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1.
Front Rehabil Sci ; 5: 1364016, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39109215

RESUMEN

Introduction: Possibilities Project Plus (PPPlus) is a free assistive device (AD) marketplace and research platform for persons with disabilities. The overall aim of PPPlus is to increase access to ADs through an integration of service, research and education. To maximize positive outcomes and reflect community needs a co-design approach informed by guiding principles of Integrated Knowledge Translation (IKT) was adopted, with examination of methods related to Experience Based Co-design. The integrated nature of PPPlus benefits from the use of specific engagement strategies that align with IKT principles to meet project objectives. The extent to which partnership and engagement strategies are specified in the rehabilitation research literature vary greatly and studies that provide information on specific strategies used to operationalize principles are limited. The objective of this manuscript is to provide a description of the co-design approach and the specific strategies that strive to achieve meaningful user engagement. By reflecting on these processes we also report on limitations and strategies for improvement. Methods: The co-design approach is highlighted through specific project activities including a representative governance structure, ongoing environmental scan and iterative Health Equity Impact Assessments (HEIA). The inherent engagement strategies that align with IKT and co-design principles are described. Discussion: The most impactful engagement strategies included early engagement of partners throughout all phases, ensuring project relevance across partners through alignment of objectives with complementary aims, using HEIAs to promote equitable outcomes from diverse stakeholders, the representative governance structure beyond individuals with disabilities and caregivers, and the use of experiences and stories to inform development. Next steps: This examination of specific strategies related to co-design focused on partnership engagement and informed targets for enhancement of the PPPlus initiative. These include being more intentional in developing a more rigorous process for evaluation that includes an assessment of strategies and their impact-especially as related to partner engagement. In addition, ongoing and enhanced efforts will focus on developing knowledge products that bring to life the most salient experience-based user stories emerging from the environmental scan with these being used to drive distinct co-creation events as well as serve other knowledge mobilization purposes (i.e., supporting policy change).

2.
Digit Health ; 10: 20552076241272618, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184017

RESUMEN

Objective: Parkwood VIP4SCI platform is a virtual e-health solution adapted from a version created for Spinal Cord Injury Ontario (SCIO) that focused on self-management skill development for persons with spinal cord injury (SCI) transitioning between stages of care, in partnership with caregivers and clinicians. This evaluation of the platform informs the usability and feasibility of a model to facilitate service care aims postrehabilitation. Design: Participants: Inpatients and outpatients admitted to the SCI Rehabilitation Program (n = 31), and a mix of interdisciplinary clinicians on the Rehabilitation Team (n = 20). Caregivers participated at the discretion of the patient.Interventions: Inpatients were randomized into two groups (Platform or Standard Care (i.e., delayed access)). Outpatients were given access at enrollment. Pre-post assessments were completed using surveys, and platform analytics were collected. Weekly check-ins were introduced to increase engagement. Focus groups were held with a subset of participants near study completion. Results: VIP4SCI was viewed as usable and feasible. Platform satisfaction assessed on a -3 to +3 scale ranged from +0.9 to 2.5, demonstrating positive agreement. Self-efficacy related to self-management ranged from 5.4 to 7.6 out of 10. The educational resource hub was identified as the most beneficial feature. Lack of clinician uptake was a barrier to integration into day-to-day practice. Conclusions: Platform usage was low among all groups despite the perceived need for facilitating care coordination with consistent and intentional self-management programming. Despite the lack of uptake, partly due to challenges associated with the pandemic, conclusions on platform features and barriers to implementation will help to inform future programming.

