Epigenetic programming for obesity and noncommunicable disease: From womb to tomb.

Several epidemiological, clinical and experimental studies in recent decades have shown the relationship between exposure to stressors during development and health outcomes later in life. The characterization of these susceptible phases, such as preconception, gestation, lactation and adolescence, and the understanding of factors that influence the risk of an adult individual for developing obesity, metabolic and cardiovascular diseases, is the focus of the DOHaD (Developmental Origins of Health and Disease) research line. In this sense, advancements in molecular biology techniques have contributed significantly to the understanding of the mechanisms underlying the observed phenotypes, their morphological and physiological alterations, having as a main driving factor the epigenetic modifications and their consequent modulation of gene expression. The present narrative review aimed to characterize the different susceptible phases of development and associated epigenetic modifications, and their implication in the development of non-communicable diseases. Additionally, we provide useful insights into interventions during development to counteract or prevent long-term programming for disease susceptibility.

Spinal Cord Stimulation Modulates Rat Cortico-Basal Ganglia Locomotor Circuit.

OBJECTIVE: The cortico-basal ganglia circuit is crucial to understanding locomotor behavior and movement disorders. Spinal cord stimulation modulates that circuit, which is a promising approach to restoring motor functions. However, the effects of electrical spinal cord stimulation in the healthy brain motor circuit in pre- and postgait are poorly understood. Thus, this report aims to evaluate, through electrophysiological analyses, the dynamic spectral features of motor networks underlying locomotor initiation with spinal cord stimulation. MATERIALS AND METHODS: Wistar male rats underwent spinal cord stimulation (current 30-150 µA, frequency 100, 333, and 500 Hz) with the electrophysiological recording of the caudate and putamen nuclei, primary and secondary motor cortices, and primary somatosensory cortex. Video tracking recorded treadmill locomotion and extracted the motor planning and gait initiation. RESULTS: Spectral analysis of segments of gait initiation (pre- and postgait), with stimulation off, showed increased low-frequency activity. Postgait initiation showed increased alpha and beta rhythms and decreased delta rhythm with the stimulation off. Overall, the stimulation frequencies reduced alpha and beta rhythms in all brain areas during movement initiation. Regarding movement planning, such an effect was observed in the sensorimotor area, comprising the delta and alpha rhythms. CONCLUSION: This study showed a short-term effect of spinal cord stimulation on the brain areas of the motor circuit, suggesting possible facilitation of movement planning and starting through neuromodulation. Thus, the electrophysiological characterization of this study may contribute to understanding basal ganglia networks and developing new approaches to treat movement disorders in the gait initiation phase.

Development of Immobilized Carreira (Phosphoramidite, Olefin) Ligands and Application in Iridium-Catalyzed Asymmetric Allylic Amination.

A family of polystyrene-supported (phosphoramidite, olefin) ligands L1-L4, based on the original design by Defieber and Carreira, has been developed and applied in iridium-catalyzed asymmetric allylic amination of unmasked allylic alcohols (27 examples, up to 99% ee). Among them, functional resins L1 and L4 exhibit important advantages such as easy preparation, ligand recyclability, and easy handling for sequential use. As a distinctive advantage, the catalytic use of the iridium complexes of L1 and L4 allows the straightforward reuse of a high percentage of the expensive iridium metal involved in the complexes, which is not achievable under homogeneous conditions with the corresponding monomeric complexes.

Pro- and anti-inflammatory adipokines are associated with cardiometabolic risk markers in Brazilian schoolchildren.

