Measures Of Function Research Articles

Evaluating Changes in Adult Cochlear Implant Users' Brain and Behavior Following Auditory Training.

To describe the effects of two types of auditory training on both behavioral and physiological measures of auditory function in cochlear implant (CI) users, and to examine whether a relationship exists between the behavioral and objective outcome measures. This study involved two experiments, both of which used a within-subject design. Outcome measures included behavioral and cortical electrophysiological measures of auditory processing. In Experiment I, 8 CI users participated in a music-based auditory training. The training program included both short training sessions completed in the laboratory as well as a set of 12 training sessions that participants completed at home over the course of a month. As part of the training program, study participants listened to a range of different musical stimuli and were asked to discriminate stimuli that differed in pitch or timbre and to identify melodic changes. Performance was assessed before training and at three intervals during and after training was completed. In Experiment II, 20 CI users participated in a more focused auditory training task: the detection of spectral ripple modulation depth. Training consisted of a single 40-minute session that took place in the laboratory under the supervision of the investigators. Behavioral and physiologic measures of spectral ripple modulation depth detection were obtained immediately pre- and post-training. Data from both experiments were analyzed using mixed linear regressions, paired t tests, correlations, and descriptive statistics. In Experiment I, there was a significant improvement in behavioral measures of pitch discrimination after the study participants completed the laboratory and home-based training sessions. There was no significant effect of training on electrophysiologic measures of the auditory N1-P2 onset response and acoustic change complex (ACC). There were no significant relationships between electrophysiologic measures and behavioral outcomes after the month-long training. In Experiment II, there was no significant effect of training on the ACC, although there was a small but significant improvement in behavioral spectral ripple modulation depth thresholds after the short-term training. This study demonstrates that auditory training improves spectral cue perception in CI users, with significant perceptual gains observed despite cortical electrophysiological responses like the ACC not reliably predicting training benefits across short- and long-term interventions. Future research should further explore individual factors that may lead to greater benefit from auditory training, in addition to optimization of training protocols and outcome measures, as well as demonstrate the generalizability of these findings.

Validity and Reliability of Dysphagia Outcome Severity Scale (DOSS) When Used to Rate Flexible Endoscopic Evaluations of Swallowing (FEES).

The Dysphagia Outcome and Severity Scale is used both clinically and within dysphagia research, internationally. Although it was developed using videofluoroscopic swallowing studies, it is frequently used to rate Flexible Endoscopic Evaluations of Swallowing. The validity and reliability of DOSS-use with FEES, however, has not previously been evaluated. This study investigated the validity and rater reliability of clinicians using DOSS to rate FEES. Eleven Speech-Language Pathologists (SLPs) with varied dysphagia experience were recruited to review and DOSS-rate 17 soundless FEES (198 bolus swallows) recorded from 11 heterogenic dysphagic patients (2 cases with repeat FEES) and 4 healthy adults. The SLPs DOSS-ratings were compared against the initial comprehensive dysphagia evaluation (including patient diagnosis, interview, cranial nerve and complete FEES assessment) with Functional Oral Intake Scale (FOIS) and DOSS outcome measures. The SLPs were blinded to patient details and comprehensive dysphagia examination. Re-randomised rating of FEES cases occurred two weeks later (intra rater reliability). Criterion validity for DOSS-ratings (compared against comprehensive dysphagia evaluation with FOIS and DOSS) were strong-very strong (rs=0.858 and 0.936 respectively; p < 0.001). Inter rater reliability demonstrated high agreement (α = 0.891), also intra rater reliability demonstrated almost perfect agreement (Kw = 0.945). This study's results, with strong-very strong criterion validity and high rater reliability by SLPs, adds to the evidence for DOSS-use with FEES. Future validity research comparing DOSS with both FEES and VFSS simultaneously is recommended.

Autonomic and Enteric Profiling May Help Predict Response to Diverse Obesity Therapies.