3.
Lab Chip ; 24(17): 4096-4104, 2024 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-39086302

RESUMEN

Electrochemical sensors provide an affordable and reliable approach towards the detection and monitoring of important biological species ranging from simple ions to complex biomolecules. The ability to miniaturize electrochemical sensors, coupled with their affordability and simple equipment requirements for signal readout, permits the use of these sensors at the point-of-care where analysis using non-invasively obtainable biofluids is receiving growing interest by the research community. This paper describes the design, fabrication, and integration of a 3D printed Mg2+ potentiometric sensor into a 3D printed microfluidic device for the quantification of Mg2+ in low-sample volume biological fluids. The sensor employs a functionalized 3D printable photocurable methacrylate-based ion-selective membrane affixed to a carbon-mesh/epoxy solid-contact transducer for the selective determination of Mg2+ in sweat, saliva and urine. The 3D printed Mg2+ ion-selective electrode (3Dp-Mg2+-ISE) provided a Nernstian response of 27.5 mV per decade with a linear range of 10 mM to 39 µM, covering the normal physiological and clinically relevant levels of Mg2+ in biofluids. 3Dp-Mg2+-ISEs selectively measure Mg2+ over other biologically present cations - sodium, potassium, calcium, ammonium - as well as provide high stability in the analytical signal with a drift of just 13 µV h-1 over 10 hours. Comparison with poly(vinylchloride)-based Mg2+-ISEs showed distinct advantages to the use of 3Dp-Mg2+-ISEs, with respect to stability, resilience towards biofouling and importantly providing a streamlined and rapid approach towards mass production of selective and reliable sensors. The miniaturization capabilities of 3D printing coupled with the benefits of microfluidic analysis (i.e., low sample volumes, minimal reagent consumption, automation of multiple assays, etc.), provides exciting opportunities for the realization of the next-generation of point-of-care diagnostic devices.


Asunto(s)
Dispositivos Laboratorio en un Chip , Magnesio , Impresión Tridimensional , Magnesio/química , Humanos , Potenciometría/instrumentación , Diseño de Equipo , Técnicas Analíticas Microfluídicas/instrumentación , Electrodos de Iones Selectos , Saliva/química
4.
Anat Rec (Hoboken) ; 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39072999

RESUMEN

Resolving the phylogenetic relationships of early amniotes, in particular stem reptiles, remains a difficult problem. Three-dimensional morphological analysis of well-preserved stem-reptile specimens can reveal important anatomical data and clarify regions of phylogeny. Here, we present the first thorough description of the unusual early Permian stem reptile Bolosaurus major, including the first comprehensive description of a bolosaurid braincase. We describe previously obscured details of the palate, allowing for insight into bolosaurid feeding mechanics. Aspects of the rostrum, palate, mandible, and neurocranium suggest that B. major had a particularly strong bite. We additionally found B. major has a surprisingly slender stapes, similar to that of the middle Permian stem reptile Macroleter poezicus, which may suggest enhanced hearing abilities compared to other Paleozoic amniotes (e.g., captorhinids). We incorporated our new anatomical information into a large phylogenetic matrix (150 OTUs, 590 characters) to explore the relationship of Bolosauridae among stem reptiles. Our analyses generally recovered a paraphyletic "Parareptilia," and found Bolosauridae to diverge after Captorhinidae + Araeoscelidia. We also included B. major within a smaller matrix (10 OTUs, 27 characters) designed to explore the interrelationships of Bolosauridae and found all species of Bolosaurus to be monophyletic. While reptile relationships still require further investigation, our phylogeny suggests repeated evolution of impedance-matching ears in Paleozoic stem reptiles.

5.
Front Rehabil Sci ; 5: 1336559, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887696

RESUMEN

Objective: This qualitative study aims to identify a comprehensive set of enablers and barriers to implementing an interdisciplinary experiential learning program for university students at a Canadian rehabilitation centre. Methods: A researcher conducted one-on-one semi-structured interviews with individuals from four key stakeholder groups (i.e., rehabilitation centre leadership, clinicians, university clinical coordinators, and health and rehabilitation students). Interviews and data analysis followed the Theoretical Domains Framework (TDF), which is designed to identify possible cognitive, affective, social, and environmental influences on program implementation. Interviews were transcribed verbatim, and two researchers coded data independently to identify the major themes of enablers and barriers to implementing an interdisciplinary experiential learning approach to rehabilitation care. Results: From a total of 12 interviews, domains of the TDF were identified to represent overarching themes, which were (1) enablers (i.e., reinforcement, beliefs and consequences, optimism, professional identity, knowledge, and skills), (2) barriers (i.e., environment/resources and beliefs and capabilities), and (3) program development (i.e., goals and evaluation that was not previously a TDF domain). A list of recommendations for implementing an interdisciplinary experiential learning program was created that represented qualitative data from each stakeholder group. Conclusion: This study provides insight into the potential enablers and barriers to developing an interdisciplinary experiential learning program for university students within rehabilitation centres. This type of program could enhance educational curriculums, student and clinical experiences, and patient outcomes. In this study, the findings inform recommendations for developing an interdisciplinary program in teaching hospitals and explore their potential impact. Future research and pilot studies must be conducted to fully understand the effects of implementing an interdisciplinary experiential learning approach within rehabilitation centres.