Pro- and anti-inflammatory adipokines have been regarded as potential markers of obesity and cardiometabolic comorbidities. However, few studies have evaluated this association in children. We aimed to evaluate the relationship between adipokine concentrations and cardiometabolic risk markers in Brazilian schoolchildren. This was a cross-sectional study with 378 children aged 8-9 years from Viçosa, Minas Gerais, Brazil. We measured adipokines (leptin, retinol-binding protein 4, adiponectin, and chemerin) and cardiometabolic risk markers (fasting glucose, HOMA-IR, lipid profile, and blood pressure). Cardiometabolic risk markers were compared by quintiles of adipokines with linear regression adjusted for potential confounders. Leptin was positively associated with diastolic blood pressure (P = 0.03) and HOMA-IR (P = 0.01), and retinol-binding protein 4 was positively associated with total cholesterol (P = 0.04). Each standard deviation of leptin and retinol-binding protein 4 was associated to, respectively, a 0.1 (95%CI: 0.1; 0.2), 0.3 (95%CI: 0.1; 0.6), and 2.5 (95%CI: 0.1; 4.9) units increase in diastolic blood pressure, HOMA-IR, and total cholesterol. Adiponectin was negatively associated with diastolic blood pressure (P = 0.01) and HOMA-IR (P = 0.01), and chemerin was negatively associated with glucose (P = 0.001). Each standard deviation of adiponectin and chemerin was associated to, respectively, a -0.1 (95%CI: -0.2; -0.1), -0.2 (95%CI: -0.3; -0.1), and -1.2 (95%CI: -1.9; -0.5) units decrease in diastolic blood pressure, HOMA-IR, and glucose.Conclusion: Pro- and anti-inflammatory adipokines were positively and negatively associated with cardiometabolic risk markers, respectively, among schoolchildren, indicating this relationship may be identified at earlier ages. What is Known: • Although leptin, retinol-binding protein 4, and adiponectin are well-known adipokines, a consensus regarding their relationship with cardiometabolic risk markers, especially in schoolchildren, has not yet been reached. • Chemerin is an adipokine that has been studied recently. Yet, due to its dependence on the target cell type, its functions are still a controversial topic. What is New: • Leptin was positively associated with diastolic blood pressure and HOMA-IR, and retinol-binding protein 4 was positively associated with total cholesterol. • Adiponectin was negatively associated with diastolic blood pressure and HOMA-IR, and chemerin was negatively associated with glucose.

Dietary inflammatory index scores are associated with atherogenic risk in Brazilian schoolchildren.

OBJECTIVE: To investigate the association between the Children's Dietary Inflammatory Index (C-DIITM) scores and atherogenic risk in Brazilian schoolchildren. DESIGN: A cross-sectional representative study. Three 24-h dietary recalls were performed to evaluate food consumption and to calculate C-DII scores. Blood samples were collected for the lipid profile analysis (serum total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol and triglycerides (TAG)) and to determine atherogenic indexes (Castelli risk indexes I and II, lipoprotein combined index (LCI), and atherogenic index of plasma and atherogenic coefficient (AC)). A semi-structured questionnaire was used to obtain sociodemographic characteristics and screen time. Body fat was assessed by dual-energy X-ray absorptiometry. We compared the distributions of outcomes by C-DII categories using multivariable linear regression. SETTING: Viçosa, Minas Gerais, Brazil. PARTICIPANTS: Three hundred seventy-eight children between the ages of 8 and 9 years. RESULTS: The mean C-DII score was 0·60 ± 0·94, and the prevalence of dyslipidaemia was 70 %. Children with hypercholesterolaemia and hypertriglyceridaemia had higher C-DII scores. The C-DII was directly associated with atherogenic risk. Every 1 sd of C-DII was associated with a 0·07 (0·01, 0·13), 1·94 (0·20, 3·67), 0·06 (0·002, 0·12) and 0·12 (0·02, 0·22) units higher TC:HDL cholesterol ratio, LCI, AC and accumulation of altered dyslipidaemia markers (high TC + high LDL-cholesterol + high TAG + low HDL-cholesterol), respectively. CONCLUSIONS: Dietary inflammatory potential, as estimated by the C-DII, is directly associated with atherogenic risk in Brazilian schoolchildren. This results reinforce the importance of effective nutritional policies to promote healthy eating habits and improve children's lipid profiles.

Late assessment of quality of life in patients with rectal carcinoma: comparison between sphincter preservation and definitive colostomy.

