Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation.

BACKGROUND: Aging and age-related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain's immune response, plays an important role in aged associated degeneration of central nervous system (CNS). There is a need for well characterized animal models that will allow the scientific community to understand and modulate this process. METHODS: We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their senescence resistant control mice (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and determined the appearance of Iba1+ clustered cells with aging. To analyze specific constant brain areas, we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch), and analyzed their response to systemic lipopolysaccharide (LPS)-driven inflammation. RESULTS: Aged 10 months old SAMP8 mice present many of the hallmarks of aging-dependent neuroinflammation when compared with their SAMR1 control, i.e., increase of protein aggregates, presence of Iba1+ clusters, but not an increase in the number of Iba1+ cells. We have further observed an increase of main inflammatory mediator IL-1ß, and an augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch) have been analyzed, showing that there is not a significant increase of CD45+ cells from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL-1ß) transcription is enhanced in CD45+BP cells. Furthermore, LPS-driven systemic inflammation produces inflammatory cytokines mainly in border bMyC, sensed to a lesser extent by the BP bMyC, showing that IL-1ß expression is further augmented in aged SAMP8 compared to control SAMR1. CONCLUSION: Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of pro-inflammatory cytokines such as IL-1ß, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.

Neuroinflammation and Brain Development: Possible Risk Factors in COVID-19-Infected Children.

COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus, affects children in a different way than it does in adults, with milder symptoms. However, several cases of neurological symptoms with neuroinflammatory syndromes, such as the multisystem inflammatory syndrome (MIS-C), following mild cases, have been reported. As with other viral infections, such as rubella, influenza, and cytomegalovirus, SARS-CoV-2 induces a surge of proinflammatory cytokines that affect microglial function, which can be harmful to brain development. Along with the viral induction of neuroinflammation, other noninfectious conditions may interact to produce additional inflammation, such as the nutritional imbalance of fatty acids and polyunsaturated fatty acids and alcohol consumption during pregnancy. Additionally, transient thyrotoxicosis induced by SARS-CoV-2 with secondary autoimmune hypothyroidism has been reported, which could go undetected during pregnancy. Together, those factors may pose additional risk factors for SARS-CoV-2 infection impacting mechanisms of neural development such as synaptic pruning and neural circuitry formation. The present review discusses those conditions in the perspective of the understanding of risk factors that should be considered and the possible emergence of neurodevelopmental disorders in COVID-19-infected children.

Influence of school environment on occurrence of traumatic dental injuries in 12 years old children.

BACKGROUND/AIM: Since children spend most of their time in school, some environmental characteristics of the schools may influence the occurrence of traumatic dental injuries (TDI). Therefore, the aim of this cross-sectional study was to assess the prevalence of TDI in 12 years old children in Quito, Ecuador, and its association with some school environmental aspects. MATERIAL AND METHODS: Six calibrated examiners evaluated 998 children from 31 public schools of Quito, to evaluate the occurrence of TDI in anterior teeth. School coordinators answered questionnaires on school physical conditions, promotion of health practices and the occurrence of negative episodes in school. The occlusion and socioeconomic status of the participants were also evaluated. Prevalence of TDI, unadjusted and adjusted by the design effect was calculated. Association between individual and contextual explanatory variables and presence of TDI were evaluated using multilevel Poisson regression analysis (P < .05). RESULTS: TDI prevalence adjusted by design effect was 20.7%. Children studying in schools with patio floor of grass and with access ramps had significantly lower prevalence of TDI than children studying in schools with patio floor of cement and with only stairs, respectively. The prevalence of TDI was also lower in children from schools that offered healthy meals or that had a proper place for oral hygiene. CONCLUSIONS: Schools with adequate physical structures and that promote health practices to their students have a lower prevalence of TDI.

Oral health of 12-year-old children in Quito, Ecuador: a population-based epidemiological survey.

