Effects of High Intensity Exercise on Central Neural Drive in Healthy Populations

Background: Current research suggests that strength gains related to central neural adaptation occur more rapidly than peripheral mechanisms5. Central neural drive (CND) is the measure of cortical output that coordinates up-regulation of agonist contraction and inhibition of antagonist musculature in voluntary muscle contractions2. Two common techniques for measuring CND are twitch interpolation and motor evoked potential from transcranial magnetic stimulation.https://jdc.jefferson.edu/dptcapstones/1008/thumbnail.jp

A Survey of Music Therapists Working in Pediatric Medical Settings in the United States

Music therapy is becoming a standard supportive care service in many pediatric hospitals across the United States. However, more detailed information is needed to advance our understanding about current clinical practice and increase availability of pediatric music therapy services. The purpose of this cross-sectional survey study was to collect and summarize data about music therapists working in pediatric medical settings. Specifically, we collected information about (1) therapist demographics, (2) organizational structure, (3) service delivery and clinical practice, and (4) administrative/supervisory responsibilities. Board-certified music therapists working in pediatric medical settings (n = 118) completed a 37-item online questionnaire. We analyzed survey data using descriptive statistics and content analysis. Findings indicated that there is a ratio of approximately one music therapist for every 100 patient beds, that one-third of respondents are the only music therapist in their setting, and that half of the surveyed positions are philanthropically funded. Prioritizing patient referrals based on acuity was common (95.7%, n = 110), with palliative care and pain as the most highly prioritized needs. More than half of respondents reported serving in high acuity areas such as the pediatric intensive care, hematology/oncology, or neonatal intensive care units. We recommend replication of this survey in five years to examine growth and change in service delivery among pediatric music therapists over time, with additional studies to (a) explore how therapist-to-patient ratios influence quality of care, (b) identify factors that contribute to sustainability of programs, and (c) determine how expansion of services support a broader population of patients and families

Unifying Community Detection Across Scales from Genomes to Landscapes

Biodiversity science encompasses multiple disciplines and biological scales from molecules to landscapes. Nevertheless, biodiversity data are often analyzed separately with discipline-specific methodologies, constraining resulting inferences to a single scale. To overcome this, we present a topic modeling framework to analyze community composition in cross-disciplinary datasets, including those generated from metagenomics, metabolomics, field ecology and remote sensing. Using topic models, we demonstrate how community detection in different datasets can inform the conservation of interacting plants and herbivores. We show how topic models can identify members of molecular, organismal and landscape-level communities that relate to wildlife health, from gut microbes to forage quality. We conclude with a future vision for how topic modeling can be used to design cross-scale studies that promote a holistic approach to detect, monitor and manage biodiversity

Cardiac Manifestations of Myotonic Dystrophy in a Pediatric Cohort

Myotonic dystrophy type 1 (DM1) is the most prevalent inherited neuromuscular dystrophy in adults. It is a multisystem disease with cardiac manifestations. Whilst these are well-defined in adults, there are scarce published data in the pediatric population. This study aimed to investigate the yield and progression of cardiac disease in pediatric DM1 patients, focusing on congenital DM1 (cDM1). Methods: A retrospective observational study of all pediatric DM1 patients referred to our center (December 2000-November 2020) was conducted. Patients were classified into DM1 forms according to age of symptom onset and disease severity. Patients underwent clinical and cardiac evaluation with 12-lead ECG, transthoracic echocardiography and 24-h ECG Holter monitoring. Results: 67 DM1 pediatric patients were included: 56 (83.6%) cDM1 and 11 (16.4%) non-cDM1. Median follow-up time of cDM1 patients was 8.0 [3.25-11.0] years. 49 (87.5%) cDM1 patients had baseline 12-lead ECG and 44 (78.6%) had a follow-up 12-lead-ECG, with a median follow-up time from diagnosis to baseline ECG of 2.8 [1.0-8.5] years and to follow-up ECG of 10.9 [5.7-14.2] years. Overall, 43 (87.8%) presented ECG abnormalities, most commonly in the form of asymptomatic conduction disease (n = 23, 46.9%), of which 21 (42.9%) had first degree atrioventricular block (1st AVB). There was an increase of prevalence from baseline to follow-up ECG in low QRS voltage (16.7%), poor R wave progression (13.9%), abnormal repolarisation (11.9%) and 1st AVB (7.6%). one patient (1.8%) underwent pacemaker implantation for syncope in the context of progressive conduction disease. No patients developed left ventricular systolic dysfunction. 4 (7.1%) cDM1 patients died during follow up, including three who died suddenly with no clear cause of death. Conclusions: This study is the first to analyse the prevalence and progression of ECG abnormalities in cDM1 pediatric patients. The high prevalence of abnormal findings, progressive changes and number of potentially associated events (1 pacemaker implantation and 3 unexplained sudden deaths) stresses the importance of systematic and continued cardiac evaluation of these patients

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Tethered tertiary amines as solid-state n-type dopants for solution-processable organic semiconductors

