Parents' perceived barriers to active commuting to school. Comparative study between Spanish and Ecuadorian cities.

Parents´ perceptions can influence their children´s mode of commuting to school. In this sense, the purposes of this study were to compare parental barriers towards active commuting to school (ACS) between Ecuadorian and Spanish children, and to analyze the associations between those barriers and the children's mode of commuting. Descriptive and comparative analyses were performed using Chi-square and T-student test. Associations were analyzed by several logistic regression models. Results showed that road safety is the main barrier for ACS, and that all the barriers are perceived as higher by Ecuadorian parents (p<0.001). It was also found that Ecuadorian children were less likely to be active when parents perceive greater total barriers (OR=0.15, CI=0.06, 0.40). Public policies should focus on reducing the parental barriers in order to increase ACS, specifically those related to road safety.

Fitness and fatness in children and adolescents: investigating their role in the association between physical activity and cardiometabolic health.

To verify the role of the combination of fitness and fatness in the relationship between physical activity (PA) and cardiometabolic risk in children and adolescents. This is a cross-sectional study performed with 2786 children and adolescents (6 to 17 years). Fitness was determined by the cardiorespiratory fitness (CRF) six-minute walking and running test. Waist circumference (WC) was considered a fatness indicator. A selfreported questionnaire was used to determine PA practice, whereas the clustered cardiometabolic risk score (cMetS) was calculated by summing z-scores of triglycerides, total cholesterol/HDL-C ratio, systolic blood pressure, glucose, and WC. Considering the combination of CRF (fitness) and WC (fatness), the following phenotypes were created: Fit/Unfat, Fit/Fat, Unfit/Unfat and Unfit/Fat. Moderation analyses were tested using linear regression models. Significant interactions were found between PA and Unfit/Fat category (ß = -0.001; p = 0.001) only for adolescents. The interaction observed in the Unfit/Fat phenotype indicated that adolescents who practise PA for 330 minutes per week presented lower cMetS compared to those who do not practise or practise for 60 minutes respectively. The combination of fitness and fatness moderates the relationship between PA and cardiometabolic risk, suggesting that adolescents, particularly those who are less fit and present high adiposity, should be encouraged to engage in regular PA to improve their metabolic health.

Unveiling the relationship of physical literacy with muscular fitness and muscle-strengthening activities in adolescents: the EHDLA study.

Objective: This study evaluated the relationship between physical literacy (PL) and muscular fitness (MF) as well as muscle-strengthening activities (MSA) in adolescents. Methods: A secondary cross-sectional study included 823 adolescents (45.1% boys) from the Eating Healthy and Daily Life Activities Study. The Spanish Perceived Physical Literacy Instrument for Adolescents (S-PPLI) assessed the participants' perceived PL. The evaluation of MF in the young population was conducted using the Assessing the Levels of Physical Activity and Fitness (ALPHA-FIT) test battery. MSA were assessed by the following question: 'In the past week, how many days did you exercise to strengthen or tone the muscle, such as through push-ups, sit-ups or lifting weights?' To examine the associations between S-PPLI scores and handgrip strength, standing long jump and MSA days in adolescents, we employed generalised additive models. Results: Participants with high perceived physical literacty (PPL) had the highest handgrip strength (mean=25.1; PPL had the highest handgrip strength (mean=25.1; bias-corrected and accelerated (BCa) bootstrapped 95% CI 24.2 to 26.0) and standing long jump (mean=149.7; confidence interval (CI) 24.2 to 26.0) and standing long jump (mean=149.7; 24.2 to 26.0) and standing long jump (mean=149.7; BCa bootstrapped 95% CI 145.8 to 153.5). Conversely, those adolescents with low PPL had the lowest handgrip strength (mean=23.1; BCa bootstrapped 95% CI 22.3 to 23.8) and standing long jump (mean=137.3; BCa bootstrapped 95% CI 133.9 to 140.6). For MSA, adolescents with high PPL had the highest mean of MSA days (mean=3.0; BCa bootstrapped 95% CI 2.8 to 3.3), while the lowest mean was observed for those with low PPL (mean=2.0; BCa bootstrapped 95% CI 1.8 to 2.2). Conclusion: A high level of PL was associated with higher levels of MF and MSA among Spanish adolescents.

Green solvents extraction-based detoxification to enhance the enzymatic hydrolysis of steam-exploded lignocellulosic biomass and recover bioactive compounds.

