Xeropthalmia and optic neuropathy secondary to ARFID: a case report.

BACKGROUND: Patients with avoidant/restrictive food intake disorder (ARFID) commonly present with loss of weight or faltering growth in the setting of poor nutrition. However, patients with ARFID can present with micronutrient deficiencies without weight loss. In patients with ARFID, clinicians should be vigilant for micronutrient deficiencies and their presentations. CASE PRESENTATION: We report a unique case of ARFID in a twelve-year-old girl, who developed micronutrient deficiencies and presented with acute visual loss with a preceding history of impaired night vision. Ophthalmic examination revealed xerophthalmia and bilateral optic neuropathy. Investigations showed severe Vitamin A and folate deficiencies which accounted for her clinical findings. In addition, she was also found to have low Vitamin B12, copper, and Vitamin D levels. She had a history of selective eating from a young age with a diet consisting largely of carbohydrates, with no regular intake of meat, dairy, fruit and vegetables. This was not driven by weight or body image concerns. The patient's symptoms improved significantly with appropriate vitamin replacement and continued multidisciplinary care. CONCLUSIONS: This report describes a patient with ARFID presenting with visual complaints. In this case, the selective eating behaviours resulted in xeropthalmia and optic neuropathy. Micronutrient deficiencies are uncommon in developed countries. When these deficiencies are suspected, eating disorders, such as ARFID, should be considered. Similarly, clinicians caring for patients with restrictive eating disorders including ARFID should be familiar with the clinical presentations of various micronutrient deficiencies and consider evaluation and treatment for micronutrient deficiencies when clinically indicated.

Journals must expand access to peer review data.

Empirical studies on peer review bias are primarily conducted by people from privileged groups and with affiliations with the journals studied. Data access is one major barrier to conducting peer review research. Accordingly, we propose pathways to broaden access to peer review data to people from more diverse backgrounds.

Prevalence and risk factors associated with low bone mineral density in Asian adolescents with anorexia nervosa and atypical anorexia nervosa.

OBJECTIVE: This retrospective study aimed to evaluate the prevalence and risk factors for low bone mineral density (BMD) at diagnosis in Asian adolescent females with anorexia nervosa (AN) and atypical AN. METHOD: We analyzed the BMD results for 213 patients between 10 and 18 years of age, with AN and atypical AN receiving care at a pediatric hospital in Singapore. We used linear regression analyses to determine if type of eating disorder, premorbid weight, and duration of amenorrhea were risk factors for low BMD. For a subset of patients with repeat BMD evaluation, we used paired t-tests to assess the impact of weight or menstrual restoration on the change in BMD. RESULTS: The prevalence of BMD height-for-age Z-scores <-2 at presentation was higher in patients with AN (13.0%) than atypical AN (2.3%) (p = .034). In multivariate regression, a diagnosis of atypical AN was protective against low BMD at the lumbar spine (B = 0.394, p = .009) and total body less head (B = 0.774, p = .010). Duration of amenorrhea was not associated with BMD across all sites. For those with repeat BMD measures, there was significantly less deterioration in the BMD Z-scores for patients with weight or menstrual restoration (R = -0.22 ± 0.59, NR = -0.69 ± 0.43, p = .029). CONCLUSIONS: Duration of amenorrhea was not associated with BMD in this sample. A diagnosis of AN was correlated with lower BMD than atypical AN. Further research is needed to better understand the relationship between amenorrhea, weight status, and bone health in Asian adolescents with eating disorders. PUBLIC SIGNIFICANCE: In this sample, 13% of Asian adolescents with AN and 2.3% of Asian adolescents with atypical AN have low BMD. In our study population, duration of amenorrhea was not correlated with BMD. Among adolescents with AN, a history of being underweight at the highest pre-morbid BMI, is correlated with low BMD. It is important for physicians to take a thorough weight history in evaluating bone health in this population.

Baseline presentation of atypical anorexia nervosa in Singaporean adolescents: a retrospective cohort study.