BACKGROUND: There is a paucity of population-based surveys on oral health conditions in Ecuador. Thus, the aim of this study was to conduct an epidemiological survey with a representative sample of children aged 12 years from public schools of Quito, Ecuador. The aim of this initial report was to describe the methodology used in the survey, as well to present results regarding calibration procedures and prevalence of oral-health related outcomes. METHODS: We invited 33 public schools' coordinators from the urban area of Quito, and 1100 children (12 years old) to take part in this study. Six trained and calibrated examiners conducted clinical examinations using oral mirrors and ball-ended probes to assess: dental caries, traumatic dental injuries, malocclusion, gingival bleeding, presence of calculus and fluorosis. Children also responded a questionnaire on Oral Health-Related Quality of Life (OHRQoL). Individual sociodemographic data was collected through a questionnaire sent to parents. Moreover, some contextual data on school environment (infrastructure conditions, promotion of health practices and negative episodes) were also evaluated. Prevalence values, crude and weighted by sampling weights, and 95% confidence intervals (95%CI) were calculated. RESULTS: Nine hundred and ninety-eight children from 31 schools were examined from March to May 2017. The adjusted prevalence values (95%CI) for the six outcomes evaluated were: dental caries = 60.3% (55.3 to 65.0%); traumatic dental injuries = 20.7% (17.2 to 24.8%); dental fluorosis = 63.7% (58.5 to 68.5%); gingival bleeding = 92.0% (87.1 to 95.2%); presence of calculus = 69.9 (60.5 to 77.9%); and malocclusion = 25.8% (21.8 to 30.3%). Adjusted mean of number of decayed, missed or filled permanent teeth (DMF-T) was 1.61 (1.37 to 1.84). Results on OHRQoL and other contextual variables will be reported in other articles. CONCLUSION: The prevalence of the majority of oral health problems in 12-year-old children from public schools in Quito-Ecuador was compatible with those observed in other similar cities. However, periodontal health and fluorosis seem to be highly prevalent in children from Quito.

Olive Oil, Palm Oil, and Hybrid Palm Oil Distinctly Modulate Liver Transcriptome and Induce NAFLD in Mice Fed a High-Fat Diet.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. The most severe form is nonalcoholic steatohepatitis (NASH). Among risk factors for the development of NAFLD is excessive lipid intake. Since palm (P) oil is the most consumed oil in the world, we aimed to investigate the effects of high-fat diets made with P oil, hybrid palm (HP) oil, or olive (O) oil in liver. Twenty-four male mice (C57Bl/6J) were fed a high-fat diet (41% fat) containing P, HP, or O oils for 8 weeks and compared to a control (C) group fed a chow diet. Adiposity was measured with computed tomography. Body, adipose tissue, and liver weights, as well as liver fat (Bligh⁻Dyer), blood lipid profile, glucose, and liver enzymes were measured. Liver histology (hematoxylin⁻eosin) and transcriptome (microarray-based) were performed. ANOVA tests with Newman⁻Keuls were used. Body weight was increased in the P group (p < 0.001) and body fat in the O group (C vs. O p ≤ 0.01, P vs. O p ≤ 0.05, HP vs. O p ≤ 0.05). All high-fat diets disturbed the blood lipid profile and glucose, with marked effects of HP on very low-density lipoprotein cholesterol (VLDL), triglycerides, and alkaline phosphatase (p ≤ 0.001). HP had the highest liver fat (42.76 ± 1.58), followed by P (33.94 ± 1.13). O had a fat amount comparable to C (16.46 ± 0.34, 14.71 ± 0.70, respectively). P and HP oils induced hepatocyte ballooning. Transcriptome alterations of the O group were related to amino acid metabolism and fatty acid (FA) metabolism, the P group to calcium ion homeostasis, and HP oil to protein localization. Both P and HP oils induced NASH in mice via disturbed hepatocyte transcription. This raises concerns about the content of these oils in several industrialized foods.

Maternal intake of trans-unsaturated or interesterified fatty acids during pregnancy and lactation modifies mitochondrial bioenergetics in the liver of adult offspring in mice.

