SBP lança tradução de Cartilha de Desenvolvimento, elaborada pelo Centers of Disease Control and Prevention

A Sociedade Brasileira de Pediatria (SBP), em parceria com a Sociedade Paraibana de Pediatria (SPP), lança nesta semana a “Cartilha de Desenvolvimento – 2 meses a 5 anos”. O conteúdo – elaborado pelo Centers of Disease Control and Prevention (CDC), dos Estados Unidos – foi oficialmente traduzido para o Português por pediatra com expertise em Desenvolvimento Infantil e apresenta o programa “Act Early”, cujo intuito é auxiliar na identificação precoce de atrasos do neurodesenvolvimento.

Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia.

BACKGROUND: Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS: In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. RESULTS: Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. CONCLUSIONS: In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.).

Prenatal exposure to glufosinate ammonium disturbs gut microbiome and induces behavioral abnormalities in mice.

Glufosinate ammonium (GLA) is a widely used organophosphate herbicide, which could be commonly detected in body fluids of both pregnant women and newborns. Existing evidences indicate that GLA has reproductive toxicity, while data concerning the effects of prenatal GLA exposure on neurodevelopment is rather limited. Here we employed a mouse model exposed to GLA prenatally. Reduced locomotor activity, impaired memory formation and autism-like behaviors were observed in the treatment group. Marked alteration in gut microbiome of the treatment offspring mice could be found at 4th week, and seemed to recover over time. Fecal metabolomics analysis indicated remarkable changes in microbiome-related metabolism in the treatment group, which could be the cause of behavioral abnormality in mice. Present study suggested that prenatal exposure to GLA disturbed gut microbiome and metabolism, and thereby induced behavioral abnormalities in mice.

Oxygen saturations and neurodevelopmental outcomes in single ventricle heart disease.

OBJECTIVES: To evaluate whether the degree of hypoxemia following stage-I and stage-II palliative surgeries predicts neurodevelopmental outcomes at 14 months of age in children with single ventricle congenital heart disease (SVCHD). DESIGN: We analyzed longitudinal data from two Pediatric Heart Network (PHN) randomized controlled trials, with a total of 328 subjects. Oxygen saturations, measured via pulse oximetry, at time of discharge from stage-I and stage-II surgeries were the primary predictors of interest, and Bayley Scales of Infant Development-II (BSID-II) scores at 14 months old were the primary outcome measure. Relevant covariates from previously-published PHN studies were also included in regression models. RESULTS: Oxygen saturations at time of discharge from stage-I and stage-II surgeries were not related to BSID-II scores. Having one or more oxygen saturation measurements below 80% was also not associated with BSID-II scores, and neither was change in oxygen saturations over time. These relationships were not altered by inclusion of relevant covariates. CONCLUSIONS: In this large cohort of children with SVCHD, oxygen saturations post-stage-I and post-stage-II palliation surgeries as measured via pulse oximetry were not associated with neurodevelopmental outcomes at 14 months of age. The relationship between oxygen saturations and neurodevelopment in SVCHD is likely complex, and neurodevelopment is known to be affected by a number of factors. Pulse oximetry may also be an insufficient proxy for cerebral oxygen delivery. Clinically, pulse oximetry readings during the interstage and post-stage-II surgery periods are not a reliable predictor of future neurodevelopmental risk.

Does transcranial direct current stimulation during writing alleviate upper limb freezing in people with Parkinson's disease? A pilot study.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can boost motor performance in Parkinson's disease (PD) when it is applied at rest. However, the potential supplementary therapeutic effect of the concurrent application of tDCS during the training of motor tasks is largely unknown. The present study examined the effects of tDCS on upper limb motor blocks during a freezing-provoking writing task (the funnel task) requiring up- and down-stroke movements at alternating amplitudes. Ten PD patients and 10 age-matched controls underwent two sessions of writing combined with 20 min of anodal or sham tDCS on the left M1 in a randomized cross-over design. The primary outcome was the number of upper limb freezing episodes during five trials of the funnel task on a touch-sensitive tablet. PD patients showed a significant reduction in freezing episodes during tDCS compared to sham. No effects of tDCS were found for the amplitude, variability and speed of the strokes outside the freezing episodes. However, patients who reported freezing episodes in daily life (N = 6) showed a beneficial effect of tDCS on stroke characteristics. These results indicate a subgroup-dependent variability in response to non-invasive brain stimulation applied during the performance of motor tasks in PD. This warrants future studies to examine tDCS as an adjuvant tool for training programs aimed to reduce motor deficits related to freezing.

