Initial Impairment Research Articles

Elucidating therapist differences: Therapists' interpersonal skills and their effect on treatment outcome.

Therapists differ in their average treatment outcomes. However, it remains unclear which characteristics differentiate more from less effective therapists. This study examined the association between therapist interpersonal skills and treatment outcome as well as the moderating effect of initial impairment. Interpersonal skills were assessed with the Therapy-Related Interpersonal Behaviors (TRIB) scale, a group-discussion based rating system, in 99 incoming therapy trainees. The trainees treated n=1031 outpatients with psychological therapies, whose treatment outcomes were assessed with the Symptom-Checklist 90 Revised (SCL-90-R). Linear mixed models were conducted to predict outcome by therapists' interpersonal skills beyond initial impairment, number of sessions, therapist age, gender, and theoretical orientation. The moderating effect of initial impairment was calculated as cross-level interaction. The therapist effect (TE) in this sample was 5.6%. Interpersonal skills were a significant predictor of outcome (b=-0.124, p<.001) and explained 1.3% of variance beyond all control variables. The TE in the final model was VPC=.036 indicating that 26.79% of the TE were attributable to interpersonal skills. The impairment-skills interaction was significant (b=-0.172, p<.001). The effect of interpersonal skills on outcome increased with more severe initial impairment. Results were replicated in a second outcome measure (Outcome Questionnaire 30). Interpersonal skills were found to be important characteristics to differentiate between more and less effective therapists, especially when treating severely distressed patients. Considering them in therapist selection and matching, outcome prediction, and clinical training could improve the effectiveness of psychological therapies.

Encouraging arm use in stroke survivors: the impact of smart reminders during a home-based intervention

BackgroundUpper limb impairment post-stroke often leads to a predominant use of the less affected arm and consequent learned disuse of the affected side, hindering upper limb outcome. Wearable sensors such as accelerometers, combined with smart reminders (i.e., based on the amount of arm activity), offer a potential approach to promote increased use of the affected arm to improve upper limb use during daily life. This study aimed to evaluate the efficacy of wrist vibratory reminders during a six-week home-based intervention in chronic stroke survivors.MethodsWe evaluated the impact of the home-based intervention on the primary outcome, the Motor Activity Log-14 Item Version scores Amount of Use (MAL-14 AOU), and the secondary outcomes MAL-14 Quality of Movement (QOM) and sensor-derived activity metrics from the affected arm. A randomized controlled trial design was used for the study: the intervention group received personalized reminders based on individualized arm activity goals, while the control group did not receive any feedback. Mixed linear models assessed the influence of the group, week of the intervention period, and initial impairment level on MAL-14 and arm activity metrics.ResultsForty-two participants were enrolled in the study. Overall, participants exhibited modest but not clinically relevant increases in MAL-14 AOU (+ 0.2 points) and QOM (+ 0.2 points) after the intervention period, with no statistically significant differences between the intervention and control group. Feasibility challenges were noted, such as adherence to wearing the trackers and sensor data quality. However, in participants with sufficiently available sensor data (n = 23), the affected arm use extracted from the sensor data was significantly higher in the intervention group (p < 0.05). The initial impairment level strongly influenced affected arm use and both MAL-14 AOU and QOM (p < 0.01).ConclusionsThe study investigated the effectiveness of incorporating activity trackers with smart reminders to increase affected arm activity among stroke survivors during daily life. While the results regarding the increased arm use at home are promising, patient-reported outcomes remained below clinically meaningful thresholds and showed no group differences. Further, it is essential to acknowledge feasibility issues such as adherence to wearing the trackers during the intervention and missing sensor data.Trial registrationNCT03294187.

Progression of the leprosy reaction and nerve damage: A prospective cohort study in children with leprosy from the Brazilian Amazon.

