Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
Top Spinal Cord Inj Rehabil ; 30(2): 54-64, 2024.
Article in English | MEDLINE | ID: mdl-38799608

ABSTRACT

The World Health Organization (WHO) recommends that infants be breastfed exclusively for the first 6 months of age. However, there are few resources available on the effects a spinal cord injury (SCI) can have for breastfeeding mothers. It is difficult to find information to address the unique challenges women with SCI experience when planning or trying to breastfeed. Our international team, including women with SCI, health care providers, and SCI researchers, aims to address the information gap through the creation of this consumer guide. The purpose of this consumer guide is to share the most common issues women with SCI experience during breastfeeding and provide information, practical suggestions, recommendations, and key resources in lay language. General information about breastfeeding is available on the internet, in books, or from friends and health care providers. We do not intend to repeat nor replace general breastfeeding information or medical advice. Breastfeeding for mothers with SCI is complex and requires a team of health care providers with complementary expertise. Such a team may include family physician, obstetrician, physiatrist, neurologist, occupational and physical therapist, lactation consultant, midwife, and psychologist. We hope this consumer guide can serve as a quick reference guide for mothers with SCI planning of trying to breastfeed. This guide will also be helpful to health care providers as an educational tool.


Subject(s)
Breast Feeding , Mothers , Spinal Cord Injuries , Humans , Female , Mothers/psychology , Infant, Newborn , Infant
2.
Top Spinal Cord Inj Rehabil ; 30(2): 9-36, 2024.
Article in English | MEDLINE | ID: mdl-38799607

ABSTRACT

The World Health Organization (WHO) recommends that children be breastfed exclusively for the first 6 months of age. This recommendation may prove challenging for women with spinal cord injury (SCI) who face unique challenges and barriers to breastfeeding due to the impact of SCI on mobility and physiology. Tailored provision of care from health care professionals (HCPs) is important in helping women navigate these potential barriers. Yet, HCPs often lack the confidence and SCI-specific knowledge to meet the needs of mothers with SCI. An international panel of clinicians, researchers, consultants, and women with lived experience was formed to create an accessible resource that can address this gap. A comprehensive survey on breastfeeding complications, challenges, resources, and quality of life of mothers with SCI was conducted, along with an environmental scan to evaluate existing postpartum guidelines and assess their relevance and usability as recommendations for breastfeeding after SCI. Building on this work, this article provides evidence-based recommendations for HCPs, including but not limited to general practitioners, obstetricians, pediatricians, physiatrists, lactation consultants, nurses, midwives, occupational therapists, and physiotherapists who work with prospective and current mothers with SCI.


Subject(s)
Autonomic Dysreflexia , Breast Feeding , Spinal Cord Injuries , Humans , Spinal Cord Injuries/complications , Female , Autonomic Dysreflexia/etiology , Autonomic Dysreflexia/therapy , Autonomic Dysreflexia/physiopathology , Practice Guidelines as Topic , Mothers/psychology , Quality of Life , Adult
3.
Spinal Cord ; 61(1): 1-7, 2023 01.
Article in English | MEDLINE | ID: mdl-35962043

ABSTRACT

STUDY DESIGN: Systematic review. OBJECTIVES: To systematically review the evidence on the use of local analgesics, specifically lidocaine or bupivacaine, to prevent autonomic dysreflexia (AD) during iatrogenic procedures or bowel and bladder care routines in individuals with spinal cord injury (SCI). METHODS: A keyword search of MEDLINE, CINAHL, CENTRAL, Cochrane Reviews, PsycInfo, Embase, and Web of Science databases identified all English-language studies evaluating the efficacy of local analgesics in reducing AD. Included studies were either randomized controlled trials (RCTs) or quasi-experimental studies. Participants were adults with chronic SCI who received local analgesics prior to AD-triggering procedures or routines. Additionally, studies were required to report blood pressure values as an outcome. The methodology of this review followed the PRISMA checklist and was registered with PROSPERO (CRD42021219506). RESULTS: Four RCTs and two quasi-experimental studies met inclusion criteria. Results were narratively synthesized as meta-analysis was not possible due to heterogeneity across studies included in the review. All six studies administered lidocaine. Lidocaine was found to have a beneficial effect on AD in three studies, no effect in two studies and a detrimental effect in one study. CONCLUSIONS: Presently, RCTs and quasi-experimental studies on the use of lidocaine for reducing AD in individuals with SCI had small sample sizes and opposing findings. There is a strong need for definitive, well-monitored clinical trials with adequate sample sizes. Presently there is not enough compelling evidence to support or refute recommendations for the use of lidocaine from the AD management clinical practice guidelines.