6.
Healthcare (Basel) ; 12(11)2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38891159

RESUMEN

BACKGROUND: Despite preventability, 20-50% of patients with acute spinal cord injury/disease (SCI/D) develop hospital-acquired pressure injuries (PIs). The Spinal Cord Injury Implementation and Evaluation Quality Care Consortium (SCI IEQCC) aimed to mitigate PI risk through patient-reported daily skin checks alongside usual care. METHODS: This quality improvement initiative utilized an interrupted time series design, encompassing adults ≥ 18 years admitted for inpatient rehabilitation across five Ontario sites from 2020 to 2023. Patient demographics, etiology, and impairment data were obtained from a national registry, while participating sites gathered data on PI onset, location, and severity. Run charts depicted temporal trends, and statistical analyses, including chi-square and logistic regression, compared patients with and without PIs. RESULTS: Data from 1767 discharged SCI/D patients revealed that 26% had ≥1 PI, with 59% being prevalent and 41% incident. Most severe PIs (stages III and IV and unstageable) were acquired prior to admission. Process indicator fidelity was reasonable at 68%. Patients with PIs experienced longer hospital stays, lower Functional Independence Measure (FIM) changes, and FIM efficiency during rehabilitation. CONCLUSIONS: PI prevalence is increasing, particularly sacral injuries at admission, while incident cases have decreased since 2021 due to regular skin checks. This trend calls for proactive health system interventions to reduce costs and improve patient outcomes.

7.
Dev Biol ; 512: 35-43, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38710381

RESUMEN

The larval stage of the Drosophila melanogaster life cycle is characterized by rapid growth and nutrient storage that occur over three instar stages separated by molts. In the third instar, the steroid hormone ecdysone drives key developmental processes and behaviors that occur in a temporally-controlled sequence and prepare the animal to undergo metamorphosis. Accurately staging Drosophila larvae within the final third instar is critical due to the rapid developmental progress at this stage, but it is challenging because the rate of development varies widely across a population of animals even if eggs are laid within a short period of time. Moreover, many methods to stage third instar larvae are cumbersome, and inherent variability in the rate of development confounds some of these approaches. Here we demonstrate the usefulness of the Sgs3-GFP transgene, a fusion of the Salivary gland secretion 3 (Sgs3) and GFP proteins, for staging third instar larvae. Sgs3-GFP is expressed in the salivary glands in an ecdysone-dependent manner from the midpoint of the third instar, and its expression pattern changes reproducibly as larvae progress through the third instar. We show that Sgs3-GFP can easily be incorporated into experiments, that it allows collection of developmentally-equivalent individuals from a mixed population of larvae, and that its use enables precise assessment of changing levels of hormones, metabolites, and gene expression during the second half of the third instar.


Asunto(s)
Drosophila melanogaster , Ecdisona , Proteínas Fluorescentes Verdes , Larva , Fenotipo , Glándulas Salivales , Animales , Larva/metabolismo , Larva/genética , Glándulas Salivales/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Proteínas Fluorescentes Verdes/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Ecdisona/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Genes Reporteros , Regulación del Desarrollo de la Expresión Génica/genética , Animales Modificados Genéticamente , Metamorfosis Biológica/genética
8.
Animal ; 18(3): 101095, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38367311

RESUMEN

Milk markers have the potential to aid in the detection of cow disease in early lactation if the automation of milk analysis becomes commonplace. Characterising temporal profiles of milk markers in dairy cows will improve the understanding of basal concentrations in clinically healthy cows. The objective of this observational study was to characterise the variation and temporal profiles of colostrum and milk haptoglobin (Hp) and substance P concentrations within 21 days postcalving in clinically healthy multiparous Holstein dairy cows. Ninety Holstein dairy cows from a commercial dairy herd were included. Milk samples were collected on the day of calving (day 0), and on days 1 to 4, 7, 14, and 21 postcalving and concentrations of Hp and substance P in colostrum (days 0 to 3) and milk (days 4, 7, 14, and 21) were determined using Enzyme Linked Immunosorbent assay. Haptoglobin and substance P concentrations were, on average (raw means ± SD), 0.40 ± 0.26 µg/ml and 56.2 ± 38.7 pg/ml in colostrum, respectively, and 0.23 ± 0.23 µg/ml and 37.1 ± 27.8 pg/ml in milk, respectively. Haptoglobin and substance P were elevated and greatest 1 day postcalving (least squares mean ± SE of the mean; 0.53 ± 0.05 µg/ml and 46.5 ± 3.64 pg/ml, respectively) and substance P varied widely within 21 days postcalving. The presence of substance P in dairy cow colostrum was not documented previously. Elevated concentrations of Hp and substance P immediately postcalving may be due to physiological roles these inflammatory markers have in the dairy cow or neonate or may simply represent an accumulation in colostrum before the first milk is removed.