Changes in autonomic (ANS) and enteric nervous systems (ENS) may be involved in pathogenesis of obesity. We hypothesized that baseline autonomic and enteric parameters may predict outcomes of diverse obesity therapies. We studied ANS and ENS physiology in 37 patients (8 male, 29 female, age 45years, weight 129.7kg) at 4 centers in patients undergoing medical (9: low-calorie diet) versus invasive (22: 16 sleeve, 6 bypass) and semi-invasive (6: 2 band, 2 high energy stimulation, 2 aspiration) weight loss therapies. Weight loss was reported as percent weight loss from baseline to latest values at 1year and in some up to 5years; classified as < or > /= 20% for each group. ANS testing included sympathetic adrenergic function by measuring reflex vasoconstriction and postural adjustment ratio. ENS was measured non-invasively using cutaneous low-resolution electrogastrogram. Percent weight loss was greater with the invasive (28.5%) than semi-invasive (9.1%) or non-invasive low-calorie diet (4.4%) (p < .001). Percent weight loss at 1year (and up to 5years) corresponded to the adrenergic measure of postural adjustment ratio (r = .42, p = .012), total pulse amplitude at rest (r = .56, p < .001), and electrogastrogram standing-to-rest difference (r = .33, p = .056). Baseline autonomic and enteric function measures correspond to percentage with loss in this pilot study using diverse weight loss methods. Autonomic and enteric profiling has potential clinical use for evaluation and treatment of obesity but needed larger controlled trials.

Cognitive Profiles in Treatment-Resistant Late-Life Depression and their Impact on Treatment Outcomes

BackgroundLate-life depression (LLD) is associated with cognitive impairment, yet substantial heterogeneity exists among patients. Data on the extent of cognitive impairments is inconclusive, particularly in patients with treatment-resistant depression (TRD). We investigated the cognitive profiles of patients with treatment-resistant vs. nonresistant LLD and aimed to identify distinct cognitive subgroups. Additionally, we examined whether cognitive subgroups differentially responded to treatment with bilateral repetitive transcranial magnetic stimulation (rTMS). Methods165 patients with LLD were divided into treatment-resistant and nonresistant groups and compared to healthy controls (HC) on measures of executive function, information processing speed, verbal learning, and memory. Cluster analysis identified subgroups based on cognitive scores. Demographic and clinical variables, as well as outcomes with bilateral rTMS, were compared between cognitive subgroups. ResultsPatients with LLD, particularly TRD, exhibited significantly worse cognitive performance than HC. A three-cluster solution was found, including “Cognitively Intact” (n = 89), “Cognitively Diminished” (n = 29), and “Impaired Memory” (n = 47) subgroups. Both the “Cognitively Diminished” and “Impaired Memory” subgroups had more anxiety symptoms and a higher proportion of patients with TRD than the “Cognitively Intact” group, though the latter did not survive multiple comparison correction. No significant differences were observed in outcomes to rTMS treatment. ConclusionsPatients with LLD exhibited impairments across cognitive domains, which were more pronounced in TRD. Three identified cognitive subgroups responded similarly to rTMS treatment, indicating its effectiveness across cognitive profiles, especially when medications are not tolerated. Future research should examine the relationship among cognitive subgroups, cognitive decline, and neurodegeneration.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment

IntroductionThis study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes.MethodsWe measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM).ResultsSignificant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not.DiscussionOur data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Midterm results for revision total knee arthroplasty for component malrotation

IntroductionAccurate positioning of components in total knee arthroplasty (TKA) is essential to a satisfactory outcome. Significant malrotation may lead to chronic pain, stiffness, and dysfunction. This study aims to quantify improvements in functional outcomes following revision surgery for malrotation of either one or both components in TKA versus revision for aseptic loosening. MethodsThis was a retrospective review of TKAs that matched and compared the two-year functional outcomes of the malrotation group to a functionally similar aseptic loosening group. Functional outcomes were compared between groups using Short Form (SF-12), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Knee Society Functional Score (KSFS). Student t-tests and chi-squared or Fisher’s tests were used for statistical analysis. ResultsOf the patients revised, 24 had malrotation and 57 had aseptic loosening. A total of 16 femoral and 17 tibial components were revised for malrotation. All 16 femoral components were internally malrotated (mean –4.8 ± 4.1 degrees; range, −0.5 to −16.6). Of the tibial components, 15 were internally malrotated, (mean −9.5 ± 6.6 degrees; range, −2.2 to –23.5) and 2 were externally malrotated (mean 4.6 ± 2.1 degrees; range, 3.1 to 6.0). All functional outcome measures significantly improved comparably within both groups preoperatively to 24 months postoperatively. At 24 months, functional outcome measures were comparable between the groups and WOMAC function scores were significantly higher in the malrotation group. ConclusionRevision TKA for malrotation can yield clinically and statistically significant functional improvements, similar in magnitude to those seen following revision TKA for aseptic loosening. Level of EvidenceLevel III

Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant.