Timing for cranioplasty to improve neurological outcome: A systematic review.

INTRODUCTION: Cranioplasty is a surgical technique applied for the reconstruction of the skullcap removed during decompressive craniectomy (DC). Cranioplasty improves rehabilitation from a motor and cognitive perspective. However, it may increase the possibility of postoperative complications, such as seizures and infections. Timing of cranioplasty is therefore crucial even though literature is controversial. In this study, we compared motor and cognitive effects of early cranioplasty after DC and assess the optimal timing to perform it. METHODS: A literature research was conducted in PubMed, Web of Science, and Cochrane Library databases. We selected studies including at least one of the following test: Mini-Mental State Examination, Rey Auditory Verbal Learning Test immediate and 30-min delayed recall, Digit Span Test, Glasgow Coma Scale, Glasgow Outcome Scale, Coma Recovery Scale-Revised, Level of Cognitive Functioning Scale, Functional Independence Measure, and Barthel Index. RESULTS: Six articles and two systematic reviews were included in the present study. Analysis of changes in pre- and postcranioplasty scores showed that an early procedure (within 90 days from decompressive craniectomy) is more effective in improving motor functions (standardized mean difference [SMD] = 0.51 [0.05; 0.97], p-value = 0.03), whereas an early procedure did not significantly improve neither MMSE score (SMD = 0.06 [-0.49; 0.61], p-value = 0.83) nor memory functions (SMD = -0.63 [-0.97; -0.28], p-value < 0.001). No statistical significance emerged when we compared studies according to the timing from DC. CONCLUSIONS: It is believed that cranioplasty performed from 3 to 6 months after DC may significantly improve both motor and cognitive recovery.

Improved Mental and Motor Development During 3 Years of GH Treatment in Very Young Children With Prader-Willi Syndrome.

Context: Infants and toddlers with Prader-Willi syndrome (PWS) have mental and motor developmental delay. Short-term data suggest a positive effect of GH on mental and motor development in infants and children with PWS. There are, however, no longer-term results about the effects of GH treatment on mental and motor development. Objective: To investigate the longer-term effects of GH on psychomotor development in infants and toddlers with PWS and the effect of age at start of GH treatment on psychomotor development. Design: Prospective cohort study during 3 years of GH treatment. Setting: The PWS Reference Center in the Netherlands. Intervention: All children were treated with GH 1 mg/m2/d (≈0.035 mg/kg/d). Main Outcome Measures: Mental and motor developmental age assessed with Bayleys Scales of Infant Development II and expressed as percentage of the expected development (100%). Results: During 3 years of GH, mean (SEM) mental development increased from 58.1% (2.8) at baseline to 79.6% (3.7), and motor development increased from 41.9% (2.9) to 78.2% (3.9; both P < 0.01). A lower baseline psychomotor development and a younger age at start of GH treatment were associated with a higher increase in mental and motor development (P < 0.01). Conclusions: Mental and motor development increased significantly during 3 years of GH treatment, reducing the gap between infants with PWS and healthy peers. A younger age at start of GH treatment leads to greater improvement in psychomotor development.

Child dietary intake of folate and vitamin B12 and their neurodevelopment at 24 and 30 months of age.

OBJECTIVE: To evaluate whether child dietary intake of folate and vitamin B12, is associated with mental and psychomotor development in Mexican children, respectively, at 24 and 30 months of age. MATERIALS AND METHODS: Information about neurodevelopment and dietary intake of folate and vitamin B12 at 24 and 30 months of age among 229 children belonging to a perinatal cohort was analyzed longitudinally. Dietary information was assessed using a semi-quantitative food frequency questionnaire, and neurodevelopment by Bayley Scale of Infant Development II. RESULTS: At 30 months of age, dietary folate intake was marginally associated with increased Mental Development Index (MDI) (b=8.33; 95%CI -0.48, 17.14; p=0.06). Nonsignificant positive associations of vitamin B12 with MDI were found. Psychomotor Development Index (PDI) was not associated with these nutrients. CONCLUSIONS: Dietary folate intake in early childhood may benefit the mental development of children.

