Psychosocial outcomes with the Omnipod® 5 Automated Insulin Delivery System in caregivers of very young children with type 1 diabetes.

AIM: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psychosocial outcomes following use of the tubeless Omnipod® 5 AID System in caregivers of very young children. MATERIALS AND METHODS: This 3-month single-arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.0-5.9 years with T1D to use the Omnipod 5 AID System. Caregivers completed questionnaires assessing psychosocial outcomes-diabetes distress (Problem Areas in Diabetes), hypoglycaemia confidence (Hypoglycemia Confidence Scale), well-being (World Health Organization 5 Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), insulin delivery satisfaction (Insulin Delivery Satisfaction Survey) and system usability (System Usability Scale) at baseline with standard therapy and after 3 months of AID use. RESULTS: Following 3 months of Omnipod 5 use, caregivers experienced significant improvements across all measures, including diabetes-related psychosocial outcomes (Problem Areas in Diabetes; p < 0.0001, Hypoglycemia Confidence Scale; p < 0.01), well-being (World Health Organization 5 Well-Being Index; p < 0.0001) and perceived system usability (System Usability Scale; p < 0.0001). Significant improvements were seen in the Pittsburgh Sleep Quality Index total score and the overall sleep quality, sleep duration and efficiency subscales (all p < 0.05). Insulin Delivery Satisfaction Survey scores improved on all subscales (greater satisfaction, reduced burden and reduced inconvenience; all p < 0.0001). CONCLUSIONS: Caregivers face unique challenges when managing T1D in very young children. While glycaemic metrics have unquestioned importance, these results evaluating psychosocial outcomes reveal additional meaningful benefits and suggest that the Omnipod 5 AID System alleviates some of the burdens caregivers face with diabetes management.

Evidence for adaptation of colourful truffle-like fungi for birds in Aotearoa-New Zealand.

Propagule dispersal is a crucial aspect of the survival and reproduction of sessile organisms, such as plants and fungi. As such, the colours of fleshy fruits serve as a visual cue for animal dispersers. However, little is known about how, or whether, specific traits of fungal fruiting bodies, such as colour or shape, attract animal dispersers, and additionally the identities of fungal dispersers are poorly understood. Globally, most truffle-like fungi are dull-coloured, subterranean, and likely have scents that are attractive to mammalian dispersers. In Aotearoa-New Zealand, however, brightly coloured truffle-like fungi that emerge from the forest floor have seemingly proliferated. This proliferation has prompted the hypothesis that they are adapted to dispersal by a bird-dominated fauna. In our study, we used the literature and citizen science data (GBIF) to explore whether colourful species occur at a higher proportion of the total truffle-like fungi flora in Aotearoa-New Zealand than elsewhere in the world. In addition, we tested for a relationship between biotic factors (avian frugivory and forest cover) and abiotic factors (precipitation, radiation, and temperature) and the prevalence of brightly coloured truffle-like fungi across the world. The most colourful truffle-like fungi are in three defined regions: Australia, South and Central America and the Caribbean, and Aotearoa-NZ. Potential dispersers and the environment both relate to the distribution of truffle-like fungi: we found that increasing levels of frugivory were associated with higher proportions of colourful truffle-like fungi. This finding provides new insights into drivers of certain fungal traits, and their interactions between birds and fungi. Unique ecosystems, such as Aotearoa-NZ's bird-dominated biota, provide fascinating opportunities to explore how plants and fungi interact with the sensory systems of animals.

Resonant breathing improves self-reported symptoms and wellbeing in people with Long COVID.

Introduction: Long COVID involves debilitating symptoms, many of which mirror those observed with dysautonomia, and care must be taken with rehabilitation for autonomic dysfunction to avoid post-exertional malaise/post-exertional symptom exacerbation. Resonant breathing (breathing slowly at a defined rate of breaths per minute) requires less exertion and can potentially improve autonomic function. The objective of this work was to report on the impact of a resonant breathing program on self-reported symptoms and wellbeing in people with Long COVID. Methods: A retrospective analysis of de-identified data was completed in a convenience sample of people with Long COVID, who participated in the Meo Health (formerly known as Stasis HP) resonant breathing program. Participants completed baseline and follow up surveys. Results: Data were available for 99 participants. Most measures of symptoms and wellbeing improved at follow up, with the largest differences per participant seen in sense of wellness (47.3%, p < 0.0001), ability to focus (57.5%, p < 0.0001), ability to breathe (47.5%, p < 0.0001), ability to control stress (61.8%, p < 0.0001) and sleep quality (34.9%, p = 0.0002). Most (92%) participants reported improvement at follow up on the Patient Global Impression of Change Scale. Conclusion: Self-reported symptoms and wellbeing improved in people with Long COVID completing resonant breathing. Resonant breathing can be considered as an option within the broader treatment plan of people with Long COVID.

