SYNGAP1 encephalopathy:A distinctive generalized developmental and epileptic encephalopathy

Objective To delineate the epileptology, a key part of the SYNGAP1 phenotypic spectrum, in a large patient cohort. Methods Patients were recruited via investigators' practices or social media. We included patients with (likely) pathogenic SYNGAP1 variants or chromosome 6p21.32 microdeletions incorporating SYNGAP1. We analyzed patients' phenotypes using a standardized epilepsy questionnaire, medical records, EEG, MRI, and seizure videos. Results We included 57 patients (53% male, median age 8 years) with SYNGAP1 mutations (n = 53) or microdeletions (n = 4). Of the 57 patients, 56 had epilepsy: generalized in 55, with focal seizures in 7 and infantile spasms in 1. Median seizure onset age was 2 years. A novel type of drop attack was identified comprising eyelid myoclonia evolving to a myoclonic-atonic (n = 5) or atonic (n = 8) seizure. Seizure types included eyelid myoclonia with absences (65%), myoclonic seizures (34%), atypical (20%) and typical (18%) absences, and atonic seizures (14%), triggered by eating in 25%. Developmental delay preceded seizure onset in 54 of 56 (96%) patients for whom early developmental history was available. Developmental plateauing or regression occurred with seizures in 56 in the context of a developmental and epileptic encephalopathy (DEE). Fifty-five of 57 patients had intellectual disability, which was moderate to severe in 50. Other common features included behavioral problems (73%); high pain threshold (72%); eating problems, including oral aversion (68%); hypotonia (67%); sleeping problems (62%); autism spectrum disorder (54%); and ataxia or gait abnormalities (51%). Conclusions SYNGAP1 mutations cause a generalized DEE with a distinctive syndrome combining epilepsy with eyelid myoclonia with absences and myoclonic-atonic seizures, as well as a predilection to seizures triggered by eating.</p

Intra- and interindividual attack frequency variability of chronic cluster headache

BackgroundThe lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration.MethodsWe analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency.ResultsWeekly median (14.4 [8.2–24.0]) and instantaneous (14.2 [8.0–24.5]) attack frequency recordings were similar (p = 0.20; Bland-Altman plot). Median weekly attack frequency was 15.3 (range 4.2–140) and highest during spring (p = 0.001) compared to the other seasons. Relative attack frequency variability decreased with increasing attack frequency (p = 0.010). We tabulated the weekly attack frequency estimation accuracies compared to, and the associated deviations from, the 12-week gold standard for different lengths of the observation period.ConclusionWeekly retrospective attack frequency recording is as good as instantaneous recording and more convenient. Attack frequency is highest in spring. Participants with ≥3 daily attacks show less attack frequency variability than those wit

Depreissia decipiens, an enigmatic canopy spider from Borneo revisited (Araneae, Salticidae), with remarks on the distribution and diversity of canopy spiders in Sabah, Borneo

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Supplementary Material for: Determinants of Advanced Bone Age in Childhood Obesity

Background: Childhood obesity is associated with advanced bone age (BA). Previous studies suggest that androgens, oestrogens, sex hormone-binding globulin, and insulin are responsible for this phenomenon, but results are contradictory and might be biased by confounders. We aim to elucidate this matter by applying a multivariate approach. Method: We performed a correlation analysis of BA standard deviation score (SDS) with age- and sex-specific SDS for androgens, oestrogens, and with indicators of insulin secretion derived from oral glucose tolerance testing, in a group of obese children. A multivariate analysis was performed to investigate which parameters were independently predictive of BA SDS. Results: In this cohort (n = 101; mean age 10.9 years; mean BA 11.8 years; mean BMI SDS 3.3), BMI SDS was significantly correlated to BA SDS (r = 0.55, p &lt; 0.001). In a regression analysis in the total cohort (B = 0.27, p &lt; 0.001) as well as in females (B = 0.34, p = 0.042), males (B = 0.31, p = 0.006), and pubertal children (B = 0.32, p = 0.046), dehydroepiandrosterone sulphate (DHEAS) showed a positive, independent association with BA SDS. No association with indicators of insulin secretion was found. Conclusion: BMI SDS is highly correlated to BA SDS in obese children. Increased DHEAS has a central role in advanced BA in obese children

Needs and perceptions regarding healthy eating among people at risk of food insecurity: a qualitative analysis