Subject(s)
Autonomic Dysreflexia , Spinal Cord Injuries , Adult , Humans , Autonomic Dysreflexia/drug therapy , Autonomic Dysreflexia/etiology , Autonomic Dysreflexia/prevention & control , Spinal Cord Injuries/complications , Spinal Cord Injuries/drug therapy , Lidocaine/therapeutic use , Bupivacaine , Analgesics/therapeutic use
4.
PLoS One ; 17(12): e0278425, 2022.
Article in English | MEDLINE | ID: mdl-36512558

ABSTRACT

INTRODUCTION: Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled "Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury" is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. METHODS AND ANALYSIS: Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. ETHICS AND DISSEMINATION: Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders.


Subject(s)
Spinal Cord Injuries , Spinal Cord Stimulation , Humans , Urinary Bladder , Quality of Life , Spinal Cord , Randomized Controlled Trials as Topic
5.
Spinal Cord ; 60(9): 837-842, 2022 09.
Article in English | MEDLINE | ID: mdl-35459928

ABSTRACT

STUDY DESIGN: Narrative review. OBJECTIVES: To evaluate the availability and quality of breastfeeding guidelines for women with spinal cord injury (SCI). SETTING: International Collaboration on Repair Discoveries (ICORD), Department of Medicine, Vancouver, BC. METHODS: An environmental scan restricted to English language literature was performed to identify existing postpartum and breastfeeding guidelines. Guidelines were evaluated using a structured, validated tool (AGREE II) by 13 appraisers [medical/research experts (n = 10) and those with lived experience (n = 3)] from Vancouver and two international sites. Seven guidelines were evaluated across Domain 1 of the AGREE II tool to determine if they were applicable to mothers with SCI/physical disabilities. Domains 2 to 7 were evaluated if the guideline made mention of the SCI population. RESULTS: Of the seven guidelines evaluated, only one mentioned SCI (Postpartum Care in SCI from BC Women's Hospital). Other guidelines were excluded from further evaluation as they did not address the issue of breastfeeding in women with SCI. The overall scaled score for this guideline was 34.5%. There was significant variability between domains but no AGREE II domain scored greater than 50%, indicating substantial limitations. CONCLUSIONS: Current breastfeeding guidelines are not targeted to persons with SCI. The one guideline that made mention of women with SCI had significant global deficits. This highlights the importance of developing guidelines for health care providers focused specifically on women with SCI to support and optimize breastfeeding in this unique population for the benefit of mother and infant across the lifespan.


Subject(s)
Disabled Persons , Spinal Cord Injuries , Breast Feeding , Female , Health Personnel , Humans
6.
Nat Med ; 28(2): 260-271, 2022 02.
Article in English | MEDLINE | ID: mdl-35132264

ABSTRACT

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.


Subject(s)
Spinal Cord Injuries , Spinal Cord Stimulation , Humans , Leg , Paralysis/rehabilitation , Spinal Cord/physiology , Spinal Cord Injuries/rehabilitation , Walking/physiology
7.
Nature ; 590(7845): 308-314, 2021 02.
Article in English | MEDLINE | ID: mdl-33505019

ABSTRACT

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival1-3, impairs neurological recovery4,5, increases the risk of cardiovascular disease6,7, and reduces quality of life8,9. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord10, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury11, and restored walking after paralysis12. Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This 'neuroprosthetic baroreflex' controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI.