PURPOSE: Patients with cancer of the lower and middle rectum who are candidates for curative surgery often have negative opinions on definitive colostomy. The purpose of this study is to compare the quality of life (QoL) of patients who undergo standard treatment for rectal cancer with sphincter preservation or definitive colostomy. METHODS: A total of 125 patients with adenocarcinoma of the lower or middle rectum who underwent radical surgery with curative intent with a follow-up ≥ 1 year were recruited: 83 patients (group 1) were subjected to low anterior resection and low colorectal or coloanal anastomosis-thus preserving their sphincter-and 42 (group 2) were treated with abdominoperineal resection, followed by terminal definitive colostomy. QoL was assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. RESULTS: Health and global quality of life were similar between groups; however, patients who underwent definitive colostomy had higher scores on the emotional (p value = 0.016) and cognitive function scales (p value = 0.017). Patients with sphincter preservation presented with more symptoms that were related to stool frequency (p value < 0.001), intestinal constipation (p value = 0.005), fecal incontinence (p value = 0.001), buttock pain (p value = 0.023), and nausea and vomiting (p value = 0.036), whereas patients with permanent colostomy had higher scores for dysuria (p value = 0.033). CONCLUSION: Although global QoL scores did not differ between groups, patients who underwent definitive colostomy had significantly better functional and symptom scale scores, reflecting greater function with fewer symptoms.

Lower vitamin D intake is associated with low HDL cholesterol and vitamin D insufficiency/deficiency in Brazilian children.

OBJECTIVE: To evaluate the association of vitamin D intake with dyslipidaemia and vitamin D insufficiency/deficiency in Brazilian children and identify the main food group sources of this nutrient in the sample. DESIGN: A cross-sectional study carried out with a representative sample. Blood was collected after 12 h of fasting. Laboratory tests were performed to determine total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol, TAG, apoB, apoA1, 25-hydroxyvitamin D and parathyroid hormone. Dietary intake was evaluated by a 24 h recall. SETTING: Viçosa, Minas Gerais, Brazil. SUBJECTS: Children between 8 and 9 years old enrolled in urban schools (n 378). RESULTS: We found an elevated prevalence of inadequate vitamin D intake (91·3 %), dyslipidaemia (72·8 %) and vitamin D insufficiency/deficiency (56·2 %). The food groups that contributed the most to vitamin D intake were dairy products and fish. Lower vitamin D intake was associated with increased prevalence of both low HDL-C (prevalence ratio=2·51; 95 % CI 1·02, 6·18; P<0·05) and vitamin D insufficiency/deficiency (prevalence ratio=1·61; 95 % CI 1·01, 2·58; P<0·05). CONCLUSIONS: Given the elevated prevalence of inadequate vitamin D intake and its association with low HDL-C and vitamin D insufficiency/deficiency, it is important to develop specific actions in food and nutritional education as well as programmes that stimulate and facilitate access to vitamin D food sources, such as dairy products and fish.

Reducing measurement errors during functional capacity tests in elders.

BACKGROUND: Accuracy is essential to the validity of functional capacity measurements. AIM: To evaluate the error of measurement of functional capacity tests for elders and suggest the use of the technical error of measurement and credibility coefficient. METHODS: Twenty elders (65.8 ± 4.5 years) completed six functional capacity tests that were simultaneously filmed and timed by four evaluators by means of a chronometer. A fifth evaluator timed the tests by analyzing the videos (reference data). RESULTS: The means of most evaluators for most tests were different from the reference (p < 0.05), except for two evaluators for two different tests. There were different technical error of measurement between tests and evaluators. The Bland-Altman test showed difference in the concordance of the results between methods. Short duration tests showed higher technical error of measurement than longer tests. In summary, tests timed by a chronometer underestimate the real results of the functional capacity. DISCUSSION: Difference between evaluators' reaction time and perception to determine the start and the end of the tests would justify the errors of measurement. CONCLUSION: Calculation of the technical error of measurement or the use of the camera can increase data validity.

Effect of Uncaria tomentosa extract on purinergic enzyme activities in lymphocytes of rats submitted to experimental adjuvant arthritis model.

BACKGROUND: Considering that adjuvant arthritis is an experimental model of arthritis widely used for preclinical testing of numerous anti-arthritic agents, which were taken by a large number of patients worldwide, it is of great interest to investigate the therapeutic action of compounds with anti-inflammatory properties, such as Uncaria tomentosa extract. Moreover, there are no studies demonstrating the effect of U. tomentosa on the metabolism of adenine nucleotides published so far. Thus, the purpose of the present study is to investigate the effects of U. tomentosa extract on E-NTPDase and E-ADA activities in lymphocytes of Complete Freund's Adjuvant (CFA) arthritis induced rats. METHODS: To evaluate the effect of U. tomentosa extract on the activity of E-NTPDase and ADA in lymphocytes, the rats were submitted to an experimental adjuvant arthritis model. Peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Data were analyzed by a one- or two-way ANOVA. Post hoc analyses were carried out by the Student-Newman-Keuls (SNK) Multiple Comparison Test. RESULTS: E-NTPDase activity was increased in arthritic untreated. Arthritic rats which received U. tomentosa extract, presented similar results to the control group. However, results obtained for adenosine hydrolysis by E-ADA were not altered in arthritic rats. U. tomentosa extract did not alter E-NTPDase and E-ADA activity in healthy animals. CONCLUSIONS: The present investigation supports the hypothesis that the increased E-NTPDase activity verified in arthritic rats might be an attempt to maintain basal levels of ATP and ADP in the extracellular medium, since the arthritis induction causes tissue damage and, consequently, large amounts of ATP are released into this milieu. Also, it highlights the possibility to use U. tomentosa extract as an adjuvant to treat arthritis.