The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women.

OBJECTIVE: Human aging is accompanied by a decrease in growth hormone secretion and serum insulin-like growth factor (IGF)-1 levels. Also, loss of muscle mass and strength and impairment of physical performance, ending in a state of frailty, are seen in elderly. We aimed to investigate whether handgrip strength, physical performance and recurrent falls are related to serum IGF-1 levels in community-dwelling elderly. DESIGN: Observational cohort study (cross-sectional and prospective). METHODS: We studied the association between IGF-1 and handgrip strength, physical performance and falls in participants of the Longitudinal Aging Study Amsterdam. A total of 1292 participants were included (633 men, 659 women). Serum IGF-1 levels were divided into quartiles (IGF-1-Q1 to IGF-1-Q4). Data on falls were collected prospectively for a period of 3 years. All analyses were stratified for age and physical activity and adjusted for relevant confounders. RESULTS: Men with a low physical activity score in IGF-1-Q1 and IGF-1-Q2 of the younger age group had a lower handgrip strength compared to IGF-1-Q4. In younger more active males in IGF-1-Q2 physical performance was worse. Recurrent fallers were less prevalent in older, low active males with low IGF-1 levels. In females, recurrent fallers were more prevalent in older, more active females in IGF-1-Q2. IGF-1 quartile may predict changes in handgrip strength and physical performance in men and women. CONCLUSIONS: Our results indicate that lower IGF-1 levels are associated with lower handgrip strength and worse physical performance, but less recurrent fallers especially in men. Associations were often more robust in IGF-1-Q2. Future studies on this topic are desirable.

Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth.

OBJECTIVE: To evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. STUDY DESIGN: We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. RESULTS: Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). CONCLUSION: Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci.

Influencia de la hipotiroxinemia gestacional en el desarrollo neuropsicológico de la descendencia / Influence of gestational hypothyroxinemia on neuropsychological development of the offspring

El objetivo del presente trabajo es analizar cómo la hipotiroxinemia gestacional puede afectar al neurodesarrollo fetal, así como las posibles medidas preventivas y/o de tratamiento frente a dicha disfunción. Las hormonas tiroideas son compuestos químicos esenciales para el correcto desarrollo del cerebro y del sistema nervioso central fetal durante las primeras etapas del embarazo. Un déficit de yodo durante este periodo puede alterar los parámetros tiroideos funcionales maternos y desencadenar ciertas disfunciones como la hipotiroxinemia gestacional. Este trastorno, caracterizado por bajos niveles de tiroxina libre con niveles normales de hormona estimulante de la tiroides, causa errores de migración neuronal en el cerebro fetal en desarrollo y alteraciones en la citoarquitectura de la corteza y el hipocampo. Debido a ello, se observa un peor desarrollo cognitivo y psicomotor en la descendencia, además de un aumento en las probabilidades de padecer ciertas enfermedades psiquiátricas. A pesar de que el deterioro mental no suele ser tan severo como el de los niños cuyas madres padecen otra disfunción tiroidea gestacional, el número de embarazadas afectadas suele ser mayor. Por ello, se debe asegurar un suministro adecuado de yodo a todas las embarazadas con el objetivo de disminuir la hipotiroxinemia. La administración de levotiroxina, forma sintética de la tiroxina, desde el primer trimestre hasta el final del embarazo en el tratamiento de dicho trastorno parece disminuir el riesgo de retraso cognitivo y psicomotor de la descendencia, aunque los estudios sobre su efectividad aún son escasos y poco concluyentes (AU)