Subject(s)
Baroreflex , Biomimetics , Hemodynamics , Prostheses and Implants , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/therapy , Animals , Disease Models, Animal , Female , Humans , Male , Neural Pathways , Primates , Rats , Rats, Inbred Lew , Sympathetic Nervous System/cytology , Sympathetic Nervous System/physiology
8.
ACS Pharmacol Transl Sci ; 3(5): 907-920, 2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33073190

ABSTRACT

IBNtxA (3-iodobenzoyl naltrexamine) is a novel µ-opioid receptor (MOR) agonist which is structurally related to the MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, resulting in anti-nociception with reduced side effects, including no conditioned place preference (CPP) when tested at a single dose. IBNtxA represents an intriguing lead compound for preclinical drug development targeting truncated MOR splice variants, but further evaluation of its in vivo pharmacological profile is necessary. The purpose of this study was to independently verify the antinociceptive properties of IBNtxA and to examine more completely the rewarding properties and discriminative stimulus effects of IBNtxA, allowing broader assessment of IBNtxA as a candidate for further medications development. A dose of 3 mg/kg IBNtxA was equipotent to 10 mg/kg morphine in a hot-plate analgesia assay. In drug discrimination testing using mice trained to discriminate between 3 mg/kg IBNtxA and vehicle, the κ-agonist U-50488 fully substituted for IBNtxA. MOR agonist morphine, δ-agonist SNC162, NOP agonist SCH 221510, and MOR/NOP partial agonist buprenorphine each partially substituted for IBNtxA. IBNtxA up to 3 mg/kg did not produce a place preference in CPP. Pretreatment with 3 mg/kg IBNtxA but not 1 mg/kg IBNtxA attenuated acquisition of place preference for 10 mg/kg morphine. A dose of 3 mg/kg IBNtxA attenuated morphine-induced hyperlocomotion but did not alter naloxone-precipitated morphine withdrawal. Overall, IBNtxA has a complicated opioid receptor pharmacology in vivo. These results indicate that IBNtxA produces potent anti-nociception and has low abuse liability, likely driven by substantial κ agonist signaling effects.

9.
Disabil Rehabil ; 42(2): 240-246, 2020 01.
Article in English | MEDLINE | ID: mdl-30273077

ABSTRACT

Purpose: To (1) evaluate the level of agreement between individually calibrated accelerometers and the self-reported Physical Activity Recall Assessment for People with Spinal Cord Injury when assessing moderate-vigorous physical activity; and (2) qualitatively examine the different components of physical activity each measure assesses.Materials/methods: Nineteen manual wheelchair users with chronic spinal cord injury (19.0 ± 12.9 years post injury, C5-L2 injury level) wore a wrist and spoke accelerometer for one week then returned to the lab and completed the Physical Activity Recall Assessment for People with Spinal Cord Injury for their last 3 days of accelerometer wear.Results: Bland-Altman plots revealed low levels of agreement between the two measures when measuring total (bias = -5.6 ± 70.41 min/d, 95% agreement limits = -143.6-132.4 min/d), wheeled (bias = -9.7 ± 30.2 min/d, 95% agreement limits = -69.0-49.5 min/d), and non-wheeled (bias =12.3 ± 53.8 min/d, 95% agreement limits = -93.1-117.6 min/d) moderate-vigorous physical activity. The accelerometer was beneficial for detecting intermittent or brief activities while the self-report measure was useful for measuring lifting activities (e.g., resistance training) and wheeling on inclined surfaces.Conclusion: Total and wheeled moderate-vigorous physical activity measured by an accelerometer and a self-report measure showed low agreement at the individual level. Additional research is needed to examine whether physical activity may be best measured using accelerometers and a self-report measure concurrently.Implications for RehabilitationAccurate physical activity measurement has important implications for understanding the relationship between physical activity and health outcomes.Many limitations exist to accurately measuring physical activity in people with spinal cord injury.The most commonly used measures of physical activity in spinal cord injury are accelerometers and the self-reported Physical Activity Recall Assessment for People with Spinal Cord Injury.Accelerometers and the Physical Activity Recall Assessment for People with Spinal Cord Injury show low levels of agreement, highlighting that there are differences in the specific physical activity patterns that each measure is able to capture.


