exhibited acceptable reliability and structural validity for assessing sedentary behavior among university students from low-income regions.

Sleep restriction in children can trigger the development of problems such as impaired cognition, behavioral problems, cardiovascular problems, and obesity. In addition, the inflammatory profile of children can also be influenced by sleep restriction. The aimed to review and analyze the association between time and sleep quality with inflammatory biomarkers in children and adolescents. Three electronic databases (MEDLINE, Web of Science and Scopus) were searched from August 30, 2022. The search strategy used the following descriptors: children and adolescents; sleep, and inflammatory profile. This review protocol is registered in the PROSPERO database (CRD42020188969). We obtained 2.724 results of articles with potentially relevant titles. Sixteen percent of the articles were excluded because they were duplicates, 84.3% were excluded after reading the title, and 0.9% were studied from systematic reviews or textbooks (0.9%). Accelerometers are the most commonly used method for the objective measurement of sleep time, while the PSQI questionnaire is the most commonly used subjective method to measure sleep quality. The results indicated an inconsistent association between sleep time and CRP in the literature. Sixty percent of studies used the Pittsburgh Sleep Quality Index (PSQI) for subjective assessment of sleep quality and possible sleep disorders. However, only one retrieved study showed significant association between sleep quality and CRP. Thus, sleep time does not present significant association with inflammatory biomarkers; whereas, poor sleep quality shows positive association with CRP with a lower magnitude., Competing Interests: 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., (© 2023 The Author(s).)

Newly emerging data suggest that several neutrophil defense mechanisms may play a role in both aggravating and protecting against malaria. These exciting findings suggest that the balance of these cells in the host body may have an impact on the pathogenesis of malaria. To fully understand the role of neutrophils in severe forms of malaria, such as cerebral malaria (CM), it is critical to gain a comprehensive understanding of their behavior and functions. This study investigated the dynamics of neutrophil and T cell responses in C57BL/6 and BALB/c mice infected with Plasmodium berghei ANKA, murine models of experimental cerebral malaria (ECM) and non-cerebral experimental malaria, respectively. The results demonstrated an increase in neutrophil percentage and neutrophil-T cell ratios in the spleen and blood before the development of clinical signs of ECM, which is a phenomenon not observed in the non-susceptible model of cerebral malaria. Furthermore, despite the development of distinct forms of malaria in the two strains of infected animals, parasitemia levels showed equivalent increases throughout the infection period evaluated. These findings suggest that the neutrophil percentage and neutrophil-T cell ratios may be valuable predictive tools for assessing the dynamics and composition of immune responses involved in the determinism of ECM development, thus contributing to the advancing of our understanding of its pathogenesis.

Adeno-associated viral (AAV) vectors represent one of the leading platforms for gene delivery. Nevertheless, their small packaging capacity restricts their use for diseases requiring large-gene delivery. To overcome this, dual-AAV vector systems that rely on protein trans-splicing were developed, with the split-intein Npu DnaE among the most-used. However, the reconstitution efficiency of Npu DnaE is still insufficient, requiring higher vector doses. In this work, two split-inteins, Cfa and Gp41-1, with reportedly superior trans-splicing were evaluated in comparison with Npu DnaE by transient transfections and dual-AAV in vitro co-transductions. Both Cfa and Gp41-1 split-inteins enabled reconstitution rates that were over two-fold higher than Npu DnaE and 100% of protein reconstitution. The impact of different vector preparation qualities in split-intein performances was also evaluated in co-transduction assays. Higher-quality preparations increased split-inteins' performances by three-fold when compared to low-quality preparations (60-75% vs. 20-30% full particles, respectively). Low-quality vector preparations were observed to limit split-gene reconstitutions by inhibiting co-transduction. We show that combining superior split-inteins with higher-quality vector preparations allowed vector doses to be decreased while maintaining high trans-splicing rates. These results show the potential of more-efficient protein-trans-splicing strategies in dual-AAV vector co-transduction, allowing the extension of its use to the delivery of larger therapeutic genes.

Blood coagulation is a vital process for humans and other species. Following an injury to a blood vessel, a cascade of molecular signals is transmitted, inhibiting and activating more than a dozen coagulation factors and resulting in the formation of a fibrin clot that ceases the bleeding. In this process, the Coagulation factor V (FV) is a master regulator, coordinating critical steps of this process. Mutations to this factor result in spontaneous bleeding episodes and prolonged hemorrhage after trauma or surgery. Although the role of FV is well characterized, it is unclear how single-point mutations affect its structure. In this study, to understand the effect of mutations, we created a detailed network map of this protein, where each node is a residue, and two residues are connected if they are in close proximity in the three-dimensional structure. Overall, we analyzed 63 point-mutations from patients and identified common patterns underlying FV deficient phenotypes. We used structural and evolutionary patterns as input to machine learning algorithms to anticipate the effects of mutations and anticipated FV-deficiency with fair accuracy. Together, our results demonstrate how clinical features, genetic data and in silico analysis are converging to enhance treatment and diagnosis of coagulation disorders., (© 2023. The Author(s).)