A novel strategy for pre-treated biomass detoxification combining emerging green solvents and low environmental impact extraction technologies was evaluated. Steam-exploded biomass was subjected to microwave-assisted or orbital shaking extraction using bio-based or eutectic solvents. The extracted biomass was enzymatically hydrolysed. The potential of this detoxification methodology was studied in terms of phenolic inhibitors extraction and sugar production improvement. The effect of adding a post-extraction water washing step before hydrolysis was also evaluated. Excellent results were achieved when steam-exploded biomass was subjected to the microwave-assisted extraction combined with the washing step. The highest sugar production was achieved when ethyl lactate was used as extraction agent (49.80 ± 3.10 g total sugar/L) over the control (30.43 ± 0.34 g total sugar/L). Results suggested that a detoxification step based on green solvents would be a promising option to extract phenolic inhibitors, which can be revalorized as antioxidants, and improve the sugar production from the extracted pre-treated biomass.

The added effect of non-pharmaceutical interventions and lifestyle behaviors on vaccine effectiveness against severe COVID-19 in Chile: A matched case-double control study.

BACKGROUND: World Health Organization approved vaccines have demonstrated relatively high protection against moderate to severe COVID-19. Prospective vaccine effectiveness (VE) designs with first-hand data and population-based controls are nevertheless rare. Neighborhood compared to hospitalized controls, may differ in compliance to non-pharmacuetical interventions (NPI) compliance, which may influence VE results in real-world settings. We aimed to determine VE against COVID-19 intensive-care-unit (ICU) admission using hospital and community-matched controls in a prospective design. METHODS: We conducted a multicenter, observational study of matched cases and controls (1:3) in adults ≧18 years of age from May to July 2021. For each case, a hospital control and two community controls were matched by age, gender, and hospital admission date or neighborhood of residence. Conditional logistic regression models were built, including interaction terms between NPIs, lifestyle behaviors, and vaccination status; the model's ß coefficients represent the added effect these terms had on COVID-19 VE. RESULTS: Cases and controls differed in several factors including education level, obesity prevalence, and behaviors such as compliance with routine vaccinations, use of facemasks, and routine handwashing. VE was 98·2% for full primary vaccination and 85·6% for partial vaccination when compared to community controls, and somewhat lower, albeit not significantly, compared to hospital controls. A significant added effect to vaccination in reducing COVID-19 ICU admission was regular facemask use and VE was higher among individuals non-compliant with the national vaccine program, and/or tonroutine medical visits during the prior year. CONCLUSION: VE against COVID-19 ICU admission in this stringent prospective case-double control study reached 98% two weeks after full primary vaccination, confirming the high effectiveness provided by earlier studies. Face mask use and hand washing were independent protective factors, the former adding additional benefit to VE. VE was significantly higher in subjects with increased risk behaviors.

Polarimetric imaging for the detection of synthetic models of SARS-CoV-2: A proof of concept.

Objective: To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging. Approach: Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were prepared in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-µL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry from87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380-420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples. Main results: The angles (from sample surface) of maximal DLP were 3° for 405 nm and 6° for 514 nm. Similar viral particles that differed only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations. Significance: Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 viral particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to a fast, cost-effective screening of SARS-CoV-2 and other pathogens when combined with other imaging modalities.

Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation.

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer's disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI-MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model.

Enhanced Recovery of Natural Antioxidants from Grape Waste Using Natural Eutectic Solvents-Based Microwave-Assisted Extraction.

The evaluation of sustainable solvents as alternatives to more harmful conventional solvents combined with intensification techniques to recover phenolic compounds from agri-food waste is in the spotlight. The wine industry generates large amounts of waste as a consequence of grape processing operations, which can be revalued by solvent extraction of valuable antioxidants for food and fine chemical applications. Therefore, the present study focuses on the use of natural eutectic solvents (NAESs) with benign environmental, health, and safety profiles, for valorization of grape waste in the context of a circular economy. Herein, up to 15 NAESs consisting of combinations of three hydrogen bond acceptors (choline chloride, L-proline, and betaine) and four hydrogen bond donors (1,2-propanediol, glycerol, and 1,2- and 1,3-butanediol) were evaluated for antioxidant recovery. After an initial screening of the performance of NAESs by conventional extraction, the process was intensified by microwave-assisted extraction (MAE). The extracts were analyzed by UV/VIS spectrophotometric and HPLC methods. Promising results were obtained with the solvent betaine, 1,2-butanediol [1:4], using MAE at 100 °C for 3 min. Overall, the proposed NAESs-based MAE method was successfully applied to recover target compounds from grape waste, with great prospects for the antioxidants market and sustainable development for the winery sector.

