The Impact of an Omega-3 Enriched Diet on Hyperactivity and Biochemistry in an Animal Model for Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is the most diagnosed behavioral disorder in children. It affects around 5% of children worldwide and 11% of children in the United States, with rates increasing. Pharmaceutical treatments, such as amphetamines and methylphenidates, are not effective for everyone and are known to have unwanted side effects. While the etiology of the disorder is not yet fully understood, there are clear genetic and environmental components. Nutritional insufficiencies have recently become a popular environmental risk factor under investigation. Essential fatty acids (EFA), omega-3 polyunsaturated fatty acids (PUFA) in particular, are needed for proper brain development and function. Our lab has found lower proportions of omega-3 PUFA in the phospholipids and red blood cell membranes of about 40% of the children and adults with ADHD. Other research groups have subsequently confirmed similar findings. It is not yet known why a subgroup of the ADHD population seem to display EFA insufficiency, or if supplementation can reliably prevent or alleviate symptoms of the disorder. However, multiple human and animal studies have reported a reduction in ADHD-symptoms with omega-3 PUFA supplementation. Thus, we hypothesized that an omega-3 PUFA enriched diet would reduce the ADHD symptom of hyperactivity, modulate dopamine and serotonin turnover, and increase omega-3 PUFA proportion in plasma and brain phospholipids in the Spontaneously Hypertensive Rat (SHR) animal model for ADHD. Additionally, we explored the relationship between oxidative stress, EFA status, and ADHD behavior with the prediction that SHR will display greater oxidative stress than the control strain, Wistar Kyota Rat (WKY). In order to develop a protocol that elucidates the behavioral differences between the two rat strains, we conducted a pilot study on various behavioral tests on the WKY and SHR while on standard rat chow. Results from our preliminary data led us to use the open field test as a measure of hyperactivity. In our intervention study, the omega-3 enriched diet (omega-3 diet) had no impact on measures of hyperactivity. However, our intervention successfully increased omega-3 PUFA proportions in plasma and brain phospholipid membranes. WKY had a higher proportion of eicosapentaenoic acid (EPA) in both plasma and brain than SHR, and SHR had a higher proportion of docosahexaenoic acid in plasma for both diets. Results of the liver total glutathione (GSH) analysis suggested that the omega-3 diet reduced oxidative stress, but that the SHR had lower oxidative stress than the WKY. SHR on the omega-3 diet had a lower concentration of dopamine in the neostriatum than SHR on the omega-6 dominant diet, and both rat strains on the omega-3 diet had lower serotonin concentration. Consistent with the lack of impact on behavior, dopamine and serotonin turnover were not modulated by diet. However, dopamine turnover in the SHR was lower than that in the WKY. In summary, our dietary intervention did not impact behavior, which was consistent with the lack of impact on neurotransmission, despite the alteration in phospholipid proportions. Future studies should focus on determining the most effective dose, EPA/DHA ratio, and time period for an omega-3 PUFA intervention

Chromatin signature of embryonic pluripotency is established during genome activation

available in PMC 2011 April 8.After fertilization the embryonic genome is inactive until transcription is initiated during the maternal–zygotic transition. This transition coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem cells. To study the changes in chromatin structure that accompany pluripotency and genome activation, we mapped the genomic locations of histone H3 molecules bearing lysine trimethylation modifications before and after the maternal–zygotic transition in zebrafish. Histone H3 lysine 27 trimethylation (H3K27me3), which is repressive, and H3K4me3, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by H3K4me3, including many inactive developmental regulatory genes that were also marked by H3K27me3. Sequential chromatin immunoprecipitation demonstrated that the same promoter regions had both trimethylation marks. Such bivalent chromatin domains also exist in embryonic stem cells and are thought to poise genes for activation while keeping them repressed. Furthermore, we found many inactive genes that were uniquely marked by H3K4me3. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published data sets revealed similar monovalent domains in embryonic stem cells. Moreover, H3K4me3 marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA polymerase II, as indicated by the analysis of an inducible transgene. These results indicate that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during the maternal–zygotic transition.National Institutes of Health (U.S.) (grant 1R01 HG004069)National Institutes of Health (U.S.) (grant 5R01 GM56211)Human Frontier Science Program (Strasbourg, France) (LT-00090/2007)European Molecular Biology Organization (fellowship