BACKGROUND: While atypical anorexia nervosa (AAN) has been found to present with significant physical and psychological complications, the presentation of AAN has not been described in a multi-ethnic Singaporean population. METHODS: This retrospective cohort analysis aimed to characterize the baseline presentation of adolescents with anorexia nervosa (AN) (N = 317) and AAN (N = 141) in a Singaporean cohort that presented to a specialist paediatric eating disorder program between January 2010 and October 2020 for assessment. RESULTS: In patients with AAN, there were increased proportions of males (16% vs. 7%) and of Malay ethnicity (11% vs. 4%) compared to AN. Compared to adolescents with AN, adolescents with AAN had lower rates of admission (61% vs. 81%), bradycardia (45% vs. 75%), and hypotension (7% vs. 21%) but had a higher rate of syncope (13% vs. 7%). Likewise, adolescents with AAN had higher rates of self-harm and drug overdose (14% vs. 1.5%) requiring admission, more purging (45.1% vs. 14.8%) and more shape concerns. CONCLUSION: Highlighting the severity of the illness, Singaporean adolescents with AAN presented with physical complications of malnutrition and had more severe eating disorder psychopathology and a higher frequency of other psychological comorbidities than did adolescents with AN.

Singaporean adolescents with atypical anorexia nervosa experience both physical and psychological complications of the illness.

Integrated community models: A framework combining multispecies data sources to estimate the status, trends and dynamics of biodiversity.

Data deficiencies among rare or cryptic species preclude assessment of community-level processes using many existing approaches, limiting our understanding of the trends and stressors for large numbers of species. Yet evaluating the dynamics of whole communities, not just common or charismatic species, is critical to understanding and the responses of biodiversity to ongoing environmental pressures. A recent surge in both public science and government-funded data collection efforts has led to a wealth of biodiversity data. However, these data collection programmes use a wide range of sampling protocols (from unstructured, opportunistic observations of wildlife to well-structured, design-based programmes) and record information at a variety of spatiotemporal scales. As a result, available biodiversity data vary substantially in quantity and information content, which must be carefully reconciled for meaningful ecological analysis. Hierarchical modelling, including single-species integrated models and hierarchical community models, has improved our ability to assess and predict biodiversity trends and processes. Here, we highlight the emerging 'integrated community modelling' framework that combines both data integration and community modelling to improve inferences on species- and community-level dynamics. We illustrate the framework with a series of worked examples. Our three case studies demonstrate how integrated community models can be used to extend the geographic scope when evaluating species distributions and community-level richness patterns; discern population and community trends over time; and estimate demographic rates and population growth for communities of sympatric species. We implemented these worked examples using multiple software methods through the R platform via packages with formula-based interfaces and through development of custom code in JAGS, NIMBLE and Stan. Integrated community models provide an exciting approach to model biological and observational processes for multiple species using multiple data types and sources simultaneously, thus accounting for uncertainty and sampling error within a unified framework. By leveraging the combined benefits of both data integration and community modelling, integrated community models can produce valuable information about both common and rare species as well as community-level dynamics, allowing for holistic evaluation of the effects of global change on biodiversity.

A Mediterranean Diet and Walking Intervention to Reduce Cognitive Decline and Dementia Risk in Independently Living Older Australians: The MedWalk Randomized Controlled Trial Experimental Protocol, Including COVID-19 Related Modifications and Baseline Characteristics.

BACKGROUND: Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer's disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive. OBJECTIVE: The MedWalk trial's primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment. METHODS: MedWalk, a one-year cluster-randomized controlled trial across two Australian states, recruited 60-90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation.Progress and Discussion:Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community. TRIAL REGISTRATION: Registered on the Australia New Zealand Clinical Trials Registry ANZCTR 12620000978965 (https://www.anzctr.org.au).

Deep learning with citizen science data enables estimation of species diversity and composition at continental extents.