Subject(s)
Accelerometry , Exercise , Self Report , Spinal Cord Injuries , Humans , Reproducibility of Results , Wheelchairs , Wrist Joint
10.
Nature ; 563(7729): 65-71, 2018 11.
Article in English | MEDLINE | ID: mdl-30382197

ABSTRACT

Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.


Subject(s)
Biomedical Technology , Electric Stimulation Therapy , Paralysis/rehabilitation , Spinal Cord Injuries/rehabilitation , Walking/physiology , Activities of Daily Living , Computer Simulation , Electromyography , Epidural Space , Humans , Leg/innervation , Leg/physiology , Leg/physiopathology , Locomotion/physiology , Male , Motor Neurons/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Muscle, Skeletal/physiopathology , Paralysis/physiopathology , Paralysis/surgery , Spinal Cord/cytology , Spinal Cord/physiology , Spinal Cord/physiopathology , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/surgery
11.
Arch Phys Med Rehabil ; 99(4): 684-689, 2018 04.
Article in English | MEDLINE | ID: mdl-29222006

ABSTRACT

OBJECTIVE: To create and compare individual and group-based cut-points for wrist accelerometry that correspond to moderate-to-vigorous physical activity (MVPA) in people with spinal cord injury (SCI). DESIGN: Participants completed a graded treadmill-wheeling test while being assessed for oxygen consumption, wrist-acceleration vector magnitude, and spoke acceleration. Oxygen consumption was converted to SCI metabolic equivalents (METs), and linear regression was applied to determine an individualized vector magnitude cut-point (counts per minute, VM-CPM) corresponding with MVPA (≥3 SCI METs). Multilevel linear regression was applied to determine a group MVPA cut-point. Participants then completed a 6-day monitoring period while wearing the accelerometers. SETTING: A local SCI research center. PARTICIPANTS: Manual wheelchair users (N=20; aged 31-64y; injury levels, C5 to L2) with chronic (>1y) SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mean total daily MVPA, wheeled MVPA, and nonwheeled MVPA were calculated using both the individual and group cut-points. Agreement on measures of minutes per day of MVPA between the individual and group mean cut-point method was assessed using Bland-Altman plots. RESULTS: Individual cut-points for MVPA ranged from 6040 to 21,540 VM-CPM, with a group cut-point of 11,652 (95% confidence interval, 7395-15,909). For total daily MVPA, Bland-Altman analysis revealed a bias of .22±33.0 minutes, with 95% limits of agreement from -64.5 to 64.9 minutes, suggesting a large discrepancy between total MVPA calculated from individual and group mean cut-points. CONCLUSIONS: Individual calibration of wrist-worn accelerometry is recommended for effective habitual PA monitoring in this population.


Subject(s)
Accelerometry/statistics & numerical data , Actigraphy/statistics & numerical data , Spinal Cord Injuries/physiopathology , Wearable Electronic Devices , Wheelchairs , Accelerometry/instrumentation , Accelerometry/methods , Actigraphy/instrumentation , Actigraphy/methods , Adult , Calibration , Exercise , Female , Humans , Male , Middle Aged , Reference Values , Reproducibility of Results , Time Factors , Wrist
12.
Appl Physiol Nutr Metab ; 43(5): 460-466, 2018 May.
Article in English | MEDLINE | ID: mdl-29207251

