Transcatheter Edge-to-Edge Mitral Valve Repair in a Patient With Anderson-Fabry Disease.

Severe degenerative mitral regurgitation (DMR) is one cardiac manifestation of the multiorgan metabolic enzyme disorder Anderson-Fabry Disease (AFD). Although DMR is normally managed surgically, many patients with AFD are unsuitable for this. We present the first case of mitral transcatheter edge-to-edge repair in a patient with AFD.

Psychosocial Competencies Among Clinic-Referred and Community-Based Children: Known-Groups Validity of the Psychosocial Strengths Inventory for Children and Adolescents (PSICA).

Child psychosocial competencies protect against the development of psychopathology, ameliorate existing psychosocial problems, and predict positive long-term developmental cascades. Assessment of these competencies can improve identification of children in need of psychosocial services, enrich treatment planning, and improve treatment progress and outcome monitoring. Yet, appropriate measures are limited. One promising option is the Psychosocial Strengths Inventory for Children and Adolescents (PSICA), although its discriminative properties were formerly unknown. The present study evaluated the PSICA's sensitivity, specificity, and optimal cutoff scores with 228 youth (38 clinic-referred and 190 community-based youth with case-control matching) ages 2-10 years (Mage = 5.8, 71% boys, 77% White). Results indicated large, significant discrepancies, with clinic-referred youth rated as having less overall psychosocial competence overall and across domains of compliance, prosociality, and attention. Caregivers also reported significantly less satisfaction with the psychosocial competence of clinic-referred versus community youth. Discriminative accuracy of the PSICA's Frequency and Satisfaction scales, and its subscales, were good-to-excellent. Such discriminative accuracy and empirically derived, if preliminary, cutoff scores further support the PSICA as a pragmatic, psychometrically strong tool to screen children for referral into services, and potentiate future investigations into the PSICA's use in treatment planning and evaluation.

Left atrial appendage occlusion for ischemic stroke prevention in patients with non-valvular atrial fibrillation: clinical expert opinion and consensus statement for the Asian-Pacific region.

PURPOSE: To develop a consensus statement for left atrial appendage occlusion (LAAO) in Asian-Pacific patients with non-valvular atrial fibrillation (NVAF) at risk of ischemic stroke. The need for such a region-specific consensus was indicated by the relative paucity of clinical evidence for LAAO and oral anticoagulation therapy obtained in Asian-Pacific populations and the specific stroke and bleeding characteristics of this population. METHODS: Consensus was developed by discussion and evaluation of available evidence and expert opinions during a 2-day meeting attended by clinical experts from the Asian-Pacific regions. RESULTS: The consensus statement arrived at provides recommendations based on available evidence and expert opinions regarding LAAO in Asian-Pacific patients. Gaps in the evidence and other areas requiring further research were identified. CONCLUSION: LAAO is an alternative device-based therapy in carefully selected patients with NVAF at risk of ischemic stroke. However, evidence for LAAO is primarily obtained from Caucasian populations, and data on LAAO in Asian-Pacific patients are scarce. While the present consensus statement addresses several therapy-related aspects based on careful interpretation of available evidence and expert opinions, other areas require additional evidence derived from Asian-Pacific populations.

A biomechanical analysis of the stand-up paddle board stroke: a comparative study.

