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INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. HIGHLIGHTS: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.
Subject(s)
Biomarkers , Cognitive Dysfunction , Extracellular Vesicles , Neurovascular Coupling , Humans , Cognitive Dysfunction/physiopathology , Extracellular Vesicles/metabolism , Female , Male , Aged , Biomarkers/blood , Neurovascular Coupling/physiology , Magnetic Resonance Imaging , Spectroscopy, Near-Infrared , Middle AgedABSTRACT
Background and Purpose: The effect of knee angle on electrically elicited quadriceps muscle torque has not been established. The goal of this study was to determine which knee angle allowed for the production of the greatest knee extensor maximal voluntary isometric torque (KEMVIT), the greatest electrically elicited torque, and the highest percent of KEMVIT from the knee extensor muscles. Case Description: Eighteen participants were secured in a force dynamometer with the knee positioned at 30°, 60°, and 90° flexion. Participants performed KEMVITs followed by electrically elicited contractions to their maximum tolerance. Outcomes: The mean ± SD of the peak KEMVITs was 123.7 ± 35.7 Nm, 222.6 ± 67.1 Nm, and 248.2 ± 81.1 Nm at 30°, 60°, and 90°, respectively. Significantly greater KEMVITs were produced at 60° and 90° than at 30° (p < 0.001). The mean ± SD of the maximally tolerated electrically elicited torques was 71.8 ± 18.8 Nm, 170.9 ± 70.4 Nm, and 134.6 ± 72.6 Nm at 30°, 60°, and 90°, respectively. Significantly higher torques were tolerated at 60° than at 30° (p < 0.001) and 90° (p = 0.018). The mean ± SD of the percent KEMVITs was 59.7 ± 11.7%, 78.2 ± 23.8%, and 52.6 ± 18.7% at 30°, 60°, and 90°, respectively. Significantly greater percent KEMVITs were produced at 60° than at 30° (p = 0.001) and 90° (p < 0.001). Discussion: Electrically elicited quadriceps torque production is greater at 60° as compared to 30° and 90° knee flexion.
Subject(s)
Electric Stimulation/methods , Isometric Contraction/physiology , Knee Joint/physiology , Quadriceps Muscle/physiology , Range of Motion, Articular/physiology , Adolescent , Adult , Female , Humans , Male , Torque , Young AdultABSTRACT
INTRODUCTION: The purpose of this study was to develop a multi-institutional registry to characterize the demographics, management, and outcomes of a contemporary cohort of children undergoing congenital lung malformation (CLM) resection. METHODS: After central reliance IRB approval, a web-based, secure database was created to capture retrospective cohort data on pathologically-confirmed CLMs performed between 2009 and 2015 within a multi-institutional research collaborative. RESULTS: Eleven children's hospitals contributed 506 patients. Among 344 prenatally diagnosed lesions, the congenital pulmonary airway malformation volume ratio was measured in 49.1%, and fetal MRI was performed in 34.3%. One hundred thirty-four (26.7%) children had respiratory symptoms at birth. Fifty-eight (11.6%) underwent neonatal resection, 322 (64.1%) had surgery at 1-12â¯months, and 122 (24.3%) had operations after 12 months. The median age at resection was 6.7â¯months (interquartile range, 3.6-11.4). Among 230 elective lobectomies performed in asymptomatic patients, thoracoscopy was successfully utilized in 102 (44.3%), but there was substantial variation across centers. The most common lesions were congenital pulmonary airway malformation (nâ¯=â¯234, 47.3%) and intralobar bronchopulmonary sequestration (nâ¯=â¯106, 21.4%). CONCLUSION: This multicenter cohort study on operative CLMs highlights marked disease heterogeneity and substantial practice variation in preoperative evaluation and operative management. Future registry studies are planned to help establish evidence-based guidelines to optimize the care of these patients. LEVEL OF EVIDENCE: Level II.
Subject(s)
Lung , Registries , Respiratory System Abnormalities , Humans , Infant , Infant, Newborn , Lung/abnormalities , Lung/surgery , Prenatal Diagnosis , Respiratory System Abnormalities/diagnosis , Respiratory System Abnormalities/epidemiology , Respiratory System Abnormalities/surgery , Retrospective StudiesABSTRACT
PURPOSE: The purpose of this study was to evaluate the clinical presentation and operative outcomes of patients with congenital lobar emphysema (CLE) within a large multicenter research consortium. METHODS: After central reliance IRB-approval, a retrospective cohort study was performed on all operatively managed lung malformations at eleven participating children's hospitals (2009-2015). RESULTS: Fifty-three (10.5%) children with pathology-confirmed CLE were identified among 506 lung malformations. A lung mass was detected prenatally in 13 (24.5%) compared to 331 (73.1%) in non-CLE cases (pâ¯<â¯0.0001). Thirty-two (60.4%) CLE patients presented with respiratory symptoms at birth compared to 102 (22.7%) in non-CLE (pâ¯<â¯0.0001). The most common locations for CLE were the left upper (nâ¯=â¯24, 45.3%), right middle (nâ¯=â¯16, 30.2%), and right upper (nâ¯=â¯10, 18.9%) lobes. Eighteen (34.0%) had resection as neonates, 30 (56.6%) had surgery at 1-12â¯months of age, and five (9.4%) had resections after 12â¯months. Six (11.3%) underwent thoracoscopic excision. Median hospital length of stay was 5.0â¯days (interquartile range, 4.0-13.0). CONCLUSIONS: Among lung malformations, CLE is associated with several unique features, including a low prenatal detection rate, a predilection for the upper/middle lobes, and infrequent utilization of thoracoscopy. Although respiratory distress at birth is common, CLE often presents clinically in a delayed and more insidious fashion. LEVEL OF EVIDENCE: Level III.
Subject(s)
Pulmonary Emphysema/congenital , Child , Child, Preschool , Dyspnea , Humans , Infant , Midwestern United States/epidemiology , Pulmonary Emphysema/epidemiology , Pulmonary Emphysema/surgery , Respiratory System Abnormalities , Retrospective Studies , Thoracoscopy/statistics & numerical dataABSTRACT
Study Design A controlled laboratory study, with a single-blind, block-randomization crossover design. Objectives To compare the electrically elicited knee extensor torque produced by 3 clinically available waveforms: 2500-Hz burst-modulated alternating current (BMAC), 1000-Hz BMAC, and 1000-Hz burst-modulated biphasic square-wave pulsed current (BMBPC). Background Neuromuscular electrical stimulation (NMES) is the therapeutic use of electrical current to strengthen muscle. Muscle torque produced by NMES is limited by discomfort. Methods The knee extensor maximal volitional isometric torque (KEMVIT) of 33 able-bodied participants (18 female) was measured and used to normalize the electrically elicited knee extensor torque to produce a percent of KEMVIT (%KEMVIT). Electrically elicited isometric knee extensor torque was measured in response to each of the waveforms at the participants' maximum tolerance. Results The average maximum tolerated stimulation produced 32.0 ± 16.7 %KEMVIT with 2500-Hz BMAC, 38.2 ± 18.4 %KEMVIT with 1000-Hz BMAC, and 42.2 ± 17.1 %KEMVIT with 1000-Hz BMBPC. Tukey honest significant difference (HSD) post hoc testing revealed a statistically significant difference between 2500-Hz BMAC and 1000-Hz BMAC (P = .046), and between 2500-Hz BMAC and 1000-Hz BMBPC (P<.001). No statistically significant difference was found between 1000-Hz BMAC and 1000-Hz BMBPC (P = .267). Conclusion For eliciting maximum knee extensor muscle torque, 1000-Hz BMBPC and 1000-Hz BMAC were similarly effective, and 2500-Hz BMAC was less effective. J Orthop Sports Phys Ther 2018;48(3):217-224. Epub 19 Dec 2017. doi:10.2519/jospt.2018.7601.
Subject(s)
Electric Stimulation/methods , Quadriceps Muscle/physiology , Torque , Adolescent , Adult , Cross-Over Studies , Electric Stimulation Therapy/methods , Female , Humans , Isometric Contraction/physiology , Male , Middle Aged , Muscle Strength/physiology , Single-Blind Method , Young AdultABSTRACT
Osteoarthritis (OA) is a degenerative joint disease with a high prevalence in dogs. Mesenchymal stem cells (MSCs) have been used to treat humans, dogs, and horses with OA. This report describes a prospective, randomized, blinded, and placebo-controlled clinical efficacy study of intraarticular allogeneic adipose stem cells for the treatment of dogs with OA. Health assessments and measurements of pain and activity impairment were performed at baseline and at selected time points through day 60. The primary outcome variable was the owner Client-Specific Outcome Measurement (CSOM) and secondary measures included veterinary pain on manipulation, veterinary global score, and owner global score. The dogs were treated with either a saline placebo or a single dose of allogeneic adipose-derived MSCs in either one or two joints. Seventy-four dogs were statistically analyzed for efficacy outcomes. Success in the primary outcome variable, CSOM, was statistically improved in the treated dogs compared to the placebo dogs (79.2 versus 55.4%, p = 0.029). The veterinary pain on manipulation score (92.8 versus 50.2%, p = 0.017) and the veterinary global score (86.9 versus 30.8%, p = 0.009) were both statistically improved in treated dogs compared to placebo. There was no detected significant difference between treated and placebo dogs in the incidence of adverse events or negative health findings. Allogeneic adipose-derived stem cell treatment was shown to be efficacious compared to placebo. This large study of dogs also provides valuable animal clinical safety and efficacy outcome data to our colleagues developing human stem cell therapy.
ABSTRACT
STUDY DESIGN: Single-blind, block-randomization crossover design. OBJECTIVE: To compare the knee extensor muscle torque production elicited with 2500-Hz burst-modulated alternating current (BMAC) and with a monophasic pulsed current (MPC) at the maximum tolerated stimulation intensity. BACKGROUND: Neuromuscular electrical stimulation (NMES) is often used for strengthening the quadriceps following knee surgery. Strength gains are dependent on muscle torque production, which is primarily limited by discomfort. Burst-modulated alternating current stimulation is a clinically popular waveform for NMES. Prior research has established that MPC with a relatively long pulse duration is effective for high muscle torque production. METHODS: Participants in this study were 20 adults with no history of knee injury. A crossover design was used to randomize the order in which each participant's dominant or nondominant lower extremity received NMES and the waveform (MPC or BMAC) this limb received. Stimulation intensity was incrementally increased until participants reached their maximum tolerance. The torque produced was converted to a percentage of each participant's maximum volitional isometric contraction of the respective limb. RESULTS: A general linear model for a 2-treatment, 2-period crossover design was utilized to analyze the results. The mean ± SD electrically induced percent maximum volitional isometric contraction at maximal participant tolerance was 49.5% ± 19.6% for MPC and 29.8% ± 12.4% for BMAC. This difference was statistically significant (P = .002) after accounting for treatment order and limb, which had no effect on torque production. CONCLUSION: Neuromuscular stimulation using MPC may be more efficacious than using BMAC to achieve a high torque output in patients with quadriceps weakness.
Subject(s)
Electric Stimulation/methods , Knee/physiology , Quadriceps Muscle/physiology , Cross-Over Studies , Female , Humans , Isometric Contraction/physiology , Male , Single-Blind Method , Torque , Young AdultABSTRACT
Autologous adipose-derived mesenchymal stem cell (AD-MSC) therapy involves harvesting fat from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous AD-MSC therapy in veterinary regenerative medicine has been commercially available since 2003. Previously reported results from a blinded, controlled trial in dogs with chronic osteoarthritis of the coxofemoral (hip) joint demonstrated efficacy of a single intraarticular injection of autologous AD-MSC therapy. The primary objective of the current study was to evaluate the effectiveness of this therapy in dogs with chronic osteoarthritis of the humeroradial (elbow) joints and to determine the duration of effect. Fourteen dogs were recruited. Veterinarians assessed each dog for lameness, pain on manipulation, range of motion, and functional disability using a numeric rating scale at baseline and specified intervals up to 180 days after treatment. Statistically significant improvement in outcome measures was demonstrated.
Subject(s)
Dog Diseases/therapy , Elbow Joint/pathology , Mesenchymal Stem Cell Transplantation/veterinary , Osteoarthritis/veterinary , Animals , Chronic Disease , Dogs , Female , Injections, Intra-Articular/methods , Injections, Intra-Articular/veterinary , Lameness, Animal/etiology , Lameness, Animal/therapy , Male , Mesenchymal Stem Cell Transplantation/methods , Osteoarthritis/therapy , Range of Motion, Articular , Time Factors , Transplantation, Autologous/methods , Transplantation, Autologous/veterinary , Treatment OutcomeABSTRACT
Autologous stem cell therapy in the field of regenerative veterinary medicine involves harvesting tissue, such as fat, from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous adipose-derived stem cell therapy has been commercially available since 2003, and the current study evaluated such therapy in dogs with chronic osteoarthritis of the hip. Dogs treated with adipose-derived stem cell therapy had significantly improved scores for lameness and the compiled scores for lameness, pain, and range of motion compared with control dogs. This is the first randomized, blinded, placebo-controlled clinical trial reporting on the effectiveness of stem cell therapy in dogs.
Subject(s)
Adipose Tissue/cytology , Hip Dysplasia, Canine/drug therapy , Mesenchymal Stem Cell Transplantation/veterinary , Animals , Dogs , Double-Blind Method , Female , Hip Dysplasia, Canine/pathology , Injections, Intra-Articular/veterinary , Lameness, Animal , Male , Pain Measurement/veterinary , Severity of Illness Index , Transplantation, Autologous/veterinary , Treatment Outcome , United StatesABSTRACT
BACKGROUND: How patients are informed regarding their choices of durable medical equipment (DME) providers for home-going respiratory equipment may affect their decisions about which vendor to use. When a new enhanced information program to inform home-going patients about all available respiratory DME providers was implemented, we hypothesized that patients' utilization of providers would change and that satisfaction with service would be enhanced. METHODS: The enhanced information program consisted of offering detailed descriptions of the many available providers to home-going patients. To characterize available providers, we administered a questionnaire to all respiratory DME providers listed in our area. We assembled information about the scope of services, the number and types of providers, the geographic range of service, and the providers' contact information, on a 1-page information sheet about the DME providers, which was given to all home-going patients. Case managers, who routinely help patients make such DME arrangements, were oriented about the questionnaire and given the information sheets to distribute. The study compared responses from Medicare insurees prescribed to receive home-going respiratory care equipment on discharge from The Cleveland Clinic Hospital during the periods before and after implementing the enhanced information program. Consecutive eligible patients in the before and after groups were called by two of the study investigators (ERH, DAM), at least 2 weeks after discharge, and, on their granting consent, were asked to complete a telephone survey. RESULTS: Responses were available from 75 patients in each group. Both before and after implementing the enhanced information program, patients' satisfaction with their respiratory DME service providers' services was high. The number of providers selected increased after the program from 12 to 18, and though the differences between the before and after scores were not statistically significant, there was a trend toward prompter visits to patients in their homes by DME-provider respiratory therapists. CONCLUSIONS: The enhanced information program was associated with a larger number of DME providers being selected, with preservation of a high level of patient satisfaction with DME services. The trend toward prompter respiratory therapists' visits to the home and better availability of oxygen canisters for at-home patients suggested benefits from the enhanced information program.