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Tarishi Nemani Dora Steel Marios Kaliakatsos Catherine DeVile Athina Ververi Richard Scott Spas Getov Sniya Sudhakar Alison Male Kshitij Mankad Francesco Muntoni Mary M Reilly Manju A Kurian Lucinda Carr Pinki Munot 《Journal of the peripheral nervous system : JPNS》2020,25(2):117-124
KIF1A‐related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Here we present a case series demonstrating the range of clinical, neurophysiological, and radiological features which may occur in childhood‐onset KRD. We report on all the children and young people seen at a single large tertiary centre. Data were collected through a retrospective case‐notes review. Twelve individuals from 10 families were identified. Eight different mutations were present, including four novel mutations. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress. The remaining 10 patients represented a spectrum of severity with common features including a movement disorder with spasticity and/or dystonia, subtle features of dysautonomia, sensory axonal neuropathy, varying degrees of optic atrophy and of learning and/or behavioural difficulties, and subtle or absent—but sometimes progressive—changes in white matter on MRI. Epilepsy was common among the more severely affected children. This case series demonstrates that KRD comprise a range of neurological disorders, with both the milder and the more severe forms combining central and peripheral (including autonomic) nervous system deficits. 相似文献
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Jonathan M. O. Rawson Sean R. Landman Cavan S. Reilly Laurent Bonnac Steven E. Patterson Louis M. Mansky 《Antimicrobial agents and chemotherapy》2015,59(11):6834-6843
Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ≈4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ≈155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ≈29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ≈80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity. 相似文献
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Gang Qiang Bettencourt Conceição Holton Janice Lovejoy Christopher Chelban Viorica Oconnor Emer Yuan Yun Reilly Mary M. Hanna Michael Houlden Henry 《Journal of neurology》2020,267(9):2705-2712
Journal of Neurology - To identify the genetic cause of complex neuropathy in two siblings from a consanguineous family. The patients were recruited from our clinic. Muscle biopsy and whole-exome... 相似文献
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Dawn Sinclair Eileen Savage Maria O’ Brien Anthony O’Reilly Carmel Mullaney Marie Killeen 《Journal of interprofessional care》2020,34(4):561-565
ABSTRACT This report describes the development of the first national undergraduate interprofessional standardized curriculum in chronic disease prevention for healthcare professionals in the Republic of Ireland. This project brought together for the first time all higher education institutions nationwide in a novel collaboration with the national health service i.e. the Health Service Executive (HSE), to develop a standardized national curriculum for undergraduate health care professions. The curriculum sits within the framework of Making Every Contact Count, the goal of which is to re-orientate health services to embed the ethos of prevention through lifestyle behavior change as part of the routine care of health professionals. The core focus of Making Every Contact Count is chronic disease prevention, targeting four main lifestyle risk factors for chronic disease; tobacco use, alcohol consumption, physical inactivity and unhealthy eating. Making Every Contact Count is a key component of Healthy Ireland, the Irish national framework for health and wellbeing. The aim of the curriculum is to prepare newly qualified health professionals with the skills needed to support patients to achieve lifestyle behavior change delivered as part of routine clinical care. 相似文献
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Louise Freeland Michelle O’Reilly Juliana Fleury Sarah Adams Panos Vostanis 《International Journal of Mental Health Promotion, The》2022,24(1):51-67
Social emotional literacy (SEL) interventions are widely implemented through schools, with growing evidence for a range of positive child outcomes. Increasingly, such interventions are delivered on online platforms. To date, there is limited evidence about digital SEL interventions in low- and middle-income countries (LMIC). The aim of this study was to explore the perceptions and experiences of children, parents and facilitator of the potential value of addressing SEL via tailored digital intervention. The intervention was designed to help children, in Brazil, to cope during the first COVID-19 pandemic lockdown. The intervention was delivered via a digital platform to groups of three children for 45 min per week for nine. Thirteen children, nine parents and nine facilitators were interviewed following the completion of the intervention. The data was analysed through a codebook thematic approach, which led to three themes: empowerment, participatory aspects of the intervention and digital adaptation. Overall, children’s SEL development was reported to be supported during the COVID-19 pandemic, by the application of new skills outside the sessions. Children reported a number of empowering factors such as being heard and belonging. A range of useful participatory tools were identified including storytelling, games, drawings and videos. Blended SEL interventions involving both face-to-face and web-based facilitation could be developed within a tiered model of universal mental health promotion and targeted prevention. Access to online platforms would increase reach to large numbers of children in LMIC, especially in contexts of disadvantage. 相似文献
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Andy KH Lim 《World journal of gastroenterology : WJG》2020,26(10):1020-1028
Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided. 相似文献