The quality of dietary lipids in the maternal diet can programme the offspring to diseases in later life. We investigated whether the maternal intake of palm oil or interesterified fat, substitutes for trans-unsaturated fatty acids (FA), induces metabolic changes in the adult offspring. During pregnancy and lactation, C57BL/6 female mice received normolipidic diets containing partially hydrogenated vegetable fat rich in trans-unsaturated fatty acids (TG), palm oil (PG), interesterified fat (IG) or soyabean oil (CG). After weaning, male offspring from all groups received the control diet until day 110. Plasma glucose and TAG and liver FA profiles were ascertained. Liver mitochondrial function was accessed with high-resolution respirometry by measuring VO2, fluorimetry for detection of hydrogen peroxide (H2O2) production and mitochondrial Ca2+ uptake. The results showed that the IG offspring presented a 20 % increase in plasma glucose and both the IG and TG offspring presented a 2- and 1·9-fold increase in TAG, respectively, when compared with CG offspring. Liver MUFA and PUFA contents decreased in the TG and IG offspring when compared with CG offspring. Liver MUFA content also decreased in the PG offspring. These modifications in FA composition possibly affected liver mitochondrial function, as respiration was impaired in the TG offspring and H2O2 production was higher in the IG offspring. In addition, mitochondrial Ca2+ retention capacity was reduced by approximately 40 and 55 % in the TG and IG offspring, respectively. In conclusion, maternal consumption of trans-unsaturated and interesterified fat affected offspring health by compromising mitochondrial bioenergetics and lipid metabolism in the liver.

DNGR-1(+) dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain.

The role and different origin of brain myeloid cells in the brain is central to understanding how the central nervous system (CNS) responds to injury. C-type lectin receptor family 9, member A (DNGR-1/CLEC9A) is a marker of specific DC subsets that share functional similarities, such as CD8α(+) DCs in lymphoid tissues and CD103(+) CD11b(low) DCs in peripheral tissues. Here, we analyzed the presence of DNGR-1 in DCs present in the mouse brain (bDCs). Dngr-1/Clec9a mRNA is expressed mainly in the meningeal membranes and choroid plexus (m/Ch), and its expression is enhanced by fms-like tyrosine kinase 3 ligand (Flt3L), a cytokine involved in DC homeostasis. Using Clec9a(egfp/egfp) mice, we show that Flt3L induces accumulation of DNGR-1-EGFP(+) cells in the brain m/Ch. Most of these cells also express major histocompatibility complex class II (MHCII) molecules. We also observed an increase in specific markers of cDC CD8α+ cells such as Batf-3 and Irf-8, but not of costimulatory molecules such as Cd80 and Cd86, indicating an immature phenotype for these bDCs in the noninjured brain. The presence of DNGR-1 in the brain provides a potential marker for the study of this specific brain cell subset. Knowledge and targeting of brain antigen presenting cells (APCs) has implications for the fight against brain diseases such as neuroinflammation-based neurodegenerative diseases, microbe-induced encephalitis, and brain tumors such as gliomas.

Association of children's oral health and school environment on academic performance in 12-year-old schoolchildren of Quito, Ecuador.

OBJECTIVES: The primary aim of this study was to evaluate if children's oral health and oral health-related quality of life (OHRQoL) were associated with school performance. Moreover, the study aimed to examine whether school environment factors influenced this association. METHODS: This cross-sectional study was based on a population-based sample of 998 12-year-old schoolchildren from 31 public schools in Quito, Ecuador. Trained and calibrated examiners conducted clinical exams for dental caries, dental trauma and malocclusion. Furthermore, children completed the Spanish version of the Child Perception Questionnaire (CPQ11-14 ), and their parents answered questions about socio-economic status. School coordinators provided information on the physical environment, promotion of health practices and the occurrence of negative episodes in the school. There were three outcomes: grades obtained in Spanish language and mathematics and the number of missed school days. Multilevel linear and Poisson regression models were conducted using a hierarchical approach to include the variables guided by a previously created direct acyclic graph. RESULTS: Children with dental trauma and higher CPQ11-14 scores showed lower grades and school attendance. Schoolchildren from schools with episodes of vandalism had more school days missed. CONCLUSION: The school performance of 12-year-old children is affected by dental trauma and by a worse OHRQoL, as well as a negative school environment. Therefore, supportive environments and promoting health measures in schools could overcome this worse academic performance in children with oral health problems.