The Impact of Colistin Resistance on the Activation of Innate Immunity by Lipopolysaccharide Modification.

Colistin resistance is acquired by different lipopolysaccharide (LPS) modifications. We proposed to evaluate the of effect in vivo colistin resistance acquisition on the innate immune response. We used a pair of ST11 clone Klebsiella pneumoniae strains: an OXA-48, CTX-M-15 K. pneumoniae strain susceptible to colistin (CS-Kp) isolated from a urinary infection and its colistin-resistant variant (CR-Kp) from the same patient after prolonged treatment with colistin. No mutation of previously described genes for colistin resistance (pmrA, pmrB, mgrB, phoP/Q, arnA, arnC, arnT, ugdH, and crrAB) was found in the CR-Kp genome; however, LPS modifications were characterized by negative-ion matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The strains were cocultured with human monocytes to determine their survival after phagocytosis and induction to apoptosis. Also, monocytes were stimulated with bacterial LPS to study cytokine and immune checkpoint production. The addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A of CR-Kp accounted for the colistin resistance. CR-Kp survived significantly longer inside human monocytes after being phagocytosed than did the CS-Kp strain. In addition, LPS from CR-Kp induced both higher apoptosis in monocytes and higher levels of cytokine and immune checkpoint production than LPS from CS-Kp. Our data reveal a variable impact of colistin resistance on the innate immune system, depending on the responsible mechanism. Adding Ara4N to LPS in K. pneumoniae increases bacterial survival after phagocytosis and elicits a higher inflammatory response than its colistin-susceptible counterpart.

Efficacy of school-based interventions for improving muscular fitness outcomes in children: A systematic review and meta-analysis.

The World Health Organization recommends that children should engage in an average of 60 min of moderate-to-vigorous physical activity (MVPA) per day and should perform activities that strengthen muscle and bone at least 3 days a week. Public health professionals as well as pediatric researchers have identified schools as a strategic place to promote muscular strength development. Thus, the aim of this systematic review and meta-analysis was to investigate the efficacy of school-based exercise interventions for improving muscular fitness (MF) in children. Searches were conducted in three databases. Eligible criteria were randomized and non-randomized controlled trials evaluating the effects of school-based exercise interventions on MF (i.e. muscular strength, muscular power, and local muscular endurance) in children under 13 years of age. Risk of bias by the National Institutes of Health tool was appraised, and pooled effect sizes (Hedges'g) were calculated using random-effects inverse-variance analyses. Seventeen studies enrolling 1653 children (28% girls were analyzed). Exercise interventions, mostly combined interventions targeting selected domains of MF, were associated with significant moderate increases in local muscular endurance (g = 0.65 95% CI, 0.13 to 1.17, p = 0.020; I2 = 85.0%) and muscular strength and muscular power (g = 0.33 95% CI, 0.16 to 0.51, p = 0.001; I2 = 59.3%), with higher effects using interventions with ≥3 sessions per week. Our findings indicate that school-based exercise that includes strength building exercises may improve MF in children and, consequently, prepare modern day youth for the demands of exercise and sport activities. HighlightsSchool-based muscle and bone strengthening exercises performed at least 3 days per week may serve to support the development of muscular fitness in girls and boysIntegrative interventions that include a variety of strength and conditioning activities seem to be a promising strategy to promote muscular fitness in school environmentFuture research should standardize assessment methods for use with children in the school context and should include interventions with girlsIt is of interest to a growing number of health care providers, fitness professionals and physical education teachers to encourage participation in well-designed muscle and bone strengthening exercises.

Environmental and health risk implications of unregulated emissions from advanced biofuels in a Euro 6 engine.