The present study analyzes how gestational hypothyroxinemia can affect fetal neurodevelopment, as well as the preventive and/or treatment measures against this dysfunction. Thyroid hormones, which are iodinated amino acids, are essential chemical compounds for the right fetal brain and central nervous system development during early stages of pregnancy. An iodine deficiency during this period may alter maternal functional thyroid parameters and trigger certain dysfunctions such as maternal hypothyroxinemia, which has a varied etiology. This disorder, which is characterized by low levels of free thyroxine combined with normal levels of thyroid stimulating hormone, causes neuronal migration mistakes in the developing fetal brain and alterations in the cortex and hippocampus cytoarchitecture. Due to this, a worse cognitive and psychomotor development in the offspring and an increase in the probabilities of suffering certain psychiatric diseases are observed. Although mental impairment is not usually as severe as that of children whose mothers have other thyroid dysfunction during pregnancy, the number of affected people is usually higher. This is why an adequate iodine supply should be ensured to all pregnant women in order to reduce hypothyroxinemia. Levothyroxine administration, a synthetic form of thyroxine, from the first trimester to the end of pregnancy in the treatment of this disorder seems to reduce the risk of cognitive and psychomotor delay of the offspring, although studies of its effectiveness are still scarce and inconclusive (AU)

Corticospinal tract atrophy and motor fMRI predict motor preservation after functional cerebral hemispherectomy.

OBJECTIVE The potential loss of motor function after cerebral hemispherectomy is a common cause of anguish for patients, their families, and their physicians. The deficits these patients face are individually unique, but as a whole they provide a framework to understand the mechanisms underlying cortical reorganization of motor function. This study investigated whether preoperative functional MRI (fMRI) and diffusion tensor imaging (DTI) could predict the postoperative preservation of hand motor function. METHODS Thirteen independent reviewers analyzed sensorimotor fMRI and colored fractional anisotropy (CoFA)-DTI maps in 25 patients undergoing functional hemispherectomy for treatment of intractable seizures. Pre- and postoperative gross hand motor function were categorized and correlated with fMRI and DTI findings, specifically, abnormally located motor activation on fMRI and corticospinal tract atrophy on DTI. RESULTS Normal sensorimotor cortical activation on preoperative fMRI was significantly associated with severe decline in postoperative motor function, demonstrating 92.9% sensitivity (95% CI 0.661-0.998) and 100% specificity (95% CI 0.715-1.00). Bilaterally robust, symmetric corticospinal tracts on CoFA-DTI maps were significantly associated with severe postoperative motor decline, demonstrating 85.7% sensitivity (95% CI 0.572-0.982) and 100% specificity (95% CI 0.715-1.00). Interpreting the fMR images, the reviewers achieved a Fleiss' kappa coefficient (κ) for interrater agreement of κ = 0.69, indicating good agreement (p < 0.01). When interpreting the CoFA-DTI maps, the reviewers achieved κ = 0.64, again indicating good agreement (p < 0.01). CONCLUSIONS Functional hemispherectomy offers a high potential for seizure freedom without debilitating functional deficits in certain instances. Patients likely to retain preoperative motor function can be identified prior to hemispherectomy, where fMRI or DTI suggests that cortical reorganization of motor function has occurred prior to the operation.

A role for astrocytes in cerebellar deficits in frataxin deficiency: Protection by insulin-like growth factor I.

Inherited neurodegenerative diseases such as Friedreich's ataxia (FRDA), produced by deficiency of the mitochondrial chaperone frataxin (Fxn), shows specific neurological deficits involving different subset of neurons even though deficiency of Fxn is ubiquitous. Because astrocytes are involved in neurodegeneration, we analyzed whether they are also affected by frataxin deficiency and contribute to the disease. We also tested whether insulin-like growth factor I (IGF-I), that has proven effective in increasing frataxin levels both in neurons and in astrocytes, also exerts in vivo protective actions. Using the GFAP promoter expressed by multipotential stem cells during development and mostly by astrocytes in the adult, we ablated Fxn in a time-dependent manner in mice (FGKO mice) and found severe ataxia and early death when Fxn was eliminated during development, but not when deleted in the adult. Analysis of underlying mechanisms revealed that Fxn deficiency elicited growth and survival impairments in developing cerebellar astrocytes, whereas forebrain astrocytes grew normally. A similar time-dependent effect of frataxin deficiency in astrocytes was observed in a fly model. In addition, treatment of FGKO mice with IGF-I improved their motor performance, reduced cerebellar atrophy, and increased survival. These observations indicate that a greater vulnerability of developing cerebellar astrocytes to Fxn deficiency may contribute to cerebellar deficits in this inherited disease. Our data also confirm a therapeutic benefit of IGF-I in early FRDA deficiency.