NFATc3 promotes Ca(2+) -dependent MMP3 expression in astroglial cells.

Increase in intracellular calcium ([Ca(2+) ]i ) is a key mediator of astrocyte signaling, important for activation of the calcineurin (CN)/nuclear factor of activated T cells (NFAT) pathway, a central mediator of inflammatory events. We analyzed the expression of matrix metalloproteinase 3 (Mmp3) in response to increases in [Ca(2+) ]i and the role of the CN/NFAT pathway in this regulation. Astrocyte Mmp3 expression was induced by overexpression of a constitutively active form of NFATc3, whereas other MMPs and tissue inhibitor of metalloproteinases (TIMP) were unaffected. Mmp3 mRNA and protein expression was also induced by calcium ionophore (Io) and 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (Bz-ATP) and Mmp3 upregulation was prevented by the CN inhibitor cyclosporin A (CsA). Ca(2+) -dependent astrocyte Mmp3 expression was also inhibited by actinomycin D, and a Mmp3 promoter luciferase reporter was efficiently activated by increased [Ca(2+) ]i , indicating regulation at the transcriptional level. Furthermore, Ca(2+) /CN/NFAT dependent Mmp3 expression was confirmed in pure astrocyte cultures derived from neural stem cells (Ast-NSC), demonstrating that the induced Mmp3 expression occurs in astrocytes, and not microglial cells. In an in vivo stab-wound model of brain injury, MMP3 expression was detected in NFATc3-positive scar-forming astrocytes. Because [Ca(2+) ]i increase is an early event in most brain injuries, these data support an important role for Ca(2+) /CN/NFAT-induced astrocyte MMP3 expression in the early neuroinflammatory response. Understanding the molecular pathways involved in this regulation could provide novel therapeutic targets and approaches to promoting recovery of the injured brain.

Effectiveness of nutritional interventions to prevent nonprogressive congenital and perinatal brain injuries: a systematic review and meta-analysis of randomized trials.

CONTEXT: Nutritional interventions for newborns with brain injury are scarce, and there are gaps in the knowledge of their mechanisms of action in preventing the occurrence of cerebral palsy (CP) or the incidence of other developmental disabilities. OBJECTIVE: The objective of this review was to assess the effect of nutritional interventions in preventing nonprogressive congenital or perinatal brain injuries, or in improving outcomes related to neurological development. DATA SOURCES: Randomized trials on any nutritional intervention for pregnant women at risk of preterm delivery, or for children with low birth weight, preterm, or with confirmed or suspected microcephaly, CP, or fetal alcohol syndrome disorders (FASDs) were retrieved from MEDLINE, Embase, Scopus, Web of Science, LILACS, and CENTRAL databases from inception to September 17, 2020. DATA EXTRACTION: Data extraction, risk of bias (Cochrane Risk of Bias tool 2), and quality of evidence (GRADE approach) were assessed by 2 authors. DATA ANALYSIS: Pooled risk ratios (RRs) with 95% confidence intervals were calculated using a random-effects meta-analysis. Seventeen studies were included on intravenous interventions (magnesium sulfate [n = 5], amino acids [n = 4], vitamin A [n = 1], and N-acetylcysteine [n = 1]); enteral interventions (vitamin D [n = 1], prebiotic [n = 1], nutrient-enriched formula [n = 1], and speed of increasing milk feeds [n = 1]); and oral interventions (choline [n = 1] and docosahexaenoic acid, choline, and uridine monophosphate [n = 1]). All studies assessed CP, except 1 on FASDs. Eight studies were judged as having high risk of bias. Five studies (7413 babies) with high-quality evidence demonstrated decreased risk of childhood CP (RR = 0.68, 95% CI: 0.52-0.88) with magnesium sulfate. Interventions with amino acids had no effect on CP prevention or other outcomes. Except for 1 study, no other intervention decreased the risk of CP or FASDs. CONCLUSION: Although different types of nutritional interventions were found, only those with antenatal magnesium sulfate were effective in decreasing CP risk in preterm infants. Well-designed, adequately powered randomized clinical trials are required.