Objectives: Movement behaviors and abdominal obesity are associated with higher inflammatory biomarkers. However, the role of waist circumference as a mediating factor is still unknown. Thus, our aims were to (1) test the associations between 24-hour movement behavior variables (physical activity, sedentary behavior, and sleep), abdominal obesity, and pro- and anti-inflammatory biomarkers; and (2) investigate whether abdominal obesity had a mediating effect between the investigated associations., Methods: This multicenter cross-sectional study included 3591 adolescents (aged 12-17 y) from 4 Brazilian cities. Waist circumference (in centimeters; at half the distance between the iliac crest and at the lower costal margin), 24-hour movement behaviors (validated questionnaire), high-sensitive C-reactive protein, and adiponectin (serum plasma) were evaluated. We used multiple mediation regression models (95% confidence interval) to determine if waist circumference mediated the association between 24-hour movement behaviors and pro- and anti-inflammatory biomarkers., Results: The results revealed that screen time and moderate to vigorous physical activity were not associated with pro- or anti-inflammatory biomarkers. However, sleep duration (in hours per day) was negatively associated with pro- (C-reactive protein, β = -0.08; 95% confidence interval, -0.38 to -0.02) and anti- (adiponectin, β = -0.31; 95% confidence interval, -2.13 to -0.12) inflammatory biomarkers. Our results also showed that waist circumference mediated the association between sleep duration and high-sensitive C-reactive protein (2.7%), and adiponectin (2.8%)., Conclusion: Sleep duration was inversely associated with pro- and anti-inflammatory biomarkers, and these relations were mediated by abdominal obesity. Therefore, adolescents having healthy sleep can have implications for reducing waist circumference and inflammatory indicators.

Purpose: To test the feasibility, reliability, and validity of the Satisfaction with Life Scale (SWLS) in an online format in university students from a low-income region., Methods: This was a psychometric study, involving a study of reliability (n = 117) and validity (n = 195) in university students from a region with a Gini index of 0.56. The scale was applied at two time points with an interval of 2 weeks. This scale measures satisfaction with life based on five statements and responses ranging from 1 to 7 (strongly disagree to strongly agree). We conducted the reliability assessment using temporal stability and internal consistency and construct validity assessment by internal structure solution., Results: All SWLS items showed acceptable (rho > 0.30) and significant (p < 0.05) temporal stability and acceptable internal consistency (alpha > 0.70). In construct validity (internal structure), we identified a factor with an explained variance of 59.0% in the exploratory factor analysis. Additionally, in the confirmatory factor analysis, we identified a one-factor structure solution for SWLS with an acceptable model fitting (chi-square/degrees of freedom [X 2 /df] = 6.53; Tucker-Lewis Index [TLI] = 0.991; Comparative Fit Index [CFI] = 0.996; root mean square error of approximation [RMSEA] = 0.040; standardized root mean-squared residual [SRMR] = 0.026)., Conclusion: The Satisfaction with Life Scale, in the online format, is a reliable and valid tool for university students in a low-income context., (© 2023. The Author(s).)

Introduction: Blood coagulation is an essential process to cease bleeding in humans and other species. This mechanism is characterized by a molecular cascade of more than a dozen components activated after an injury to a blood vessel. In this process, the coagulation factor VIII (FVIII) is a master regulator, enhancing the activity of other components by thousands of times. In this sense, it is unsurprising that even single amino acid substitutions result in hemophilia A (HA)-a disease marked by uncontrolled bleeding and that leaves patients at permanent risk of hemorrhagic complications. Methods: Despite recent advances in the diagnosis and treatment of HA, the precise role of each residue of the FVIII protein remains unclear. In this study, we developed a graph-based machine learning framework that explores in detail the network formed by the residues of the FVIII protein, where each residue is a node, and two nodes are connected if they are in close proximity on the FVIII 3D structure. Results: Using this system, we identified the properties that lead to severe and mild forms of the disease. Finally, in an effort to advance the development of novel recombinant therapeutic FVIII proteins, we adapted our framework to predict the activity and expression of more than 300 in vitro alanine mutations, once more observing a close agreement between the in silico and the in vitro results. Discussion: Together, the results derived from this study demonstrate how graph-based classifiers can leverage the diagnostic and treatment of a rare disease., Competing Interests: TL received consulting fees from Pola Chemical Industries, Yokohama, Japan for projects unrelated to the current study, and speaker honoraria from Sanofi Japan. The remaining 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 Ferreira, Nogueira, Rios and Lopes.)