Leprosy reactions being closely related to damage to peripheral nerves and physical disabilities associated with disease progression. Disabilities in childhood can have a devastating effect with impaired children's cognitive, emotional, social, and educational development. We followed up the progression of leprosy reactions in children identifying associated factors with the emergence and/or worsening of nerve damage. A prospective longitudinal cohort study was performed in patients under 15 years of age affected by leprosy reactions diagnosed at the Leprosy referral unit in the Amazon region of Brazil. The follow-up time was a cohort for 2 years from diagnosis. A clinical evaluation and the simplified neurological were performed at diagnosis and every 6 months, until the end of the follow-up period. Of the 77 children monitored, 38 had reactions and were recruited. Only 23.7% (9/38) of patients improved their initial neurological impairment and 42.1% (16/38) had progression of the leprosy reaction with worsening of the initial nerve damage. Two or more reaction episodes, nerve damage and two or more nerves affected at diagnosis, isolated neuritis, silent neuritis and low educational level of caregiver had a significant association with the emergence and/or worsening of neural damage. A high proportion of children had progression of the leprosy reaction with worsening neural damage. The absence of warning signs of inflammation, such as pain and exacerbation of skin lesions, appears to contribute to the worse prognosis of reactions. Early diagnosis, systematic monitoring especially of neural function, beyond the educate caregivers to recognize the reactional episode early and to helping with children's self-care are very important measures to minimize the emergence or worsening of neural damage resulting from leprosy reactions.

Prognostic factors affecting ALS progression through disease tollgates.

Understanding factors affecting the timing of critical clinical events in ALS progression. We captured ALS progression based on the timing of critical events (tollgates), by augmenting 6366 patients' data from the PRO-ACT database with tollgate-passed information using classification. Time trajectories of passing ALS tollgates after the first visit were derived using Kaplan-Meier analyses. The significant prognostic factors were found using log-rank tests. Decision-tree-based classifications identified significant ALS phenotypes characterized by the list of body segments involved at the first visit. Standard (e.g., gender and onset type) and tollgate-related (phenotype and initial tollgate level) prognostic factors affect the timing of ALS tollgates. For instance, by the third year after the first visit, 80-100% of bulbar-onset patients vs. 43-48% of limb-onset patients, and 65-73% of females vs. 42-49% of males lost the ability to talk and started using a feeding tube. Compared to the standard factors, tollgate-related factors had a stronger effect on ALS progression. The initial impairment level significantly impacted subsequent ALS progression in a segment while affected segment combinations further characterized progression speed. For instance, patients with normal speech (Tollgate Level 0) at the first visit had less than a 10% likelihood of losing speech within a year, while for patients with Tollgate Level 1 (affected speech), this likelihood varied between 23 and 53% based on additional segment (leg) involvement. Tollgate- and phenotype-related factors have a strong effect on the timing of ALS tollgates. All factors should be jointly considered to better characterize patient groups with different progression aggressiveness.

Voluntary Swallowing Initiation Difficulty After Dorsomedial Prefrontal Cortex Damage: A Case Report.

The dorsomedial prefrontal cortex plays a critical role in movement initiation, and damage to this area can impair this function. Here we present the case of an individual who had difficulty with voluntary initiation of liquid swallowing after surgical removal of a glioblastoma from the right dorsomedial prefrontal cortex. This individual had no difficulty swallowing solids, perhaps because of the additional external movement triggers (eg, chewing) involved. Liquid swallowing involves fewer movement triggers and requires a quicker application of force during the oral propulsive phase when liquids are transferred from the oral cavity to the oropharynx. This individual did not have buccofacial apraxia or apraxia of speech, which are often associated with swallowing apraxia linked to damage in the precentral, premotor, and inferior frontal gyri. To our knowledge, few studies have focused on movement initiation impairments affecting the upper extremities and speech, and cases involving swallowing are notably rare.

