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Nature Jul 2023Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and...
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility, these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS.
Topics: Humans; Young Adult; Aging; Brain; Brain Stem; Case-Control Studies; Cognitive Reserve; Disease Progression; Educational Status; Genome-Wide Association Study; Homozygote; Mobility Limitation; Multiple Sclerosis; Protective Factors; Time Factors
PubMed: 37380766
DOI: 10.1038/s41586-023-06250-x -
The Journal of Manual & Manipulative... Dec 2023To determine the long-term clinical effects of spinal manipulative therapy (SMT) or mobilization (MOB) as an adjunct to neurodynamic mobilization (NM) in the management... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To determine the long-term clinical effects of spinal manipulative therapy (SMT) or mobilization (MOB) as an adjunct to neurodynamic mobilization (NM) in the management of individuals with Lumbar Disc Herniation with Radiculopathy (DHR).
DESIGN
Parallel group, single-blind randomized clinical trial.
SETTING
The study was conducted in a governmental tertiary hospital.
PARTICIPANTS
Forty (40) participants diagnosed as having a chronic DHR (≥3 months) were randomly allocated into two groups with 20 participants each in the SMT and MOB groups.
INTERVENTIONS
Participants in the SMT group received high-velocity, low-amplitude manipulation, while those in the MOB group received Mulligans' spinal mobilization with leg movement. Each treatment group also received NM as a co-intervention, administered immediately after the SMT and MOB treatment sessions. Each group received treatment twice a week for 12 weeks.
OUTCOME MEASURES
The following outcomes were measured at baseline, 6, 12, 26, and 52 weeks post-randomization; back pain, leg pain, activity limitation, sciatica bothersomeness, sciatica frequency, functional mobility, quality of life, and global effect. The primary outcomes were pain and activity limitation at 12 weeks post-randomization.
RESULTS
The results indicate that the MOB group improved significantly better than the SMT group in all outcomes ( < 0.05), and at all timelines (6, 12, 26, and 52 weeks post-randomization), except for sensory deficit at 52 weeks, and reflex and motor deficits at 12 and 52 weeks. These improvements were also clinically meaningful for neurodynamic testing and sensory deficits at 12 weeks, back pain intensity at 6 weeks, and for activity limitation, functional mobility, and quality of life outcomes at 6, 12, 26, and 52 weeks of follow-ups. The risk of being improved at 12 weeks post-randomization was 40% lower (RR = 0.6, CI = 0.4 to 0.9, = 0.007) in the SMT group compared to the MOB group.
CONCLUSION
This study found that individuals with DHR demonstrated better improvements when treated with MOB plus NM than when treated with SMT plus NM. These improvements were also clinically meaningful for activity limitation, functional mobility, and quality of life outcomes at long-term follow-up.
TRIAL REGISTRATION
Pan-African Clinical Trial Registry: PACTR201812840142310.
Topics: Humans; Intervertebral Disc Displacement; Radiculopathy; Sciatica; Low Back Pain; Manipulation, Spinal; Quality of Life; Single-Blind Method
PubMed: 36950742
DOI: 10.1080/10669817.2023.2192975 -
Sensors (Basel, Switzerland) Dec 2023Mobility challenges threaten physical independence and good quality of life. Often, mobility can be improved through gait rehabilitation and specifically the use of... (Review)
Review
Mobility challenges threaten physical independence and good quality of life. Often, mobility can be improved through gait rehabilitation and specifically the use of cueing through prescribed auditory, visual, and/or tactile cues. Each has shown use to rectify abnormal gait patterns, improving mobility. Yet, a limitation remains, i.e., long-term engagement with cueing modalities. A paradigm shift towards personalised cueing approaches, considering an individual's unique physiological condition, may bring a contemporary approach to ensure longitudinal and continuous engagement. Sonification could be a useful auditory cueing technique when integrated within personalised approaches to gait rehabilitation systems. Previously, sonification demonstrated encouraging results, notably in reducing freezing-of-gait, mitigating spatial variability, and bolstering gait consistency in people with Parkinson's disease (PD). Specifically, sonification through the manipulation of acoustic features paired with the application of advanced audio processing techniques (e.g., time-stretching) enable auditory cueing interventions to be tailored and enhanced. These methods used in conjunction optimize gait characteristics and subsequently improve mobility, enhancing the effectiveness of the intervention. The aim of this narrative review is to further understand and unlock the potential of sonification as a pivotal tool in auditory cueing for gait rehabilitation, while highlighting that continued clinical research is needed to ensure comfort and desirability of use.
Topics: Humans; Quality of Life; Gait; Acoustics; Cues; Parkinson Disease
PubMed: 38202926
DOI: 10.3390/s24010065 -
Blood Advances Jul 2023Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the... (Clinical Trial)
Clinical Trial
Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the heterogeneity of these diseases has limited our understanding of these domains. The National Heart, Lung, and Blood Institute-sponsored MDS Natural History Study is a prospective cohort enrolling patients undergoing workup for suspected MDS in the setting of cytopenias. Untreated patients undergo bone marrow assessment with central histopathology review for assignment as MDS, MDS/myeloproliferative neoplasm (MPN), idiopathic cytopenia of undetermined significance (ICUS), acute myeloid leukemia (AML) with <30% blasts, or "At-Risk." HRQoL data are collected at enrollment, including the MDS-specific Quality of Life in Myelodysplasia Scale (QUALMS). Vulnerability is assessed with the Vulnerable Elders Survey. Baseline HRQoL scores from 449 patients with MDS, MDS/MPN, AML <30%, ICUS or At-Risk were similar among diagnoses. In MDS, HRQoL was worse for vulnerable participants (eg, mean Patent-Reported Outcomes Management Information Systems [PROMIS] Fatigue of 56.0 vs 49.5; P < .001) and those with worse prognosis (eg, mean Euroqol-5 Dimension-5 Level [EQ-5D-5L] of 73.4, 72.7, and 64.1 for low, intermediate, and high-risk disease; P = .005). Among vulnerable MDS participants, most had difficulty with prolonged physical activity (88%), such as walking a quarter mile (74%). These data suggest that cytopenias leading to MDS evaluation are associated with similar HRQoL, regardless of eventual diagnosis, but with worse HRQoL among the vulnerable. Among those with MDS, lower-risk disease was associated with better HRQoL, but the relationship was lost among the vulnerable, showing for the first time that vulnerability trumps disease risk in affecting HRQoL. This study is registered at www.clinicaltrials.gov as NCT02775383.
Topics: Aged; Humans; Anemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Prospective Studies; Quality of Life
PubMed: 37146263
DOI: 10.1182/bloodadvances.2022009000