Objective: To test the reliability and validity of the Dutch Eating Behavior Questionnaire (DEBQ) in an online format in university students from low-income regions., Methods: We applied the questionnaire to a sample of 195 and 117 university students from a low-income region (Gini index of 0.56) to study validity and reliability, respectively. The DEBQ consists of 33 items on eating behavior in three dimensions/factors: emotional eating, restrained eating and external eating. The questionnaire was administered twice at 2-week intervals. We tested the reliability via temporal stability and internal consistency and construct validity via exploratory and confirmatory factor analysis., Results: For reliability, we identified an acceptable Spearman correlation coefficient (rho > 0.30 and p  < 0.05) and Cronbach's alpha ( α  ≥ 0.70) for all DEBQ items. In the exploratory analysis, we identified 6 factors representing a mix of original and additional factors, with an explained variance of 69.1%. In the confirmatory analysis with structural equation modeling, we observed better global model adjustment for the 6-factor model with the Tucker-Lewis index and comparative fit index closer to one, as well as root mean square error of approximation closer to zero than the original (3-factor) model. Using generalized structural equation modeling, we also observed a better fit in latent class modeling for the 6-factor model (AIC: 16990.67; BIC. 17874.38) than for the 3-factor model (AIC: 17904.09; BIC: 18342.67)., Conclusion: The online format of the DEBQ has acceptable reliability and validity for measuring eating behavior in university students from low-income regions., 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., (© 2023 de Carvalho, Cardoso, Feuerstein, Sousa, Collese, Torres-Leal, Nascimento-Ferreira and De Moraes.)

Summary: Blood coagulation is a vital process for humans and other species. Following an injury to a blood vessel, a cascade of molecular signals is transmitted, inhibiting and activating more than a dozen coagulation factors and resulting in the formation of a fibrin clot that ceases the bleeding. In this process, antithrombin (AT), encoded by the SERPINC1 gene is a key player regulating the clotting activity and ensuring that it stops at the right time. In this sense, mutations to this factor often result in thrombosis-the excessive coagulation that leads to the potentially fatal formation of blood clots that obstruct veins. Although this process is well known, it is still unclear why even single residue substitutions to AT lead to drastically different phenotypes. In this study, to understand the effect of mutations throughout the AT structure, we created a detailed network map of this protein, where each node is an amino acid, and two amino acids are connected if they are in close proximity in the three-dimensional structure. With this simple and intuitive representation and a machine-learning framework trained using genetic information from more than 130 patients, we found that different types of thrombosis have emerging patterns that are readily identifiable. Together, these results demonstrate how clinical features, genetic data and in silico analysis are converging to enhance the diagnosis and treatment of coagulation disorders., Supplementary Information: Supplementary data are available at Bioinformatics Advances online., (© The Author(s) 2022. Published by Oxford University Press.)

We systematically reviewed the literature about the validity and reliability of barriers and facilitators of sedentary behavior questionnaires for children and adolescents, considering accelerometers as the reference method. We included studies that assessed the agreement between the barriers and facilitators of sedentary behavior through a questionnaire and an objective measure (e.g., accelerometry). We searched four electronic databases (MEDLINE/PubMed, CINAHL, Web of Science, and SCOPUS): these databases were searched for records from inception to 5 March 2021, and updated to November 2022. The search strategy used the following descriptors: children and adolescents; barriers or facilitators; questionnaires; accelerometers; and validation or reliability coefficient. Studies identified in the search were selected independently by two reviewers. The inclusion criteria were: (i) population of children and adolescents, (ii) original studies, (iii) subjective and objective measurement methods, (iv) studies that report validity or reliability, and (v) population without specific diseases. Seven studies were eligible for our review. The main exclusion reasons were studies that did not report validity or reliability coefficients (56.6%) and non-original studies (14.5%). The participants' ages in the primary studies ranged from 2 to 18 years. Cronbach's alpha coefficient was the most reported reliability assessment among the eligible articles, while Pearson and Spearman's coefficients were prevalent for validity. The reliability of self-report questionnaires for assessing sedentary behavior ranged from r = 0.3 to 1.0. The validity of the accelerometers ranged from r = -0.1 to 0.9. Family environment was the main factor associated with sedentary behavior. Our findings suggest that questionnaires assessing the barriers and facilitators of sedentary behavior are weak to moderate. PROSPERO Registration (CRD42021233945).

Introduction: Due to the restrictions imposed to control the COVID-19 pandemic, there has been an increase in studies based on online surveys. However, there are important concerns about the validity and generalizability of results from online surveys. Thus, we aimed to test the reliability and validity of the online version of the International Physical Activity Questionnaire short form (IPAQ-SF) among college students from low-income regions., Methods: This was a methodological feasibility study with a random stratified sample from a college located in the state of Maranhão in the city of Imperatriz (Brazil). The sample consisted of 195 college students (at least 17 years of age) to evaluate the validity and 117 students to evaluate the reliability. All data were collected in a self-reported online format (via Google Forms) twice, with an interval of 2 weeks. We used Spearman's correlation analysis for the reliability study. Additionally, we applied exploratory and confirmatory factor analysis to evaluate the structural validity., Results: The questionnaire showed acceptable (rho > 0.30) and significant ( p < 0.05) reliability, except for the question about the duration of sitting time on a weekend day. When assessing the construct validity (exploratory analysis), we identified a single factor that explained 88.8% of the variance. The 1-factor model showed acceptable model fit (SRMR = 0.039; CFI = 0.96; TLI = 0.90) in confirmatory analysis., Conclusions: The online version of the IPAQ-SF has acceptable reliability among college students from low-income regions and maintains the structure of the construct regarding to physical activity.