The Effect of Therapists' Interpersonal Skills on Therapeutic Alliance

Therapists' interpersonal skills play a significant role in outcome differences between therapists. Similarly, the strength of the therapeutic alliance is influenced by therapist characteristics. Therefore, the aim of this study was to capture therapist differences in the alliance and to examine the effect of therapists' interpersonal skills on the therapeutic alliance. Interpersonal skills of 99 incoming therapists were measured in a group discussion using the Therapy-Related Interpersonal Behaviors (TRIB) scale. The therapists treated n=1031 psychotherapy outpatients as part of their clinical training. The alliance was assessed at the end of therapy using the Assessment for Signal Clients (ASC). Hierarchical linear models were used to predict the alliance from interpersonal skills, controlling for other patient and therapist variables. Initial impairment was examined as a moderator of the effect. The therapist effect (TE) on the alliance was 7.3%. Interpersonal skills were a significant predictor of the alliance (b=0.104, p<0.001) and could explain 1.8% of the total variance beyond all control variables. The TE was reduced to 5.7%, meaning that 23.0% of the therapist differences in the alliance could be attributed to interpersonal skills. Although the moderation effect of initial impairment was only marginally significant (b=0.069, p=0.061), the association between interpersonal skills and alliance disappeared with low patient impairment. The TRIB scale can measure interpersonal skills before the start of training. The prediction should be considered in the context of the several years' temporal distance between the measurements of interpersonal skills and the alliance, applicable to the selective sample of therapists chosen for the training. Interpersonal skills can predict the alliance. The influence of therapists' interpersonal skills on the alliance increases with the initial impairment of patients, while there is no significant relationship with low-impaired patients. Using video-based rating systems, interpersonal skills of individual therapists can be measured automatically, therapists with deficits can be identified, and targeted training can be provided.

The anti-inflammatory cytokine interferon-gamma as a potential therapeutic target of Alzheimer’s disease: a retrospective observational study

The age-related neurodegenerative disease Alzheimer’s disease is characterized by progressive cognitive decline and neurodegeneration and is often accompanied by inflammation within the central nervous system. This study investigated the role of interferon-gamma, an anti-inflammatory cytokine, in Alzheimer’s disease pathogenesis. Our findings highlight three critical insights: first, there was a significant reduction in interferon-gamma expression at the early stages of Alzheimer’s disease, suggesting an initial impairment in immune function. Second, we identified a novel correlation between the expression levels of interferon-gamma and its receptors, which may indicate a mechanism through which interferon-gamma signaling is altered in Alzheimer’s disease. Third, we observed an increase in entropy and determinant values for interferon-gamma and its receptors, suggesting that systemic dysregulation likely contributes to disease progression. Our study underscores the pivotal role of interferon-gamma in Alzheimer’s disease and highlights its potential as a therapeutic target.

Frequently Suspected, Rarely Confirmed: The Complex Diagnostic Journey of Adult-Onset MELAS—Clinical Evaluation and Cost Implications

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a rare mitochondrial disorder primarily presenting in pediatric patients, with onset after 40 years being exceptionally rare (1–6%). Here, we report a complex diagnostic journey of a 47-year-old male presenting with new-onset seizures, hemiparesis, and neurocognitive deficits. Initial work-up, including MRI, CSF analysis, and extensive antibody screening, yielded inconclusive results, prompting differential considerations such as autoimmune encephalitis and neoplastic conditions. Finally muscle biopsy findings, coupled with genetic confirmation of the m.3243A&gt;G mutation in the MT-TL1 gene, ultimately established the diagnosis of MELAS. This case depicts the atypical presentation of adult-onset MELAS without initial lactic acidemia, diabetes, or hearing impairment. The prolonged diagnostic process underscores the challenges of identifying rare diseases under today’s financial and administrative constraints. Still ee emphasize the importance of comprehensive diagnostics in rare cases to advance generall understanding and improve future patient outcomes, also amidst resource limitations.

Predictors of upper limb motor recovery in stroke survivors: a pre–post test study design

ObjectivesThe study aimed to assess the predictors of upper limb motor recovery in stroke survivors.DesignPre–post test study design.SettingConducted in two centres (First Level Hospital and University Teaching Hospital in Lusaka).ParticipantsPatients...

SCD-Tron: Leveraging Large Clinical Language Model for Early Detection of Cognitive Decline from Electronic Health Records.