Abstract Background Healthy eating behaviour is an essential determinant of overall health. This behaviour is generally poor among people at risk of experiencing food insecurity, which may be caused by many factors including perceived higher costs of healthy foods, financial stress, inadequate nutritional knowledge, and inadequate skills required for healthy food preparation. Few studies have examined how these factors influence eating behaviour among people at risk of experiencing food insecurity. We therefore aimed to gain a better understanding of the needs and perceptions regarding healthy eating in this target group. Methods We conducted a qualitative exploration grounded in data using inductive analyses with 10 participants at risk of experiencing food insecurity. The analysis using an inductive approach identified four core factors influencing eating behaviour: Health related topics; Social and cultural influences; Influences by the physical environment; and Financial influences. Results Overall, participants showed adequate nutrition knowledge. However, eating behaviour was strongly influenced by both social factors (e.g. child food preferences and cultural food habits), and physical environmental factors (e.g. temptations in the local food environment). Perceived barriers for healthy eating behaviour included poor mental health, financial stress, and high food prices. Participants had a generally conscious attitude towards their financial situation, reflected in their strategies to cope with a limited budget. Food insecurity was mostly mentioned in reference to the past or to others and not to participants’ own current experiences. Participants were familiar with several existing resources to reduce food-related financial strain (e.g. debt assistance) and generally had a positive attitude towards these resources. An exception was the Food Bank, of which the food parcel content was not well appreciated. Proposed interventions to reduce food-related financial strain included distributing free meals, facilitating social contacts, increasing healthy food supply in the neighbourhood, and lowering prices of healthy foods. Conclusion The insights from this study increase understanding of factors influencing eating behaviour of people at risk of food insecurity. Therefore, this study could inform future development of potential interventions aiming at helping people at risk of experiencing food insecurity to improve healthy eating, thereby decreasing the risk of diet-related diseases

Whole Genome Sequencing in Personalized Oncology - Poster

Poster presented at Health RI conference about 'Whole Genome Sequencing in Personalized Oncology' covering rationale, goals, data flow, workflow, and relevance to HEALTH-RI

Data from: Long‐term follow‐up, quality of life and survival of Lambert‐Eaton myasthenic syndrome patients

Objective To study survival and characterize long-term functional impairments as well as health-related quality of life (HRQOL) of Lambert-Eaton myasthenic syndrome (LEMS) patients. Methods In this observational study, survival of LEMS patients, separately for non-tumor (NT) and small-cell lung cancer (SCLC), was compared to the Dutch general population and to patients with SCLC. Disease course in LEMS patients was recorded retrospectively. Several scales for functional impairments and health-related quality of life were assessed. Results We included 150 LEMS patients. Survival was similar to the general population in 65 NT-LEMS patients. Tumor survival was significantly longer in 81 SCLC-LEMS patients compared to non-LEMS SCLC patients (overall median survival 17 vs. 7.0 months, p&lt;0.0001). At diagnosis, 39 patients (62%) of 63 patients with complete follow-up data were independent for ADL activities, improving to 85% at 1-year follow-up. Physical HRQOL composite score (55.9) was significantly lower than in the general population (76.3, p&lt;0.0001) and comparable to myasthenia gravis (60.5) Mental HRQOL composite score was 71.8 in LEMS patients, comparable to the general population (77.9, p=0.19) and myasthenia gravis (70.3). Conclusions This study shows NT-LEMS patients have normal survival. SCLC-LEMS patients have an improved tumor survival, even after correcting for tumor stage. A majority of LEMS patients report a stable disease course and remain or become independent for self-care after treatment

Additional file 7 of Developmental programming in human umbilical cord vein endothelial cells following fetal growth restriction

Additional file 7. Table S5: All MsigDB gene modules, as determined by CAMERA, in gene list ranked based on a comparison of: differential expression of FGR versus control (FGR–control). Modules sorted by significance

Microcirculatory alterations in critically ill COVID-19 patients analyzed using artificial intelligence

Abstract Background The sublingual microcirculation presumably exhibits disease-specific changes in function and morphology. Algorithm-based quantification of functional microcirculatory hemodynamic variables in handheld vital microscopy (HVM) has recently allowed identification of hemodynamic alterations in the microcirculation associated with COVID-19. In the present study we hypothesized that supervised deep machine learning could be used to identify previously unknown microcirculatory alterations, and combination with algorithmically quantified functional variables increases the model’s performance to differentiate critically ill COVID-19 patients from healthy volunteers. Methods Four international, multi-central cohorts of critically ill COVID-19 patients and healthy volunteers (n = 59/n = 40) were used for neuronal network training and internal validation, alongside quantification of functional microcirculatory hemodynamic variables. Independent verification of the models was performed in a second cohort (n = 25/n = 33). Results Six thousand ninety-two image sequences in 157 individuals were included. Bootstrapped internal validation yielded AUROC(CI) for detection of COVID-19 status of 0.75 (0.69–0.79), 0.74 (0.69–0.79) and 0.84 (0.80–0.89) for the algorithm-based, deep learning-based and combined models. Individual model performance in external validation was 0.73 (0.71–0.76) and 0.61 (0.58–0.63). Combined neuronal network and algorithm-based identification yielded the highest externally validated AUROC of 0.75 (0.73–0.78) (P &lt; 0.0001 versus internal validation and individual models). Conclusions We successfully trained a deep learning-based model to differentiate critically ill COVID-19 patients from heathy volunteers in sublingual HVM image sequences. Internally validated, deep learning was superior to the algorithmic approach. However, combining the deep learning method with an algorithm-based approach to quantify the functional state of the microcirculation markedly increased the sensitivity and specificity as compared to either approach alone, and enabled successful external validation of the identification of the presence of microcirculatory alterations associated with COVID-19 status