Effective solutions to conserve biodiversity require accurate community- and species-level information at relevant, actionable scales and across entire species' distributions. However, data and methodological constraints have limited our ability to provide such information in robust ways. Herein we employ a Deep-Reasoning Network implementation of the Deep Multivariate Probit Model (DMVP-DRNets), an end-to-end deep neural network framework, to exploit large observational and environmental data sets together and estimate landscape-scale species diversity and composition at continental extents. We present results from a novel year-round analysis of North American avifauna using data from over nine million eBird checklists and 72 environmental covariates. We highlight the utility of our information by identifying critical areas of high species diversity for a single group of conservation concern, the North American wood warblers, while capturing spatiotemporal variation in species' environmental associations and interspecific interactions. In so doing, we demonstrate the type of accurate, high-resolution information on biodiversity that deep learning approaches such as DMVP-DRNets can provide and that is needed to inform ecological research and conservation decision-making at multiple scales.

Interactions between Mediterranean Diet Supplemented with Dairy Foods and the Gut Microbiota Influence Cardiovascular Health in an Australian Population.

The impact of a Mediterranean diet on the intestinal microbiome has been linked to its health benefits. We aim to evaluate the effects of a Mediterranean diet supplemented with dairy foods on the gut microbiome in Australians at risk of cardiovascular disease. In a randomised controlled cross-over study, 34 adults with a systolic blood pressure ≥120 mmHg and with risk factors for cardiovascular disease were randomly allocated to a Mediterranean diet with 3-4 daily serves of dairy foods (Australian recommended daily intake (RDI) of 1000-1300 mg per day (MedDairy)) or a low-fat (LFD) control diet. Between each 8-week diet, participants underwent an 8-week washout period. Microbiota characteristics of stool samples collected at the start and end of each diet period were determined by 16S rRNA amplicon sequencing. MedDairy-associated effects on bacterial relative abundance were correlated with clinical, anthropometric, and cognitive outcomes. No change in the overall faecal microbial structure or composition was observed with either diet (p > 0.05). The MedDairy diet was associated with changes in the relative abundance of several bacterial taxa, including an increase in Butyricicoccus and a decrease in Colinsella and Veillonella (p < 0.05). Increases in Butyricicoccus relative abundance over 8 weeks were inversely correlated with lower systolic blood pressure (r = -0.38, p = 0.026) and positively correlated with changes in fasting glucose levels (r = 0.39, p = 0.019), specifically for the MedDairy group. No significant associations were observed between the altered taxa and anthropometric or cognitive measures (p > 0.05). Compared to a low-fat control diet, the MedDairy diet resulted in changes in the abundance of specific gut bacteria, which were associated with clinical outcomes in adults at risk of CVD.

Developing a Mediterranean Healthy Food Basket and an Updated Australian Healthy Food Basket Modelled on the Australian Guide to Healthy Eating.

INTRODUCTION: Australian healthy food baskets are typically modelled off the Government Guidelines for healthy eating. However, these baskets have not been updated recently, nor has there been a Mediterranean Diet basket developed for an Australian population despite research suggesting high adherence is possible and subsequent health benefits observed. Food baskets typically only present the nutrition profile or the cost of a basket, seldom both. METHODS: Baskets were developed based on the Australian Guide to Healthy Eating, The Mediterranean Diet and typical Australian dietary intake (Western Diet). Four reference families were created based on data from Australian censuses and population statistics. Seven-day meal plans for reference families were entered into Foodworks software and aimed to meet 100% of nutrition and energy requirements. Basket costs were calculated from Coles Australia online. RESULTS: The AGHE basket met all NRVs except for VLCN3 for the 7-year-old male (73% adequate intake). The Mediterranean Diet met all NRVs except zinc (44-year-old male) ranging from 98 to 257% of the RDI. The Western Diet failed to meet NRVs for numerous nutrients. The MedDiet baskets were generally cheaper ($78 for a one-person household to $285 for a four-person household) than AGHE and Western Diet. DISCUSSION: Meeting nutrition requirements over seven days for zinc can be challenging for males. Fortified products provide an opportunity to improve nutrient profile; however, nutrient intake should equilibrate over time. Further, cost saving strategies can increase affordability. This research suggests a MedDiet is not more costly than a typical Western Diet or healthy AGHE diet.

A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.

BACKGROUND: Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. METHODS AND FINDINGS: We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. CONCLUSIONS: These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.

Communication of anticancer drug benefits and related uncertainties to patients and clinicians: document analysis of regulated information on prescription drugs in Europe.