Early detection of cognitive decline during the preclinical stage of Alzheimer's disease is crucial for timely intervention and treatment. Clinical notes, often found in unstructured electronic health records (EHRs), contain valuable information that can aid in the early identification of cognitive decline. In this study, we utilize advanced large clinical language models, fine-tuned on clinical notes, to improve the early detection of cognitive decline. We collected clinical notes from 2,166 patients spanning the 4 years preceding their initial mild cognitive impairment (MCI) diagnosis from the Enterprise Data Warehouse (EDW) of Mass General Brigham (MGB). To train the model, we developed SCD-Tron, a large clinical language model on 4,949 note sections labeled by experts. For evaluation, the trained model was applied to 1,996 independent note sections to assess its performance on real-world unstructured clinical data. Additionally, we used explainable AI techniques, specifically SHAP values, to interpret the models predictions and provide insight into the most influential features. Error analysis was also facilitated to further analyze the model's prediction. SCD-Tron significantly outperforms baseline models, achieving notable improvements in precision, recall, and AUC metrics for detecting Subjective Cognitive Decline (SCD). Tested on many real-world clinical notes, SCD-Tron demonstrated high sensitivity with only one false negative, crucial for clinical applications prioritizing early and accurate SCD detection. SHAP-based interpretability analysis highlighted key textual features contributing to model predictions, supporting transparency and clinician understanding. SCD-Tron offers a novel approach to early cognitive decline detection by applying large clinical language models to unstructured EHR data. Pretrained on real-world clinical notes, it accurately identifies early cognitive decline and integrates SHAP for interpretability, enhancing transparency in predictions.

Alteration in EEG Delta and Beta Power During Working Memory Performance Differentiates Patients with Parkinson's Disease with and without Dementia.

Working memory (WM) impairment is a common and progressive abnormality in Parkinson's disease (PD), which ultimately leads to dementia. Individuals with PD exhibit altered electroencephalogram (EEG) patterns while engaging in tasks that require WM. The study examined the EEG patterns associated with WM maintenance in PD patients. The study consisted of two groups of PD patients with a sign of dementia (PDD) who had a Mini Mental State Examination (MMSE) score ≤24, PD patients with no sign of dementia (PDND) with an MMSE score >24, and a group of healthy individuals serving as controls (CON). We obtained EEG during a word memorization task using a 128-channel system. The spectral power of the EEG was computed using the fast Fourier transformation algorithm. Compared to both PDND and CON groups, PDD group exhibited higher power in the delta and beta frequency bands. Conversely, there was a notable decrease in power in the gamma band in both the PDD and PDND groups compared to the CON group. In addition, the PDD group exhibited higher power in the gamma band compared to the PDND group. Power in the alpha (LA1, LA2, and UA) and theta bands was greater in PDND and PDD compared to CON, but was similar between PDND and PDD groups. While performing WM tasks, PDD exhibits increased delta and beta power. These findings can be used as a quantitative biomarker to evaluate the severity of initial WM impairments, which could potentially develop into dementia in the future.

Characterizing the progression from mild cognitive impairment to dementia: a network analysis of longitudinal clinical visits

BackgroundWith the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare.ObjectiveWe aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, of the participants in Mayo Clinic Study of Aging (MCSA) from initial mild cognitive impairment (MCI) diagnosis to dementia onset through network analysis.MethodsWe used the data from the MCSA, a prospective population-based cohort study of cognitive aging, and examined the changing association among variables (i.e., participants’ health conditions) from the first visit of MCI diagnosis to the visit of dementia onset using network analysis. The number of participants for this study are 97 with the number of visits ranging from 2 visits (30 months) to 7 visits (105 months). We identified the network communities among variables from three-fold collection of instances: (i) the first MCI diagnosis, (ii) progression to dementia, and (iii) dementia diagnosis. We determine the variables that play a significant role in the dementia onset, aiming to identify and prioritize specific variables that prominently contribute towards developing dementia. In addition, we explore the sex-specific impact of variables in relation to dementia, aiming to investigate potential differences in the influence of certain variables on dementia onset between males and females.ResultsWe found correlation among certain variables, such as neuropsychiatric symptoms and chronic conditions, throughout the progression from MCI to dementia. Our findings, based on patterns and changing variables within specific communities, reveal notable insights about the time-lapse before dementia sets in, and the significance of progression of correlated variables contributing towards dementia onset. We also observed more changes due to certain variables, such as cognitive and functional scores, in the network communities for the people who progressed to dementia compared to those who does not. Most changes for sex-specific analysis are observed in clinical dementia rating and functional activities questionnaire during MCI onset are followed by chronic diseases, and then by NPI-Q scores.ConclusionsNetwork analysis has shown promising potential to capture significant longitudinal changes in health conditions, spanning from the MCI diagnosis to dementia progression. It can serve as a valuable analytic approach for monitoring the health status of individuals in cognitive impairment assessment. Furthermore, our findings indicate a notable sex difference in the impact of specific health conditions on the progression of dementia.

Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration.

In many neurological conditions, early-stage neural circuit adaption can preserve relatively normal behaviour. In some diseases, spinal motoneurons progressively degenerate yet movement is initially preserved. We therefore investigated whether these neurons and associated microcircuits adapt in a mouse model of progressive motoneuron degeneration. Using a combination of in vitro and in vivo electrophysiology and super-resolution microscopy, we found that, early in the disease, neurotransmission in a key pre-motor circuit, the recurrent inhibition mediated by Renshaw cells, is reduced by half due to impaired quantal size associated with decreased glycine receptor density. This impairment is specific, and not a widespread feature of spinal inhibitory circuits. Furthermore, it recovers at later stages of disease. Additionally, an increased probability of release from proprioceptive afferents leads to increased monosynaptic excitation of motoneurons. We reveal that in motoneuron degenerative conditions, spinal microcircuits undergo specific multiphasic homeostatic compensations that may contribute to preservation of force output.

An Update on Spinal Cord Injury and Current Management

» Spinal cord injury is associated with increased lifelong cost and decreased life expectancy.» Current treatment guidelines have been limited to studies of small effect sizes and limited availability of randomized control trials.» Recovery is best correlated with the initial American Spinal Injury Association impairment scale grade with A and B less likely to recover regarding ambulation as compared with C and D grades.» Surgical intervention within less than 24 hours, especially in the cervical spine, has been associated with some motor improvement.» The use of mean arterial pressure goals and steroids to maintain perfusion and decrease secondary injury requires further study to elucidate clearer evidence-based results.

Predictive utility of self-efficacy in early stroke rehabilitation

ABSTRACT Introduction A biopsychosocial approach entailing person-centered factors provides valuable insight to post-stroke rehabilitation potential. The consideration of an individual’s belief in their capabilities, known as self-efficacy, may prove especially informative in the inpatient rehabilitation setting where motor learning often occurs. Objective To assess the predictive utility of self-efficacy in functional independence status change during inpatient rehabilitation. Methods Individuals with stroke admitted to an inpatient rehabilitation facility (IRF) completed an assessment battery near IRF admission and discharge involving motor assessments, participant-reported self-efficacy (Stroke Self-Efficacy Questionnaire), and functional independence status evaluation (sum of self-care and mobility Quality Indicators (QI) from the IRF-Patient Assessment Instrument). Linear regression was performed to determine the predictive performance of self-efficacy on QI change during IRF stay while accounting for age, time post-stroke, and IRF length of stay. Regression procedures were repeated for separate subgroups based on initial motor impairment level. Results Thirty individuals with stroke (14 females, age = 67.0 ± 9.80 years, 10.4 ± 3.46 days post-stroke) were enrolled. Self-efficacy at IRF admission explained a significant percentage of variance in QI Change for the cohort (R2 = 30.7%, p = .001) and for the moderate to severe motor impairment subgroup (n = 12; R2 = 49.9%, p = .010). After accounting for confounders, self-efficacy remained a significant predictor for the cohort (n = 30) model. Discussion Findings generated from this work support the predictive utility of self-efficacy in early post-stroke motor recovery. The inclusion of self-efficacy in a multi-faceted evaluation framework may therefore optimize rehabilitation outcomes by providing therapists with additional knowledge to better tailor an individual’s care.

Respiratory-swallow patterning and oropharyngeal swallowing impairment in patients undergoing evaluation for lung transplant.