Does the school environment exert influence on quality of life related to traumatic dental injury in children?

The aim of this cross-sectional study was to assess whether favorable factors related to school characteristics have a positive effect on the impact of traumatic dental injury (TDI) on oral health-related quality of life (OHRQoL). An epidemiological survey of oral health was conducted with 12-year-old schoolchildren from Quito, Ecuador. Children were examined for TDI, dental caries, and malocclusion. Individual socioeconomic data were also collected. Information on the physical environment, health practices, and occurrence of negative episodes at school was collected from the school coordinators. The Child Perceptions Questionnaire 11-14 (CPQ11-14) was used to evaluate the OHRQoL (outcome variable). Multilevel Poisson regression analysis was conducted. Severe TDI was associated with higher CPQ11-14 scores, even in the multiple model adjusted for oral health conditions, sex, individual socioeconomic variables, and school-related variables. Children from schools that had an appropriate tooth-brushing environment for their students exhibited a lower impact on OHRQoL, even after adjustment for the occurrence of TDI and other variables. A favorable school environment may exert a positive effect on OHRQoL, independent of the occurrence of TDI.

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

Chronic nutritional restriction of omega-3 fatty acids induces a pro-inflammatory profile during the development of the rat visual system.

Modern western diets have been associated with a reduced proportion of dietary omega-3 fatty acids leading to decreased levels of DHA (docosahexaenoic acid) in the brain. Low DHA content has been associated with altered development of visual acuity in infants and also with an altered time course of synapse elimination and plasticity in subcortical visual nuclei in rodents. Microglia has an active role in normal developmental processes such as circuitry refinement and plasticity, and its activation status can be modulated by omega-3 (ω3) and omega-6 (ω6) essential fatty acids. In the present study, we investigated the impact of dietary restriction of DHA (ω3-), through the chronic administration of a coconut-based diet as the only fat source. This dietary protocol resulted in a reduction in DHA content in the retina and superior colliculus (SC) and in a neuroinflammatory outcome during the development of the rodent visual system. The ω3- group showed changes in microglial morphology in the retina and SC and a corresponding altered pattern of pro-inflammatory cytokine expression. Early and late fish oil protocols supplementation were able to restore DHA levels. The early supplementation also decreased neuroinflammatory markers in the visual system. The present study indicates that a chronic dietary restriction of omega-3 fatty acids and the resulting deficits in DHA content, commonly observed in Western diets, interferes with the microglial profile leading to an inflamed microenvironment which may underlie a disruption of synapse elimination, altered topographical organization, abnormal plasticity, and duration of critical periods during brain development.

Maternal omega-3 intake differentially affects the endocannabinoid system in the progeny`s neocortex and hippocampus: Impact on synaptic markers.

Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and the endocannabinoid system (ECS) modulate several functions through neurodevelopment including synaptic plasticity mechanisms. The interplay between n-3PUFA and the ECS during the early stages of development, however, is not fully understood. This study investigated the effects of maternal n-3PUFA supplementation (n-3Sup) or deficiency (n-3Def) on ECS and synaptic markers in postnatal offspring. Female rats were fed with a control, n-3Def, or n-3Sup diet from 15 days before mating and during pregnancy. The cerebral cortex and hippocampus of mothers and postnatal 1-2 days offspring were analyzed. In the mothers, a n-3 deficiency reduced CB1 receptor (CB1R) protein levels in the cortex and increased CB2 receptor (CB2R) in both cortex and hippocampus. In neonates, a maternal n-3 deficiency reduced the hippocampal CB1R amount while it increased CB2R. Additionally, total GFAP isoform expression was increased in both cortex and hippocampus in neonates of the n-3Def group. Otherwise, maternal n-3 supplementation increased the levels of n-3-derived endocannabinoids, DHEA and EPEA, in the cortex and hippocampus and reduced 2-arachidonoyl-glycerol (2-AG) concentrations in the cortex of the offspring. Furthermore, maternal n-3 supplementation also increased PKA phosphorylation in the cortex and ERK phosphorylation in the hippocampus. Synaptophysin immunocontent in both regions was also increased. In vitro assays showed that the increase of synaptophysin in the n-3Sup group was independent of CB1R activation. The findings show that variations in maternal dietary omega-3 PUFA levels may impact differently on the ECS and molecular markers in the cerebral cortex and hippocampus of the progeny.

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization.

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19. ONE-SENTENCE SUMMARY: Plitidepsin, an inhibitor of SARS-Cov-2 in vitro , is safe and positively influences the outcome of patients hospitalized with COVID-19.

NFATc3 controls tumour growth by regulating proliferation and migration of human astroglioma cells.

Calcium/Calcineurin/Nuclear Factor of Activated T cells (Ca/CN/NFAT) signalling pathway is the main calcium (Ca2+) dependent signalling pathway involved in the homeostasis of brain tissue. Here, we study the presence of NFATc members in human glioma by using U251 cells and a collection of primary human glioblastoma (hGB) cell lines. We show that NFATc3 member is the predominant member. Furthermore, by using constitutive active NFATc3 mutant and shRNA lentiviral vectors to achieve specific silencing of this NFATc member, we describe cytokines and molecules regulated by this pathway which are required for the normal biology of cancer cells. Implanting U251 in an orthotopic intracranial assay, we show that specific NFATc3 silencing has a role in tumour growth. In addition NFATc3 knock-down affects both the proliferation and migration capacities of glioma cells in vitro. Our data open the possibility of NFATc3 as a target for the treatment of glioma.

Were policies in Brazil effective to reducing trans fat from industrial origin in foods?

OBJECTIVE: To determine the trans fatty acids content of processed foods frequently consumed by adults living in a Rio de Janeiro, Brazil, after the enactment of a mandatory trans fatty acids labelling policy. METHODS: Between February 2014 and January 2015, a specifically dietary questionnaire was completed by 107 adults to assess the frequency of processed foods consumption. The most commonly consumed products from the survey, including vegetable oils, margarine, biscuits, snacks, cheese bread (pão de queijo), french fries, cheeseburger and ice cream, were then analyzed for their trans fatty acids content using gas chromatography with a flame ionization detector. RESULTS: Differences in the levels of trans fatty acids were observed among 22 products analyzed, considering that trans fatty acids content ranged between 0.0 g/100 g in samples of cream cracker biscuit 1 and olive oil to 0.83 g/100 g in samples of cheeseburger (fast food), 0.51 g/100 g in samples of frozen pão de queijo and 12.92 g/100 g in samples of chocolate sandwich cookies with cream filling 2. The overall trans fatty acids content of the different samples of margarine brands was 0.20 g/100 g for brand 1 and 0.0 g/100 g for brand 2. These data are significantly lower than those observed in a survey conducted in 2003, when the regulation had been enacted. CONCLUSIONS: Our data indicate that Brazilian regulation is very likely implicated in the observed drop in trans fatty acids of the most processed foods but has yet to eliminate them, which reinforces the urgent need to revise the legislation, since a minimum amount of trans fat does not mean that the food product does not contain this type of fat.