A causal link between autoantibodies and neurological symptoms in long COVID.

Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reported dizziness. Our findings suggest that targeting AABs could benefit some LC patients.

Ecological dynamics of moa extinctions reveal convergent refugia that today harbour flightless birds.

Human settlement of islands across the Pacific Ocean was followed by waves of faunal extinctions that occurred so rapidly that their dynamics are difficult to reconstruct in space and time. These extinctions included large, wingless birds called moa that were endemic to New Zealand. Here we reconstructed the range and extinction dynamics of six genetically distinct species of moa across New Zealand at a fine spatiotemporal resolution, using hundreds of thousands of process-explicit simulations of climate-human-moa interactions, which were validated against inferences of occurrence and range contraction from an extensive fossil record. These process-based simulations revealed important interspecific differences in the ecological and demographic attributes of moa and established how these differences influenced likely trajectories of geographic and demographic declines of moa following Polynesian colonization of New Zealand. We show that despite these interspecific differences in extinction dynamics, the spatial patterns of geographic range collapse of moa species were probably similar. It is most likely that the final populations of all moa species persisted in suboptimal habitats in cold, mountainous areas that were generally last and least impacted by people. We find that these refugia for the last populations of moa continue to serve as isolated sanctuaries for New Zealand's remaining flightless birds, providing fresh insights for conserving endemic species in the face of current and future threats.

Reconstructing colonization dynamics to establish how human activities transformed island biodiversity.

Drivers and dynamics of initial human migrations across individual islands and archipelagos are poorly understood, hampering assessments of subsequent modification of island biodiversity. We developed and tested a new statistical-simulation approach for reconstructing the pattern and pace of human migration across islands at high spatiotemporal resolutions. Using Polynesian colonisation of New Zealand as an example, we show that process-explicit models, informed by archaeological records and spatiotemporal reconstructions of past climates and environments, can provide new and important insights into the patterns and mechanisms of arrival and establishment of people on islands. We find that colonisation of New Zealand required there to have been a single founding population of approximately 500 people, arriving between 1233 and 1257 AD, settling multiple areas, and expanding rapidly over both North and South Islands. These verified spatiotemporal reconstructions of colonisation dynamics provide new opportunities to explore more extensively the potential ecological impacts of human colonisation on New Zealand's native biota and ecosystems.

Sex differences in symptomatology and immune profiles of Long COVID.

Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection 1-7 . However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals 8 with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC. We found that female and male participants with LC experienced different sets of symptoms, and distinct patterns of organ system involvement, with female participants suffering from a higher symptom burden. Machine learning approaches identified differential sets of immune features that characterized LC in females and males. Males with LC had decreased frequencies of monocyte and DC populations, elevated NK cells, and plasma cytokines including IL-8 and TGF-ß-family members. Females with LC had increased frequencies of exhausted T cells, cytokine-secreting T cells, higher antibody reactivity to latent herpes viruses including EBV, HSV-2, and CMV, and lower testosterone levels than their control female counterparts. Testosterone levels were significantly associated with lower symptom burden in LC participants over sex designation. These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex-specific pathology.

Biomonitoring tool for New Zealand peatlands: Testate amoebae and vascular plants as promising bioindicators.

In the last two centuries, a high proportion of peatlands have been lost or severely degraded across the world. The value of peatlands is now well-recognised for biodiversity conservation, flood management, and carbon mitigation, with peatland restoration now central to many government policies for climate action. A challenge, however, is to determine 'natural' and 'disturbed' conditions of peatlands to establish realistic baselines for assessing degradation and setting restoration targets. This requires a tool or set of tools that can rapidly and reliably capture peatland condition across space and time. Our aim was to develop such a tool based on combined analysis of plant and testate amoebae; a group of shelled protists commonly used as indicators of ecological change in peatlands. The value of testate amoebae is well established in Northern Hemisphere Sphagnum-dominated peatlands; however, relatively little work has been undertaken for Southern Hemisphere peat forming systems. Here we provide the first assessment and comparison of the bioindicator value of testate amoebae and vascular plants in the context of Southern Hemisphere peatlands. Our results further demonstrate the unique ecohydrological dynamics at play in New Zealand peat forming systems that set them apart from Northern Hemisphere peatlands. Our results show that plant and testate amoeba communities provided valuable information on peatland condition at different scales, we found that testate amoebae tracked changes in the abiotic variables (depth to water table, pH, and conductivity) more closely than vascular plants. Our results further demonstrate that functional traits of testate amoebae showed promising relationships with disturbance. Amoeba test compression, aperture position and test size were linked to changes in hydrology driven by fluctuations in ground water tables; however, trait responses manifested differently in ombrotrophic and minerotrophic peatlands. Overall, testate amoebae provide a promising bioindicator for tracking degradation in New Zealand peatlands and a potential additional tool to assess peatland condition.

Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV1) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82; P < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.

Relationships between body composition, anthropometrics, and standard lipid panels in a normative population.

Introduction: More than one third of adults in the United States (US) meet the clinical criteria for a diagnosis of metabolic syndrome, but often diagnosis is challenging due to healthcare access, costs and discomfort with the process and invasiveness associated with a standard medical examination. Less invasive and more accessible approaches to collecting biometric data may have utility in identifying individuals at risk of diagnoses, such as metabolic syndrome or dyslipidemia diagnoses. Body composition is one such source of biometric data that can be non-invasively acquired in a home or community setting that may provide insight into an individual's propensity for a metabolic syndrome diagnosis. Here we investigate possible associations between body composition, anthropometrics and lipid panels in a normative population. Methods: Healthy participants visited the Lab100 clinic location at a hospital setting in New York City and engaged in a wellness visit led by a nurse practitioner. Blood was analyzed at point-of-care using the Abbott Piccolo Xpress portable diagnostic analyzer (Abbott Laboratories, IL, USA) and produced direct measures of total cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), very-low density lipoprotein (VLDL-C), and triglycerides (TG). Body composition and anthropometric data were collected using two separate pieces of equipment during the same visit (Fit3D and InBody570). Regression analysis was performed to evaluate associations between all variables, after adjusting for age, sex, race, AUDIT-C total score (alcohol use), and current smoking status. Results: Data from 199 participants were included in the analysis. After adjusting for variables, percentage body fat (%BF) and visceral fat levels were significantly associated with every laboratory lipid value, while waist-to-hip ratio also showed some significant associations. The strongest associations were detected between %BF and VLDL-C cholesterol levels (t = 4.53, p = 0.0001) and Triglyceride levels (t = 4.51, p = 0.0001). Discussion: This initial, exploratory analysis shows early feasibility in using body composition and anthropometric data, that can easily be acquired in community settings, to identify people with dyslipidemia in a normative population.

Dysautonomia, but Not Cardiac Dysfunction, Is Common in a Cohort of Individuals with Long COVID.

Despite the prevalence of dysautonomia in people with Long COVID, it is currently unknown whether Long COVID dysautonomia is routinely accompanied by structural or functional cardiac alterations. In this retrospective observational study, the presence of echocardiographic abnormalities was assessed. Left ventricular (LV) chamber sizes were correlated to diagnostic categories and symptoms via standardized patient-reported outcome (PRO) questionnaires. A total of 203 individuals with Long COVID without pre-existing cardiac disease and with available echocardiograms were included (mean age, 45 years; 67% female). Overall, symptoms and PRO scores for fatigue, breathlessness, quality of life, disability, anxiety and depression were not different between those classified with post-COVID dysautonomia (PCD, 22%) and those unclassified (78%). An LV internal diameter at an end-diastole z score < -2 was observed in 33 (16.5%) individuals, and stroke volume (SV) was lower in the PCD vs. unclassified subgroup (51.6 vs. 59.2 mL, 95% C.I. 47.1-56.1 vs. 56.2-62.3). LV end-diastolic volume (mean diff. (95% CI) -13 [-1--26] mL, p = 0.04) and SV (-10 [-1--20] mL, p = 0.03) were smaller in those individuals reporting a reduction in physical activity post-COVID-19 infection, and smaller LVMI was weakly correlated with worse fatigue (r = 0.23, p = 0.02). The majority of individuals with Long COVID report shared symptoms and did not demonstrate cardiac dysfunction on echocardiography.

Modified forced expiration technique using expiratory resistance in adults with cystic fibrosis.

BACKGROUND: Participation in airway clearance techniques (ACT) is important to minimise development of irreversible airway obstruction in patients with cystic fibrosis (CF). Positive expiratory pressure (PEP) and expiratory resistance devices (ERD) are often used as they can improve collateral ventilation and aid in the shearing of mucus from airways. This project looked to identify whether utilising an ERD during a forced expiration technique (FET) improves ease of expectoration, sputum amount and coughing frequency in patients with CF. METHOD: Patients with CF admitted for a respiratory exacerbation completed two sessions of 10 cycles of their usual ACT with half of the FET components performed with an ERD, half with FET alone. RESULTS: EOE, sputum wet weight, cough frequency and patient preference were similar between groups. Improved EOE without the ERD was found in participants who usually use PEP for their ACT regime. CONCLUSION: Combining the FET with a PEP mask did not improve EOE and other outcomes in this small study. Investigating the efficacy of this technique within a larger population is warranted.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

A high ratio of linoleic acid (n-6 PUFA) to alpha-linolenic acid (n-3 PUFA) adversely affects early stage of human neuronal differentiation and electrophysiological activity of glutamatergic neurons in vitro.