Although swallowing impairment is prevalent following lung transplantation, baseline respiratory and swallowing characteristics are often overlooked. Respiratory disease processes may predispose lung transplant candidates to altered respiratory-swallow patterning and swallowing impairment. This cross-sectional study included patients referred for a Modified Barium Swallow Study during lung transplant evaluation. Swallowing impairment was measured using the Modified Barium Swallow Impairment Profile and Penetration-Aspiration Scale. Respiratory plethysmographic signals synchronized with videofluoroscopy were analyzed to determine phase patterning, pause duration, and rate. Mixed-effects logistic regression was used to identify linkages between respiratory and swallowing measures. Fifty patients were included and demonstrated delayed swallow initiation (49/50), oral residue (37/50), incomplete pharyngoesophageal segment opening (35/50), and esophageal retention (43/50). Airway invasion occurred infrequently (10/50). Atypical respiratory patterning was significantly associated with impairment in pharyngeal swallow initiation (OR [95% CI] = 1.76 [1.16, 2.68], p = 0.009), laryngeal elevation (OR [95% CI] = 1.45 [1.01, 2.07], p = 0.044), and laryngeal vestibular closure (OR [95% CI] = 2.57 [1.48, 4.46], p < 0.001). Increased pause duration was associated with impaired initiation (OR [95% CI] = 2.24 [1.20, 4.16], p = 0.011), laryngeal elevation (OR [95% CI] = 1.18 [1.03, 1.36], p = 0.018), laryngeal closure (OR [95% CI] = 1.28 [1.9, 1.50], p = 0.003), and tongue base retraction (OR [95% CI] = 1.33 [1.13, 1.56], p < 0.001). Patients undergoing evaluation for lung transplant demonstrated impaired swallowing and phase patterning. Preliminary findings implicate the need for further evaluation of respiratory-swallow coordination and its potential role in swallowing impairment before and after lung transplantation.

Long COVID patients' brain activation is suppressed during walking and severer symptoms lead to stronger suppression.

This research aims to study the factors contributing to Long COVID and its effects on motor and cognitive brain regions using population surveys and brain imaging. The goal is to provide new insights into the neurological effects of the illness and establish a basis for addressing neuropsychiatric symptoms associated with Long COVID. Study 1 used a cross-sectional design to collect data on demographic characteristics and factors related to Long COVID symptoms in 551 participants. In Study 2, subjects with Long COVID and SARS-CoV-2 uninfected individuals underwent fNIRS monitoring while performing various tasks. Study 1 found that gender, age, BMI, Days since the first SARS-CoV-2 infection, and Symptoms at first onset influenced Long COVID performance. Study 2 demonstrated that individuals in the SARS-CoV-2 uninfected group exhibited greater activation of cognitive function-related brain regions than those in the Long COVID group while performing a level walking task. Furthermore, individuals in the Long COVID group without functional impairment displayed higher activation of brain regions associated with motor function during a weight-bearing walking task than those with functional impairment. Among individuals with Long COVID, those with mild symptoms at onset exhibited increased activation of brain regions linked to motor and cognitive function relative to those with moderate symptoms at onset. Individuals with Long COVID exhibited decreased activation in brain regions associated with cognitive and motor function compared to SARS-CoV-2 uninfected individuals. Moreover, those with more severe initial symptoms or functional impairment displayed heightened inhibition in these brain regions.

Outcome prediction in psychological therapy with continuous time dynamic modeling of affective states and emotion regulation.