BACKGROUND: Stand-up paddle boarding (SUP) is a rapidly growing global aquatic sport, with increasing popularity among participants within recreation, competition and rehabilitation. To date, few scientific studies have focused on SUP. Further, there is no research examining the biomechanics of the SUP paddle stroke. The purpose of this study was to investigate whether variations in kinematics existed among experienced and inexperienced SUP participants using three-dimensional motion analysis. This data could be of significance to participants, researchers, coaches and health practitioners to improve performance and inform injury minimization strategies. METHODS: A cross-sectional observational design study was performed with seven experienced and 19 inexperienced paddlers whereby whole-body kinematic data were acquired using a six-camera Vicon motion capture system. Participants paddled on a SUP ergometer while three-dimensional range of motion (ROM) and peak joint angles were calculated for the shoulders, elbows, hips and trunk. Mann-Whitney U tests were conducted on the non-normally distributed data to evaluate differences between level of expertise. RESULTS: Significant differences in joint kinematics were found between experienced and inexperienced participants, with inexperienced participants using greater overall shoulder ROM (78.9° ± 24.9° vs 56.6° ± 17.3°, p = 0.010) and less hip ROM than the experienced participants (50.0° ± 18.5° vs 66.4° ± 11.8°, p = 0.035). Experienced participants demonstrated increased shoulder motion at the end of the paddle stoke compared to the inexperienced participants (74.9° ± 16.3° vs 35.2° ± 28.5°, p = 0.001 minimum shoulder flexion) and more extension at the elbow (6.0° ± 9.2° minimum elbow flexion vs 24.8° ± 13.5°, p = 0.000) than the inexperienced participants. DISCUSSION: The results of this study indicate several significant kinematic differences between the experienced and inexperienced SUP participants. These variations in technique were noted in the shoulder, elbow and hip and are evident in other aquatic paddling sports where injury rates are higher in these joints. These finding may be valuable for coaches, therapists and participants needing to maximize performance and minimize injury risk during participation in SUP.

Derivation of oligodendrocyte progenitor cells from human embryonic stem cells.

The directed differentiation of human pluripotent stem cells into specific, determined, and high-purity cell types can provide a means to study the cellular and molecular mechanisms of development and to generate cells for potential therapeutic applications. The ability to derive homogeneous cell populations obviates the need for transgene expression or cell sorting methods and can improve selection efficiency, lineage differentiation, cell viability, and clinical utility. Compared to undifferentiated pluripotent stem cells, high-purity cell phenotypes for clinical therapeutic strategies are expected to enhance engraftment, potentiate clinical efficacy, and decrease the risk of adverse effects such as dedifferentiation or teratoma formation. Clinical interest in the derivation of oligodendrocyte progenitor cells from pluripotent stem cells is based on research that demonstrates the effectiveness of progenitor cell transplants to improve outcomes after spinal cord injury. Here, we describe a protocol to generate oligodendroglial lineage-specific cells in high purity from human embryonic stem cells.

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury.

Evidence that cell transplants can improve recovery outcomes in spinal cord injury (SCI) models substantiates treatment strategies involving cell replacement for humans with SCI. Most pre-clinical studies of cell replacement in SCI examine thoracic injury models. However, as most human injuries occur at the cervical level, it is critical to assess potential treatments in cervical injury models and examine their effectiveness using at-level histological and functional measures. To directly address cervical SCI, we used a C5 midline contusion injury model and assessed the efficacy of a candidate therapeutic for thoracic SCI in this cervical model. The contusion generates reproducible, bilateral movement and histological deficits, although a number of injury parameters such as acute severity of injury, affected gray-to-white matter ratio, extent of endogenous remyelination, and at-level locomotion deficits do not correspond with these parameters in thoracic SCI. On the basis of reported benefits in thoracic SCI, we transplanted human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into this cervical model. hESC-derived OPC transplants attenuated lesion pathogenesis and improved recovery of forelimb function. Histological effects of transplantation included robust white and gray matter sparing at the injury epicenter and, in particular, preservation of motor neurons that correlated with movement recovery. These findings further our understanding of the histopathology and functional outcomes of cervical SCI, define potential therapeutic targets, and support the use of these cells as a treatment for cervical SCI.

Stem cell-based cell replacement strategies for the central nervous system.

During human development, cells of the blastocyst inner cell mass proliferate and give rise to each cell in the human body. It is that potential which focuses intense interest on these stem cells as a substrate for cell-based regenerative medicine. An increased understanding of the interrelation of processes that govern the formation of various cell types will allow for the directed differentiation of stem cells into specified cells or tissues that can ameliorate the effects of disease or damage. Perhaps the most difficult cells and tissues to derive for use in cell replacement strategies are the diverse neurons, glia and complex networks of the central nervous system (CNS). Here we present emerging perspectives on the development of neuronal and glial cells from stem cells for clinical application to CNS diseases and injury.