ABSTRACT

There are known sex differences in blood pressure regulation. The differences are related to ovarian hormones that influence ß-adrenergic receptors and the transduction of muscle sympathetic nerve activity. Oral contraceptives (OC) modulate the ovarian hormonal profile in women and therefore may alter the cardiovascular response. We questioned if OC would alter the absolute pressor response to static exercise and influence the day-to-day variability of the response. Healthy men (n = 11) and women (n = 19) completed a familiarization day and 2 experimental testing days. Women were divided into those taking (W-OC, n = 10) and not taking (W-NC, n = 9) OC. Each experimental testing day involved isometric handgripping exercise, at 30% of maximal force, followed by circulatory occlusion to isolate the metaboreflex. Experimental days in men were 7-14 days apart. The first experimental testing in W-OC occurred 2-7 days after the start of the active phase of their OC. Women not taking OC were tested during the early and late follicular phase of the menstrual cycle as determined by commercial ovulation monitor. The increase in mean arterial pressure (MAP) during exercise was significantly lower in W-NC (95 ± 4 mm Hg) compared with men (114 ± 4 mm Hg) and W-OC (111 ± 3 mm Hg) (P < 0.05), with the differences preserved during circulatory occlusion. The rise in MAP was significantly correlated between the 2 testing days in men (r = 0.72, P < 0.01) and W-OC (r = 0.77, P < 0.05), but not in W-NC (r = 0.17, P = 0.67), indicating greater day-to-day variation in W-NC. In conclusion, OC modulate the exercise pressor response in women and minimize day-to-day variability in the exercise metaboreflex.


Subject(s)
Blood Pressure , Contraceptives, Oral/administration & dosage , Exercise , Muscle, Skeletal/drug effects , Reflex/drug effects , Adult , Body Mass Index , Cardiovascular System/drug effects , Female , Follicular Phase/drug effects , Hand Strength , Heart Rate/drug effects , Humans , Male , Muscle, Skeletal/physiology , Receptors, Adrenergic, alpha/blood , Receptors, Adrenergic, beta/blood , Sex Factors , Young Adult
13.
Int J Med Robot ; 14(1)2018 Feb.
Article in English | MEDLINE | ID: mdl-29063680

ABSTRACT

BACKGROUND: Orthopaedic training programs are incorporating arthroscopic simulations into their residency curricula. There is a need for a physical shoulder simulator that accommodates lateral decubitus and beach chair positions, has realistic anatomy, allows for an objective measure of performance and provides feedback to trainees. METHODS: A physical shoulder simulator was developed for training basic arthroscopic skills. Sensors were embedded in the simulator to provide a means to assess performance. Subjects of varying skill level were invited to use the simulator and their performance was objectively assessed. RESULTS: Novice subjects improved their performance after practice with the simulator. A survey completed by experts recognized the simulator as a valuable tool for training basic arthroscopic skills. CONCLUSIONS: The physical shoulder simulator helps train novices in basic arthroscopic skills and provides objective measures of performance. By using the physical shoulder simulator, residents could improve their basic arthroscopic skills, resulting in improved patient safety.


Subject(s)
Arthroscopy/education , Arthroscopy/instrumentation , Orthopedics/methods , Shoulder/surgery , Simulation Training , Arthroscopy/methods , Clinical Competence , Computer Simulation , Curriculum , Education, Medical, Graduate , Equipment Design , Humans , Internship and Residency , Patient Safety , Shoulder Joint/surgery
14.
Sensors (Basel) ; 17(8)2017 Aug 05.
Article in English | MEDLINE | ID: mdl-28783069

ABSTRACT

Minimally invasive skills assessment methods are essential in developing efficient surgical simulators and implementing consistent skills evaluation. Although numerous methods have been investigated in the literature, there is still a need to further improve the accuracy of surgical skills assessment. Energy expenditure can be an indication of motor skills proficiency. The goals of this study are to develop objective metrics based on energy expenditure, normalize these metrics, and investigate classifying trainees using these metrics. To this end, different forms of energy consisting of mechanical energy and work were considered and their values were divided by the related value of an ideal performance to develop normalized metrics. These metrics were used as inputs for various machine learning algorithms including support vector machines (SVM) and neural networks (NNs) for classification. The accuracy of the combination of the normalized energy-based metrics with these classifiers was evaluated through a leave-one-subject-out cross-validation. The proposed method was validated using 26 subjects at two experience levels (novices and experts) in three arthroscopic tasks. The results showed that there are statistically significant differences between novices and experts for almost all of the normalized energy-based metrics. The accuracy of classification using SVM and NN methods was between 70% and 95% for the various tasks. The results show that the normalized energy-based metrics and their combination with SVM and NN classifiers are capable of providing accurate classification of trainees. The assessment method proposed in this study can enhance surgical training by providing appropriate feedback to trainees about their level of expertise and can be used in the evaluation of proficiency.