To date, many prediction studies in psychotherapy research have used cross-sectional data to predict treatment outcome. The present study used intensive longitudinal assessments and continuous time dynamic modeling (CTDM) to investigate the temporal dynamics of affective states and emotion regulation in the early phase of therapy and their ability to predict treatment outcome. Ninety-one patients undergoing psychological treatment at a university outpatient clinic took part in a 2-week ecological momentary assessment (EMA) period. Participants answered self-report measures on positive affect (PA), negative affect, and emotion regulation (ER) four times a day. Hierarchical Bayesian CTDM was conducted to identify temporal effects within (autoregressive) and between (cross-regressive) PA, negative affect, and ER. The resulting CTDM parameters, simple EMA parameters (e.g., mean), and cross-sectional predictors were entered into a LASSO model to be examined as predictors of treatment outcome at Session 15. Two significant predictors were identified: initial impairment and the continuous time cross-effect of PA on ER. The final model explained 40% of variance in treatment outcome, with the cross-effect (PA-ER) accounting for 4% of variance beyond initial impairment. The results demonstrate that temporal patterns of affective EMA data are valuable for the mapping of individual differences and the prediction of treatment outcome. This information can be used to provide therapists with feedback to personalize treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Beneficial Effects on Exercise Capacity Associated with a Combination of Lactoferrin, Lysozyme, Lactobacillus, Resveratrol, Vitamins, and Oligoelements in Patients with Post-COVID-19 Syndrome: A Single-Center Retrospective Study.

Background/Objectives: Although long-term COVID-19 symptoms are common, little is known about the management of post-COVID-19 condition. The aim of the current report is to evaluate the effects of a combination of lactoferrin, lysozyme, lactobacillus, resveratrol, vitamins, and oligoelements (PIRV-F20®) on the exercise capacity of post-COVID-19 patients. Methods: A retrospective analysis of consecutive patients referred to a specific outpatient clinic dedicated to post-COVID-19 condition from April 2022 to April 2023 was conducted. Subjects of both sexes, aged ≥18 years, with previous COVID-19 in the preceding 12 months, persistent symptoms consistent with post-COVID syndrome, and initial exercise impairment were included. Exclusion criteria were as follows: active cancer, end-stage conditions, severe musculoskeletal conditions, or patients with a history of limited functional capacity, pregnancy, or breastfeeding. Patients who reported having taken PIRV-F20® for at least 6 weeks were compared to patients who refused this treatment. Six-minute walking distance was the primary endpoint. Results: Forty-four patients (56.8% women, aged 49.1 ± 18.1 years) were included in the study. The group of patients who reported having taken PIRV-F20® exhibited a significant improvement of 6MWD (median: +40 m; IQR: 10-65 m, p vs. baseline: 0.02), which was significantly superior (p: 0.01) when compared to the controls (median: +10 m; IQR: -5-30 m). No differences were found with regard to muscular strength, echocardiographic parameters, and perception of symptoms. Conclusions: Post-COVID-19 individuals who reported having taken PIRV-F20® for at least six weeks showed a significant improvement in exercise capacity. This finding should be confirmed in larger, prospective, randomized controlled trials.

A novel transgenic mouse model highlights molecular disruptions involved in the pathogenesis of Dent disease 1

Dent disease (DD) is a hereditary renal disorder characterized by low molecular weight (LMW) proteinuria and progressive renal failure. Inactivating mutations of the CLCN5 gene encoding the 2Cl-/H+exchanger ClC-5 have been identified in patients with DD type 1. ClC-5 is essentially expressed in proximal tubules (PT) where it is thought to play a role in maintaining an efficient endocytosis of LMW proteins. However, the exact pathological roles of ClC-5 in progressive dysfunctions observed in DD type 1 are still unclear. To address this issue, we designed a mouse model carrying the most representative type of ClC-5 missense mutations found in DD patients. These mice showed a characteristic DD type 1 phenotype accompanied by altered endo-lysosomal system and autophagy functions. With ageing, KI mice showed increased renal fibrosis, apoptosis and major changes in cell metabolic functions as already suggested in previous DD models. Furthermore, we made the interesting new discovery that the Lipocalin-2-24p3R pathway might be involved in the progression of the disease. These results suggest a crosstalk between the proximal and distal nephron in the pathogenesis mechanisms involved in DD with an initial PT impairment followed by the Lipocalin-2 internalisation and 24p3R overexpression in more distal segments of the nephron. This first animal model of DD carrying a pathogenic mutation of Clcn5 and our findings pave the way aimed at exploring therapeutic strategies to limit the consequences of ClC-5 disruption in patients with DD type 1 developing chronic kidney disease.