The use of conventional and advanced biofuels is part of the efforts to reduce greenhouse gases and harmful exhaust gaseous emissions. This study investigates the unregulated emissions in gas and particles from a Euro 6b diesel engine, operated with four unconventional and advanced biofuels (two hydrogenated terpenic biofuels, a polyoxymethylene dimethyl ether, and a glycerol-derived biofuel), blended with diesel fuel and pure hydrotreated vegetable oil as base biofuel. The engine was operated following WLTC starting from cold-engine conditions. Gas phase samples were collected at each phase of the driving cycle and particulate matter (PM) samples were collected from a dilution tunnel at the end of the driving cycle. A total of 16 PAH and 13 carbonyls were analyzed. In addition, the apoptotic index induced by gas and particle emissions was determined. In the gaseous phase, the total PAH and carbonyl emission factors were higher at the low-speed phase for all fuels. Gas-phase PAH emission factors exceeded particle-bound PAH. Carbonyl emission factors ranged from 0.12 ± 0.012 to 25.3 ± 4.2 mg/km, markedly exceeding gaseous PAH emissions, which ranged from 20.7 ± 1.5 to 51.7 ± 8.9 µg/km. Diesel fuel exhibited the highest carbonyl emissions and its blend with 20% of hydrogenated turpentine exhibited the highest PAH emissions at the end of the WLTC, both due to high emissions at the low-speed phase. Although particle-bound PAH comprise only a small fraction of total PAH emissions, both phases (gas and particles) contributed approximately equal to the toxicity associated with carcinogenic PAH. The apoptotic cells percentage increased in a dose-dependent manner and was significantly higher in cells exposed to gas phase-derived samples. The apoptotic index induced by particulate matter samples did not show a concentration-response effect for any of the fuels.

CoQ10 reduces glioblastoma growth and infiltration through proteome remodeling and inhibition of angiogenesis and inflammation.

PURPOSE: Most monotherapies available against glioblastoma multiforme (GBM) target individual hallmarks of this aggressive brain tumor with minimal success. In this article, we propose a therapeutic strategy using coenzyme Q10 (CoQ10) as a pleiotropic factor that crosses the blood-brain barrier and accumulates in cell membranes acting as an antioxidant, and in mitochondrial membranes as a regulator of cell bioenergetics and gene expression. METHODS: Xenografts of U251 cells in nu/nu mice were used to assay tumor growth, hypoxia, angiogenesis, and inflammation. An orthotopic model was used to explore microglial infiltration, tumor growth, and invasion into the brain parenchyma. Cell proliferation, migration, invasion, proteome remodeling, and secretome were assayed in vitro. Conditioned media were used to assay angiogenesis, monocyte chemoattraction, and differentiation into macrophages in vitro. RESULTS: CoQ10 treatment decreased tumor volume in xenografts and orthotopic models, although its effect on tumor cell proliferation was not direct. Tumors from mice treated with CoQ10 were less hypoxic and vascularized, having less infiltration from inflammatory cells. Treatment-induced downregulation of HIF-1α and NF-kB led to a complete remodeling of the tumor cells proteome and secretome, impacting angiogenesis, monocyte infiltration, and their differentiation into macrophages. Besides, tumor cell migration and invasion were drastically restricted by mechanisms involving modulation of the actin cytoskeleton and downregulation of matrix metalloproteases (MMPs). CONCLUSIONS: CoQ10 has a pleiotropic effect on GBM growth, targeting several hallmarks simultaneously. Thus, its integration into current treatments of this fatal disease should be considered.

Recovery of Phenolic Compounds from Orange Peel Waste by Conventional and Assisted Extraction Techniques Using Sustainable Solvents.

BACKGROUND: The valorization of orange peel waste (OPW) through the extraction of bioactive compounds is a clear example of the circular economy. OPW contains many value-added compounds, among which bioactive phenolic compounds (flavonoids and phenolic acids) could be extracted and used for industrial applications, such as pharmaceuticals or cosmetics. METHODS: In this work, the extraction of phenolic compounds from orange peel was carried out by conventional (orbital shaker) and assisted (ultrasound and microwave) extraction techniques using deionized water, 80% (v/v) ethanol in water, and ethyl acetate as solvents. The effect of temperature, extraction time, and type of technique was evaluated and discussed following spectrophotometric (total phenolic content and total flavonoid content) and high-performance liquid chromatography (HPLC) analyses of the extracts. RESULTS: The most effective extraction in terms of efficiency was achieved by microwave-assisted extraction using 80% (v/v) ethanol in water as the extraction solvent, at 373 K for 6 min, which obtained 7.2 ± 0.1 mg gallic acid equivalent (GAE)/g OPW and 13.3 ± 0.1 mg quercetin equivalent (QE)/g OPW, with the main bioactive compound extracted being hesperidin (58.2 ± 0.2 mg/g OPW). The most effective extraction in terms of energy consumption was achieved using ultrasound-probe-assisted extraction, yielding 8.8 ± 0.0 mg GAE/g OPW; 17.1 ± 0.1 mg QE/g OPW; 40.0 ± 0.2 mg hesperidin/g OPW, with an energy consumption of 18 kJ. CONCLUSIONS: Ultrasound and microwave-assisted extractions can be considered efficient extraction technologies for the valorization of OPW as they reduce extraction time and energy consumption and increase extraction yield.