Intercellular adhesion molecule-1 (ICAM-1) facilitates inflammation via leucocyte recruitment and has been implicated in heart failure with preserved ejection fraction (HFpEF). Approximately 35% of African American individuals carry a copy of an ICAM1 missense variant (rs5491; p.K56M), which is associated with an increased risk of HFpEF. The pathways by which rs5491 increases HFpEF risk are not well defined. We evaluated the circulating immune cell profile of rs5491. Among African American individuals in the Multi-Ethnic Study of Atherosclerosis, we evaluated the associations of rs5491 with 29 circulating peripheral blood mononuclear cell subsets. The top immune cells were then related to echocardiographic measures of structure and function. Among 502 individuals with immune cell profiling (mean age 63years, 51% female), 191 individuals (38%) had at least one copy of rs5491. Each additional rs5491 allele was significantly associated with higher proportions of Tc17 CD8+ cytotoxic T cells (β=1.34, SE=0.45, P=9.5×10-5) and Tc2 CD8+ cytotoxic T cells (β=1.19, SE=0.44, P=0.00012). There were no other associations noted between rs5491 and the remaining immune cells. A higher proportion of Tc17 cells was significantly associated with a higher left ventricular ejection fraction, E/e' average and right ventricular systolic pressure (RVSP), while a higher proportion of Tc2 cells was significantly associated with a higher RVSP. The ICAM1 p.K56M variant (rs5491) carries a distinct and inflammatory T-cell subset profile. These cytotoxic T cells are in turn associated with alterations in cardiac function and adverse haemodynamics later in life, thus providing insight into pathways by which rs5491 may increase the risk of HFpEF.

Overground Gait Training With a Wearable Robot in Children With Cerebral Palsy: A Randomized Clinical Trial.

Cerebral palsy (CP) is the most common developmental motor disorder in children. Robot-assisted gait training (RAGT) using a wearable robot can provide intensive overground walking experience. To investigate the effectiveness of overground RAGT in children with CP using an untethered, torque-assisted, wearable exoskeletal robot. This multicenter, single-blind randomized clinical trial was conducted from September 1, 2021, to March 31, 2023, at 5 rehabilitation institutions in Korea. Ninety children with CP in Gross Motor Function Classification System levels II to IV were randomized. The RAGT group underwent 18 sessions of RAGT during 6 weeks, whereas the control group received standard physical therapy for the same number of sessions during the same period. The primary outcome measure was the Gross Motor Function Measure 88 (GMFM-88) score. Secondary outcome measures were the GMFM-66, Pediatric Balance Scale, selective control assessment of the lower extremity, Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), 6-minute walking test scores (distance and oxygen consumption), muscle and fat mass via bioelectrical impedance analysis, and gait parameters measured via 3-dimensional analysis. All assessments were performed for all patients at baseline, at the end of the 6-week intervention, and after the 4-week follow-up. Of the 90 children (mean [SD] age, 9.51 [2.48] years; 49 [54.4%] male and 41 [45.6%] female) in the study, 78 (86.7%) completed the intervention, with 37 participants (mean [SD] age, 9.57 [2.38] years; 19 [51.4%] male) and 41 participants (mean [SD] age, 9.32 [2.37] years; 26 [63.4%] male) randomly assigned to the RAGT and control groups, respectively. Changes in the RAGT group significantly exceeded changes in the control group in GMFM-88 total (mean difference, 2.64; 95% CI, 0.50-4.78), GMFM-E (mean difference, 2.70; 95% CI, 0.08-5.33), GMFM-66 (mean difference, 1.31; 95% CI, 0.01-2.60), and PEDI-CAT responsibility domain scores (mean difference, 2.52; 95% CI, 0.42-4.63), indicating independence in daily living at postintervention assessment. At the 4-week follow-up, the RAGT group showed significantly greater improvements in balance control (mean difference, 1.48; 95% CI, 0.03-2.94) and Gait Deviation Index (mean difference, 6.48; 95% CI, 2.77-10.19) compared with the control group. In this randomized clinical trial, overground RAGT using a wearable robot significantly improved gross motor function and gait pattern. This new torque-assisted wearable exoskeletal robot, based on assist-as-needed control, may complement standard rehabilitation by providing adequate assistance and therapeutic support to children with CP. CRIS Identifier: KCT0006273.