Subject(s)
Motor Skills , Clinical Competence , Feedback
15.
Dev Cell ; 41(3): 274-286.e5, 2017 05 08.
Article in English | MEDLINE | ID: mdl-28457793

ABSTRACT

The proneural transcription factor Neurogenin3 (Ngn3) plays a critical role in pancreatic endocrine cell differentiation, although regulation of Ngn3 protein is largely unexplored. Here we demonstrate that Ngn3 protein undergoes cyclin-dependent kinase (Cdk)-mediated phosphorylation on multiple serine-proline sites. Replacing wild-type protein with a phosphomutant form of Ngn3 increases α cell generation, the earliest endocrine cell type to be formed in the developing pancreas. Moreover, un(der)phosphorylated Ngn3 maintains insulin expression in adult ß cells in the presence of elevated c-Myc and enhances endocrine specification during ductal reprogramming. Mechanistically, preventing multi-site phosphorylation enhances both Ngn3 stability and DNA binding, promoting the increased expression of target genes that drive differentiation. Therefore, multi-site phosphorylation of Ngn3 controls its ability to promote pancreatic endocrine differentiation and to maintain ß cell function in the presence of pro-proliferation cues and could be manipulated to promote and maintain endocrine differentiation in vitro and in vivo.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Differentiation/physiology , Insulin-Secreting Cells/metabolism , Islets of Langerhans/cytology , Nerve Tissue Proteins/metabolism , Animals , Cyclin-Dependent Kinases/metabolism , Homeodomain Proteins/metabolism , Humans , Mice , Pancreas/metabolism , Phosphorylation , Signal Transduction/physiology
16.
Exp Physiol ; 102(2): 154-163, 2017 02 01.
Article in English | MEDLINE | ID: mdl-28004433

ABSTRACT

NEW FINDINGS: What is the central question of this study? How does early versus delayed initiation of passive hindlimb cycling, as well as detraining, affect cardiac function and blood pressure control in a rodent model of spinal cord injury? What is the main finding and its importance? Early or delayed initiation of hindlimb cycling improves cardiac and haemodynamic function in spinal cord injury, although the benefits of early administration are more pronounced. We also demonstrate the need for exercise to be maintained, because detraining rapidly reverses the cardiac and haemodynamic benefits. Spinal cord injury (SCI) reduces physical activity and alters descending supraspinal cardiovascular control, predisposing this population to early onset of cardiovascular disease. We used a T3 SCI rodent model to investigate the effect of early versus delayed passive hindlimb cycling (PHLC), as well as the effect of detraining on cardiac dysfunction and blood pressure control, including autonomic dysreflexia (AD). Twenty male Wistar rats were divided into an early PHLC initiation group followed by a period of detraining (PHLC starting day 6 post-SCI, for 4 weeks, followed by 4 weeks of detraining; 'early PHLC/detraining' group) and a delayed PHLC intervention group (no PHLC for first 5 weeks post-SCI, followed by PHLC for 4 weeks; 'no PHLC/delayed PHLC' group). At 5 weeks post-SCI, the no PHLC/delayed PHLC group exhibited a decline in almost all cardiac indices (all P < 0.029), which was maintained in the early PHLC/detraining group. Also, the severity of induced AD was reduced in the early PHLC/detraining versus no PHLC/delayed PHLC group (all P < 0.0279). At 9 weeks post-SCI, no PHLC/delayed PHLC animals exhibited a reversal of cardiac dysfunction such that all indices were not different from pre-SCI, whereas early PHLC/detraining rats exhibited a reduction in all cardiac indices relative to pre-SCI (all P < 0.049), except ejection fraction. Between weeks 7 and 9 post-SCI, the no PHLC/delayed PHLC rats exhibited fewer spontaneous AD events than the early PHLC/detraining rats (P < 0.01). We show, for the first time, that delayed exercise promotes similar improvements in cardiac and haemodynamic function to those observed with early initiation. Furthermore, exercise needs to be maintained, because detraining reduces these cardiohaemodynamic benefits.