Increased quality of life in patients with breakthrough cancer pain after individualized therapy: the CAVIDIOM study.

Aim: To evaluate the quality of life (QoL) in patients with breakthrough cancer pain (BTcP) in Spanish medical oncology departments. Patients & methods: In a prospective, observational, multicenter study, we assessed QoL using the EQ-5D-5L instrument at baseline and after 15 and 30 days of individualized BTcP therapy, as well as BTcP characteristics and treatment. Results: Patients (n = 118) were mainly women, over 64 years old and with advanced cancer. QoL improved at 15 (p = 0.013) and 30 days (p = 0.011) versus baseline. Individualized BTcP therapy consisted mostly of rapid-onset opioids (transmucosal fentanyl at doses of 67-800 µg) according to the physician evaluation. BTcP improved, including statistically significant reductions in intensity, duration, number of episodes in the last 24 h and time to onset of BTcP relief. Conclusion: QoL increased after individualized pain therapy in patients with advanced cancer and BTcP in medical oncology departments.

Cancer patients can experience flares of pain, called breakthrough pain (BTcP), despite treatment with painkillers. Although BTcP can be excruciating, its intensity and other characteristics depend on several factors, including its treatment. However, even if treated, BTcP can impair quality of life for cancer patients. We assessed quality of life in 118 patients with advanced cancer and BTcP treated in 13 medical oncology departments across Spain. We treated BTcP with individualized therapy, taking into account both pain-related and patient-related factors. We also measured quality of life using a specific, widely-used questionnaire at the study visits: at onset of individualized pain therapy and after 3, 15 and 30 days' treatment. At each visit, flare-up pain therapy was adjusted or maintained as necessary. Throughout the study, quality of life and sleep quality improved for all participants. Furthermore, there was a greater reduction in intensity, duration and frequency of BTcP. The most common treatments for flare-ups were low doses of rapid-onset opioids (fentanyl given by sublingual, buccal or nasal administration), which were much better tolerated than high-dose opioids. Overall, the study showed that quality of life in patients with advanced cancer and BTcP increased after individualized pain therapy, mainly with low doses of rapid-onset opioids.

Coulometer from a Digitally Controlled Galvanostat with Photometric Endpoint Detection.

In this work, a coulometer was developed from a digitally controlled galvanostat. A simple colorimeter based on a RGB LED was used as a light emitter coupled to light detectors, while light dependent resistance (LDR) and photodiodes have been developed as endpoint detectors. Both hardware and software have been adapted from the original galvanostat design. Regarding the hardware, new electrical signal conditioners (filters and voltage dividers) were included to optimize the working system. The software was developed based on an open source Arduino UNO microcontroller. The different variables that control the titration process are managed by an add-in module for Excel data acquisition software that is freely available. A study of the possible variables that influence the titration process has been carried out. The system was tested with two classical coulometric titrations such as iodometry (thiosulfate, ascorbic acid) and acid/base (potassium acid phthalate as standard). The developed system is versatile as different endpoint color indicators can be employed (starch and phenolphthalein for the investigated reactions). Different experimental arrangements have been studied: the nature of the electrodes (Pt, Ag), type of cells (two separate compartments or a single compartment), and light detectors (LDR, photodiode). The influence of several experimental parameters (both electrical, light, and integration time) was studied and chosen to obtain the best performance of the complete system. Reproducibility results below 1% can be obtained under controlled conditions. In the case of acid/base titrations, the presence of atmospheric carbon dioxide was detected, whose interference was mainly affected by the stirring rate and the titration time.

Contactless Ultrasonic Cavitation for the Prevention of Shunt Obstruction in Hydrocephalus: A Proof-of-Concept Study.