Introduction: There is a growing interest in the possibility of dietary supplementation with polyunsaturated fatty acids (PUFAs) for treatment and prevention of neurodevelopmental and neuropsychiatric disorders. Studies have suggested that of the two important classes of polyunsaturated fatty acids, omega-6 (n-6) and omega-3 (n-3), n-3 polyunsaturated fatty acids support brain development and function, and when used as a dietary supplement may have beneficial effects for maintenance of a healthy brain. However, to date epidemiological studies and clinical trials on children and adults have been inconclusive regarding treatment length, dosage and use of specific n-3 polyunsaturated fatty acids. The aim of this study is to generate a simplified in vitro cell-based model system to test how different n-6 to n-3 polyunsaturated fatty acids ratios affect human-derived neurons activity as a cellular correlate for brain function and to probe the mechanism of their action. Methods: All experiments were performed by use of human induced pluripotent stem cells (iPSCs). In this study, we examined the effect of different ratios of linoleic acid (n-6) to alpha-linolenic acid in cell growth medium on induced pluripotent stem cell proliferation, generation of neuronal precursors and electrophysiology of cortical glutamatergic neurons by multielectrode array (MEA) analysis. Results: This study shows that at a n-6:n-3 ratio of 5:1 polyunsaturated fatty acids induce stem cell proliferation, generating a large increase in number of cells after 72 h treatment; suppress generation of neuronal progenitor cells, as measured by decreased expression of FOXG1 and Nestin in neuronal precursor cells (NPC) after 20 days of development; and disrupt neuronal activity in vitro, increasing spontaneous neuronal firing, reducing synchronized bursting receptor subunits. We observed no significant differences for neuronal precursor cells treated with ratios 1:3 and 3:1, in comparison to 1:1 control ratio, but higher ratios of n-6 to n-3 polyunsaturated fatty acids adversely affect early stages of neuronal differentiation. Moreover, a 5:1 ratio in cortical glutamatergic neurons induce expression of GABA receptors which may explain the observed abnormal electrophysiological activity.

Protein intake and postprandial hyperglycemia in children and adolescents with type 1 diabetes mellitus, a pilot study.

BACKGROUND AND AIMS: To describe the change in glucose and the resulting postprandial hyperglycemia (PPH) that occurs after dietary protein intake (PI) in children with type 1 diabetes (T1D). METHODS: We conducted a self-controlled, non-randomized, prospective pilot study in children with T1D who were given whey protein isolate drinks (carbohydrate-free, fat-free) of increasing protein amounts (0, 12.5, 25, 37.5, 50, and 62.5 gm) on 6 sequential nights. The glucose levels were monitored with continuous glucose monitors (CGM) and glucometers for 5 h after PI. PPH was defined as glucose elevations over baseline of ≥50 mg/dL. RESULTS: Thirty-eight subjects were recruited, and eleven subjects (6 females, 5 males) completed the intervention. Subjects had a mean (range) age of 11.6 (6-16) years, diabetes duration of 6.1 (1.4-15.5) years, HbA1c of 7.2 (5.2-8.6) % and weight of 44.5 (24.3-63.2) kg. PPH was detected in 1/11, 5/11, 6/10, 6/9, 5/9, and 8/9 subjects after receiving 0, 12.5, 25, 37.5, 50, and 62.5 gm of protein, respectively. CONCLUSIONS: In children with T1D, the association between PPH and PI was observed at smaller protein amounts compared to studies done in adults.

