Mass Inversion at the Lifshitz Transition in Monolayer Graphene by Diffusive, High-Density, On-Chip Doping.

Experimental setups for charge transport measurements are typically not compatible with the ultrahigh vacuum conditions for chemical doping, limiting the charge carrier density that can be investigated by transport methods. Field-effect methods, including dielectric gating and ionic liquid gating, achieve too low a carrier density to induce electronic phase transitions. To bridge this gap, we developed an integrated flip-chip method to dope graphene by alkali vapor in the diffusive regime, suitable for charge transport measurements at ultrahigh charge carrier density. We introduce a cesium droplet into a sealed cavity filled with inert gas to dope a monolayer graphene sample by the process of cesium atom diffusion, adsorption, and ionization at the graphene surface, with doping beyond an electron density of 4.7 × 1014 cm-2 monitored by operando Hall measurement. The sealed assembly is stable against oxidation, enabling measurement of charge transport versus temperature and magnetic field. Cyclotron mass inversion is observed via the Hall effect, indicative of the change in Fermi surface geometry associated with the Liftshitz transition at the hyperbolic M point of monolayer graphene. The transparent quartz substrate also functions as an optical window, enabling nonresonant Raman scattering. Our findings show that chemical doping, hitherto restricted to ultrahigh vacuum, can be applied in a diffusive regime at ambient pressure in an inert gas environment and thus enable charge transport studies in standard cryogenic environments.

Spatially resolved multiomics of human cardiac niches.

The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system1. The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG+ and IgA+ plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.

Mapping interindividual dynamics of innate immune response at single-cell resolution.

Common genetic variants across individuals modulate the cellular response to pathogens and are implicated in diverse immune pathologies, yet how they dynamically alter the response upon infection is not well understood. Here, we triggered antiviral responses in human fibroblasts from 68 healthy donors, and profiled tens of thousands of cells using single-cell RNA-sequencing. We developed GASPACHO (GAuSsian Processes for Association mapping leveraging Cell HeterOgeneity), a statistical approach designed to identify nonlinear dynamic genetic effects across transcriptional trajectories of cells. This approach identified 1,275 expression quantitative trait loci (local false discovery rate 10%) that manifested during the responses, many of which were colocalized with susceptibility loci identified by genome-wide association studies of infectious and autoimmune diseases, including the OAS1 splicing quantitative trait locus in a COVID-19 susceptibility locus. In summary, our analytical approach provides a unique framework for delineation of the genetic variants that shape a wide spectrum of transcriptional responses at single-cell resolution.

Glycaemic patterns of male professional athletes with type 1 diabetes during exercise, recovery and sleep: Retrospective, observational study over an entire competitive season.

AIMS: To analyse glycaemic patterns of professional athletes with type 1 diabetes during a competitive season. MATERIALS AND METHODS: We analysed continuous glucose monitoring data of 12 professional male cyclists with type 1 diabetes during exercise, recovery and sleep on days with competitive exercise (CE) and non-competitive exercise (NCE). We assessed whether differences exist between CE and NCE days and analysed associations between exercise and dysglycaemia. RESULTS: The mean glycated haemoglobin was 50 ± 5 mmol/mol (6.7 ± 0.5%). The athletes cycled on 280.8 ± 28.1 days (entire season 332.6 ± 18.8 days). Overall, time in range (3.9-10 mmol/L) was 70.0 ± 13.7%, time in hypoglycaemia (<3.9 mmol/L) was 6.4 ± 4.7% and time in hyperglycaemia (>10 mmol/L) was 23.6 ± 12.5%. During the nights of NCE days, athletes spent 10.1 ± 7.4% of time in hypoglycaemia, particularly after exercise in the endurance zones. The CE days were characterized by a higher time in hyperglycaemia compared with NCE days (25.2 ± 12.5% vs. 22.2 ± 12.1%, p = .012). This was driven by the CE phase, where time in range dropped to 60.4 ± 13.0% and time in hyperglycaemia was elevated (38.5 ± 12.9%). Mean glucose was higher during CE compared with NCE sessions (9.6 ± 0.9 mmol/L vs. 7.8 ± 1.1 mmol/L, p < .001). The probability of hyperglycaemia during exercise was particularly increased with longer duration, higher intensity and higher variability of exercise. CONCLUSIONS: The analysis of glycaemic patterns of professional endurance athletes revealed that overall glycaemia was generally within targets. For further improvement, athletes, team staff and caregivers may focus on hyperglycaemia during competitions and nocturnal hypoglycaemia after NCE.