BACKGROUND: Obstructive failure of implanted shunts is the most common complication in the treatment of hydrocephalus. Biological material and debris accumulate in the inner walls of the valve and catheters block the normal flow of the drained cerebrospinal fluid causing severe symptoms with high morbidity and mortality. Unfortunately, at present, there is no effective preventive protocol or cleaning procedure available. OBJECTIVE: To assess whether externally applied, focused ultrasound beams can be used to resuspend deposits accumulated in brain shunts safely. METHODS: A computational model of an implanted brain shunt was implemented to test the initial design parameters of a system comprising several ultrasound transducers. Under laboratory conditions, configurations with 3 and 4 transducers were arranged in a triangle and square pattern with their radiation axis directed towards a target model of the device, 2 catheters and a brain shunt filled with water and deposited graphite powder. The ultrasound beams were then concentrated on the device across a head model. RESULTS: The computational model revealed that by using only 3 transducers, the acoustic field intensity on the valve was approximately twice that on the brain surface suggesting that acoustic cavitation could be selectively achieved. Resuspension of graphite deposits inside the catheters and the valve were then physically demonstrated and video-recorded with no temperature increase. CONCLUSION: The technology presented here has the potential to be used routinely as a noninvasive, preventive cleaning procedure to reduce the likelihood of obstruction-related events in patients with hydrocephalus treated with an implanted shunt.

From pregnancy to breastfeeding: adequate maternal body mass index is essential to prevent a high body mass index in your children.

OBJECTIVES: To verify the associations between prenatal and perinatal factors with offspring body mass index (BMI) and the moderator role of maternal BMI in this relationship. METHODS: Cross-sectional study developed with 1,562 children and adolescents aged between 6 and 17 years, as well as their mothers, from southern Brazil. The prenatal and perinatal factors, weight, and height for the calculation of maternal BMI were self-reported. For the calculation of BMI, weight and height of the child/adolescent were measured on an anthropometric scale with a coupled stadiometer. Linear regression models were used for the moderation analysis. All analyzes were adjusted for the mother's and child's age, sex, sexual maturation, skin color/race, and educational level. RESULTS: cesarean as type of delivery (ß=0.66; 95% CI=0.22 1.04; p=0.002) and pregnancy complications (ß=0.60; 95% CI=0.15 1.04; p=0.002) were positively associated with offspring BMI. Schoolchildren who were breastfed for 4-6 months showed -0.56 kg/m2 of BMI (95% CI=-1.06-0.06; p=0.02). Birth weight was also associated with BMI, with low weight being inversely (ß=-0.59; 95% CI=-1.03-0.15; p=0.008), while overweight was positively related (ß=0.84; 95% CI=0.08 1.60; p=0.02). The moderation analysis indicated a positive interaction between the mother's BMI and cesarean, pregnancy complications, and smoking with the offspring's BMI. On the other hand, there was an inverse association between breastfeeding from 7 to 12 months and the offspring BMI, only in mothers with high BMI. CONCLUSIONS: Adequate maternal BMI is essential to prevent a high BMI in their children, especially when considering the influence of prenatal and perinatal risk factors.

Generation of Human Nociceptor-Enriched Sensory Neurons for the Study of Pain-Related Dysfunctions.

In vitro models of the peripheral nervous system would benefit from further refinements to better support studies on neuropathies. In particular, the assessment of pain-related signals is still difficult in human cell cultures. Here, we harnessed induced pluripotent stem cells (iPSCs) to generate peripheral sensory neurons enriched in nociceptors. The objective was to generate a culture system with signaling endpoints suitable for pharmacological and toxicological studies. Neurons generated by conventional differentiation protocols expressed moderate levels of P2X3 purinergic receptors and only low levels of TRPV1 capsaicin receptors, when maturation time was kept to the upper practically useful limit of 6 weeks. As alternative approach, we generated cells with an inducible NGN1 transgene. Ectopic expression of this transcription factor during a defined time window of differentiation resulted in highly enriched nociceptor cultures, as determined by functional (P2X3 and TRPV1 receptors) and immunocytochemical phenotyping, complemented by extensive transcriptome profiling. Single cell recordings of Ca2+-indicator fluorescence from >9000 cells were used to establish the "fraction of reactive cells" in a stimulated population as experimental endpoint, that appeared robust, transparent and quantifiable. To provide an example of application to biomedical studies, functional consequences of prolonged exposure to the chemotherapeutic drug oxaliplatin were examined at non-cytotoxic concentrations. We found (i) neuronal (allodynia-like) hypersensitivity to otherwise non-activating mechanical stimulation that could be blocked by modulators of voltage-gated sodium channels; (ii) hyper-responsiveness to TRPV1 receptor stimulation. These findings and several other measured functional alterations indicate that the model is suitable for pharmacological and toxicological studies related to peripheral neuropathies.