BEAT CF pulmonary exacerbations core protocol for evaluating the management of pulmonary exacerbations in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a rare, inherited, life-limiting condition predominantly affecting the lungs, for which there is no cure. The disease is characterized by recurrent pulmonary exacerbations (PEx), which are thought to drive progressive lung damage. Management of these episodes is complex and generally involves multiple interventions targeting different aspects of disease. The emergence of innovative trials and use of Bayesian statistical methods has created renewed opportunities for studying heterogeneous populations in rare diseases. Here, we present the protocol for the BEAT CF PEx cohort, a prospective, multi-site, perpetual, platform enrolling adults and children with CF. The BEAT CF PEx cohort will be used to evaluate the comparative effectiveness of interventions for the treatment of PEx requiring intensive therapy (PERITs), with a primary focus on short-term improvements in lung function. This will be achieved through the conduct of cohort-nested studies, including adaptive clinical trials, within the BEAT CF PEx cohort. This protocol will outline key features of the BEAT CF PEx cohort, including the design, implementation, data collection and management, governance and analysis, and dissemination of results. METHODS: This platform will be conducted across multiple sites, commencing with CF treatment centers in Australia. People of all ages with a clinical diagnosis of CF will be eligible to participate, except those who have previously received a lung transplant. Data including demographic and clinical information, treatment details, and outcomes (including safety, microbiology, and patient-reported outcome measures including quality of life scores) will be systematically collected and securely stored via a digital centralized trial management system (CTMS). The primary endpoint is the absolute change in the percentage predicted forced expiratory volume in 1 s (ppFEV1) from the commencement of intensive therapy to 7 to 10 days afterwards. DISCUSSION: The BEAT CF PEx cohort will report clinical, treatment, and outcome data for PEx among people with CF and is intended to serve as a core (master) protocol for future nested, interventional trials evaluating treatment(s) for these episodes. The protocols for nested sub-studies are beyond the scope of this document and will be reported separately. TRIAL REGISTRATION: ANZCTR BEAT CF Platform - ACTRN12621000638831. Registration date: Sept. 26, 2022.

What Is a Honeymoon in Type 1, Can It Go into Remission?

Type 1 diabetes is a chronic autoimmune disorder that results in destruction of insulin-producing cells in the pancreas. The autoimmune process is thought to be waxing and waning resulting in variable endogenous insulin secretion ability. An example of this is the honeymoon phase or partial remission phase of type 1 diabetes, during which optimal control of blood glucoses can be maintained with significantly reduced exogenous insulin, and occasionally exogenous insulin can be temporarily discontinued altogether. Understanding this phase is important because even fairly small amounts of endogenous insulin secretion is associated with reduced risk of severe hypoglycemia and microvascular complications.

NRSF/REST lies at the intersection between epigenetic regulation, miRNA-mediated gene control and neurodevelopmental pathways associated with Intellectual disability (ID) and Schizophrenia.

Genetic evidence indicates disrupted epigenetic regulation as a major risk factor for psychiatric disorders, but the molecular mechanisms that drive this association remain to be determined. EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a genetic disorder linked with neurodevelopmental disorders and associated with schizophrenia. Here, we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. We further show that EHMT1 regulates NRSF/REST indirectly via repression of miRNA and leads to aberrant neuronal gene regulation and neurodevelopment timing. Expression of a NRSF/REST mRNA that lacks the miRNA-binding sites restores neuronal gene regulation to EHMT1 deficient cells. Significantly, the EHMT1-regulated miRNA gene set not only controls NRSF/REST but is enriched for association for Intellectual Disability (ID) and schizophrenia. This reveals a broad molecular interaction between H3K9 demethylation, NSRF/REST regulation and risk for ID and Schizophrenia.

Comorbidities increase COVID-19 hospitalization in young people with type 1 diabetes.

OBJECTIVES: We evaluated COVID-19 outcomes in children and young adults with type 1 diabetes (T1D) to determine if those with comorbidities are more likely to experience severe COVID-19 compared to those without. RESEARCH DESIGN AND METHODS: This cross-sectional study included questionnaire data on patients <25 years of age with established T1D and laboratory-confirmed COVID-19 from 52 sites across the US between April 2020 and October 2021. We examined patient factors and COVID-19 outcomes between those with and without comorbidities. Multivariate logistic regression analysis examined the odds of hospitalization among groups, adjusting for age, HbA1c, race and ethnicity, insurance type and duration of diabetes. RESULTS: Six hundred fifty-one individuals with T1D and COVID-19 were analyzed with mean age 15.8 (SD 4.1) years. At least one comorbidity was present in 31%, and more than one in 10%. Obesity and asthma were the most frequently reported comorbidities, present in 19% and 17%, respectively. Hospitalization occurred in 17% of patients and 52% of hospitalized patients required ICU level care. Patients with at least one comorbidity were almost twice as likely to be hospitalized with COVID-19 than patients with no comorbidities (Odds ratio 2.0, 95% CI: 1.3-3.1). This relationship persisted after adjusting for age, HbA1c, race and ethnicity (minority vs nonminority), insurance type (public vs. private), and duration of diabetes. CONCLUSIONS: Our findings show that comorbidities increase the risk for hospitalization with COVID-19 in children and young adults highlighting the need for tailored COVID-19 prevention and treatment strategies in T1D.