Participation of the TRPV1 receptor in the development of acute gout attacks.

OBJECTIVE: The aim of the present study was to investigate the participation of TRPV1 in an acute gout attack model. METHODS: Experiments were conducted to evaluate the participation of TRPV1 in the nociceptive and inflammatory responses (oedema, plasma extravasation, leucocyte infiltration and also IL-1ß production) triggered by IA (ankle) administration of monosodium urate (MSU) in rats using selective antagonist TRPV1 receptor, defunctionalization of sensory fibres and increased immunoreactivity. We have also analysed the inflammatory response. The participation of mast cells in the MSU-induced nociception and inflammation was evaluated using a mast cell stabilizer and a mast cell degranulator compound. RESULTS: We observed that MSU (1.25 mg/site) injected into the rat ankle joint elicited ongoing pain-like behaviour, hyperalgesia, allodynia and articular oedema as well as plasma extravasation, leucocyte infiltration and IL-1ß production in lavage fluid. All of these events were inhibited by the co-administration of the selective TRPV1 receptor antagonist SB366791 (10 nmol/site). MSU crystals also increased the immunoreactivity of the TRPV1 receptor in the articular tissue of injected animals. Furthermore, the defunctionalization of TRPV1-positive sensory neurons also significantly reduced MSU-induced ongoing pain-like behaviour, hyperalgesia and oedema. CONCLUSION: Thus we demonstrate that TRPV1 acts on sensory neurons and plays a relevant role in the nociception and inflammation induced by IA MSU, indicating it as a potential target to treat acute gout attacks.

Transient receptor potential ankyrin 1 receptor stimulation by hydrogen peroxide is critical to trigger pain during monosodium urate-induced inflammation in rodents.

OBJECTIVE: Gout is a common cause of inflammatory arthritis and is provoked by the accumulation of monosodium urate (MSU) crystals. However, the underlying mechanisms of the pain associated with acute attacks of gout are poorly understood. The aim of this study was to evaluate the role of transient receptor potential ankyrin 1 (TRPA-1) and TRPA-1 stimulants, such as H2 O2 , in a rodent model of MSU-induced inflammation. METHODS: MSU or H2 O2 was injected into the hind paws of rodents or applied in cultured sensory neurons, and the intracellular calcium response was measured in vitro. Inflammatory or nociceptive responses in vivo were evaluated using pharmacologic, genetic, or biochemical tools and methods. RESULTS: TRPA-1 antagonism, TRPA-1 gene deletion, or pretreatment of peptidergic TRP-expressing primary sensory neurons with capsaicin markedly decreased MSU-induced nociception and edema. In addition to these neurogenic effects, MSU increased H2 O2 levels in the injected tissue, an effect that was abolished by the H2 O2 -detoxifying enzyme catalase. H2 O2 , but not MSU, directly stimulated sensory neurons through the activation of TRPA-1. The nociceptive responses evoked by MSU or H2 O2 injection were attenuated by the reducing agent dithiothreitol. In addition, MSU injection increased the expression of TRPA-1 and TRP vanilloid channel 1 (TRPV-1) and also enhanced cellular infiltration and interleukin-1ß levels, and these effects were blocked by TRPA-1 antagonism. CONCLUSION: Our results suggest that MSU injection increases tissue H2 O2 , thereby stimulating TRPA-1 on sensory nerve endings to produce inflammation and nociception. TRPV-1, by a previously unknown mechanism, also contributes to these responses.