OBJECTIVE: To evaluate the frequency with which relevant and accurate information about the benefits and related uncertainties of anticancer drugs are communicated to patients and clinicians in regulated information sources in Europe. DESIGN: Document content analysis. SETTING: European Medicines Agency. PARTICIPANTS: Anticancer drugs granted a first marketing authorisation by the European Medicines Agency, 2017-19. MAIN OUTCOME MEASURES: Whether written information on a product addressed patients' commonly asked questions about: who and what the drug is used for; how the drug was studied; types of drug benefit expected; and the extent of weak, uncertain, or missing evidence for drug benefits. Information on drug benefits in written sources for clinicians (summaries of product characteristics), patients (patient information leaflets), and the public (public summaries) was compared with information reported in regulatory assessment documents (European public assessment reports). RESULTS: 29 anticancer drugs that received a first marketing authorisation for 32 separate cancer indications in 2017-19 were included. General information about the drug (including information on approved indications and how the drug works) was frequently reported across regulated information sources aimed at both clinicians and patients. Nearly all summaries of product characteristics communicated full information to clinicians about the number and design of the main studies, the control arm (if any), study sample size, and primary measures of drug benefit. None of the patient information leaflets communicated information to patients about how drugs were studied. 31 (97%) summaries of product characteristics and 25 (78%) public summaries contained information about drug benefits that was accurate and consistent with information in regulatory assessment documents. The presence or absence of evidence that a drug extended survival was reported in 23 (72%) summaries of product characteristics and four (13%) public summaries. None of the patient information leaflets communicated information about the drug benefits that patients might expect based on study findings. Scientific concerns about the reliability of evidence on drug benefits, which were raised by European regulatory assessors for almost all drugs in the study sample, were rarely communicated to clinicians, patients, or the public. CONCLUSIONS: The findings of this study highlight the need to improve the communication of the benefits and related uncertainties of anticancer drugs in regulated information sources in Europe to support evidence informed decision making by patients and their clinicians.

Peer review perpetuates barriers for historically excluded groups.

Peer review is central to the scientific process and scientists' career advancement, but bias at various stages of the review process disadvantages some authors. Here we use peer review data from 312,740 biological sciences manuscripts across 31 studies to (1) examine evidence for differential peer review outcomes based on author demographics, (2) evaluate the efficacy of solutions to reduce bias and (3) describe the current landscape of peer review policies for 541 ecology and evolution journals. We found notably worse review outcomes (for example, lower overall acceptance rates) for authors whose institutional affiliations were in Asia, for authors whose country's primary language is not English and in countries with relatively low Human Development Indices. We found few data evaluating efficacy of interventions outside of reducing gender bias through double-blind review or diversifying reviewer/editorial boards. Despite evidence for review outcome gaps based on author demographics, few journals currently implement policies intended to mitigate bias (for example, 15.9% of journals practised double-blind review and 2.03% had reviewer guidelines that mentioned social justice issues). The lack of demographic equity signals an urgent need to better understand and implement evidence-based bias mitigation strategies.

Adherence to a Mediterranean Diet for 6 Months Improves the Dietary Inflammatory Index in a Western Population: Results from the MedLey Study.

Increasing evidence supports that a higher dietary inflammatory index (DII®) score is associated with inflammation and cardiovascular disease (CVD) risk, events, and mortality. This randomized trial sought to determine if a change to a Mediterranean diet resulted in a reduction in the DII score, and then it evaluated the relationship between the DII and cardiometabolic outcomes following the administration of a traditional Mediterranean diet in older Australian adults. A total of 152 Australian adults (mean age 71 ± 5 years) was randomly allocated either a MedDiet (n = 80) or to continue their habitual diet (HabDiet) (n = 72) for 6 months. Diet and cardiovascular outcomes were measured at baseline and 3 and 6 months of the intervention. DII and energy-adjusted DII (E-DIITM) scores were calculated from 3-day weighed food records. There was a significant reduction in the DII score at 2 and 4 months for the MedDiet group (−1.40 ± 0.20 p < 0.001 and −1.47 ± 0.20 p < 0.001, respectively), which was significantly different from the HabDiet group over time (p < 0.001). The HabDiet DII score did not change significantly at the 2 and 4 months timepoints (0.47 ± 0.21 p = 0.35 and 0.54 ± 0.21 p = 0.21, respectively). The improvement in the DII in the MedDiet group was not related to any cardiometabolic outcome. Baseline cross-sectional analyses identified a positive association between the E-DII score and average BMI, body weight, WHR, abdominal adiposity, and SBP, and a negative association with HDL-C. We demonstrate that a MedDiet intervention significantly reduced DII scores compared with a habitual Australian diet in older Australians. This could be beneficial for healthy ageing and the avoidance of chronic disease in Western populations.