Right Ventricular and Right Atrial Strain Are Associated with Kidney Dysfunction in Acute Heart Failure

Background: In acute heart failure (HF), low cardiac output and venous congestion are pathophysiological mechanisms that contribute to renal function impairment. This study investigated the association between advanced echocardiographic measures of right ventricular and atrial function and renal impairment in patients with acute HF. Methods and Results: A total of 377 patients hospitalized for acute HF were prospectively evaluated. Estimated glomerular filtration rate (eGFR) on admission was measured using the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Advanced echocardiographic assessment was performed on admission. Patients with eGFR &lt; 45 mL/min/1.73 m2 were more likely to have chronic heart failure, chronic atrial fibrillation, and type 2 diabetes mellitus compared to patients with eGFR ≥ 45 mL/min/1.73 m2. Patients with lower eGFR had lower cardiac output, higher mean E/e’ ratio, larger right ventricular (RV) size, worse RV free wall longitudinal strain, more impaired right atrial (RA) reservoir strain, and more frequent severe tricuspid regurgitation. RV free wall longitudinal strain and RA reservoir strain were the only independent echocardiographic associates of low eGFR, whereas cardiac output was not. Conclusions: Impaired RV and RA longitudinal strain were independently associated with eGFR &lt; 45 mL/min/1.73 m2 in acute HF, while reduced cardiac output was not. This suggests that RV and RA dysfunction underlying venous congestion and increased renal afterload are more important pathophysiological determinants of renal impairment in acute HF than reduced cardiac output.

Slow walking speed and health-related exit from employment among older workers over 5 years of follow-up: evidence from the Health and Employment After Fifty (HEAF) cohort study

IntroductionWith demographic changes, there is increasing demand for individuals and governments to lengthen working lives. Jobs that are very physically demanding are likely to be more difficult to sustain at...

Substance use by homeless clinic attenders in Sydney.

Describe patterns of substance use and comorbid conditions among clinic attenders in homeless shelters in Sydney. Retrospective cohort study of 2498 people who attended a psychiatric clinic at one of three homeless hostels between February 2008 and May 2020. Multivariable logistic regression was used to identify factors associated with self-reported substance use, psychiatric diagnosis and measures of social function. A total of 2041 of the 2498 (81.7%) reported the harmful use of at least one substance, with alcohol (61.8%), cannabis (50.9%) and stimulant drugs (34.9%) the three most common. Those reporting the regular use of two or more substances (1466, 58.7%) were more likely to have a history of early life and adult trauma, a diagnosis of personality disorder, a criminal conviction, receive the Disability Support Pension, be chronically homeless and sleep in the open. The study found a high rate of polysubstance use among homeless clinic attenders in Sydney, and an increase in the prevalence of substance use compared to previous studies. Substance use is both a cause and a consequence of homelessness, and services to address substance use have to be part of any program to reduce homelessness and sleeping in the open.

Learning Interpretable Brain Functional Connectivity Via Self-Supervised Triplet Network With Depth-Wise Attention.