A scarcity of stable n-type doping strategies compatible with facile processing has been a major impediment to the advancement of organic electronic devices. Localizing dopants near the cores of conductive molecules can lead to improved efficacy of doping. We and others recently showed the effectiveness of tethering dopants covalently to an electron-deficient aromatic molecule using trimethylammonium functionalization with hydroxide counterions linked to a perylene diimide core by alkyl spacers. In this work, we demonstrate that, contrary to previous hypotheses, the main driver responsible for the highly effective doping observed in thin films is the formation of tethered tertiary amine moieties during thin film processing. Furthermore, we demonstrate that tethered tertiary amine groups are powerful and general n-doping motifs for the successful generation of free electron carriers in the solid-state, not only when coupled to the perylene diimide molecular core, but also when linked with other small molecule systems including naphthalene diimide, diketopyrrolopyrrole, and fullerene derivatives. Our findings help expand a promising molecular design strategy for future enhancements of n-type organic electronic materials

A marine bacterial enzymatic cascade degrades the algal polysaccharide ulvan

International audienc

Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies

Dominant mutations in the skeletal muscle ryanodine receptor (RYR1) gene are well-recognized causes of both malignant hyperthermia susceptibility (MHS) and central core disease (CCD). More recently, recessive RYR1 mutations have been described in few congenital myopathy patients with variable pathology, including multi-minicores. Although a clinical overlap between patients with dominant and recessive RYR1 mutations exists, in most cases with recessive mutations the pattern of muscle weakness is remarkably different from that observed in dominant CCD. In order to characterize the spectrum of congenital myopathies associated with RYR1 mutations, we have investigated a cohort of 44 patients from 28 families with clinical and/or histopathological features suggestive of RYR1 involvement. We have identified 25 RYR1 mutations, 9 of them novel, including 12 dominant and 13 recessive mutations. With only one exception, dominant mutations were associated with a CCD phenotype, prominent cores and predominantly occurred in the RYR1 C-terminal exons 101 and 102. In contrast, the 13 recessive RYR1 mutations were distributed evenly along the entire RYR1 gene and were associated with a wide range of clinico-pathological phenotypes. Protein expression studies in nine cases suggested a correlation between specific mutations, RyR1 protein levels and resulting phenotype: in particular, whilst patients with dominant or recessive mutations associated with typical CCD phenotypes appeared to have normal RyR1 expression, individuals with more generalized weakness, multi-minicores and external ophthalmoplegia had a pronounced depletion of the RyR1 protein. The phenomenon of protein depletion was observed in some patients compound heterozygous for recessive mutations at the genomic level and silenced another allele in skeletal muscle, providing additional information on the mechanism of disease in these patients. Our data represent the most extensive study of RYR1-related myopathies and indicate complex genotype-phenotype correlations associated with mutations differentially affecting assembly and function of the RyR1 calcium release channe

Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample

Background: While ovarian cancer is recognised as having identifiable early symptoms, understanding of the key determinants of symptom awareness and early presentation is limited. A population-based survey of ovarian cancer awareness and anticipated delayed presentation with symptoms was conducted as part of the International Cancer Benchmarking Partnership (ICBP). Methods: Women aged over 50 years were recruited using random probability sampling (n = 1043). Computer-assisted telephone interviews were used to administer measures including ovarian cancer symptom recognition, anticipated time to presentation with ovarian symptoms, health beliefs (perceived risk, perceived benefits/barriers to early presentation, confidence in symptom detection, ovarian cancer worry), and demographic variables. Logistic regression analysis was used to identify the contribution of independent variables to anticipated presentation (categorised as < 3 weeks or ≥ 3 weeks). Results: The most well-recognised symptoms of ovarian cancer were post-menopausal bleeding (87.4%), and persistent pelvic (79.0%) and abdominal (85.0%) pain. Symptoms associated with eating difficulties and changes in bladder/bowel habits were recognised by less than half the sample. Lower symptom awareness was significantly associated with older age (p ≤ 0.001), being single (p ≤ 0.001), lower education (p ≤ 0.01), and lack of personal experience of ovarian cancer (p ≤ 0.01). The odds of anticipating a delay in time to presentation of ≥ 3 weeks were significantly increased in women educated to degree level (OR = 2.64, 95% CI 1.61 – 4.33, p ≤ 0.001), women who reported more practical barriers (OR = 1.60, 95% CI 1.34 – 1.91, p ≤ 0.001) and more emotional barriers (OR = 1.21, 95% CI 1.06 – 1.40, p ≤ 0.01), and those less confident in symptom detection (OR = 0.56, 95% CI 0.42 – 0.73, p ≤ 0.001), but not in those who reported lower symptom awareness (OR = 0.99, 95% CI 0.91 – 1.07, p = 0.74). Conclusions: Many symptoms of ovarian cancer are not well-recognised by women in the general population. Evidence-based interventions are needed not only to improve public awareness but also to overcome the barriers to recognising and acting on ovarian symptoms, if delays in presentation are to be minimised