Challenges and opportunities for using natural history collections to estimate insect population trends.

Natural history collections (NHC) provide a wealth of information that can be used to understand the impacts of global change on biodiversity. As such, there is growing interest in using NHC data to estimate changes in species' distributions and abundance trends over historic time horizons when contemporary survey data are limited or unavailable. However, museum specimens were not collected with the purpose of estimating population trends and thus can exhibit spatiotemporal and collector-specific biases that can impose severe limitations to using NHC data for evaluating population trajectories. Here we review the challenges associated with using museum records to track long-term insect population trends, including spatiotemporal biases in sampling effort and sparse temporal coverage within and across years. We highlight recent methodological advancements that aim to overcome these challenges and discuss emerging research opportunities. Specifically, we examine the potential of integrating museum records and other contemporary data sources (e.g. collected via structured, designed surveys and opportunistic citizen science programs) in a unified analytical framework that accounts for the sampling biases associated with each data source. The emerging field of integrated modelling provides a promising framework for leveraging the wealth of collections data to accurately estimate long-term trends of insect populations and identify cases where that is not possible using existing data sources.

Disentangling direct and indirect effects of extreme events on coastal wetland communities.

One of the primary ways in which climate change will impact coastal freshwater wetlands is through changes in the frequency, intensity, timing and distribution of extreme weather events. Disentangling the direct and indirect mechanisms of population- and community-level responses to extreme events is vital to predicting how species composition of coastal wetlands will change under future conditions. We extended static structural equation modelling approaches to incorporate system dynamics in a multi-year multispecies occupancy model to quantify the effects of extreme weather events on a coastal freshwater wetland system. We used data from an 8-year study (2009-2016) on St. Marks National Wildlife Refuge in Florida, USA, to quantify species-specific and community-level changes in amphibian and fish occupancy associated with two flooding events in 2012 and 2013. We examine how physical changes to the landscape, including potential changes in salinity and increased wetland connectivity, may have contributed to or exacerbated the effects of these extreme weather events on the biota of isolated coastal wetlands. We provide evidence that the primary effects of flooding on the amphibian community were through indirect mechanisms via changes in the composition of the sympatric fish community that may have had lethal (i.e. through direct predation) or non-lethal (i.e. through direct or indirect competitive interactions) effects. In addition, we have shown that amphibian species differed in their sensitivity to direct flooding effects and indirect changes in the fish community and wetland-specific conductance, which led to variable responses across the community. These effects led to the overall decline in amphibian species richness from 2009 to 2016, suggesting that wetland-breeding amphibian communities on St. Marks National Wildlife Refuge may not be resilient to predicted changes in coastal disturbance regimes because of climate change. Understanding both direct and indirect effects, as well as species interactions, is important for predicting the effects of a changing climate on individual species, communities and ecosystems.

Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients.