Brain connectivity analysis in preictal phases of seizure induced by pentylenetetrazol in rats.

Abnormal patterns of brain connectivity characterize epilepsy. However, little is known about these patterns during the stages preceding a seizure induced by pentylenetetrazol (PTZ). To investigate brain connectivity in male Wistar rats during the preictal phase of PTZ-induced seizures (60 mg/kg), we recorded local field potentials in the primary motor (M1) cortex, the ventral anterior (VA) nucleus of the thalamus, the hippocampal CA1 area, and the dentate gyrus (DG) during the baseline period and after PTZ administration. While there were no changes in power density between the baseline and preictal periods, we observed an increase in directional functional connectivity in theta from the hippocampal formation to M1 and VA, as well as in middle gamma from DG to CA1 and from CA1 to M1, and also in slow gamma from M1 to CA1. These findings are supported by increased phase coherence between DG-M1 in theta and CA1-M1 in middle gamma, as well as enhanced phase-amplitude coupling of delta-middle gamma in M1 and delta-fast gamma in CA1. Interestingly, we also noted a slight decrease in phase synchrony between CA1 and VA in slow gamma. Together, these results demonstrate increased functional connectivity between brain regions during the PTZ-induced preictal period, with this increase being particularly driven by the hippocampal formation.

Modulation of gene expression and influence of gene polymorphisms related to genotoxicity and redox status on occupational exposure to inhaled anesthetics.

The extensive use of inhalational anesthetics contributes to both indoor and outdoor (environmental) pollution. The influence of genetic susceptibility on DNA damage and oxidative stress and the possible modulation of gene expression have not yet been investigated upon occupational exposure to waste anesthetic gases (WAGs). This study assessed 8-oxoguanine DNA glycosylase 1 (OGG1) and superoxide dismutase 2 (SOD2) gene expression, which are related to oxidized DNA repair and antioxidant capacity, respectively, and the influence of their polymorphisms (OGG1 rs1052133 and SOD2 rs4880) in 100 professionals highly exposed to WAGs and 93 unexposed volunteers (control group). Additionally, X-ray repair cross complementing 1 (XRCC1 rs25487 and rs1799782) and ataxia telangiectasia mutated (ATM rs600931) gene polymorphisms as well as genetic instability (micronucleus-MN and nuclear bud-NBUD) and oxidative stress (malondialdehyde-MDA and ferric reducing antioxidant power-FRAP) biomarkers were assessed in the groups (control and exposed) and in the subgroups of the exposed group according to job occupation (anesthesiologists versus surgeons/technicians). Except for the ATM TT controls (associated with increased FRAP), there were no influences of OGG1, XRCC1, ATM, and SOD2 polymorphisms on MN, NBUD, MDA, and FRAP values in exposed or control subjects. No significant difference in the expression of either gene evaluated (OGG1 and SOD2) was found between the exposed and control groups. Increased OGG1 expression was observed among OGG1 -/Cys individuals only in the control group. Among the exposed group, anesthesiologists had a greater duration of WAG exposure (both h/week and years) than surgeons/technicians, which was associated with increased MDA and decreased antioxidant capacity (FRAP) and SOD2 expression (redox status). Higher expression of OGG1 was found in -/Cys surgeons/technicians than in anesthesiologists with the same genotype. Increased antioxidant capacity was noted in the surgeons/technicians carrying the ATM T allele and in those carrying XRCC1 -/Gln. Increased MN was influenced by OGG1 -/Cys in surgeons/technicians. Anesthesiologists with ATM CC exhibited increased MN, and those carrying the C allele (CC/CT genotype) exhibited increased NBUD. SOD2 polymorphism did not seem to be relevant for WAG exposure. These findings contribute to advancing the knowledge on genetic susceptibility/gene expression/genetic instability/oxidative stress, including differences in job occupation considering the workload, in response to occupational exposure to WAGs.

Evolution of adolescents' dietary patterns in Northeast Brazil from 2008 to 2018.