A nutrigenomics approach for the study of anti-aging interventions: olive oil phenols and the modulation of gene and microRNA expression profiles in mouse brain.

PURPOSE: Middle-aged C57Bl/6J mice fed for 6 months with extra-virgin olive oil rich in phenols (H-EVOO, phenol dose/day: 6 mg/kg) showed cognitive and motor improvement compared to controls fed the same olive oil deprived of phenolics (L-EVOO). The aim of the present study was to evaluate whether these behavioral modifications were associated with changes in gene and miRNA expression in the brain. METHODS: Two brain areas involved in cognitive and motor processes were chosen: cortex and cerebellum. Gene and miRNA profiling were analyzed by microarray and correlated with performance in behavioral tests. RESULTS: After 6 months, most of the gene expression changes were restricted to the cerebral cortex. The genes modulated by aging were mainly down-regulated, and the treatment with H-EVOO was associated with a significant up-regulation of genes compared to L-EVOO. Among those, we found genes previously associated with synaptic plasticity and with motor and cognitive behavior, such as Notch1, BMPs, NGFR, GLP1R and CRTC3. The agrin pathway was also significantly modulated. miRNAs were mostly up-regulated in old L-EVOO animals compared to young. However, H-EVOO-fed mice cortex displayed miRNA expression profiles similar to those observed in young mice. Sixty-three miRNAs, out of 1203 analyzed, were significantly down-regulated compared to the L-EVOO group; among them, we found miRNAs whose predicted target genes were up-regulated by the treatment, such as mir-484, mir-27, mir-137, mir-30, mir-34 and mir-124. CONCLUSIONS: We are among the first to report that a dietary intervention starting from middle age with food rich in phenols can modulate at the central level the expression of genes and miRNAs involved in neuronal function and synaptic plasticity, along with cognitive, motor and emotional behavior.

[Psychomotor education and speech therapy when weaning a child off artificial feeding]. / Psychomotricité et orthophonie lors du sevrage d'une nutrition artificielle chez l'enfant.

To support children and their families with weaning off artificial nutrition, a psychomotor therapist and speech therapist from the 'Pierre Robin syndrome and congenital sucking-swallowing disorders' specialist rare disease centre at Necker-Enfant Malades hospital in Paris, have set up a joint consultation, as a complement to medical consultations. This programme shows how speech therapy and psychomotor education can complement each other in order to help children and their parents during this difficult period.

Neuroprotective actions of pterostilbene on hypoxic-ischemic brain damage in neonatal rats through upregulation of heme oxygenase-1.

Neonatal hypoxic-ischemic (HI) brain damage causes acute mortality and morbidity in newborns and long-term neurological disorders in the survivors. Pterostilbene (PTE) is a natural compound possessing various biological and pharmacological activities. In the present study, we aimed to investigate the effect of PTE on neonatal HI brain damagein P7 rat model and to explore the possible mechanisms. Neonatal HI brain damage was induced in rat pups (P7). Prior to the induction of HI injury, PTE was injected with or without zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase-1 (HO-1). ZnPP was used to test whether abnormal changes of HO-1 expression were involved in the effect of PTE. The results showed that PTE exhibited excellent neuroprotective effects against neonatal HI brain injury, as evidenced by the decrease of brain infarct volume, brain edema, neurological score, and improvement in motor coordination motor deficit and working memory deficit. PTE pretreatment decreased the expression of several proinflammatory cytokines, including TNFα, IL-1ß, IL-6, and key transcription factor p65 NF-κB, and reduced the number of TUNEL-stained neurons, indicating the inhibition of inflammation and programmed cell death. Moreover, PTE pretreatment decreased thiobarbituric acid reactive substances content, increased superoxide dismutase activity and decreased reactive oxygen species level, indicating that PTE played an important antioxidant role. Furthermore, ZnPP was able to inhibit PTE-induced suppression of oxidative stress, programmed cell death, inflammation and brain damage. In conclusion, PTE pretreatment prevented HI-induced brain injury in newborns through HO-1-mediated reduction of oxidative stress, programmed cell death, and inflammation, and final improvement of histological and functional injury. Overall, the data that obtained in rat model provide novel insights into the pathogenesis of neonatal HI brain injury and may be translational to human clinical intervention for HI-associated brain injury in newborns.

Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia.

Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.

Oral administration of curcumin relieves behavioral alterations and oxidative stress in the frontal cortex, hippocampus, and striatum of ovariectomized Wistar rats.

Menopause occurs gradually and is characterized by increased susceptibility to developing mood disorders. Several studies have suggested treatments based on the antioxidant properties of vitamins and herbal compounds as an alternative to hormone replacement therapies, with few or none reporting toxicity. The present study was performed to explore the effects of curcumin oral supplementation on anxiety-like behavior and oxidative stress parameters in different central nervous system (CNS) areas of ovariectomized (OVX) rats. Female Wistar rats were randomly divided into either sham-operated or OVX groups. Sham-operated group (n=8) and an OVX group (n=11) were treated with vehicle, and the other two OVX groups received curcumin at 50 or 100mg/kg/day doses (n=8/group). Elevated plus maze (EPM) test was performed on the 28th day of treatment. On the 30th day, animals were killed and the dissected brain regions were removed and stored at-80°C until analysis. Ovariectomy induced deficit in the locomotor activity and increased anxiety-like behavior. Moreover, OVX rats showed increased lipid oxidized in the frontal cortex and striatum, increased hippocampal and striatal carbonylated protein level, and decreased striatal thiol content of non-protein fraction indicative of a glutathione (GSH) pool. Curcumin oral treatment for 30days reduced oxidative stress in the CNS areas as well as the behavior alterations resulting from ovariectomy. Curcumin supplementation attenuated most of these parameters to sham comparable values, suggesting that curcumin could have positive effects against anxiety-like disturbances and brain oxidative damage due to hormone deprivation.

Magnesium sulfate, chorioamnionitis, and neurodevelopment after preterm birth.

OBJECTIVE: To assess the neuroprotective effect of magnesium sulfate (MgSO4 ) in preterm children exposed to chorioamnionitis. DESIGN: A secondary analysis of a multicentre randomised controlled trial of antenatal MgSO4 administered to women at risk of preterm birth for the prevention of cerebral palsy (CP). Singleton, non-anomalous pregnancies with clinical chorioamnionitis, delivering at ≥24 weeks of gestation, were selected. Cases were exposed to antepartum MgSO4 ; controls received placebo. SETTING: Multicentre randomised controlled trial. POPULATION: Singleton, non-anomalous pregnancies with clinical chorioamnionitis, delivering at ≥24 weeks of gestation. METHODS: All data were analysed by intention to treat. Univariate and multivariate analyses were performed. MAIN OUTCOME MEASURES: Primary outcome was a composite of stillbirth, death by the age of 1 year, or moderate or severe CP by the age of 2 years. Secondary outcomes included a composite neonatal outcome as well as neurodevelopmental delay, defined as Bayley II mental and psychomotor developmental indices <70 at the age of 2 years. Subgroup analysis assessed these outcomes in children born at <28 weeks of gestation. RESULTS: A total of 396 children were included, with 192 (48.5%) randomised to MgSO4 . Maternal and delivery characteristics were similar between the groups. The primary outcome occurred in 14.1% of children exposed to MgSO4 and 12.7% of children exposed to placebo (relative risk, RR 1.29; 95% CI 0.70-2.38). Rates of stillbirth, death, moderate-severe CP, and neurodevelopmental delay did not differ between groups. In the subgroup analysis of children born at <28 weeks of gestation, there was no difference in the rates of the primary outcome, nor in the secondary outcomes assessed. [Correction added on 02 March 2016 after online publication: There were errors in statistical data analysis and these have been corrected throughout the article.] CONCLUSIONS: Among children at risk for early preterm delivery exposed to chorioamnionitis, antenatal administration of MgSO4 was not associated with improved neurodevelopmental outcome. We do not recommend any change in the guidelines on the administration of MgSO4 for neuroprotection based on this study. TWEETABLE ABSTRACT: MgSO4 was not associated with improved neurodevelopmental outcome in setting of chorioamnionitis.

Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

BACKGROUND: Infants born preterm are at increased risk of developing cognitive and motor impairment compared with infants born at term. Early developmental interventions have been provided in the clinical setting with the aim of improving overall functional outcomes for these infants. Long-term benefits of these programmes remain unclear. OBJECTIVES: Primary objective To compare the effectiveness of early developmental intervention programmes provided post hospital discharge to prevent motor or cognitive impairment in preterm (< 37 weeks) infants versus standard medical follow-up of preterm infants at infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Secondary objectives To perform subgroup analyses to determine the following.• Effects of gestational age, birth weight and brain injury (periventricular leukomalacia (PVL)/intraventricular haemorrhage (IVH)) on cognitive and motor outcomes when early intervention is compared with standard follow-up. ∘ Gestational age: < 28 weeks, 28 to < 32 weeks, 32 to < 37 weeks. ∘ Birth weight: < 1000 grams, 1000 to < 1500 grams, 1500 to < 2500 grams. ∘ Brain injury: absence or presence of grade III or grade IV IVH or cystic PVL (or both) or an abnormal ultrasound/magnetic resonance image (MRI) before initiation of the intervention.• Effects of interventions started during inpatient stay with a post-discharge component versus standard follow-up care.• Effects of interventions focused on the parent-infant relationship, infant development or both compared with standard follow-up care.To perform sensitivity analysis to identify the following.• Effects on motor and cognitive impairment when early developmental interventions are provided within high-quality randomised trials with low risk of bias for sequence generation, allocation concealment, blinding of outcome measures and selective reporting bias. SEARCH METHODS: The search strategy of the Cochrane Neonatal Review Group was used to identify randomised and quasi-randomised controlled trials of early developmental interventions provided post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Advanced, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE (1966 to August 2015). SELECTION CRITERIA: Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age. Interventions could commence on an inpatient basis but had to include a post-discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. Rates of cerebral palsy were documented. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted and entered data. Cognitive and motor outcomes were pooled by four age groups: infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Meta-analysis using RevMan 5.1 was carried out to determine the effects of early developmental interventions at each age range. Subgroup analyses focused on gestational age, birth weight, brain injury, commencement of the intervention, focus of the intervention and study quality. MAIN RESULTS: Twenty-five studies met the inclusion criteria (3615 randomly assigned participants). Only 12 of these studies were randomised controlled trials with appropriate allocation concealment. Variability was evident with regard to focus and intensity of the intervention, participant characteristics and length of follow-up. Meta-analysis led to the conclusion that intervention improved cognitive outcomes at infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.32 standard deviations (SDs), 95% confidence interval (CI) 0.16 to 0.47; P value < 0.001; 16 studies; 2372 participants) and at preschool age (intelligence quotient (IQ); SMD 0.43 SDs, 95% CI 0.32 to 0.54; P value < 0.001; eight studies; 1436 participants). However, this effect was not sustained at school age (IQ: SMD 0.18 SDs, 95% CI -0.08 to 0.43; P value = 0.17; five studies; 1372 participants). Heterogeneity between studies for cognitive outcomes at infancy and at school age was significant. With regards to motor outcomes, meta-analysis of 12 studies showed a significant effect in favour of early developmental interventions at infancy only; however, this effect was small (motor scale DQ: SMD 0.10 SDs, 95% CI 0.01 to 0.19; P value = 0.03; 12 studies; 1895 participants). No effect was noted on the rate of cerebral palsy among survivors (risk ratio (RR) 0.82, 95% CI 0.52 to 1.27; seven studies; 985 participants). Little evidence showed a positive effect on motor outcomes in the long term, but only five included studies reported outcomes at preschool age (n = 3) or at school age (n = 2). AUTHORS' CONCLUSIONS: Early intervention programmes for preterm infants have a positive influence on cognitive and motor outcomes during infancy, with cognitive benefits persisting into preschool age. A great deal of heterogeneity between studies was due to the variety of early developmental intervention programmes tested and to gestational ages of included preterm infants; thus, comparisons of intervention programmes were limited. Further research is needed to determine which early developmental interventions are most effective in improving cognitive and motor outcomes, and to discern the longer-term effects of these programmes.