Asunto(s)
Calostro , Leche , Embarazo , Femenino , Bovinos , Animales , Haptoglobinas , Sustancia P , Lactancia/fisiología
9.
J Immunol ; 212(1): 43-56, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37955416

RESUMEN

Serum Ab concentrations, selection for higher affinity BCRs, and generation of higher Ab affinities are important elements of immune response optimization and functions of germinal center (GC) reactions. B cell proliferation requires nutrients to support the anabolism inherent in clonal expansion. Glucose usage by mouse GC B cells has been reported to contribute little to their energy needs, with questions raised as to whether glucose uptake or glycolysis increases in GC B cells compared with their naive precursors. Indeed, metabolism can be highly flexible, such that supply shortage along one pathway may be compensated by increased flux on others. We now show that reduction of the glucose transporter GLUT1 in mice after establishment of a preimmune B cell repertoire, even after initiation of the GC B cell gene expression program, decreased initial GC B cell population numbers, affinity maturation, and plasma cell outputs. Glucose oxidation was heightened in GC B cells, but this hexose flowed more into the pentose phosphate pathway, whose activity was important in controlling reactive oxygen species (ROS) and Ab-secreting cell production. In modeling how glucose usage by B cells promotes the Ab response, the control of ROS appeared insufficient. Surprisingly, the combination of galactose, which mitigated ROS, with provision of mannose, an efficient precursor to glycosylation, supported robust production of and normal Ab secretion by Ab-secreting cells under glucose-free conditions. Collectively, the findings indicate that GCs depend on normal glucose influx, especially in plasma cell production, but reveal an unexpected metabolic flexibility in hexose requirements.


Asunto(s)
Centro Germinal , Glucosa , Ratones , Animales , Glucosa/metabolismo , Especies Reactivas de Oxígeno , Anticuerpos , Diferenciación Celular
10.
Biosens Bioelectron ; 248: 115971, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38154328

RESUMEN

Apomorphine is a dopamine agonist that is used for the management of Parkinson's disease and has been proven to effectively decrease the off-time duration, where the symptoms recur, in Parkinson's disease patients. This paper describes the design and fabrication of the first potentiometric sensor for the determination of apomorphine in bulk and human plasma samples. The fabrication protocol involves stereolithographic 3D printing, which is a unique tool for the rapid fabrication of low-cost sensors. The solid-contact apomorphine ion-selective electrode combines a carbon-mesh/thermoplastic composite as the ion-to-electron transducer and a 3D printed ion-selective membrane, doped with the ionophore calix[6]arene. The sensor selectively measures apomorphine in the presence of other biologically present cations - sodium, potassium, magnesium, and calcium - as well as the commonly prescribed Parkinson's pharmaceutical, levodopa (L-Dopa). The sensor demonstrated a linear, Nernstian response, with a slope of 58.8 mV/decade over the range of 5.0 mM-9.8 µM, which covers the biologically (and pharmaceutically) relevant ranges, with a limit of detection of 2.51 µM. Moreover, the apomorphine sensor exhibited good stability (minimal drift of just 188 µV/hour over 10 h) and a shelf-life of almost 4 weeks. Experiments performed in the presence of albumin, the main plasma protein to which apomorphine binds, demonstrate that the sensor responds selectively to free-apomorphine (i.e., not bound or complexed forms). The utility of the sensor was confirmed through the successful determination of apomorphine in spiked human plasma samples.