Brain functional connectivity has been routinely explored to reveal the functional interaction dynamics between the brain regions. However, conventional functional connectivity measures rely on deterministic models fixed for all participants, usually demanding application-specific empirical analysis, while deep learning approaches focus on finding discriminative features for state classification, thus having limited capability to capture the interpretable functional connectivity characteristics. To address the challenges, this study proposes a self-supervised triplet network with depth-wise attention(TripletNet-DA) to generate the functional connectivity: 1) TripletNet-DA firstly utilizes channel-wise transformations for temporal data augmentation, where the correlated & uncorrelated sample pairs are constructed for self-supervised training, 2) Channel encoder is designed with a convolution network to extract the deep features, while similarity estimator is employed to generate the similarity pairs and the functional connectivity representations with prominent patterns emphasized via depth-wise attention mechanism, 3) TripletNet-DA applies Triplet loss with anchor-negative similarity penalty for model training, where the similarities of uncorrelated sample pairs are minimized to enhance model's learning capability. Experimental results on pathological EEG datasets(Autism Spectrum Disorder, Major Depressive Disorder) indicate that 1) TripletNet-DA demonstrates superiority in both ASD discrimination and MDD classification than the state-of-the-art counterparts in various frequency bands, where the connectivity features in beta & gamma bands have respectively achieved the accuracy of 97.05%,98.32% for ASD discrimination, 89.88%,91.80% for MDD classification in the eyes-closed condition, and 90.90%,92.26% for MDD classification in the eyes-open condition, 2) TripletNet-DA enables to uncover significant differences of functional connectivity between the ASD EEG and the TD ones, and the prominent connectivity links are in accordance with the empirical findings that frontal lobe demonstrates more connectivity links and significant frontal-temporal connectivity occurs in the beta band, thus providing potential biomarkers for clinical ASD analysis.

Combined effects of functional task training with electrical stimulation on motor abilities and balance in children with diplegia

BackgroundChildren with spastic diplegic cerebral palsy (CP) often demonstrate gluteus medius weakness that causes balance deficits and frequent falling during walking.PurposeThe aim of the study was to evaluate the combined effects of functional task training with electrical stimulation of bilateral hip abductor muscles on motor abilities (standing and walking) and balance in children with spastic diplegic CP.MethodsThirty children with diplegic CP of both sexes whose ages ranged from 7 to 10 years were assigned randomly into two equal groups. For both groups, motor abilities were assessed by gross motor function measure (GMFM), and balance (static and dynamic) was assessed by the humac balance system before and after the study. The control group received a functional training program focusing on standing walking and balance exercises. While children in the study group received the same functional training program with bilateral electrical stimulation of gluteus medius muscles for 50 min. The treatment program for both groups was conducted for 3 sessions/week for 8 weeks.ResultsThere were statistically significant differences between the control and study group post-treatment in GMFM as well as the center of pressure test and weight shift test in favor of the study group (p < 0.05).ConclusionUsing functional task training with electrical stimulation for treatment of children with spastic diplegic CP have significant effects on improving their motor abilities and balance that suggests using it in rehabilitation for these children.

The development of the Moments of Flourishing Experience Scale: a new scale to measure positive, affect-based flourishing state experiences

ABSTRACT Flourishing has been a focus of positive psychology, with increased attention to its translation into psychotherapy practice. Flourishing is an emergent process manifested in momentary experiential states characterized by positive emotions. A conceptualization of flourishing as an innate potential that psychotherapeutic interventions can help cultivate informs the development of this scale. The current study details the development of the Moments of Flourishing Experience Scale (MFES), a 23-item scale. The data were obtained from four different studies involving a total of 1472 adults (normative sample n = 1312; clinical sample n = 160). A bifactor model with four distinct positive affective experience subscales, yielded by factor analysis and then supported by a confirmatory factor analysis, was as follows: Calm & Self-Acceptance; Vitality; Generosity of Spirit & Gratitude; and Connection & Purpose. Across studies, the MFES showed discriminant validity from psychopathology measures and convergent validity with positive psychological functioning measures. The overall scale, as well as each of four subscales, also demonstrated strong reliability in both general and clinical populations. The MFES has initial psychometric support for the study of flourishing and shows promise as a tool to study flourishing as both outcome and process in psychotherapy.

Eye-brain connections revealed by multimodal retinal and brain imaging genetics

The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer’s disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.

House dust metagenome and pulmonary function in a US farming population

BackgroundChronic exposure to microorganisms inside homes can impact respiratory health. Few studies have used advanced sequencing methods to examine adult respiratory outcomes, especially continuous measures. We aimed to identify metagenomic profiles in house dust related to the quantitative traits of pulmonary function and airway inflammation in adults. Microbial communities, 1264 species (389 genera), in vacuumed bedroom dust from 779 homes in a US cohort were characterized by whole metagenome shotgun sequencing. We examined two overall microbial diversity measures: richness (the number of individual microbial species) and Shannon index (reflecting both richness and relative abundance). To identify specific differentially abundant genera, we applied the Lasso estimator with high-dimensional inference methods, a novel framework for analyzing microbiome data in relation to continuous traits after accounting for all taxa examined together.ResultsPulmonary function measures (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio) were not associated with overall dust microbial diversity. However, many individual microbial genera were differentially abundant (p-value < 0.05 controlling for all other microbial taxa examined) in relation to FEV1, FVC, or FEV1/FVC. Similarly, fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, was unrelated to overall microbial diversity but associated with differential abundance for many individual genera. Several genera, including Limosilactobacillus, were associated with a pulmonary function measure and FeNO, while others, including Moraxella to FEV1/FVC and Stenotrophomonas to FeNO, were associated with a single trait.ConclusionsUsing state-of-the-art metagenomic sequencing, we identified specific microorganisms in indoor dust related to pulmonary function and airway inflammation. Some were previously associated with respiratory conditions; others were novel, suggesting specific environmental microbial components contribute to various respiratory outcomes. The methods used are applicable to studying microbiome in relation to other continuous outcomes.3hzq1LfdnyTZVYvBm7QT8RVideo

Enzyme replacement therapy and immunotherapy lead to significant functional improvement in two children with Pompe disease: a case report

BackgroundPompe disease, a rare autosomal recessive disorder caused by acid alpha-glucosidase deficiency, results in progressive glycogen accumulation and multisystem dysfunction. Enzyme replacement therapy with recombinant human acid alpha-glucosidase is the standard of care; however, some patients develop anti-recombinant human acid alpha-glucosidase antibodies, leading to reduced efficacy. This case report presents two infants with early-onset Pompe disease who developed IgG antibodies to enzyme replacement therapy and were subsequently treated with methotrexate, highlighting the importance of monitoring antibody development and exploring alternative therapeutic approaches.Case presentationPatient 1, a 10-month-old female from Bogota, Colombia, presented with generalized hypotonia, macroglossia, hyporeflexia, and mild left ventricular hypertrophy. Diagnostic tests confirmed early-onset Pompe disease, and enzyme replacement therapy was started at 12 months. Due to a lack of improvement and high anti-recombinant human acid alpha-glucosidase IgG antibody titers (1:1800), methotrexate was started at 18 months. After 8 months of combined therapy, antibody titers were negative and significant improvement in motor function was observed using the Gross Motor Function Measure 88. Patient 2, a 7-year-old female from Bogota, Colombia, was diagnosed with early-onset Pompe disease at 12 months and initiated enzyme replacement therapy. At 5 years of age, she experienced frequent falls and grip strength alterations. Functional tests revealed motor development delay, generalized hypotonia, and positive anti-recombinant human acid alpha-glucosidase IgG antibody titers (6400). Methotrexate was initiated, leading to a reduction in falls and antibody titers (3200) after 6 months, with no adverse events or complications. Motor function improvement was assessed using the Motor Function Measurement 32.ConclusionsThe presented cases highlight the importance of monitoring patients for anti-recombinant human acid alpha-glucosidase antibody development during enzyme replacement therapy and the potential benefit of methotrexate as an immunomodulatory agent in early-onset Pompe disease. Early diagnosis and timely initiation of enzyme replacement therapy, combined with prophylactic immune tolerance induction, may improve clinical outcomes and reduce the development of anti-recombinant human acid alpha-glucosidase antibodies. The cases also highlight the importance of objective motor function assessment tools, such as Gross Motor Function Measure 88 and Motor Function Measurement 32, in assessing treatment response. Further research is needed to optimize treatment regimens, monitor long-term effects, and address the current limitations of enzyme replacement therapy in Pompe disease.

Virtual Reality for Sub-Acute Pain After Orthopedic Traumatic Musculoskeletal Injuries: A Mixed Methods Pilot Study.

Acute orthopedic traumatic musculoskeletal injuries are prevalent, costly, and often lead to persistent pain and functional limitations. Psychological risk factors (pain catastrophizing and anxiety) exacerbate these outcomes but are often overlooked in acute orthopedic care. Addressing gaps in current treatment approaches, this mixed methods pilot study explored the use of a therapeutic virtual reality (VR; RelieVRx), integrating mindfulness and cognitive behavioral therapy, for pain self-management at home following orthopedic injury. We enrolled 10 adults with recent orthopedic injuries and elevated pain catastrophizing or pain anxiety from Level 1 Trauma Clinics within the Mass General Brigham healthcare system. Participants completed daily RelieVRx sessions at home for 8 weeks, which included pain education, relaxation, mindfulness, games, and dynamic breathing biofeedback. Primary outcomes were a-priori feasibility, appropriateness, acceptability, satisfaction, and safety. Secondary outcomes were pre-post measures of pain, physical function, sleep, depression, and mechanisms (pain self-efficacy, mindfulness, and coping). The VR and study procedures met or exceeded all benchmarks. We observed preliminary improvements in pain, physical functioning, sleep, depression, and mechanisms. Qualitative exit interviews confirmed high satisfaction with RelieVRx and yielded recommendations for promoting VR-based trials with orthopedic patients. The results support a larger randomized clinical trial of RelieVRx versus a sham placebo control to replicate the findings and explore mechanisms. There is potential for self-guided VR to promote evidence-based pain management strategies and address the critical mental health care gap for patients following acute orthopedic injuries.

Recovery from sport-induced muscle damage in relation to match-intervals in major events

Muscle damage could affect the next match performance in sports when the time to recover from a previous match is shorter. We examined the interval between matches in nine team sports (e.g., soccer, rugby, field hockey, basketball, volleyball, baseball) and two racket sports (badminton, tennis) in World Cups held in 2022-2023, 2020 Tokyo Olympic Games and Gland Slam in 2023. We then performed narrative review using three electronic databases (PubMed, Scopus, Google Scholar) to get information about muscle damage and recovery in the 11 sports, and discussed whether the intervals in the events would be enough for athletes. We found that the match intervals varied among sports and events ranging from 0 to 17 days. The interval was the shortest for softball (0–2 days) and the longest (5–17 days) for rugby. Regarding muscle damage, changes in muscle function and/or performance measures after a match were not reported for cricket, volleyball and softball, but some information was available for other sports, although the studies did not necessarily use athletes who participated in the major events. It was found that recovery was longer for soccer and rugby than other sports. Importantly, the match-intervals in the events did not appear to accommodate the recovery time required from the previous match in many sports. This could increase a risk of injury and affect players’ conditions and health. Changing the match-intervals may be difficult, since it affects the budget of sporting events, but an adequate interval between matches should be considered for each sport from the player’s and coach's point of view.

BOLD fMRI responses to amplitude-modulated sounds across age in adult listeners

Abstract Age-related alterations in the auditory system have been suggested to affect the processing of temporal envelope amplitude modulations (AM) at different levels of the auditory hierarchy, yet few studies have used functional magnetic resonance imaging (fMRI) to study this noninvasively in humans with high spatial resolution. In this study, we utilized sparse-sampling fMRI at 3 Tesla (3T) to investigate regional blood oxygenation level-dependent (BOLD) responses to AM noise stimuli in 65 individuals ranging in age from 19 to 77 years. We contrasted BOLD responses to AM noise stimuli modulated at 4 Hz or 80 Hz with responses to unmodulated stimuli. This allowed us to derive functional measures of regional neural sensitivity to the imposed AM. Compared with unmodulated noise, slowly varying 4 Hz AM noise stimuli elicited significantly greater BOLD responses in the left and right auditory cortex along the Heschl’s gyrus (HG). BOLD responses to the 80 Hz AM stimuli were significantly greater than responses to unmodulated stimuli in putatively primary auditory cortical regions in the lateral HG. BOLD responses to 4 Hz AM stimuli were significantly greater in magnitude than responses to 80 Hz AM stimuli in auditory cortical regions. We find no discernible effects of age on the functional recruitment of the auditory cortex by AM stimuli. While the results affirm the involvement of the auditory cortex in processing temporal envelope rate information, they provide no support for age-related effects on these measures. We discuss potential caveats in assessing age-related changes in responses to AM stimuli in the auditory pathway.