Neuropathic pain (NP) is a complex health problem that includes sensorial manifestations such as evoked and ongoing pain. Cannabidiol (CBD) has shown potential in the treatment of NP and the combination between opioids and cannabinoids has provided promising results on pain relief. Thus, our study aimed to investigate the effect of treatment combination between CBD and morphine on evoked and ongoing pain, and the effect of CBD on morphine-induced tolerance in the model of chronic constriction injury (CCI) of the sciatic nerve in rats. Mechanical thresholds (i.e., evoked pain) were evaluated before and 7 days after surgery. We also employed a 4-day conditioned place preference (CPP) protocol, to evaluate relief of ongoing pain (6-9 days after surgery). Treatment with morphine (2 and 4 mg/kg) or CBD (30 mg/kg) induced a significant antinociceptive effect on evoked pain. The combination of CBD (30 mg/kg) and morphine (1 mg/kg) produced an enhanced antinociceptive effect, when compared to morphine alone (1 mg/Kg). Treatment with morphine (1 and 2 mg/kg) or CBD (30 mg/kg) alone failed to induce significant scores in the CPP test. However, combined treatment of CBD (30 mg/kg) and morphine (1 mg/kg) provided significant positive scores, increased the number of entrances in the drug-paired chamber in the CPP test and did not alter locomotor activity in rats. Lastly, treatment with CBD partially attenuated morphine-induced tolerance. In summary, our results support the indication of CBD as an adjuvant to opioid therapy for the attenuation of NP and opioid-induced analgesic tolerance., Competing Interests: Conflict of interest JASC is a member of the International Advisory Board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE) – National Health and Medical Research Council (NHMRC). JASC has received travel support to attend scientific meetings and personal consultation fees from BSPG-Pharm. JASC is a coinventor of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,” Def. US number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi AW, Kapczinski F, Hallak JEC, Guimarães FS, Crippa JAS, Breuer A). Universidade de São Paulo (USP) has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1) and has an agreement with Prati-Donaduzzi to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” JASC is a coinventor of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same,” INPI on September 16th, 2016 (BR 112018005423–2). The other authors declare that they have no conflicts of interest. JASC is a consultant and/or has received speaker fees and/or sits on the advisory board and/or receives research funding from Janssen-Cilag, Torrent Pharm, Prati-Donaduzzi, PurMed Global, and BSPG Pharm over the past 3 years., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Information about the reliability and validity of questionnaires in low- and middle-income countries remains scarce. Objective: To test the reliability and predictive validity of a food and beverage marketing/advertising questionnaire for South American children and adolescents. Methods: A sample of 330 children (3-10 years old) and 215 adolescents (11-18 years old) was included from seven South American cities: Buenos Aires, Lima, Medellín, Montevideo, Santiago, Sao Paulo, and Teresina. The questionnaire consisted of seven questions about food and beverage marketing/advertising and decision influence. We assessed the reliability using temporal stability (2-week interval) and internal consistency. We assessed the predictive validity based on the risk of excess weight. Results: In children, reliability agreement from κ coefficients ranged from 63.7% to 86.3%, and Cronbach's α (internal consistency estimate) ranged from 0.14 to 0.75. In adolescents, the reliability agreement ranged from 78.9% to 85.7%, and Cronbach's α ranged from 0.14 to 0.76. Exploratory factor analysis revealed two factors for both age groups. The predictive probabilities for excess weight ranged from 22.3% to 61.1% in children and from 24.9% to 64.1% in adolescents. Conclusions: The screen/marketing media questionnaire is a reliable and valid measure for the pediatric population from low- and middle-income countries. This subjective tool provides a feasible screening measure for the influence of advertising on children and adolescents at risk of overweight and obesity.

Introduction: Obesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income. The composition of movement behaviors within a 24 h period may have important implications for obesity, metabolic and mental health in cross-sectional data. However, a longitudinal study is needed to confirm the findings from the primarily cross-sectional evidence. The COVID-19 pandemic has been associated with cardiometabolic outcomes and has impeded healthy behavior., Objectives: The first objective is to evaluate the time elapsed since the diagnosis of not meeting 24 h movement guidelines and the potential subsequent onset of metabolic syndrome in undergraduate students from low-income regions within 4 years of follow up. The second objective is to test the association between 24 h movement, mental wellbeing, eating behaviors, and abdominal obesity in the period of this pandemic., Methods: The 24 h movement behavior and metabolic syndrome (24 h-MESYN) study is a multicentre cohort study that will include participants from two Brazilian cities within the 2022-2025 period to asses the first objective, and also a nested case-control study at the baseline will be carried out to evaluate the second objective. Previously, we conducted a feasibility study in the academic year of 2021 to assessing the psychometric properties of subjective tools, refine our study protocol, and adjust the epidemiological conditions of the cohort's subsequent phases (like as prevalence of exposure of interest, sampling process, and study adherence). Statistical tests as Cohen's kappa agreement; factorial analysis; logistic, Poisson and linear regression; and Kaplan-Meier analysis will be performed, in accordance with the objectives., 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 Nascimento-Ferreira, Marin, Abrão Ferreira, Oliveira, Bandeira, Silva Sousa, Miranda de Sousa, de Almeida Cardoso, Conceição da Silva, Rosa, de Carvalho, Pereira de Carvalho Silva, Franco, Torres-Leal, Barbosa de Carvalho and Ferreira de Moraes.)