Asunto(s)
Técnicas Biosensibles , Enfermedad de Parkinson , Humanos , Apomorfina , Enfermedad de Parkinson/tratamiento farmacológico , Electrodos de Iones Selectos , Preparaciones Farmacéuticas , Potenciometría
11.
R Soc Open Sci ; 10(10): 230968, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37830017

RESUMEN

Most living reptile diversity is concentrated in Squamata (lizards, including snakes), which have poorly known origins in space and time. Recently, †Cryptovaranoides microlanius from the Late Triassic of the United Kingdom was described as the oldest crown squamate. If true, this result would push back the origin of all major lizard clades by 30-65 Myr and suggest that divergence times for reptile clades estimated using genomic and morphological data are grossly inaccurate. Here, we use computed tomography scans and expanded phylogenetic datasets to re-evaluate the phylogenetic affinities of †Cryptovaranoides and other putative early squamates. We robustly reject the crown squamate affinities of †Cryptovaranoides, and instead resolve †Cryptovaranoides as a potential member of the bird and crocodylian total clade, Archosauromorpha. Bayesian total evidence dating supports a Jurassic origin of crown squamates, not Triassic as recently suggested. We highlight how features traditionally linked to lepidosaurs are in fact widespread across Triassic reptiles. Our study reaffirms the importance of critically choosing and constructing morphological datasets and appropriate taxon sampling to test the phylogenetic affinities of problematic fossils and calibrate the Tree of Life.

12.
bioRxiv ; 2023 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-37745429

RESUMEN

Antibody secretion into sera, selection for higher affinity BCR, and the generation of higher Ab affinities are important elements of immune response optimization, and a core function of germinal center reactions. B cell proliferation requires nutrients to support the anabolism inherent in clonal expansion. Glucose usage by GC B cells has been reported to contribute little to their energy needs, with questions raised as to whether or not glucose uptake or glycolysis increases in GC B cells compared to their naïve precursors. Indeed, metabolism can be highly flexible, such that supply shortage along one pathway may be compensated by increased flux on others. We now show that elimination of the glucose transporter GLUT1 after establishment of a pre-immune B cell repertoire, even after initiation of the GC B cell gene expression program, decreased initial GC B cell population numbers, affinity maturation, and PC outputs. Glucose oxidation was heightened in GC B cells, but this hexose flowed more into the pentose phosphate pathway (PPP), whose activity was important in controlling reactive oxygen (ROS) and ASC production. In modeling how glucose usage by B cells promotes the Ab response, the control of ROS appeared insufficient. Surprisingly, the combination of galactose, which mitigated ROS, with provision of mannose - an efficient precursor to glycosylation - supported robust production of and normal Ab secretion by ASC under glucose-free conditions. Collectively, the findings indicate that GC depend on normal glucose influx, especially in PC production, but reveal an unexpected metabolic flexibility in hexose requirements. KEY POINTS: Glucose influx is critical for GC homeostasis, affinity maturation and the generation of Ab-secreting cells.Plasma cell development uses the Pentose Phosphate Pathway, and hexose sugars maintain redox homeostasis.PCs can develop and achieve robust Ab secretion in the absence of glucose using a combination of hexose alternatives.

13.
Digit Health ; 9: 20552076231183555, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37426589

RESUMEN

Objective: Mild traumatic brain injuries (mTBIs) are common and may result in persisting symptoms. Mobile health (mHealth) applications enhance treatment access and rehabilitation. However, there is limited evidence to support mHealth applications for individuals with an mTBI. The primary purpose of this study was to evaluate user experiences and perceptions of the Parkwood Pacing and Planning™ application, an mHealth application developed to help individuals manage their symptoms following an mTBI. The secondary purpose of this study was to identify strategies to improve the application. This study was conducted as part of the development process for this application. Methods: A mixed methods co-design encompassing an interactive focus group and a follow-up survey was conducted with patient and clinician-participants (n = 8, four per group). Each group participated in a focus group consisting of an interactive scenario-based review of the application. Additionally, participants completed the Internet Evaluation and Utility Questionnaire (UQ). Qualitative analysis on the interactive focus group recordings and notes was performed using phenomenological reflection through thematic analyses. Quantitative analysis included descriptive statistics of demographic information and UQ responses. Results: On average, clinician and patient-participants positively rated the application on the UQ (4.0 ± .3, 3.8 ± .2, respectively). User experiences and recommendations for improving the application were categorized into four themes: simplicity, adaptability, conciseness, and familiarity. Conclusion: Preliminary analyses indicates patients and clinicians have a positive experience when using the Parkwood Pacing and Planning™ application. However, modifications that improve simplicity, adaptability, conciseness, and familiarity may further improve the user's experience.