The impact of an omega-3 enriched diet on hyperactivity and biochemistry in an animal model of attentiondeficit/ hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is the most diagnosed behavioral disorder in children. It affects around 5% of children worldwide and 11% of children in the United States, with rates increasing. Pharmaceutical treatments, such as amphetamines and methylphenidates, are not effective for everyone and are known to have unwanted side effects. While the etiology of the disorder is not yet fully understood, there are clear genetic and environmental components. Nutritional insufficiencies have recently become a popular environmental risk factor under investigation. Essential fatty acids (EFA), omega-3 polyunsaturated fatty acids (PUFA) in particular, are needed for proper brain development and function. Our lab has found lower proportions of omega-3 PUFA in the phospholipids and red blood cell membranes of about 40% of the children and adults with ADHD. Other research groups have subsequently confirmed similar findings. It is not yet known why a subgroup of the ADHD population seem to display EFA insufficiency, or if supplementation can reliably prevent or alleviate symptoms of the disorder. However, multiple human and animal studies have reported a reduction in ADHD-symptoms with omega-3 PUFA supplementation. Thus, we hypothesized that an omega-3 PUFA enriched diet would reduce the ADHD symptom of hyperactivity, modulate dopamine and serotonin turnover, and increase omega-3 PUFA proportion in plasma and brain phospholipids in the Spontaneously Hypertensive Rat (SHR) animal model for ADHD. Additionally, we explored the relationship between oxidative stress, EFA status, and ADHD behavior with the prediction that SHR will display greater oxidative stress than the control strain, Wistar Kyota Rat (WKY). In order to develop a protocol that elucidates the behavioral differences between the two rat strains, we conducted a pilot study on various behavioral tests on the WKY and SHR while on standard rat chow. Results from our preliminary data led us to use the open field test as a measure of hyperactivity. In our intervention study, the omega-3 enriched diet (omega-3 diet) had no impact on measures of hyperactivity. However, our intervention successfully increased omega-3 PUFA proportions in plasma and brain phospholipid membranes. WKY had a higher proportion of eicosapentaenoic acid (EPA) in both plasma and brain than SHR, and SHR had a higher proportion of docosahexaenoic acid in plasma for both diets. Results of the liver total glutathione (GSH) analysis suggested that the omega-3 diet reduced oxidative stress, but that the SHR had lower oxidative stress than the WKY. SHR on the omega-3 diet had a lower concentration of dopamine in the neostriatum than SHR on the omega-6 dominant diet, and both rat strains on the omega-3 diet had lower serotonin concentration. Consistent with the lack of impact on behavior, dopamine and serotonin turnover were not modulated by diet. However, dopamine turnover in the SHR was lower than that in the WKY. In summary, our dietary intervention did not impact behavior, which was consistent with the lack of impact on neurotransmission, despite the alteration in phospholipid proportions. Future studies should focus on determining the most effective dose, EPA/DHA ratio, and time period for an omega-3 PUFA intervention

Key findings from the ‘Australians’ drug use: adapting to pandemic threats (ADAPT)’ study wave 4. ADAPT bulletin no. 4.

The Australians' Drug Use: Adapting to Pandemic Threats (ADAPT) Study is exploring the short and long-term impact of the COVID-19 pandemic on the experiences of Australians who use illicit drugs. Findings will be used to ensure drug-related issues during COVID-19 are better understood and more accurately represented, so as to better inform drug treatment and harm reduction in Australia. Australians who regularly (i.e. at least once a month) used illicit drugs in 2019 were invited to complete an online survey initially and follow-up surveys in 2 months, 4 months and 12 months. Participants could opt to complete the Wave 1 survey only. This bulletin outlines preliminary findings from the 197 participants who completed ALL surveys from Waves 1-4, describing changes in drug use and behaviours, health ratings and drug/mental health treatment access and engagement pre- and post-COVID-19 restrictions (i.e., since March 2020)

Australians' drug use: adapting to pandemic threats (ADAPT) study: ADAPT bulletin no. 1.

The Australians' Drug Use: Adapting to Pandemic Threats (ADAPT) Study is exploring the short and long-term impact of the COVID-19 pandemic on the experiences of Australians who use illicit drugs. Findings will be used to ensure drug-related issues during COVID-19 are better understood and more accurately represented, so as to better inform drug treatment and harm reduction in Australia. Australians who regularly (i.e. at least once a month) used illicit drugs in 2019 were invited to complete an online survey initially and follow-up surveys in 2 months, 4 months, 6 months, 12 months, 2 years and 3 years. Participants could opt to complete the Wave 1 survey only. This bulletin describes changes in drug use and behaviours, harm reduction behaviours, health ratings and drug/mental health treatment access and engagement pre- and post-COVID-19 restrictions (i.e., since March 2020) among a sample of Australians who regularly use illicit drugs

To the Point: Medical Education Reviews-Ongoing Call for Faculty Development

This article in the To the Point series will focus on best practices regarding faculty development in medical education in the field of obstetrics and gynecology. Faculty development is an essential component in achieving teacher and learner satisfaction as well as improving learner outcomes. The Liaison Committee on Medical Education requires medical school faculty to have the capability and longitudinal commitment to be effective teachers. Although many programs have been created to address faculty development, there remains a paucity of literature documenting the impact of these programs on learner outcomes. We reviewed the qualities of an excellent medical educator, expectations regarding medical school teaching faculty, elements of comprehensive faculty development programs, and outcome measures for evaluating the effectiveness of these programs