Introduction: Cross-sectional association between the neighborhood-built environment and physical activity (PA) has been demonstrated previously, indicating the importance of neighborhood perception characteristics such as walkability, safety, and the connectivity of streets on PA levels. Our study aimed to assess the longitudinal data from participants of the Multi-Ethnic Study of Atherosclerosis (MESA) to evaluate the potential relationship between perceived environment and PA patterns. Methods: We analyzed data from a subset of participants (n = 3097) with available PA data who participated in a prospective cohort conducted from 2000 to 2018. The exposure variables were the perceived aspects of the neighborhood environment and the perception of safety, and the outcome was patterns of PA. Patterns were defined as categories reflecting meeting versus not meeting PA guidelines over time. We created the following categories: adopters (individuals who did not meet guidelines at baseline but met guidelines at Exam 6), relapsers (individuals who met guidelines at baseline but did not meet guidelines at Exam 6), maintainers (individuals who met guidelines both at baseline and Exam 6), and insufficiently active (individuals who did not meet guidelines at either baseline or Exam 6). The maintainers' group was considered the reference category. We estimated the relative risk to assess the magnitude effect of the association between environmental perceptions and the outcome. Results: Individuals who reported that lack of parks and playgrounds was "not a problem" in their neighborhood had a 2.3-times higher risk of decreasing their physical activity (i.e., the "relapser" category) compared to maintainers. After full adjustment, perceiving poor sidewalks as "somewhat a serious problem" was associated with a 64% lower risk of becoming an adopter than a maintainer. When compared to those who perceive the neighborhood as "very safe", perception of the neighborhood as "safe" to "not at all safe" (ratings 3, 4, and 5, respectively, on the perceived safety scale) was significantly associated with being classified in the adopter category. Conclusions: As the first longitudinal study of the association of perceived environment and physical activity within the MESA cohort, we conclude that a few aspects are longitudinally associated with being physically active among adults.

The designing of ensembles is widely adopted when single machine learning methods fail to obtain satisfactory performances by analyzing complex data characterized by being imbalanced, high-dimensional, and noisy. Such a failure is a well-known statistical challenge when the learning algorithm searches for a model in a large space of hypotheses and the data do not significantly represent the problem, thus not inducing it from a space of admissible functions towards the best global model. We have addressed this issue in a real-world application, whose main objective was to identify whether users were wearing masks inside public transportation during the COVID-19 pandemic. Several studies have already pointed that face masks are an important and efficient non-pharmacological strategy to reduce the virus spread. In this sense, we designed an approach using Convolutional Neural Networks (CNN) to track the adoption of masks in different transportation lines, regions, days, and time. Aiming at reaching this goal, we propose an ensemble of face detectors and a CNN architecture, called MaskNet, to analyze all public-transport passengers and provide valuable information to policymakers, which are able to dedicate efforts to more effective advertisements and awareness work. In practice, our approach is running in a real scenario in Salvador (Brazil)., Competing Interests: Conflict of InterestsThe authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Introduction: Essential oils are complex mixtures of volatile compounds, primarily composed of terpenes and abundant aromatic plants. For example, Cymbopogon citratus (lemongrass) is an aromatic plant that produces a monoterpene-rich essential oil, and studies show that this essential oil has excellent antioxidant activity. Erythrocytes incubated under high sugar levels are constantly exposed to reactive oxygen species, which results in the oxidation of their membranes., Objective: The aim of this article is to investigate the antioxidant activity of lemongrass essential oil and its protective effect on erythrocytes exposed to high levels of glucose., Materials and Methods: The essential oil was obtained by steam dragging distillation; blood cell suspensions were incubated with glucose 5, 20, 50, and 100 mmol/L. The amount of TBARS produced was measured at 532 nm. In addition, the percentage of antioxidant activity was assessed by DPPH free radical assay., Results: Lemongrass essential oil showed an increase in the antioxidant activity up to 240 mg/ml, while ascorbic acid used as positive control showed a dose-dependent increase in antioxidant activity starting at 1 mmol/L up to 18 mmol/L. However, such a lemongrass dose prevented peroxidation in erythrocytes incubated under a high glucose media, whereas ascorbic acid showed a protective effect only at a concentration of 1 mmol/L., Conclusion: Lemongrass essential oil has high antioxidant activity compared to standard antioxidant as ascorbic acid, and also acts as a protective agent against erythrocyte lipoperoxidation due to hyperglycemia in vitro., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: To develop and validate risk scores for predicting abdominal obesity in South American children and adolescents based on extrinsic and intrinsic variables., Methods: Children (n = 358) and adolescents (n = 369) from seven South American cities from the South American Youth Cardiovascular and Environmental (SAYCARE) Study. The primary outcome was abdominal obesity. Potential predictors were based on sociodemographic, maternal, environmental, and behavioural factors and nutritional status. In multilevel logistic models, associated variables were tested to build the scores, which were internally validated., Results: We identified 120 children and 98 adolescents who were abdominally obese. We found at least five variables associated with the outcome in children with unacceptable predictive capacity. However, in adolescents, we found that biological sex, age, maternal body mass index (BMI), active commuting by bike, soft drink consumption (for risk score A), and weight (for score B) can predict abdominal obesity. Both scores, A and B, showed acceptable performance in the ROC curve [areas under curve: 0.70 (95% CI: 0.56-0.82) and 0.95 (95% CI: 0.89-1.00), respectively]., Conclusion: The SAYCARE risk scores present accurate, individualised estimates for identifying adolescents who are at risk of developing abdominal obesity. However, these have not been externally validated., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Context: Blood cutoff values for vitamin A deficiency in children aged 3-10 years have not been addressed in the literature., Objective: To identify blood retinol concentrations for determining severe vitamin A deficiency in children aged 3-10 years., Data Sources: The MEDLINE, Web of Science, Embase, and Scopus databases were searched., Data Extraction: Two reviewers independently extracted article data and assessed quality., Data Analysis: The hierarchical summary receiver operating characteristic models were applied for the diagnostic accuracy meta-analysis. This review is registered at PROSPERO (identifier: CRD42020149367)., Results: A total of 15 articles met the eligibility criteria, and 9 were included in the diagnostic accuracy meta-analysis. The summary estimates (95%CI) were: Sensitivity, 0.39 (0.20-0.62); specificity, 0.79 (0.65-0.88); positive likelihood ratio, 1.85 (1.33-2.57); and negative likelihood ratio, 0.77 (0.60-0.99). The area under the curve of the overall analysis was 0.68 (95%CI 0.63-0.72)., Conclusions: Blood retinol concentrations have low diagnostic accuracy for severe vitamin A deficiency in children aged 3-10 years. Therefore, there is unclear evidence about the preferable cutoff point for determining severe vitamin A deficiency in children in this age group., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

FFQ are one of the most widely used tools of research into nutritional epidemiology, and many studies have been conducted in several countries using this dietary assessment method. The present study aimed to evaluate the relative validity of FFQ, in comparison with other methods, in assessing dietary intake of children and adolescents, through a systematic review. Four electronic databases (Embase, PubMed, Scopus and Web of Science) found sixty-seven articles, which met the inclusion criteria (healthy children and adolescents from 3 to 18 years of age; journal articles written in English, Spanish and Portuguese between 1988 and March 2019; results showing the comparison between the FFQ with other methods of assessment of dietary intake). The articles were analysed by two independent reviewers. A meta-analysis was conducted using correlation coefficients as estimate effects between the FFQ and the reference standard method. Subgroup analysis and meta-regression were performed to identify the probable source of heterogeneity. In fifty-five of the sixty-seven studies, a single dietary assessment method was used to evaluate the FFQ; nine combined the two methods and three used three reference methods. The most widely used reference method was the 24-h recall, followed by the food record. The overall relative validity of the FFQ to estimate energy, macronutrient, certain micronutrient and certain food item intakes in children and adolescents may be considered weak. The study protocol was registered in PROSPERO under number CRD42016038706.

Objectives: To assess the psychometric properties of 4-item questionnaire about sleep habits and time in South American children (3-10 years) and adolescents (11-18 years)., Material and Methods: We evaluated 459 participants from seven South American cities. Two items from week and weekend days wake up time and bedtime were asked twice, with a 2-week interval. We calculated time spent in bed (subtracting wake up time from bedtime). Participants also answered the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) sleep time questionnaire., Results: The questionnaire showed acceptable temporal stability in children and adolescents on total days (rho≥0.30; p<0.05). For total days, the questionnaire presented acceptable convergent validity only in children (rho from 0.48 to 0.62; p≤0.01) compared with the HELENA questionnaire., Conclusion: The 4-item questionnaire is a reliable and valid tool for children; however, its validity is not consistent in adolescents for sleep habits and time.

After two decades of clinical trials, gene therapy demonstrated effectiveness in the treatment of a series of diseases. Currently, several gene therapy products are approved and used in the clinic. Lentiviral vectors (LVs) are one of the most used transfer vehicles to deliver genetic material and the vector of choice to modify hematopoietic cells to correct primary immunodeficiencies, hemoglobinopathies, and leukodystrophies. LVs are also widely used to modify T cells to treat cancers in immunotherapies (e.g., chimeric antigen receptors T cell therapies, CAR-T). In genome editing, LVs are used to deliver sequence-specific designer nucleases and DNA templates. The approval LV gene therapy products (e.g., Kymriah, for B-cell Acute lymphoblastic leukemia treatment; LentiGlobin, for β-thalassemia treatment) reinforced the need to improve their bioprocess manufacturing. The production has been mostly dependent on transient transfection. Production from stable cell lines facilitate GMP compliant processes, providing an easier scale-up, reproducibility and cost-effectiveness. The establishment of stable LV producer cell lines presents, however, several difficulties, with the cytotoxicity of some of the vector proteins being a major challenge. Genome editing technologies pose additional challenges to LV producer cells. Herein the major bottlenecks, recent achievements, and perspectives in the development of LV stable cell lines are revised., (© 2020 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.)