Background: Systemic administration of marrow stromal cells (MSCs) leads to the release of a broad range of factors mediating recovery in rodent stroke models. The release of these factors could depend on the various cell types within the peripheral blood as they contact systemically administered MSCs. In this study, we assessed the immunomodulatory interactions of MSCs with peripheral blood derived monocytes (Mϕ) collected from acute stroke patients. Methods: Peripheral blood from stroke patients was collected at 5-7 days (N = 5) after symptom onset and from age-matched healthy controls (N = 5) using mononuclear cell preparation (CPT) tubes. After processing, plasma and other cellular fractions were removed, and Mϕ were isolated from the mononuclear fraction using CD14 microbeads. Mϕ were then either cultured alone or co-cultured with MSCs in a trans-well cell-culture system. Secretomes were analyzed after 24 h of co-cultures using a MAGPIX reader. Results: Our results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5-7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1ß, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared to the secretions from monocytes alone. When MSCs were added to monocytes from stroke patients, they decreased the levels of IL-1ß, and increased the levels of IL-10 significantly more as compared to when they were added to monocytes from control patients. Conclusion: The systemic circulation of stroke patients may differentially interact with MSCs to release soluble factors integral to their paracrine mechanisms of benefit. Our study finds that the effect of MSCs on Mϕ is different on those derived from stroke patients blood as compared to healthy controls. These findings suggest immunomodulation of peripheral immune cells as a therapeutic target for MSCs in patients with acute stroke.

Molecular and behavioral consequences of Ube3a gene overdosage in mice.

Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a severe neurodevelopmental disorder characterized by intellectual disability, impaired motor coordination, and autism spectrum disorder. Chromosomal multiplication of the UBE3A gene is presumed to be the primary driver of Dup15q pathophysiology, given that UBE3A exhibits maternal monoallelic expression in neurons and that maternal duplications typically yield far more severe neurodevelopmental outcomes than paternal duplications. However, studies into the pathogenic effects of UBE3A overexpression in mice have yielded conflicting results. Here, we investigated the neurodevelopmental impact of Ube3a gene overdosage using bacterial artificial chromosome-based transgenic mouse models (Ube3aOE) that recapitulate the increases in Ube3a copy number most often observed in Dup15q. In contrast to previously published Ube3a overexpression models, Ube3aOE mice were indistinguishable from wild-type controls on a number of molecular and behavioral measures, despite suffering increased mortality when challenged with seizures, a phenotype reminiscent of sudden unexpected death in epilepsy. Collectively, our data support a model wherein pathogenic synergy between UBE3A and other overexpressed 15q11.2-q13.1 genes is required for full penetrance of Dup15q syndrome phenotypes.

Long-Term Adherence to a Mediterranean Diet 1-Year after Completion of the MedLey Study.

Mediterranean populations enjoy the health benefits of a Mediterranean diet (MedDiet), but is it feasible to implement such a pattern beyond the Mediterranean region? The MedLey trial, a 6-month MedDiet intervention vs habitual diet in older Australians, demonstrated that the participants could maintain high adherence to a MedDiet for 6 months. The MedDiet resulted in improved systolic blood pressure (BP), endothelial dilatation, oxidative stress, and plasma triglycerides in comparison with the habitual diet. We sought to determine if 12 months after finishing the MedLey study, the participants maintained their adherence to the MedDiet principles and whether the reduction in the cardiovascular disease (CVD) risk factors that were seen in the trial were sustained. Participants completed a food frequency questionnaire, and a 15-point MedDiet adherence score (MDAS; greater score = greater adherence) was calculated. Home BP was measured over 6 days, BMI was assessed, and fasting plasma triglycerides were measured. The data were analysed using intention-to-treat linear mixed effects models with a group × time interaction term, comparing data at baseline, 2, 4, and 18 months (12 months post-trial). At 18 months (12 months after finishing the MedLey study), the MedDiet group had a MDAS of 7.9 ± 0.3, compared to 9.6 ± 0.2 at 4 months (p < 0.0001), and 6.7 ± 0.2 (p < 0.0001), at baseline. The MDAS in the HabDiet group remained unchanged over the 18-month period (18 months 6.9 ± 0.3, 4 months 6.9 ± 0.2, baseline 6.7 ± 0.2). In the MedDiet group, the consumption of olive oil, legumes, fish, and vegetables remained higher (p < 0.01, compared with baseline) and discretionary food consumption remained lower (p = 0.02) at 18 months. These data show that some MedDiet principles could be adhered to for 12 months after finishing the MedLey trial. However, improvements in cardiometabolic health markers, including BP and plasma triglycerides, were not sustained. The results indicate that further dietary support for behaviour change may be beneficial to maintaining high adherence and metabolic benefits of the MedDiet.