OBJECTIVE: To evaluate the evolution of the dietary patterns of adolescents in the northeast region of Brazil. METHODS: Secondary analysis of data from the Pesquisa de Orçamentos Familiares (POF - Household Budget Surveys), collected by the Brazilian Institute of Geography and Statistics (IBGE) in the years 2008-2009 and 2017-2018. A total of 3,095 adolescents were evaluated in 2008-2009 and 3,015 in 2017-2018. Food consumption was assessed using two dietary records in 2008-2009 and two 24-hour recalls in 2017-2018, applied on non-consecutive days. Based on these data, principal components factor analysis (PCFA) was performed, followed by orthogonal rotation of the varimax type, to derive dietary patterns, stratified by sex. The results were described as means or percentage frequencies, with their respective 95% confidence intervals. RESULTS: Three main dietary patterns were identified among adolescents from the northeast region of Brazil. Among boys, in 2008-2009, the patterns were called snacks, traditional Brazilian, and coffee; and in 2017-2018, traditional Brazilian, snacks, and mixed, in this order of representativeness of the group's eating habits. Among female adolescents, in 2008-2009, the patterns were snacks, traditional Brazilian, and coffee; and in 2017-2018, traditional Brazilian, snacks, and processed meats. CONCLUSION: The dietary patterns identified in 2008-2009 and 2017-2018 were similar in both genders; however, the snacks pattern, which explained most of the data variability in 2008-2009, was replaced by the traditional Brazilian.

Comparison between inhalational anesthetics in terms of DNA damage and immunological markers.

This study compared genetic damage and immunological markers between surgical patients who underwent inhalational anesthesia with isoflurane or sevoflurane. Blood samples were collected from surgical patients (n = 18 in the isoflurane group and n = 17 in the sevoflurane group) at baseline (before the anesthesia procedure) and the day after anesthesia. DNA damage was detected using an alkaline comet assay; proinflammatory interleukin (IL)-6 was detected by flow cytometry, and white blood cells were detected via an automatic hematology analyzer. The characteristics of both groups were similar, and neither of the two anesthetics induced DNA damage. Similarly, mild neutrophilia was observed after anesthesia in both groups. Increased IL-6 levels were observed 1 day after anesthesia regardless of the type of anesthetic, but this increase was greater in the isoflurane group. Our study suggested that isoflurane and sevoflurane administration may contribute to changes in the immune parameters measured, though no genotoxic hazard was identified, in healthy adult patients who undergo low-stress surgery.

Modulation of gene expression and inflammation but not DNA damage after sevoflurane anesthesia.

This study assessed, for the first time, the expression of the genes hOGG1, TP53, and IL-6 in leukocytes by real-time quantitative polymerase chain reaction in surgical patients before (baseline), during (2 h of anesthesia) and 1 day after sevoflurane anesthesia. Additionally, DNA damage was detected by the comet assay, serum interleukin (IL)-6 was detected by flow cytometry, and differential leukocyte counting was also performed. TP53 and hOGG1 expression was downregulated on the day after anesthesia compared to before anesthesia. However, IL-6 expression did not change, and no DNA damage induction was observed during or after anesthesia. At the systemic level, mild neutrophilia and an increase in IL-6 levels occurred after anesthesia. Our findings suggest that sevoflurane anesthesia downregulates gene expression (hOGG1 and TP53) and contributes to an inflammatory status (increased systemic IL-6 and mild neutrophilia) but is not associated with DNA damage in patients without comorbidities who undergo minor elective surgery.

Evaluation of genetic instability, oxidative stress, and metabolism-related gene polymorphisms in workers exposed to waste anesthetic gases.

Professionals who work in operating rooms (ORs) may be exposed daily to waste anesthetic gases (WAGs) due to the use of inhalational anesthetics. Considering the controversial findings related to genetic damage and redox status in addition to a lack of knowledge about the effect of polymorphisms in genes related to phase I and II detoxification upon occupational exposure to WAGs, this cross-sectional study is the first to jointly evaluate biomarkers of genetic instability, oxidative stress, and susceptibility genes in professionals occupationally exposed to high trace amounts of halogenated (≥ 7 ppm) and nitrous oxide (165 ppm) anesthetics in ORs and in individuals not exposed to WAGs (control group). Elevated rates of buccal micronucleus (MN) and nuclear bud (NBUD) were observed in the exposure group and in professionals exposed aged more than 30 years. Exposed males showed a higher antioxidant capacity, as determined by the ferric reducing antioxidant power (FRAP), than exposed females; exposed females had higher frequencies of MN and NBUD than nonexposed females. Genetic instability (MN) was observed in professionals with greater weekly WAG exposure, and those exposed for longer durations (years) exhibited oxidative stress (increased lipid peroxidation and decreased FRAP). Polymorphisms in metabolic genes (cytochrome P450 2E1 (CYP2E1) and glutathione S-transferases (GSTs)) did not exert an effect, except for the effects of the GSTP1 (rs1695) AG/GG polymorphism on FRAP (both groups) and GSTP1 AG/GG and GSTT1 null polymorphisms, which were associated with greater FRAP values in exposed males. Minimizing WAG exposure is necessary to reduce impacts on healthcare workers.