14.
Anal Chim Acta ; 1273: 341546, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37423672

RESUMEN

Parkinson's disease (PD) is one of the leading neurological disorders negatively impacting health on a global scale. Patients diagnosed with PD require frequent monitoring, prescribed medications, and therapy for extended periods as symptom severity worsens. The primary pharmaceutical treatment for PD patients is levodopa (L-Dopa) which reduces many symptoms experienced by PD patients (e.g., tremors, cognitive ability, motor dysfunction, etc.) through the regulation of dopamine levels in the body. Herein, the first detection of L-Dopa in human sweat using a low-cost 3D printed sensor with a simple and rapid fabrication protocol combined with a portable potentiostat wirelessly connected to a smartphone via Bluetooth is reported. By combining saponification and electrochemical activation into a single protocol, the optimized 3D printed carbon electrodes were able to simultaneously detect uric acid and L-Dopa throughout their biologically relevant ranges. The optimized sensors provided a sensitivity of 83 ± 3 nA/µM from 24 µM to 300 nM L-Dopa. Common physiological interferents found in sweat (e.g., ascorbic acid, glucose, caffeine) showed no influence on the response for L-Dopa. Lastly, a percent recovery of L-Dopa in human sweat using a smartphone-assisted handheld potentiostat resulted in the recovery of 100 ± 8%, confirming the ability of this sensor to accurately detect L-Dopa in sweat.


Asunto(s)
Levodopa , Enfermedad de Parkinson , Humanos , Sudor , Teléfono Inteligente , Enfermedad de Parkinson/tratamiento farmacológico , Impresión Tridimensional
15.
BMC Neurol ; 23(1): 266, 2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37442947

RESUMEN

BACKGROUND: Most individuals living with spinal cord injuries/diseases (SCI/D) or stroke experience at least one fall each year; hence, the development of interventions and technologies that target balance control is needed. The purpose of this study was to identify and explore the priorities for balance-focused interventions and technologies from the perspectives of end-users to assist with the design of an intervention that combines functional electrical stimulation (FES) with visual feedback training for standing balance. METHODS: Two individuals with SCI/D, one individual with stroke, two physical therapists (PT) and one hospital administrator were recruited. Participants attended three focus group meetings that followed a participatory co-design approach. A semi-structured interview guide, developed from the FAME (Feasibility, Appropriateness, Meaningfulness, Effectiveness, Economic Evidence) framework, was used to lead the discussion, querying participants' experiences with balance deficits and interventions, and FES. Meetings were audio-recorded and transcribed verbatim. An iterative and reflexive inductive thematic analysis was applied to the transcripts by three researchers. RESULTS: Four themes were identified: (1) Balance is meaningful for daily life and rehabilitation. Participants acknowledged various factors influencing balance control and how balance deficits interfered with participation in activities. End-users stressed the importance of continuing to work on one's balance after discharge from hospital-based rehabilitation. (2) Desired characteristics of balance interventions. Participants explained that balance interventions should be tailored to an individual's unique needs and goals, relevant to their lives, balance their safety and risk, and be engaging. (3) Prior experiences with FES to inform future therapeutic use. Participants with stroke or SCI/D described initial apprehension with FES, but experienced numerous benefits that motivated them to continue with FES. Challenges with FES were mentioned, including wires, cost, and time of set up. (4) Potential role of FES in balance interventions. Participants felt that FES would complement balance interventions; however, they had not experienced this combination of therapies previously. CONCLUSIONS: End-users described how their experiences with balance deficits, rehabilitation, and FES informed their priorities for balance interventions. The findings inform the design and implementation of future balance interventions for individuals with SCI/D or stroke, including an intervention involving FES and visual feedback training.


