Nut consumption in Australia does not meet recommended levels, and concern regarding the impact of nuts on body weight is a reported barrier to regular intake, due to their high energy content(1). Nut intake is not associated with higher body weight(2), which may be explained by their lower metabolisable energy(3). Hence, total energy intake may be overestimated among nut consumers. Nut consumption patterns in Australia are also unknown. This study aimed to describe the metabolisable energy from nuts, and nut consumption patterns of the Australian population. A previously developed nut-specific database was expanded to include the metabolisable energy of nuts based on nut type and form, and applied to the 2011-12 National Nutrition and Physical Activity Survey (NNPAS). Mean metabolisable energy was compared to mean energy intake determined using Atwater factors for nut consumers. Additionally, nut consumption patterns were also explored, including the proportion of nuts consumed at meals and snacks, proportion of nuts consumed alone or combined with other foods, and timing of nut intake. Among nut consumers, the mean metabolisable energy from nuts, based only on nut type, was 241.24 (95% CI: 232.00, 250.49) kJ/day. The mean metabolisable energy when considering both nut type and form was 260.69 (95% CI: 250.18, 271.21) kJ/day, while energy from nuts using Atwater factors was 317.60 (95% CI: 304.85, 330.35) kJ/day. Nuts were more likely to be consumed as snacks, with approximately 63% of all nut intake (in grams) occurring as a snack. Nuts were frequently consumed with other foods and beverages, with only 27% of nuts consumed alone or with plain water. Furthermore, nuts were most often consumed after midday (68% of intake) rather than in the morning (32% of intake). Application of metabolisable energy data to the 2011-12 NNPAS has a significant impact on the calculation of energy intake from nuts. Nut consumption patterns identify most nut consumption occurring as snacks and two-thirds of nut intake occurring in the afternoon and evening. These findings may inform strategies to promote nut consumption in Australia.

Telehealth overcomes common geographical barriers to community/clinic-based healthcare and lifestyle interventions, (1,2) but whether it is a feasible and safe mode of healthcare service delivery for lifestyle-based interventions in those with non-alcoholic fatty liver disease (NAFLD) remains unknown. This study evaluated the feasibility and safety of a home exercise program with dietary advice to increase plant-based protein delivered and monitored by healthcare professionals via telehealth in adults with NAFLD. Secondary aims were to assess changes in macronutrient intake including protein from plant and animal sources, body weight, physical activity and physical function. This was a 12-week pilot feasibility randomised controlled trial conducted in 28 inactive adults (>45 years) with NAFLD. Participants were randomly allocated to receive: 1) a home-based, muscle strengthening exercise program (3 days/week) delivered and monitored remotely by an exercise physiologist using the TeleHab exercise platform/app (VALD Health) plus support from a nutritionist to increase daily protein intake to ~1.2-1.5 g/kg/day from predominately plant-based sources and behavioural change support delivered via 3-4 weekly text messages (Pro-Ex, n = 14) or 2) usual care (UC, n = 14). Feasibility was assessed via retention (defined as ≤10% attrition), adherence [≥66% to the muscle strengthening program and ≥80% to the recommended daily protein serves [total (≥3-3½), plant (≥2) and animal (≤1-1½) per day (via protein checklist)] and safety (intervention-related adverse events). Secondary outcomes included macronutrient intake (3x24-hour records), weight (self-reported), habitual physical activity (PA) [moderate-to-vigorous (MVPA), minutes/week via the Short International Physical Activity Questionnaire], and physical function [30-second sit-to-stand (STS) performance]. Since this was a pilot feasibility study, mean group differences (6 and 12-weeks) were estimated, with 95% confidence intervals, and standardised effects [Cohen D, effect size (ES)] reported for secondary outcomes. Overall, 25 participants (89%) completed the intervention. In Pro-Ex, mean adherence to the exercise program was 52%, while adherence to the recommended plant, animal and total protein serves/day was 32%, 42% and 14% of participants, respectively. One minor exercise-related adverse event occurred from 241 completed sessions over 12 weeks. Relative to UC, Pro-Ex experienced a mean 2.7 (95%CI: 0.9, 4.4; large ES d = 1.29) increase in 30-sec STS number, 46 minute (95%CI: −153, 245; small ES d = 0.19) increase in MVPA, 1.7kg (95%CI: −3.5, 0.2; moderate ES d = 0.54) decrease in body weight, 35.2g (95%CI: 11.0, 59.3; large ES d = 1.23) increase in protein and 8.3g (95%CI:-20.5, 4.0; moderate ES d=-0.57) reduction in saturated fat. In middle-aged and older adults with NAFLD, a home exercise and plant-based dietary protein intervention delivered via telehealth was safe, but not feasible in terms of achieving the desired level of adherence. Despite this, exploratory analysis indicates this mode of healthcare service delivery could play a role to support weight management and improve physical activity and physical function in adults with NAFLD.

Energy restricted diets improve liver function(1) and habitual nut consumption has been associated with a lower prevalence of fatty liver(2). This study examined the effect of incorporating almonds in an energy restricted diet on liver health biomarkers. One Hundred and forty adults (42M:98F, 47.5 ± 10.8 years, BMI 30.7 ± 2.3 kg/m2) enrolled in a 9-month (9M) dietary intervention comprising 3 months (3M) weight loss (30% energy restriction) followed by 6 months (6M) of weight maintenance. Participants were randomly assigned to consume almonds (n = 68, AED) or isocaloric carbohydrate-rich snacks (n = 72, CRD) which provided 15% of total daily energy. At baseline (BL), 3M and 9M, fatty liver index (FLI) scores (0-100)(3) were calculated using body mass index (BMI), waist circumference (WC), fasting serum gamma-glutamyl transferase (GGT) and triglyceride (TAG) levels, and other liver health biomarkers were assessed by ultrasound (volume, visual appearance and elastography (a marker of stiffness due to fibrosis)). Intention to treat analyses were conducted using mixed effects modelling (fixed effects group and time, with participants as the random effect). Significant reductions from BL occurred over time (all p<0.001 for 3M and 9M) with no difference between groups (AED vs CRD, P>0.05) in BMI (3M: −2.44 ± 0.20 vs −2.32 ± 0.20, 9M: −2.83 ± 0.19 vs −2.81 ± 0.19 kg/m2), WC (3M: −8.04 ± 0.79 vs −7.00 ± 0.81, 9M: −8.72 ± 0.83 vs −9.14 ± 0.81 cm), TAG (3M: −0.24± 0.08 vs −0.22 ± 0.09, 9M: −0.37 ± 0.09 vs −0.21 ± 0.09 mmol/L), FLI score (3M: −23.8 ± 2.0 vs −17.6 ± 2.1, 9M: −23.8 ± 2.0 vs −17.6 ± 2.1), and liver volume (3M: −134.56 ± 38.30 vs −100.96 ± 37.25, 9M: −113.68 ± 37.42 vs −110.64 ± 35.47cm3). Significantly greater reductions occurred for AED compared to CRD at 3M and 9M in GGT (p = 0.003) (3M: −9.68 ± 1.93 vs −0.01 ± 2.00, 9M: −7.75 ± 2.06 vs −2.78 ± 2.15 IU/L) and liver visual assessment scores (p = 0.03) (3M: −0.58 ± 0.24 vs −0.45 ± 0.23, 9M: −1.33 ± 0.23 vs −0.50 ± 0.22). There were no significant changes in liver elastography over time or between groups. Energy restriction improved body composition and reduced the extent of fatty liver and liver size but did not change liver stiffness. The inclusion of almonds in an energy restricted diet demonstrated additional benefits to some liver health biomarkers providing support for almonds being incorporated into lifestyle interventions to improve liver function.

Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.