Potentials of ES cell therapy in neurodegenerative diseases.

Neurodegenerative diseases comprise a heterogeneous spectrum of neural disorders that cause severe and progressive cognitive and motor deficits. A histological hallmark of these disorders is the occurrence of disease-specific cell death in specific regional subpopulations of neurons, such as the loss of dopaminergic neurons in the substantia nigra in Parkinson's disease. Neurodegenerative disease can also possibly occur from the loss or dysfunction of selected glial cell subsets, such as the dysfunction of supportive glial cells around somatic motor neurons in amyotrophic lateral sclerosis. The central nervous system (CNS), unlike many other tissues, has a very limited capacity for self-repair. Mature nerve cells lack the ability to regenerate, although endogenous neural stem cells exist in the adult brain that do have very limited ability to generate new functional neurons in response to injury. Rapid advances in stem cell biology have opened an alternative, fascinating perspective of neurogenesis by activation of endogenous neural stem cells and/or transplantation of in vitro-expanded stem cells and/or their neuronal- or glial-differentiated progeny. Embryonic stem (ES) cells, because of their ability to provide seemingly unlimited supply of specific cell types, their amenability to genetic engineering manipulations, and their broad developmental potential, are expected to become a cell source and biological delivery system for use in a variety of neurodegenerative diseases, and are likely to play a role in the development of novel cell-based therapies for these indications. However, before the full potential of ES cells can be realized for regenerative medicine, we need to understand mechanisms regulating their proliferation, differentiation into therapeutically relevant cells, and most importantly in the case of neuronal and glial lineages, to characterize their functional properties. In the present review we will be focusing on the factors and methodologies responsible for differentiation of ES cell into different neural precursors and neural cell lineages with particular emphasis on the potential research and clinical applications of ES cells in the field of neurodegenerative disease.

Prehydration alone is sufficient to prevent contrast-induced nephropathy after day-only angiography procedures--a randomised controlled trial.

BACKGROUND: Contrast agents used in angiography procedures for patients with cardiovascular disease are known to cause contrast-induced nephropathy (CIN), which may be partially due to the production of nephrotoxic oxygen-free radicals. It is uncertain whether administration of intravenous (IV) anti-oxidant, N-acetylcysteine (NAC), can prevent reduction in renal function and whether this is a cost-effective approach. METHODS: Sixty-five day-only patients with renal impairment (mean serum creatinine concentration 0.16+/-0.03 mmol/l) due to undergo coronary or peripheral angiography and/or stenting were randomly assigned to IV NAC 300 or 600 mg immediately before and after the procedure or IV fluid alone. RESULTS: Of the 60 patients with complete data, none had acute CIN (increase in serum creatinine concentration > or = 0.044 mmol/l, 48 h after administration of contrast agent). Eight patients (13%) have demonstrated an increase in their serum creatinine concentration > or = 0.044 mmol/l 30 days after administration of contrast agent: 2/19 (11%) in the control group, 2/21 (10%) in the 600 mg NAC group and 4/20 (20%) the 300 mg NAC group (p = 0.66). The mean volumes of contrast agent used and prehydration given for each of the three groups did not differ significantly (p > 0.83). There was significant improvement in creatinine clearance within each group from baseline to 30 days (p < or = 0.03), but no significant difference between the groups at 48 h and 30 days (p > or = 0.43). Considering the cost of NAC and its administration, we estimate that this would translate to a saving of dollar 26,637 per annum. CONCLUSION: For day-stay patients with mild-to-moderate chronic renal impairment undergoing angiography and/or intervention, prehydration alone is less complicated and more cost-effective than a combination of IV NAC (at doses used) and hydration.

Salvage stenting for acute renal failure secondary to renal artery stenosis.

We present two cases of successful, emergency renal artery stenting in the setting of acute renal failure requiring dialysis secondary to renal artery stenosis. Early reopening of the stenotic renal artery led to the resolution of acute renal failure and obviated the need for further dialysis in both cases.