Asunto(s)
Terapia por Estimulación Eléctrica , Traumatismos de la Médula Espinal , Accidente Cerebrovascular , Humanos , Traumatismos de la Médula Espinal/rehabilitación , Terapia por Ejercicio , Accidente Cerebrovascular/terapia , Estimulación Eléctrica
16.
J Phys Chem B ; 127(26): 5772-5788, 2023 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-37357785

RESUMEN

Fluorescent proteins (FPs) have had an enormous impact on molecular and cellular biology and are employed in a wide range of studies of molecular structure and dynamics. Yet, only a modest number of papers have published molecular dynamics (MD) parameters describing FPs. And despite the development of a wide range of FPs, there has been no careful development of MD parameters across a series of FPs. In this work, we present MD parameters describing six fluorescent protein chromophores (EGFP, EBFP, EYFP, ECFP, mCherry, and DsRed) for use with the Cornell et al. ( J. Am. Chem. Soc. 1995, 117, 5179-5197) family of AMBER force fields, including ff14SB and ff19SB. We explore a wide range of solvent dielectric constants for determining the chromophore equilibrium geometry and evaluate the impact of the modeled solvent on the final atomic charges. We also present our methodological approach in which we considered all six chromophores together with a focus on modularity, transferability, and balance with existing force fields. The parameters given here make it easy to employ MD simulations to study any of the six systems, whereas the methodology makes it easy for anyone to extend this work to develop consistent parameters for additional fluorescent proteins. The results of our own MD simulations are presented, showing that the classical MD parameters yield chromophore structural distributions that compare well with QM/MM simulations.


Asunto(s)
Simulación de Dinámica Molecular , Estructura Molecular , Solventes
17.
Curr Opin Clin Nutr Metab Care ; 26(3): 210-218, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36942895

RESUMEN

PURPOSE OF REVIEW: Systemic cancer therapy-associated skeletal muscle wasting is emerging as a powerful impetus to the overall loss of skeletal muscle experienced by patients with cancer. This review explores the clinical magnitude and biological mechanisms of muscle wasting during systemic cancer therapy to illuminate this adverse effect. Emerging strategies for mitigation are also discussed. RECENT FINDINGS: Clinical findings include precise, specific measures of muscle loss over the course of chemotherapy, targeted therapy and immunotherapy. All these therapeutic classes associate with quantitatively important muscle loss, independent of tumor response. Parallel experimental studies provide understanding of the specific molecular basis of wasting, which can include inhibition of protein synthesis, proliferation and differentiation, and activation of inflammation, reactive oxygen species, autophagy, mitophagy, apoptosis, protein catabolism, fibrosis and steatosis in muscle. Strategies to mitigate these muscle-specific adverse effects of cancer therapy remain in the earliest stages of development. SUMMARY: The adverse side effect of cancer therapy on skeletal muscle has been largely ignored in the development of cancer therapeutics. Given the extent to which loss of muscle mass and function can bear on patients' function and quality of life, protection/mitigation of these side effects is a research priority.


Asunto(s)
Miotoxicidad , Neoplasias , Humanos , Miotoxicidad/metabolismo , Miotoxicidad/patología , Calidad de Vida , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Neoplasias/metabolismo
18.
Spinal Cord Ser Cases ; 9(1): 1, 2023 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-36646680

RESUMEN

STUDY DESIGN: Cross-sectional equipment inventory. OBJECTIVES: The objective of this study was to describe the equipment used in activity-based therapy (ABT) programs for individuals with spinal cord injury or disorder (SCI/D) across Canada. SETTINGS: Publicly funded and private SCI/D care settings. METHODS: A survey on equipment available for ABT for different therapeutic goals was answered by Canadian sites providing SCI/D rehabilitation. Information about the setting and type of client were also collected. The survey results were compiled into an inventory of the reported types and use of ABT related equipment, with equipment grouped into varying levels of technology. Descriptive statistics and qualitative descriptive analysis were used to answer the questions: (1) 'who' used the equipment, (2) 'what' types of equipment are used, (3) 'why' (i.e., for which therapeutic goals), and (4) 'how' it is used. RESULTS: Twenty-two sites from eight Canadian provinces completed the survey. Reported equipment was classified into 5 categories (from low to high-tech). Most equipment reported was used to train balance. The high-tech equipment reported as available, was mostly used for walking training and strengthening of the lower limbs. Low-tech equipment was reported as being used most frequently, while high-tech devices, although available, were reported as infrequently or rarely used. CONCLUSIONS: A large spectrum of equipment with varying levels of technology were reported as available, but were inconsistently used to provide ABT interventions across sites. In order to increase the clinical use of available equipment for ABT, education tools such as protocols regarding ABT principles and implementation are needed.


Asunto(s)
Traumatismos de la Médula Espinal , Caminata , Humanos , Estudios Transversales , Canadá , Traumatismos de la Médula Espinal/rehabilitación , Tecnología
19.
J Spinal Cord Med ; 46(1): 6-25, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-33596167

RESUMEN

CONTEXT: Endocrine-metabolic disease (EMD) is associated with functional disability, social isolation, hospitalization and even death in individuals living with a chronic spinal cord injury (SCI). There is currently very low-quality evidence that rehabilitation interventions can reduce EMD risk during chronic SCI. Non-randomized trials and alternative study designs are excluded from traditional knowledge synthesis. OBJECTIVE: To characterize evidence from level 3-4 studies evaluating rehabilitation interventions for their effectiveness to improve EMD risk in community-dwelling adults with chronic SCI. METHODS: Systematic searches of MEDLINE PubMed, EMBASE Ovid, CINAHL, Cochrane Database of Systematic Reviews, and PsychInfo were completed. All longitudinal trials, prospective cohort, case-control studies, and case series evaluating the effectiveness of rehabilitation/therapeutic interventions to modify/associate with EMD outcomes in adults with chronic SCI were eligible. Two authors independently selected studies and abstracted data. Mean changes from baseline were reported for EMD outcomes. The Downs and Black Checklist was used to rate evidence quality. RESULTS: Of 489 articles identified, 44 articles (N = 842) were eligible for inclusion. Individual studies reported statistically significant effects of electrical stimulation-assisted training on lower-extremity bone outcomes, and the combined effects of exercise and dietary interventions to improve body composition and cardiometabolic biomarkers (lipid profiles, glucose regulation). In contrast, there were also reports of no clinically important changes in EMD outcomes, suggesting lower quality evidence (study bias, inconsistent findings). CONCLUSION: Longitudinal multicentre pragmatic studies involving longer-term exercise and dietary intervention and follow-up periods are needed to fully understand the impact of these rehabilitation approaches to mitigate EMD risk. Our broad evaluation of prospective cohort and case-control studies provides new perspectives on alternative study designs, a multi-impairment paradigm approach of studying EMD outcomes, and knowledge gaps related to SCI rehabilitation.


Asunto(s)
Enfermedades del Sistema Endocrino , Enfermedades Metabólicas , Traumatismos de la Médula Espinal , Adulto , Humanos , Terapia por Ejercicio , Estudios Prospectivos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Revisiones Sistemáticas como Asunto
20.
Physiother Theory Pract ; 39(2): 395-404, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34895020

RESUMEN

BACKGROUND: Parkinson's disease (PD) can affect hand function since the beginning of the motor symptoms. OBJECTIVE: To compare the ability of different hand function tests to: 1) distinguish individuals with PD from healthy controls; 2) differentiate stages of the disease; and 3) indicate changes over time due to disease progression. METHODS: Twenty-four individuals with PD (Hoehn and Yahr: I-III) and 24 age- and sex-matched controls performed the Jebsen-Taylor Hand Function Test (JTHFT), the Nine-Hole Peg Test (9HPT), and the maximum grip and the maximum pinch strength tests using their right and left hands. Eight individuals with PD (six females and two males) were reassessed after 18 months. The ROC analyses and Mann-Whitney U tests (for disease progression) using the average performance of the hands were done. RESULTS: Individuals with PD presented worse test performances than controls, except for the writing subtest of the JTHFT and the grip strength test. The JTHFT without the writing subtest (JTHFTnoW) was the most accurate to discriminate PD from controls (AUC = 0.899; sensitivity 75% and specificity 95.8%). The 9HPT and the simulated feeding and moving large, light objects JTHFT subtests were sensitive to distinguish stages, while the 9HPT, the moving small, common objects JTHFT subtest, and the grip strength were sensitive to changes with disease progression. CONCLUSION: The JTHFTnoW was highly discriminative of the hand function impairments in PD. TwoJTHFT subtests were the most sensitives to distinguish PD stages (i.e. simulated feeding JTHFT subtest) and disease progression (i.e. moving small, common objects JTHFT subtest).


Asunto(s)
Enfermedad de Parkinson , Femenino , Humanos , Masculino , Mano , Fuerza de la Mano , Enfermedad de Parkinson/diagnóstico , Extremidad Superior , Destreza Motora , Estudios de Casos y Controles
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