Clinical Considerations and Practical Advice for People Living With Type 2 Diabetes Who Undertake Regular Exercise or Aim to Exercise Competitively.

This article provides practical tips for advising people with type 2 diabetes on how to engage in regular exercise safely and effectively. Its focus is on individuals who wish to exceed the minimum physical activity recommendation of 150 minutes/week of moderate-intensity exercise or even compete in their chosen sport. Health care professionals who work with such individuals must have a basic understanding of glucose metabolism during exercise, nutritional requirements, blood glucose management, medications, and sport-related considerations. This article reviews three key aspects of individualized care for physically active people with type 2 diabetes: 1) initial medical assessment and pre-exercise screenings, 2) glucose monitoring and nutritional considerations, and 3) the combined glycemic effects of exercise and medications.

Effects of postprandial exercise on blood glucose levels in adults with type 1 diabetes: a review.

People with type 1 diabetes experience challenges in managing blood glucose around exercise. Previous studies have examined glycaemic responses to different exercise modalities but paid little attention to participants' prandial state, although this is an important consideration and will enhance our understanding of the effects of exercise in order to improve blood glucose management around activity. This review summarises available data on the glycaemic effects of postprandial exercise (i.e. exercise within 2 h after a meal) in people with type 1 diabetes. Using a search strategy on electronic databases, literature was screened until November 2022 to identify clinical trials evaluating acute (during exercise), subacute (≤2 h after exercise) and late (>2 h to ≤24 h after exercise) effects of postprandial exercise in adults with type 1 diabetes. Studies were systematically organised and assessed by exercise modality: (1) walking exercise (WALK); (2) continuous exercise of moderate intensity (CONT MOD); (3) continuous exercise of high intensity (CONT HIGH); and (4) interval training (intermittent high-intensity exercise [IHE] or high-intensity interval training [HIIT]). Primary outcomes were blood glucose change and hypoglycaemia occurrence during and after exercise. All study details and results per outcome were listed in an evidence table. Twenty eligible articles were included: two included WALK sessions, eight included CONT MOD, seven included CONT HIGH, three included IHE and two included HIIT. All exercise modalities caused consistent acute glycaemic declines, with the largest effect size for CONT HIGH and the smallest for HIIT, depending on the duration and intensity of the exercise bout. Pre-exercise mealtime insulin reductions created higher starting blood glucose levels, thereby protecting against hypoglycaemia, in spite of similar declines in blood glucose during activity between the different insulin reduction strategies. Nocturnal hypoglycaemia occurred after higher intensity postprandial exercise, a risk that could be diminished by a post-exercise snack with concomitant bolus insulin reduction. Research on the optimal timing of postprandial exercise is inconclusive. In summary, individuals with type 1 diabetes exercising postprandially should substantially reduce insulin with the pre-exercise meal to avoid exercise-induced hypoglycaemia, with the magnitude of the reduction depending on the exercise duration and intensity. Importantly, pre-exercise blood glucose and timing of exercise should be considered to avoid hyperglycaemia around exercise. To protect against late-onset hypoglycaemia, a post-exercise meal with insulin adjustments might be advisable, especially for exercise in the evening or with a high-intensity component.

Adolescent and Young Adult Response to Hypothetical E-Liquid Flavor Restrictions.

OBJECTIVE: Rates of e-cigarette use among adolescents and young adults (AYAs) remain high despite several federal policy changes intended to limit their availability and appeal. The current study examined how restricting flavors would affect current AYA users' intentions to discontinue vaping, as a function of their current flavor preference. METHOD: In a national cross-sectional survey, AYA e-cigarette users (N = 1,414) completed measures of e-cigarette use, device type, e-liquid flavor (tobacco, menthol, cool mint, fruit ice, fruit/sweet), and intent to discontinue e-cigarette use in response to hypothetical federal product standards (i.e., tobacco and menthol or tobacco-only e-liquid). Logistic regression was used to model the association of preferred flavor with odds of discontinuing e-cigarette use (vs. continuing), for menthol and tobacco hypothetical product standards. RESULTS: Overall, 38.8% of the sample reported intent to discontinue using their e-cigarette if tobacco and menthol-flavored e-liquid were the only options available, whereas 70.8% would discontinue under a tobacco-only product standard. AYAs preferring fruit/sweet flavor were most sensitive to either restricted scenario, with odds of discontinuing use ranging from adjusted odds ratio (aOR) = 2.22 to aOR = 2.38 under a tobacco and menthol product standard and aOR = 1.33 to aOR = 2.59 under a tobacco-only product standard, compared with other flavor preferences. In addition, AYAs using cooling flavors (e.g., fruit ice) reported higher odds of discontinuing use under a tobacco-only product standard, compared with menthol flavor users, indicating an important distinction between these groups. CONCLUSIONS: Results indicate potential for flavor restrictions to reduce use of e-cigarettes among AYAs and suggest that a tobacco flavor product standard may result in the greatest discontinuation of use.

Evaluating the "Optimal Competition Parenting Workshop" Using the RE-AIM Framework: A 4-Year Organizational-Level Intervention in British Junior Tennis.

The purpose of the current study was to utilize the RE-AIM (i.e., reach, effectiveness, adoption, implementation, and maintenance) framework to evaluate the national-level scale-out of the Lawn Tennis Association's "Optimal Competition Parenting Workshop" (OCPW) across a 4-year period. During 2018, 65 workshops were run across the United Kingdom, 1,043 parents registered, and 933 parents attended. Adopting a quasi-experimental design, multilevel analyses revealed significant increases in parents' (n = 130) task goal orientation and competition tennis parenting efficacy, as well as significant decreases in ego goal orientation and unpleasant emotions. Children's perceptions of both mother- and father-initiated ego-involving motivational climate and their own ego goal orientation significantly decreased across time. From 2019 to 2021, a further 64 workshops were delivered to 1,110 parents with no significant differences in parents' satisfaction, enjoyment, instructor evaluation, or transfer intention over time when compared against workshop evaluations in 2018. Overall, the OCPW represents a well-received, practical, and effective brief intervention for enhancing parental involvement in junior tennis.

Differentiating Reasons for Young Adult E-cigarette Use Using Maximum Difference Choice Models.

INTRODUCTION: Understanding the reasons young adults use e-cigarettes (ie, vape)-and whether these motivations vary across groups-is essential for informing tobacco regulatory efforts. AIMS AND METHODS: An online panel of young adults who vape (n = 230; age = 18-30 years) completed a maximum difference discrete choice task for 15 reasons for vaping. Over 9 choice sets, participants were presented a subset of 5 reasons and selected the most and least important. Hierarchical bayesian analysis estimated the relative importance of each reason. Latent class analysis (LCA) identified groups with similarly ranked reasons for use. Multinomial regression evaluated the association between sample characteristics and class membership. RESULTS: Overall, relaxation had the highest probability of being the most important reason for use (14.8%), followed by harm reduction (13.2%), and flavors (10.3%). LCA identified five distinct classes, based on top reasons for use: 1. cessation (cigarette cessation [20.2%]; n = 80); 2. dependence (relaxation [20.5%] and unable to quit [19.2%]; n = 21); 3. relaxation (relaxation [20.6%]; n = 66); 4. socializing (socializing [22.2%]; n = 27); and 5. variable (boredom [10.5%] and acceptability [10.2%]; n = 36). Participants who were older, smoked cigarettes, or vaped more frequently were more likely to belong to the cessation class while those who were younger or more e-cigarette dependent were more likely to belong to the dependence class. CONCLUSIONS: Perceived reasons why young adults vape are highly heterogeneous and dependent on the type of user. Tobacco regulatory efforts targeting distinct types of vapers are needed to minimize the adverse public health impact of vaping without compromising appeal for smoking cessation. IMPLICATIONS: E-cigarette use remains high among young adults, with flavors, cost, and harm reduction (vs. combustible cigarettes) among the mostly commonly reported reasons for use. Yet, little is known about how relatively important these reasons are to the individual. Leveraging a maximum difference task, young adults' reasons for use were evaluated on a common interval scale and groups sharing similar reasons identified. Smoking cessation, dependence, relaxation, socialization, and boredom were respectively the most important reasons for use among five classes of vapers. E-cigarette regulatory policies should consider the distinct reasons for use as to not compromise their appeal for smoking cessation.

Advancing racial equity and social justice for Black communities in US tobacco control policy.

The US Food and Drug Administration (FDA) applies the Population Health Standard in tobacco product review processes by weighing anticipated health benefits against risks associated with a given commercial tobacco product at the population level. However, systemic racism (ie, discriminatory policies and practices) contributes to an inequitable distribution of tobacco-related health benefits and risks between white and Black/African Americans at the population level. Therefore, Black-centered, antiracist data standards for tobacco product review processes are needed to achieve racial equity and social justice in US tobacco control policy. Regardless of whether FDA implements such data standards, non-industry tobacco scientists should prioritise producing and disseminating Black-centred data relevant to FDA's regulatory authority. We describe how systemic racism contributes to disparities in tobacco-related outcomes and why these disparities are relevant for population-level risk assessments, then discuss four possible options for Black-centred data standards relevant to tobacco product review processes.

A novel eye-movement impairment in multiple sclerosis indicating widespread cortical damage.

In multiple sclerosis, remyelination trials have yet to deliver success like that achieved for relapse rates with disease course modifying treatment trials. The challenge is to have a clinical, functional outcome measure. Currently, there are none that have been validated, other than visual evoked potentials in optic neuritis. Like vision, quick eye movements (saccades) are heavily dependent on myelination. We proposed that it is possible to extrapolate from demyelination of the medial longitudinal fasciculus in the brainstem to quantitative assessment of cortical networks governing saccadic eye movements in multiple sclerosis. We have developed and validated a double-step saccadic test, which consists of a pair of eye movements towards two stimuli presented in quick succession (the demonstrate eye movement networks with saccades protocol). In this single-centre, cross-sectional cohort study we interrogated the structural and functional relationships of double-step saccades in multiple sclerosis. Data were collected for double-step saccades, cognitive function (extended Rao's Brief Repeatable Battery), disability (Expanded Disability Status Scale) and visual functioning in daily life (National Eye Institute Visual Function Questionnaire). MRI was used to quantify grey matter atrophy and multiple sclerosis lesion load. Multivariable linear regression models were used for analysis of the relationships between double-step saccades and clinical and MRI metrics. We included 209 individuals with multiple sclerosis (mean age 54.3 ± 10.5 years, 58% female, 63% relapsing-remitting multiple sclerosis) and 60 healthy control subjects (mean age 52.1 ± 9.2 years, 53% female). The proportion of correct double-step saccades was significantly reduced in multiple sclerosis (mean 0.29 ± 0.22) compared to controls (0.45 ± 0.22, P < 0.001). Consistent with this, there was a significantly larger double-step dysmetric saccadic error in multiple sclerosis (mean vertical error -1.18 ± 1.20°) compared to controls (-0.54 ± 0.86°, P < 0.001). Impaired double-step saccadic metrics were consistently associated with more severe global and local grey matter atrophy (correct responses-cortical grey matter: ß = 0.42, P < 0.001), lesion load (vertical error: ß = -0.28, P < 0.001), progressive phenotypes, more severe physical and cognitive impairment (correct responses-information processing: ß = 0.46, P < 0.001) and visual functioning. In conclusion, double-step saccades represent a robust metric that revealed a novel eye-movement impairment in individuals with multiple sclerosis. Double-step saccades outperformed other saccadic tasks in their statistical relationship with clinical, cognitive and visual functioning, as well as global and local grey matter atrophy. Double-step saccades should be evaluated longitudinally and tested as a potential novel outcome measure for remyelination trials in multiple sclerosis.

Multicentre, England-wide randomised controlled trial of the 'Foundations' smartphone application in improving mental health and well-being in a healthcare worker population.

BACKGROUND: Healthcare workers (HCWs) have faced considerable pressures during the COVID-19 pandemic. For some, this has resulted in mental health distress and disorder. Although interventions have sought to support HCWs, few have been evaluated. AIMS: We aimed to determine the effectiveness of the 'Foundations' application (app) on general (non-psychotic) psychiatric morbidity. METHOD: We conducted a multicentre randomised controlled trial of HCWs at 16 NHS trusts (trial registration number: EudraCT: 2021-001279-18). Participants were randomly assigned to the app or wait-list control group. Measures were assessed at baseline, after 4 and 8 weeks. The primary outcome was general psychiatric morbidity (using the General Health Questionnaire). Secondary outcomes included: well-being; presenteeism; anxiety; depression and insomnia. The primary analysis used mixed-effects multivariable regression, presented as adjusted mean differences (aMD). RESULTS: Between 22 March and 3 June 2021, 1002 participants were randomised (500:502), and 894 (89.2%) followed-up. The sample was predominately women (754/894, 84.3%), with a mean age of 44⋅3 years (interquartile range (IQR) 34-53). Participants randomised to the app had a reduction in psychiatric morbidity symptoms (aMD = -1.39, 95% CI -2.05 to -0.74), improvement in well-being (aMD = 0⋅54, 95% CI 0⋅20 to 0⋅89) and reduction in insomnia (adjusted odds ratio (aOR) = 0⋅36, 95% CI 0⋅21 to 0⋅60). No other significant findings were found, or adverse events reported. CONCLUSIONS: The app had an effect in reducing psychiatric morbidity symptoms in a sample of HCWs. Given it is scalable with no adverse effects, the app may be used as part of an organisation's tiered staff support package. Further evidence is needed on long-term effectiveness and cost-effectiveness.

Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease.

Recurrent myocardial ischemia can lead to left ventricular (LV) dysfunction in patients with coronary artery disease (CAD). In this observational cohort study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients undergoing coronary artery bypass grafting. During surgery, paired transmural LV biopsies were acquired on the beating heart from regions with and without evidence of inducible ischemia on preoperative stress perfusion cardiovascular magnetic resonance. From 33 patients, 63 biopsies were acquired, compared to analysis of LV samples from 11 donor hearts. The global myocardial adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio was reduced in patients with CAD as compared to donor LV tissue, with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained from LV segments with or without inducible ischemia revealed no significant difference in the ATP:ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Differential metabolite analysis suggested dysregulation of several intermediates in patients with reduced LV ejection fraction, including succinate. Overall, our results suggest that viable myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.

Development of a Novel Home-Based Exergame With On-Body Feedback: Usability Study.

BACKGROUND: With more than 1.4 billion adults worldwide classified as physically inactive, physical inactivity is a public health crisis leading to an increased risk of cardiometabolic diseases. Motivating and engaging training strategies are needed to tackle this public health crisis. Studies have shown that exergames, games controlled by active body movements, are potentially usable, attractive, and effective tools for home-based training. The ExerCube (by Sphery Ltd) has been developed as a physically immersive and adaptive functional fitness game. The development of a home-based version of the ExerCube could increase accessibility, reduce barriers to exercise, and provide an attractive solution to improve physical and cognitive health. OBJECTIVE: The aim was threefold: (1) to develop a usable home-based exergame system, (2) to evaluate the usability and training experience of the home-based exergame and its early-stage on-body feedback system, and (3) to identify avenues for further user-centered design iterations of the system. METHODS: A total of 15 healthy participants (mean age 25, SD 3 years) completed 2 laboratory visits consisting of four 5-minute exergame sessions. In each session, the on-body feedback system provided a different feedback modality (auditory, haptic, and visual feedback) to the participant. Following the second visit, participants completed a range of assessments, including the System Usability Scale (SUS), the Physical Activity Enjoyment Scale (PACES), the Flow Short Scale (FSS), the Immersive Experience Questionnaire (IEQ), and a rating of perceived exertions (RPEs) both physically and cognitively. Participants answered questions regarding the on-body feedback system and completed a semistructured interview. RESULTS: Usability was rated as acceptable, with a SUS score of 70.5 (SD 12). The questionnaires revealed medium-to-high values for the training experience (FSS: 5.3, SD 1; PACES: 5.3, SD 1.1; IEQ: 4.7, SD 0.9. Physical (mean 4.8, SD 1.6) and cognitive (mean 3.9, SD 1.4) RPEs were moderate. Interviews about the on-body feedback system revealed that the majority of participants liked the haptic feedback and the combination of haptic and auditory feedback the best. Participants enjoyed the distinct perceptibility, processing, and integration of the exergame and its supportive and motivating effect. The visual feedback was perceived less positively by participants but was still classified as "potentially" helpful. The auditory feedback was rated well but highlighted an area for further improvement. Participants enjoyed the training experience and described it as motivating, interactive, immersive, something new, interesting, self-explanatory, as well as physically and cognitively challenging. Moreover, 67% (n=10) of the participants could imagine exercising at home and continuing to play the exergame in the future. CONCLUSIONS: The home-based exergame and its early-stage on-body feedback system were rated as usable and an enjoyable training experience by a young healthy population. Promising avenues emerged for future design iterations.

Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies.

Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single-cell resolution. Together, these data illuminate both shared and distinct cellular and molecular architectures of human heart failure and suggest candidate therapeutic targets.

A curious case of Lactococcus garvieae bacteremia associated with adenocarcinoma.

Lactococcus garvieae is a pathogen typically acquired from the consumption of raw seafood or unpasteurized dairy products. Here, we present the unique case of a middle-aged gentleman who presented with back pain, originally thought to be muscle spasms due to poor posture and heavy lifting. Initial radiological imaging showed evidence of a lumbar epidural abscess and lung nodule. Upon further work-up, L. garvieae was isolated in blood and abscess cultures. It was later hypothesized that the L. garvieae bacteremia might have an association with adenocarcinoma of the lung.

Prevalence of burnout in medical students in Guatemala: Before and during Covid-19 pandemic comparison.

Burnout is a syndrome consisting of physical, emotional, and mental exhaustion along with depersonalization and poor sense of personal accomplishment. Often related to work conditions. Several recent studies from around the world have shown high rates of burnout among medical students in different countries. In Guatemala City, we decided to assess levels of burnout in 2017 and then again in December 2020. In the first wave from one private medical school, we had a total of 159 respondents (response rate of 56.7%) and 132 (48.5%) in the second wave. Not surprisingly rates of burnout were higher during the pandemic even though response rate is lower. Surprisingly we found that rates of depersonalization had not increased, and levels of personal accomplishment had. These findings present a mixed picture of levels of burnout in Guatemala City. Further qualitative research is indicated to explore cultural differences in order to set up appropriate and suitable intervention strategies.

DNAJC30 defect: a frequent cause of recessive Leber hereditary optic neuropathy and Leigh syndrome.

The recent description of biallelic DNAJC30 variants in Leber hereditary optic neuropathy (LHON) and Leigh syndrome challenged the longstanding assumption for LHON to be exclusively maternally inherited and broadened the genetic spectrum of Leigh syndrome, the most frequent paediatric mitochondrial disease. Herein, we characterize 28 so far unreported individuals from 26 families carrying a homozygous DNAJC30 p.Tyr51Cys founder variant, 24 manifesting with LHON, two manifesting with Leigh syndrome, and two remaining asymptomatic. This collection of unreported variant carriers confirms sex-dependent incomplete penetrance of the homozygous variant given a significant male predominance of disease and the report of asymptomatic homozygous variant carriers. The autosomal recessive LHON patients demonstrate an earlier age of disease onset and a higher rate of idebenone-treated and spontaneous recovery of vision in comparison to reported figures for maternally inherited disease. Moreover, the report of two additional patients with childhood- or adult-onset Leigh syndrome further evidences the association of DNAJC30 with Leigh syndrome, previously only reported in a single childhood-onset case.

A Brief Review on the Evolution of Technology in Exercise and Sport in Type 1 Diabetes: Past, Present, and Future.

One hundred years ago, insulin was first used to successfully lower blood glucose levels in young people living with what was then called juvenile diabetes. While insulin was not a cure for diabetes, it allowed individuals to resume a near normal life and have some freedom to eat more liberally and gain the strength they needed to live a more active lifestyle. Since then, a number of therapeutic and technical advances have arisen to further improve the health and wellbeing of individuals living with type 1 diabetes, allowing many to participate in sport at the local, regional, national or international level of competition. This review and commentary highlights some of the key advances in diabetes management in sport over the last 100 years since the discovery of insulin.

Use and Perception of Telemedicine in People with Type 1 Diabetes During the COVID-19 Pandemic: A 1-Year Follow-Up.

Background: In the spring of 2020, our research group circulated a worldwide survey with the aim of gathering information on the use and perception of telemedicine in people living with type 1 diabetes at the start of the COVID-19 pandemic. The data suggested that a large number of respondents had rapidly adopted to telemedicine, as in-person visits were not possible, and that this was perceived positively by many. In this study, we conducted a 1-year follow-up to investigate changes in opinions and experiences to telemedicine over the past year of the pandemic. Methods: An anonymous questionnaire was distributed through social media (Twitter, Facebook, and Instagram) between May 9 and May 15, 2021, using an open-access web-based platform (SurveyMonkey.com). The survey was identical to that used in the original study, covering questions relating to the use and perception of telemedicine, diabetes treatment and control, and medical supplies during the COVID-19 pandemic. The questionnaire was available in English, Spanish, German, French, and Italian. We compared the results from the two surveys descriptively and statistically, results were stratified according to age, gender, and HbA1c. Results: There were 531 survey responses from 40 countries (Europe 54%, North America 36%, South America 2%, and Africa and Asia 2%). A large percentage of respondents (67%) reported meeting with their health care provider remotely since the beginning of the pandemic, a significant increase compared with the 28% in the 2020 survey (P < 0.001). Eighty-three percent of respondents found remote appointments to be somewhat-to-extremely useful, similar to the 86% satisfaction rate in the previous survey (P = 0.061). Remote appointments were most frequently undertaken through telephone (50%) and video call (45%), which are significant changes compared with those in 2020 (72% and 28%, respectively, P < 0.001). Forty-five percent of respondents in 2021 were likely to consider remote appointments instead of in-person appointments in the future-being significantly lower than the 75% in the initial survey (P < 0.001)-whereas 37% indicated they would not. The majority of respondents (84%) reported no issues in their access to diabetes supplies and medication over the past year. Conclusions: This study showed that the use of telemedicine in the form of remote appointments increased during the COVID-19 pandemic in people living with type 1 diabetes, with high levels of satisfaction. However, a remarkable decline took place in the past year in the proportion of patients stating a willingness to continue with remote appointments beyond the pandemic. It seems that a personalized approach is needed since a substantial proportion of respondents in this follow-up still indicated a preference for in-person diabetes care, hence the use of telemedicine should be considered on an individual basis.