This review systematically investigated observational studies in humans that evaluated the dietary intake of branched-chain amino acids (BCAA) and its association with insulin resistance. A search implemented through the electronic databases of PubMed, Scopus, and Web of Science. The evaluation of insulin resistance or the risk of developing insulin resistance in humans were the variables of interest in the search for articles. After using the selection criteria, three studies included in this review. The Food Frequency Questionnaire (FFQ) was the instrument used to evaluate the diet in all of the selected studies. Overall, 1940 studies identified and three thoroughly reviewed. We found only one study with positive effects of BCAA on insulin resistance; the other two reviewed studies did not demonstrate positive effects of the dietary intake of BCAA, individually or the sum of three amino acids on variables of interest. In this sense, the associations between BCAA and insulin resistance are inconsistent, potentially due to other longitudinal outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

This review offers a systematic discussion about nanotoxicology and nanosafety associated with nanomaterials during manufacture and further biomedical applications. A detailed introduction on nanomaterials and their most frequently uses, followed by the critical risk aspects related to regulatory uses and commercialization, is provided. Moreover, the impact of nanotoxicology in research over the last decades is discussed, together with the currently available toxicological methods in cell cultures (in vitro) and in living organisms (in vivo). A special focus is given to inorganic nanoparticles such as titanium dioxide nanoparticles (TiO 2 NPs) and silver nanoparticles (AgNPs). In vitro and in vivo case studies for the selected nanoparticles are discussed. The final part of this work describes the significance of nano-security for both risk assessment and environmental nanosafety. "Safety-by-Design" is defined as a starting point consisting on the implementation of the principles of drug discovery and development. The concept "Safety-by-Design" appears to be a way to "ensure safety", but the superficiality and the lack of articulation with which it is treated still raises many doubts. Although the approach of "Safety-by-Design" to the principles of drug development has helped in the assessment of the toxicity of nanomaterials, a combination of scientific efforts is constantly urgent to ensure the consistency of methods and processes. This will ensure that the quality of nanomaterials is controlled and their safe development is promoted. Safety issues are considered strategies for discovering novel toxicological-related mechanisms still needed to be promoted.

Silicosis is an occupational lung disease caused by inhalation of silica particles. It is characterized by intense lung inflammation, with progressive and irreversible fibrosis, leading to impaired lung function. Purinergic signaling modulates silica-induced lung inflammation and fibrosis through P2X7 receptor. In the present study, we investigate the role of P2Y 12 , the G-protein-coupled subfamily prototype of P2 receptor class in silicosis. To that end, BALB/c mice received an intratracheal injection of PBS or silica particles (20 mg), without or with P2Y 12 receptor blockade by clopidogrel (20 mg/kg body weight by gavage every 48 h) - groups CTRL, SIL, and SIL + Clopi, respectively. After 14 days, lung mechanics were determined by the end-inflation occlusion method. Lung histology was analyzed, and lung parenchyma production of nitric oxide and cytokines (IL-1β, IL-6, TNF-α, and TGF-β) were determined. Silica injection reduced animal survival and increased all lung mechanical parameters in relation to CTRL, followed by diffuse lung parenchyma inflammation, increased neutrophil infiltration, collagen deposition and increased pro-inflammatory and pro-fibrogenic cytokine secretion, as well as increased nitrite production. Clopidogrel treatment prevented silica-induced changes in lung function, and significantly reduced lung inflammation, fibrosis, as well as cytokine and nitrite production. These data suggest that inhibition of P2Y 12 signaling improves silica-induced lung inflammation, preventing lung functional changes and mortality. Our results corroborate previous observations of silica-induced lung changes and expand the understanding of purinergic signaling in this process., (Copyright © 2020 Santana, Luna-Gomes, Rangel-Ferreira, Tamura, Da Graça, Machado, Zin, Takiya, Faffe and Coutinho-Silva.)

Background: Multicenter studies from Europe and the United States have developed specifically standardized questionnaires for assessing and comparing sedentary behavior, but they cannot be directly applied for South American countries. The aim of this study was to assess the reliability and validity of the South American Youth Cardiovascular and Environmental (SAYCARE) sedentary behavior questionnaire., Methods: Children and adolescents from seven South American cities were involved in the test-retest reliability (children: n = 55; adolescents: n = 106) and concurrent validity (children: n = 93; adolescents: n = 94) studies. The SAYCARE sedentary behavior questionnaire was administered twice with two-week interval and the behaviors were parent-reported for children and self-reported for adolescents. Questions included time spent watching television, using a computer, playing console games, passive playing (only in children) and studying (only in adolescents) over the past week. Accelerometer was used for at least 3 days, including at least one weekend day. We compared values of sedentary time, using accelerometers, by quartiles of reported sedentary behavior time and their sum., Results: The reliability of sedentary behavior time was moderate for children (rho ≥0.45 and k ≥ 0.40) and adolescents (rho ≥0.30). Comparisons between the questionnaire and accelerometer showed a low overall agreement, with the questionnaire systematically underreporting sedentary time in children (at least, - 332.6 ± 138.5 min/day) and adolescents (at least, - 399.7 ± 105.0 min/day)., Conclusion: The SAYCARE sedentary behavior questionnaire has acceptable reliability in children and adolescents. However, the findings of current study indicate that SAYCARE questionnaire is not surrogate of total sedentary time.