Subject(s)
Heart/physiology , Hemodynamics/physiology , Physical Conditioning, Animal/physiology , Spinal Cord Injuries/physiopathology , Animals , Autonomic Dysreflexia/physiopathology , Blood Pressure/physiology , Cardiovascular Diseases/physiopathology , Disease Models, Animal , Hindlimb/physiopathology , Male , Rats , Rats, Wistar , Spinal Cord/physiopathology
17.
Hypertension ; 68(5): 1281-1289, 2016 11.
Article in English | MEDLINE | ID: mdl-27698067

ABSTRACT

Autonomic dysreflexia (AD), which describes episodic hypertension, is highly prevalent in people with spinal cord injury (SCI). In non-SCI, primary hypertension depresses cardiac contractile reserve via ß-adrenergic mechanisms. In this study, we investigated whether AD contributes to the impairment in cardiac contractile function that accompanies SCI. We induced SCI in rodents and stratified them into sham, SCI, or SCI plus repetitive induction of AD. At 6-week post-SCI, we assessed cardiac function using in vivo (speckle-tracking echocardiography), ex vivo (working heart), and molecular approaches (Western blot). We also provide unique translational insight by comparing the relationship between the number of daily AD events and cardiac function in 14 individuals with cervical SCI. We found SCI and SCI plus repetitive induction of AD exhibited a reduction in left ventricular dimensions at 6-week post-SCI versus preinjury (P<0.049). Compared with sham, SCI exhibited a reduction in peak radial strain along with a down and rightward shift in the Starling curve (P<0.037), both of which were further depressed in SCI plus repetitive induction of AD (P<0.042). In response to ß-adrenergic stimulation, SCI plus repetitive induction of AD exhibited an attenuated increase in contractile indices (P<0.001), despite no differences in ß-receptor expression within the left ventricle. Our clinical data confirm our experimental findings by demonstrating significant associations between the number of daily AD events and markers of systolic and diastolic function along with left ventricular mechanics. Here, we provide the first evidence from a translational perspective that AD exerts insidious effects on cardiac function in rodents and humans with SCI.


Subject(s)
Autonomic Dysreflexia/complications , Hypertension/physiopathology , Myocardial Contraction/physiology , Spinal Cord Injuries/complications , Ventricular Function, Left/physiology , Animals , Autonomic Dysreflexia/physiopathology , Blood Pressure Monitoring, Ambulatory , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Disease Models, Animal , Essential Hypertension , Humans , Hypertension/etiology , Male , Multivariate Analysis , Random Allocation , Rats , Rats, Wistar , Reference Values , Regression Analysis , Risk Assessment , Sampling Studies , Spinal Cord Injuries/physiopathology
18.
Int J Group Psychother ; 55(4): 595-604, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16232115

ABSTRACT

This preliminary study investigated the effectiveness of a group-based therapeutic community for the homeless. Thirty-seven individuals residing at a homeless shelter participating in a therapeutic community were assessed across time on several variables: psychiatric symptoms, social functioning, and substance abuse. Significant initial improvements in overall distress, psychiatric symptoms, and substance abuse were found. Improvements in social functioning were exhibited in the therapeutic community participants after six months.


Subject(s)
Ill-Housed Persons/psychology , Mental Disorders/psychology , Mental Disorders/therapy , Psychotherapy, Group , Female , Humans , Male , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL