Myoclonus in Ataxia–Telangiectasia

Background: Various movement disorders can be found in ataxia–telangiectasia (AT), including ataxia, dystonia, chorea, and myoclonus, but myoclonus has rarely been described as the predominant feature in AT. Case Report: We report two AT patients with prominent myoclonus, illustrating an unusual presentation of this disorder. Sequencing of the ATM gene in the first patient revealed a homozygous truncating mutation, c.5908C >T (p.Q1970*) in exon 38 of the ATM gene, which has been previously reported as a founder mutation in the Costa Rican population. Discussion: Myoclonus can be a predominant or presenting feature in AT, even without dystoni

Intermediate Phenotypes of ATP1A3 Mutations: Phenotype–Genotype Correlations

Background: ATP1A3-related disorders include rapid-onset dystonia–parkinsonism (RDP or DYT12), alternating hemiplegia of childhood (AHC), and CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss). Case Report: We report two cases with intermediate forms between RDP and AHC. Patient 1 initially presented with the AHC phenotype, but the RDP phenotype emerged at age 14 years. The second patient presented with levodopa-responsive paroxysmal oculogyria, a finding never before reported in ATP1A3-related disorders. Genetic testing confirmed heterozygous changes in the ATP1A3 gene in both patients, one of them novel. Discussion: Intermediate phenotypes of RDP and AHC support the concept that these two disorders are part of a spectrum. We add our cases to the phenotype–genotype correlations of ATP1A3-related disorders

A Web-Based Treatment Decision Support Tool for Patients With Advanced Knee Arthritis: Evaluation of User Interface and Content Design

BACKGROUND: Data-driven surgical decisions will ensure proper use and timing of surgical care. We developed a Web-based patient-centered treatment decision and assessment tool to guide treatment decisions among patients with advanced knee osteoarthritis who are considering total knee replacement surgery. OBJECTIVE: The aim of this study was to examine user experience and acceptance of the Web-based treatment decision support tool among older adults. METHODS: User-centered formative and summative evaluations were conducted for the tool. A sample of 28 patients who were considering total knee replacement participated in the study. Participants\u27 responses to the user interface design, the clarity of information, as well as usefulness, satisfaction, and acceptance of the tool were collected through qualitative (ie, individual patient interviews) and quantitative (ie, standardized Computer System Usability Questionnaire) methods. RESULTS: Participants were older adults with a mean age of 63 (SD 11) years. Three-quarters of them had no technical questions using the tool. User interface design recommendations included larger fonts, bigger buttons, less colors, simpler navigation without extra next page click, less mouse movement, and clearer illustrations with simple graphs. Color-coded bar charts and outcome-specific graphs with positive action were easiest for them to understand the outcomes data. Questionnaire data revealed high satisfaction with the tool usefulness and interface quality, and also showed ease of use of the tool, regardless of age or educational status. CONCLUSIONS: We evaluated the usability of a patient-centered decision support tool designed for advanced knee arthritis patients to facilitate their knee osteoarthritis treatment decision making. The lessons learned can inform other decision support tools to improve interface and content design for older patients\u27 use

Career preferences of graduating medical students in China: a nationwide cross-sectional study

Background: China faces major challenges in the distribution of health professionals with serious shortages in rural areas and in the development of Primary Care Providers (PCPs). This study investigates the career preferences of medical students in China and the impact of rural backgrounds on these preferences. Methods: Medical students in the final year of their program in 16 medical schools across China completed a 58-item survey that included questions regarding their demographic characteristics, attitudes toward practice in low resource areas, postgraduate planning, self-assessed competency, university facilities assessment, and financial situation. Descriptive calculation and Logit model were used for the analysis. Results: Completed surveys from 3020 students were included in the analysis. Upon graduation, 48.5 % of the medical students preferred to work in urban public hospitals and this percentage rose to 73.6 % when students were asked to state their anticipated preference five years after graduation. Students' top three ranked reasons for preferred careers were "good career prospects", "living close to parents/families", and "remuneration". Those who preferred to work in rural areas upon graduation were more likely to be those who lived in rural areas when 1-15 years old (beta = 2.05, p < 0.001), had high school in rural areas (beta = 1.73, p < 0.001), or had parents' place of current residence in rural areas (beta = 2.12, p < 0.001). Similar results were found for those students who preferred to work in PCPs. Conclusions: To address the serious shortages of health professionals in rural areas and PCPs, medical schools should consider strategies to recruit more medical applicants with rural backgrounds and to orient students to rural and primary care interests.SCI(E)[email protected]

Investigating social deprivation and comorbid mental health diagnosis as predictors of treatment access among patients with an opioid use disorder using substance use services: a prospective cohort study

Background: Opioid use is a major public health concern across the globe. Opioid use and subsequent access to care is often shaped by co-occurring issues faced by people using opioids, such as deprivation, mental ill-health, and other forms of substance use. We investigated the role of social deprivation and comorbid mental health diagnoses in predicting re-engagement with substance use services or contact with crisis and inpatient services for individuals with opioid use disorder in secondary mental health care in inner-city London. Methods: We conducted a prospective cohort study which followed individuals diagnosed with a first episode of opioid use disorder who accessed substance use services between September 2015 and May 2020 for up to 12 months, using anonymised electronic health records. We employed negative binominal regression and Cox proportional survival analyses to assess associations between exposures and outcomes. Results: Comorbid mental health diagnoses were associated with higher contact rates with crisis/inpatient services among people with opioid use disorder: incidence rate ratios (IRR) and 95% confidence intervals (CI) were 3.91 (1.74–9.14) for non-opioid substance use comorbidity, 8.92 (1.81–64.4) for a single comorbid mental health diagnosis, and 15.9 (5.89–47.5) for multiple comorbid mental health diagnoses. Social deprivation was not associated with contact rates with crisis/inpatient services within this sample. Similar patterns were found with time to first crisis/inpatient contact. Social deprivation and comorbid mental health diagnoses were not associated with re-engagement with substance use services. Conclusion: Comorbid substance and mental health difficulties amongst people with an opioid use disorder led to earlier and more frequent contact with crisis/inpatient mental health services during the first 12 months of follow up. Given the common co-occurrence of mental health and substance use disorders among those who use opioids, a better understanding of their wider needs (such as social, financial and other non-medical concerns) will ensure they are supported in their treatment journeys

Adiponectin Gene Polymorphisms and Acute Respiratory Distress Syndrome Susceptibility and Mortality

Rationale: Adiponectin is an anti-inflammatory adipokine that is the most abundant gene product of adipose tissue. Lower levels have been observed in obesity, insulin resistance, and in critical illness. However, elevated levels early in acute respiratory failure have been associated with mortality. Polymorphisms in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined for relationships with obesity, insulin resistance and diabetes, cardiovascular disease, and to circulating adipokine levels, but many gaps in knowledge remain. The current study aims to assess the association between potentially functional polymorphisms in adiponectin-related genes with acute respiratory distress syndrome (ARDS) risk and mortality. Methods: Consecutive patients with risk factors for ARDS admitted to the ICU were enrolled and followed prospectively for development of ARDS. ARDS cases were followed through day 60 for all-cause mortality. 2067 patients were successfully genotyped using the Illumina CVD BeadChip high-density platform. Of these, 567 patients developed ARDS. Forty-four single nucleotide polymorphisms (SNPs) on ADIPOQ, ADIPOR1 and ADIPOR2 were successfully genotyped. Of these, 9 SNPs were hypothesized to be functional based on their location (promoter, exon, or 3′ untranslated region). These 9 SNPs were analyzed for association with ARDS case status and mortality among ARDS cases. Results: After multivariable analysis and adjustment for multiple comparisons, no SNPs were significantly associated with ARDS case status. Among ARDS cases, homozygotes for the minor allele of rs2082940 (ADIPOQ) had increased mortality (hazard ratio 2.61, 95% confidence interval 1.36–5.00, p = 0.0039) after adjustment for significant covariates. The significance of this association persisted after adjustment for multiple comparisons (FDR_q = 0.029). Conclusions: A common and potentially functional polymorphism in ADIPOQ may impact survival in ARDS. Further studies are required to replicate these results and to correlate genotype with circulating adiponectin levels

Occultocarpon, a new monotypic genus of Gnomoniaceae on Alnus nepalensis from China

Microfungi in the Gnomoniaceae (Diaporthales, Ascomycetes) comprise species commonly reported as pathogens and endophytes on trees and herbaceous hosts primarily from temperate forests of North America, Europe, and Japan. The diversity of Gnomoniaceae in China is poorly known, although several plant families that occur there specifically the Betulaceae are considered important hosts. An exploratory trip to Yunnan, China, resulted in the discovery of several members of the Gnomoniaceae. In this paper a new monotypic genus, Occultocarpon and its species, O. ailaoshanense, are described and illustrated. A phylogeny based on three genes (LSU, rpb2, tef1-α) reveals that O. ailaoshanense belongs to the Gnomoniaceae and forms a branch distinct from the currently known genera. Occultocarpon ailaoshanense is characterized by perithecia with thin, central to eccentric necks in groups embedded in a stroma and oblong elliptical-elongated, one-septate ascospores. Occultocarpon ailaoshanense occurs on the bark of branches of Alnus nepalensis (Betulaceae) in Yunnan, ChinaMicrofungi in the Gnomoniaceae (Diaporthales, Ascomycetes) comprise species commonly reported as pathogens and endophytes on trees and herbaceous hosts primarily from temperate forests of North America, Europe, and Japan. The diversity of Gnomoniaceae in China is poorly known, although several plant families that occur there specifically the Betulaceae are considered important hosts. An exploratory trip to Yunnan, China, resulted in the discovery of several members of the Gnomoniaceae. In this paper a new monotypic genus, Occultocarpon and its species, O. ailaoshanense, are described and illustrated. A phylogeny based on three genes (LSU, rpb2, tef1-α) reveals that O. ailaoshanense belongs to the Gnomoniaceae and forms a branch distinct from the currently known genera. Occultocarpon ailaoshanense is characterized by perithecia with thin, central to eccentric necks in groups embedded in a stroma and oblong elliptical-elongated, one-septate ascospores. Occultocarpon ailaoshanense occurs on the bark of branches of Alnus nepalensis (Betulaceae) in Yunnan, Chin

The neonicotinoid insecticide Imidacloprid repels pollinating flies and beetles at field-realistic concentrations

Neonicotinoids are widely used systemic insecticides which, when applied to flowering crops, are translocated to the nectar and pollen where they may impact upon pollinators. Given global concerns over pollinator declines, this potential impact has recently received much attention. Field exposure of pollinators to neonicotinoids depends on the concentrations present in flowering crops and the degree to which pollinators choose to feed upon them. Here we describe a simple experiment using paired yellow pan traps with or without insecticide to assess whether the commonly used neonicotinoid imidacloprid repels or attracts flying insects. Both Diptera and Coleoptera exhibited marked avoidance of traps containing imidacloprid at a field-realistic dose of 1 μg L-1, with Diptera avoiding concentrations as low as 0.01 μg L-1. This is to our knowledge the first evidence for any biological activity at such low concentrations, which are below the limits of laboratory detection using most commonly available techniques. Catch of spiders in pan traps was also slightly reduced by the highest concentrations of imidacloprid used (1 μg L-1), but catch was increased by lower concentrations. It remains to be seen if the repellent effect on insects occurs when neonicotinoids are present in real flowers, but if so then this could have implications for exposure of pollinators to neonicotinoids and for crop pollination. © 2013 Easton, Goulson

Healthâ Related Quality of Life Components in Children With Neonatal Brachial Plexus Palsy: A Qualitative Study

BackgroundCurrently, no published, validated patientâ reported outcome (PRO) measures of healthâ related quality of life (HRQOL) exist for use with neonatal brachial plexus palsy (NBPP). NBPP is a debilitating condition that occurs during the perinatal period, resulting in paralysis/paresis and loss of sensation in the affected arm. Commonly used NBPP measures are not comprehensive and do not fully account for clinically meaningful changes in function or progression of the disorder.ObjectiveTo evaluate important components of HRQOL for children with NBPP and identify where new PRO measures are needed.DesignEleven focus groups comprising children with NBPP (4), family members (6), and professional providers (1) to assess HRQOL.SettingBrachial plexus clinic.ParticipantsChildren with NBPP, their parents, and professional providers.Inclusion CriteriaChildren 7â 17 years old with NBPP; parents/caregivers at least 18 years of age; professionals with â ¥2 years’ experience providing NBPP clinical care; ability to read and speak English fluently.MethodsFocus group sessions were recorded, transcribed verbatim, and deidentified. Qualitative frequency analysis identified different aspects of HRQOL relevant to NBPP. This analysis expands on the groundedâ theory approach to qualitative analysis, including development of a domain framework, open and axial coding, selective coding, and descriptive analysis. The resulting HRQOL domain framework (and frequency analysis) was then compared to the domain framework for existing PRO measures (PROMIS and Neuroâ QoL) to identify components of HRQOL where new PRO measures are needed for NBPP.Main Outcome MeasuresNot applicable.ResultsAlthough many physical, social, and emotional health domains were captured by existing PRO measures, some significant NBPPâ specific topics emerged from qualitative analysisâ functionality, sensory, physical appearance, arm/hand compensation and preference, explaining functionality/appearance to others, and selfâ esteem and body image concerns.ConclusionsDevelopment of sensitive and specific measures capturing arm/hand function and body image would improve the clinical care of patients with NBPP.Level of EvidenceNot applicable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146831/1/pmr2383.pd

Loss of chromosome 3q is a prognostic marker in fusion-negative rhabdomyosarcoma

PURPOSE: Soft tissue sarcomas (STS) are rare mesenchymal neoplasms that frequently show complex chromosomal aberrations such as amplifications or deletions of DNA sequences or even whole chromosomes. We recently found that gain of chromosome (chr) 8 is associated with worse overall survival (OS) in STS as a group. We therefore aimed to investigate the overall copy number profile of rhabdomyosarcoma (RMS) to evaluate for prognostic signatures. METHODS: Fluorescence in situ hybridization (FISH) testing was performed on a cohort of STS to assess for chr8 gain. Copy number variation (CNV) data from the National Cancer Institute were analyzed to assess for prognostically significant CNV aberrations in RESULTS: Chr8 gain is a highly prevalent CNV in embryonal RMS and shows slightly improved prognosis. Meanwhile, loss of chr3q was associated with worse outcome in FN-RMS compared with FP-RMS. CONCLUSION: The pathogenesis of STS including FN-RMS remains poorly understood, emphasizing the need for new therapeutic advances and adequate risk stratification. Our data demonstrate that loss of chr3q is associated with poor OS in FN-RMS, supporting it as an important tool for risk stratification