Adiponectin, insulin and leptin levels in the cord plasma of the neonates from adolescent and adult mothers and their relationship with anthropometric parameters and fetal sex-gender.

OBJECTIVE: This cross-sectional study aimed to evaluate the association between leptin, insulin and adiponectin levels and anthropometric measurements of term newborns of adolescent and adult mothers. STUDY DESIGN: Umbilical cord plasma samples were obtained from 80 healthy term neonates (40 from teenagers and 40 from adult mothers) and adiponectin, insulin and leptin concentrations were measured. RESULTS: Cord plasma adiponectin levels were higher in the boys from adult mothers than in the boys of the adolescent (p < 0.05), while plasma leptin levels in the boys of the adults were significantly lower (p < 0.05) than those of girls from both groups. Univariate correlation analysis showed that leptin umbilical cord plasma levels were positively associated with birth weight in neonates from adolescents and adults. Multiple linear regression analysis revealed that leptin levels showed significant positive predictor for birth weight specifically in the adult mother. CONCLUSION: Gestational age, but not adipokines, showed to be a significant positive predictor factor of birth weight in adolescent pregnancy.

Does the school environment exert influence on quality of life related to traumatic dental injury in children?

Abstract The aim of this cross-sectional study was to assess whether favorable factors related to school characteristics have a positive effect on the impact of traumatic dental injury (TDI) on oral health-related quality of life (OHRQoL). An epidemiological survey of oral health was conducted with 12-year-old schoolchildren from Quito, Ecuador. Children were examined for TDI, dental caries, and malocclusion. Individual socioeconomic data were also collected. Information on the physical environment, health practices, and occurrence of negative episodes at school was collected from the school coordinators. The Child Perceptions Questionnaire 11-14 (CPQ11-14) was used to evaluate the OHRQoL (outcome variable). Multilevel Poisson regression analysis was conducted. Severe TDI was associated with higher CPQ11-14 scores, even in the multiple model adjusted for oral health conditions, sex, individual socioeconomic variables, and school-related variables. Children from schools that had an appropriate tooth-brushing environment for their students exhibited a lower impact on OHRQoL, even after adjustment for the occurrence of TDI and other variables. A favorable school environment may exert a positive effect on OHRQoL, independent of the occurrence of TDI.

Interesterified fat or palm oil as substitutes for partially hydrogenated fat during the perinatal period produces changes in the brain fatty acids profile and increases leukocyte-endothelial interactions in the cerebral microcirculation from the male offspring in adult life.

We investigated whether maternal intake of normolipidic diets with distinct fatty acid (FA) compositions alters the lipidic profile and influences the inflammatory status of the adult offsprings׳ brains. C57BL/6 female mice during pregnancy and lactation received diets containing either soybean oil (CG), partially hydrogenated vegetable fat rich in trans-fatty acids (TG), palm oil (PG), or interesterified fat (IG). After weaning, male offspring from all groups received control diet. The FA profile was measured in the offspring׳s brains at post-natal days 21 and 90. Brain functional capillary density as well as leukocyte-endothelial interactions in the cerebral post-capillary venules was assessed by intravital fluorescence microscopy at post-natal day 90. Inflammation signaling was evaluated through toll-like receptor 4 (TLR4) content in brain of the adult offspring. In the 21-day old offspring, the brains of the TG showed higher levels of trans FA and reduced levels of linoleic acid (LA) and total n-6 polyunsaturated fatty acids (PUFA). At post-natal day 90, TG and IG groups showed reduced levels of eicosapentaenoic acid (EPA) and total n-3 PUFA tended to be lower compared to CG. The offspring׳s brains exhibited an altered microcirculation with increased leukocyte rolling in groups TG, PG and IG and in TG group increased leukocyte adhesion. The TLR4 content of TG, IG and PG groups only tended to increase (23%; 20% and 35%, respectively). Maternal consumption of trans FA, palm oil or interesterified fat during pregnancy and lactation can trigger the initial steps of inflammatory pathways in the brain of offspring in adulthood.