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score.

Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity-related genetic risk score and atherogenic risk in Brazilian children. This is a cross-sectional study conducted in 544 children aged 4-9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity-related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi-structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual-Energy X-ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity-related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

High anesthetic exposure leads to oxidative damage and gene expression changes in physicians during medical residency: a cohort study.

Evaluation of the possible toxic effects of occupational exposure to anesthetics is of great importance, and the literature is limited in assessing the possible association between occupational exposure to anesthetics and oxidative stress and genetic damage. To contribute to the gap of knowledge in relation to cause-effect, this cohort study was the first to monitor exposure assessment and to evaluate oxidative stress, DNA damage, and gene expression (OGG1, NRF2, HO-1, and TP53) in young adult physicians occupationally exposed to the most modern halogenated anesthetics (currently the commonly used inhalational anesthetics worldwide) in addition to nitrous oxide gas during the medical residency period. Therefore, the physicians were evaluated before the beginning of the medical residency (before the exposure to anesthetics-baseline), during (1 1/2 year) and at the end (2 1/2 years) of the medical residency. Anesthetic air monitoring was performed in operating rooms without adequate ventilation/scavenging systems, and biological samples were analyzed for lipid peroxidation, protein carbonyl content, primary and oxidative DNA damage, antioxidant enzymes and plasma antioxidant capacity, and expression of some key genes. The results showed induction of lipid peroxidation, DNA damage, glutathione peroxidase activity, and NRF2 and OGG1 expression up to the end of medical residency. Plasma antioxidant capacity progressively increased throughout medical residency; oxidative DNA damage levels started to increase during medical residency and were higher at the end of residency than at baseline. Protein carbonyls increased during but not at the end of medical residency compared to baseline. The antioxidant enzyme superoxide dismutase activity remained lower than baseline during and at the end of medical residency, and HO-1 (related to antioxidant defense) expression was downregulated at the end of medical residency. Additionally, anesthetic concentrations were above international recommendations. In conclusion, high concentrations of anesthetic in the workplace induce oxidative stress, gene expression modulation, and genotoxicity in physicians during their specialization period.

Higher serum uric acid is associated with body fat, retinol-binding protein 4, and antioxidative status in Brazilian children.

OBJECTIVE: The aim of this study was to evaluate the association of serum uric acid (SUA) with adiposity, adipokines, and anti- and oxidative markers in Brazilian children. METHODS: This was a cross-sectional investigation with 378 children ages 8 to 9 y in Viçosa, Minas Gerais, Brazil. Information on sociodemographic and lifestyle characteristics was obtained via questionnaires, and body fat was determined by dual energy x-ray absorptiometry. We compared the distributions of adiposity (total and central), adipokines (adiponectin, chemerin, leptin, and retinol-binding protein 4 [RBP4]), anti- and oxidative markers (plasma ferric reducing antioxidant power [FRAP], superoxide dismutase [SOD], and malondialdehyde [MDA]) by SUA categories using linear regression. RESULTS: SUA was positively associated with total and central fat. Every standard deviation (SD) of SUA was related, respectively, to a 3.4 (95% confidence interval [CI], 2.4-4.4), 4 (95% CI, 2.8-5.1), 4.2 (95% CI, 2.9-5.5), and 3.5 (95% CI, 2.4-4.6) units higher of total, truncal, android, and gynoid fat. We found a positive association of SUA with RBP4 and FRAP, and a negative association with MDA. Every SD of SUA was related, respectively, to 0.1 (95% CI, 0.01-0.1) and 7.8 (95% CI, 5.5-10.1) units higher of RBP4 and FRAP; and to -0.3 (95% CI, -0.5 to -0.1) units lower of MDA. CONCLUSIONS: SUA was positively associated with adiposity, RBP4, and antioxidative status in Brazilian children.