Aim: There is much discussion about the advantages and disadvantages of a trial of labor after cesarean (TOLAC). Some data suggest the greater the likelihood of success, the lower the risks of TOLAC. Our goal was to identify clinical and demographic variables associated with a failed TOLAC, available at admission for spontaneous labor and until 3 h later, with the aim of building two scores for risk of failed TOLAC., Methods: This is a nested case-control study with live births to women with one previous cesarean, in a public Brazilian teaching hospital. Preterm, induction, noncephalic presentations, twins, fetal malformations were excluded. Cases were failed TOLAC, and controls, the successful TOLAC. It was accessed the association of the cases with 20 variables (P < 0.05). Associated variables were tested in multivariate analysis to build the scores, which were internally validated., Results: We included 260 TOLAC, 42 cases and 218 controls. We found 11 variables associated with failed TOLAC. In the score to be applied at admission, we included hypertension, fundal height, previous vaginal birth and dilatation at admission. In the second score hypertension, fundal height at admission, membrane status and difference in dilatation 3 h after admission. Both scores presented good performance in the receiver-operator curve (areas under curve: 0.73 and 0.84, respectively). Both scores were translated into nomograms for clinical use., Conclusion: Two scores were built for risk of failed TOLAC, to be applied at admission and 3 h later. We believe that choosing the more favorable cases makes risks of TOLAC lower., (© 2019 Japan Society of Obstetrics and Gynecology.)

RPS14, CSNK1A1, and miR-145 are universally co-deleted in the 5q- syndrome, but mouse models of each gene deficiency recapitulate only a subset of the composite clinical features. We analyzed the combinatorial effect of haploinsufficiency for Rps14, Csnk1a1, and miRNA-145, using mice with genetically engineered, conditional heterozygous inactivation of Rps14 and Csnk1a1 and stable knockdown of miR-145/miR-146a. Combined Rps14/Csnk1a1/miR-145/146a deficiency recapitulated the cardinal features of the 5q- syndrome, including (1) more severe anemia with faster kinetics than Rps14 haploinsufficiency alone and (2) pathognomonic megakaryocyte morphology. Macrophages, regulatory cells of erythropoiesis and the innate immune response, were significantly increased in Rps14/Csnk1a1/miR-145/146a deficient mice as well as in 5q- syndrome patient bone marrows and showed activation of the innate immune response, reflected by increased expression of S100A8, and decreased phagocytic function. We demonstrate that Rps14/Csnk1a1/miR-145 and miR-146a deficient macrophages alter the microenvironment and induce S100A8 expression in the mesenchymal stem cell niche. The increased S100A8 expression in the mesenchymal niche was confirmed in 5q- syndrome patients. These data indicate that intrinsic defects of the 5q- syndrome hematopoietic stem cell directly alter the surrounding microenvironment, which in turn affects hematopoiesis as an extrinsic mechanism.

Introduction: Introduction: sedentary behavior is an important target for health promotion. In this systematic review, we aimed to provide evidence to support decisions about measurement approach choices for subjectively assessing sedentary behavior in pediatric population, adopting objective methods as the reference. Methods: in this systematic review with meta-analysis, published studies were retrieved from electronic databases: Medline (PubMed), Web of Science, Embase, SPORTDiscus, BioMed Central and SCOPUS. We considered studies evaluating sedentary behavior agreement through questionnaire and/or diary in comparison with an objective measure. A total of six inclusion criteria were used. We synthesized the data using correlation coefficients (r) as an indicator of agreement estimates. The review protocol is registered in the PROSPERO database (CRD42014015138). Results: a total of 14 studies met the inclusion criteria with ages ranging from 3 to 17.5 years and provided 17 agreement analyses. Thirteen of these agreement analyses (76.5%) reported correlation coefficients. We found two major groups of sedentary activities: screen time (47.1%) and sedentary behaviors (52.9%). The pooled agreement between questionnaires and accelerometers for assessing self-reported screen time was negative (r = -0.15; CI 95%: -0.17 to -0.13). Conversely, when the sedentary behavior was assessed by questionnaires and accelerometers, the pooled agreement was positive for parent-reporting (r = 0.09; CI 95%: 0.04 to 0.13) and self-reporting (r = 0.43; CI 95%: 0.40 to 0.47) in children and adolescents, respectively. Conclusion: questionnaires have positive agreement with accelerometers for assessing sedentary behavior, whereas the agreement is negative for assessing screen time. Self-reported questionnaires are recommended methods to measure sedentary behavior in adolescents.