Maternal fish consumption during pregnancy and smoking behavioural patterns

Abstractn-3 Highly unsaturated fatty acids (HUFA), are essential components of neuronal membranes and mediate a range of complex bioactive properties including gene expression, myelination, cell-signalling and dopaminergic function. Deficits inn-3 HUFA have been linked to increased risks for addictive disorders, thus we posited that lower fish consumption would be associated with greater risks for perinatal smoking among 9640 mothers enroled in the Avon Longitudinal Study of Parents and Children. We used univariable and multivariable regression models to examine relationships between self-reported prenatal dietary intakes ofn-3 HUFA-rich foods (fish and shellfish) and maternal smoking; outcomes included cessation and the number of cigarettes smoked per d. Both before and during pregnancy, there was consistent evidence (P&lt;0·001) of protective fish intake–smoking associations; relative to mothers reporting no fish consumption, those who reported some fish consumption (&lt;340 g/week) and high fish consumption (340 g+/week) at 32 weeks of gestation showed lower likelihoods of smoking (adjustedPvalues &lt;0·001). Respective OR for these relationships were 0·87 (95% CI 0·77, 0·97) and 0·73 (95% CI 0·61, 0·86). Although the prevalence of smoking diminished, from a high of 31·6% (pre-pregnancy) to a low of 18·7% (second trimester), the magnitude of fish intake–smoking associations remained stable following adjustment for confounders. These observations suggest that greater fish orn-3 HUFA consumption should be evaluated as an intervention to reduce or prevent smoking in randomised clinical trials.</jats:p

Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

Familial dysautonomia (FD) is a developmental neuropathy of the sensory and autonomous nervous systems. The IKBKAP gene, encoding the IKAP/hELP1 subunit of the RNA polymerase II Elongator complex is mutated in FD patients, leading to a tissue-specific mis-splicing of the gene and to the absence of the protein in neuronal tissues. To elucidate the function of IKAP/hELP1 in the development of neuronal cells, we have downregulated IKBKAP expression in SHSY5Y cells, a neuroblastoma cell line of a neural crest origin. We have previously shown that these cells exhibit abnormal cell adhesion when allowed to differentiate under defined culture conditions on laminin substratum. Here, we report results of a microarray expression analysis of IKAP/hELP1 downregulated cells that were grown on laminin under differentiation or non-differentiation growth conditions. It is shown that under non-differentiation growth conditions, IKAP/hELP1 downregulation affects genes important for early developmental stages of the nervous system, including cell signaling, cell adhesion and neural crest migration. IKAP/hELP1 downregulation during differentiation affects the expression of genes that play a role in late neuronal development, in axonal projection and synapse formation and function. We also show that IKAP/hELP1 deficiency affects the expression of genes involved in calcium metabolism before and after differentiation of the neuroblastoma cells. Hence, our data support IKAP/hELP1 importance in the development and function of neuronal cells and contribute to the understanding of the FD phenotype

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Biochemical and psychological effects of omega-3/6 supplements in male adolescents with ADHD: a randomized, placebo-controlled, clinical trial

An abnormality in long chain-polyunsaturated fatty acid (LC-PUFA) levels has been implicated in Attention Deficit Hyperactivity Disorder (ADHD). Studies evaluating LC-PUFA supplementation for therapeutic efficacy in ADHD have shown mixed and therefore inconclusive results. Seventy-six male adolescents (aged 12 -16 years, M =13. 7 ) with ADHD were assessed for the effects of 12 weeks omega-3 and omega-6 supplements on biochemical and psychological outcomes in a randomized, placebo-controlled, clinical trial. The primary outcome measure was change in the Conners’ Teacher Rating Scales (CTRS) following 12 weeks of supplementation of LC-PUFA or placebo. At baseline, the placebo and treatment groups had comparable levels of LC-PUFA as measured by red blood cell phosphatidylcholine. In the treatment group, supplementation enhanced eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total omega-3 fatty acid levels. No superiority of LC-PUFAs to placebo was observed on the primary outcome. Furthermore, there were no reliable treatment effects on aggression, impulsivity, depression and anxiety. Future studies should use larger sample sizes and longer supplementation period to detect small-modest effects for clinical recommendations in ADHD

Abnormal centroparietal ERP response in predominantly medication-naive adolescent boys with ADHD during both response inhibition and execution

SUMMARY: Abnormal event-related potential (ERP) responses have been reported in children and adolescents with attention deficit hyperactivity disorder (ADHD) and a medication history compared with in healthy controls during tasks of response control and conflict inhibition. This study reports neurophysiologic correlates of a task dependent on these cognitive functions in a large, predominantly medication naive, group of adolescents with ADHD compared with that in healthy age- and intelligence quotient (IQ)-matched controls using area-under-the-curve (AUC) analysis. Fifty-four adolescents with ADHD and 55 healthy comparisons completed a hybrid conflict and response inhibition Go/NoGo ERP task. The performance data showed that children with ADHD compared with controls had deficits in both the inhibitory measures (higher commission errors) and the Go process of the task (slower reaction times and enhanced omission errors). The ERP data showed significant impairments in brain function in the ADHD relative to the control group for late, endogenous ERPs (N2, P3a, and P3b), whereas no group differences were found for the earlier P200. All findings remained when a minority of children with medication history was excluded. Furthermore, deficits were not specific to the inhibitory processes of the task but were equally observed during the execution functions. Group differences were particularly pronounced over central and centroparietal sites across all time points, presumably reflecting the midline attention system mediated by anterior and posterior cingulate that is important for generic, condition-independent visual-spatial attention and response selection processes. The findings demonstrate that adolescents with ADHD have abnormal ERP responses not only during inhibitory, but also execution-related processes and, furthermore, that these deficits are independent from medication history

Total red blood cell concentrations of [omega]-3 fatty acids are associated with emotion-elicited neural activity in adolescent boys with attention-deficit hyperactivity disorder

Affective impairment is observed in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Low levels of long-chain polyunsaturated fatty acids (LC-PUFA), specifically omega-3 (omega-3) fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD. However, nothing is known about the relationship between omega-3 and brain function in children with ADHD. In the current study, 20 adolescent boys with ADHD were assessed for total lipid fractions in red blood cells and their event-related potential (ERP) response to the presentation of facial expressions of happiness, sadness and fearfulness. The results supported the hypothesis of a positive association between eicosapentaenoic acid (EPA) and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of docosahexaenoic acid (DHA) and the right temporal N170 amplitude in response to covert expressions of fear. The arachidonic (AA)/DHA ratio was negatively associated with the right temporal N170 amplitude also to covert expressions of fear. These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings in the literature on EFA supplementation in ADHD and depression