Is the immediate effect of marathon running on novice runners' knee joints sustained within 6 months after the run? A follow-up 3.0 T MRI study.

OBJECTIVE: To evaluate changes in the knee joints of asymptomatic first-time marathon runners, using 3.0 T MRI, 6 months after finishing marathon training and run. MATERIALS AND METHODS: Six months after their participation in a baseline study regarding their knee joints, 44 asymptomatic novice marathoners (17 males, 27 females, mean age 46 years old) agreed to participate in a repeat MRI investigation: 37 completed both a standardized 4-month-long training programme and the marathon (marathon runners); and 7 dropped out during training (pre-race dropouts). The participants already underwent bilateral 3.0 T MRIs: 6 months before and 2 weeks after their first marathon, the London Marathon 2017. This study was a follow-up assessment of their knee joints. Each knee structure was assessed using validated scoring/grading systems at all time points. RESULTS: Two weeks after the marathon, 3 pre-marathon bone marrow lesions and 2 cartilage lesions showed decrease in radiological score on MRI, and the improvement was sustained at the 6-month follow-up. New improvements were observed on MRI at follow-up: 5 pre-existing bone marrow lesions and 3 cartilage lesions that remained unchanged immediately after the marathon reduced in their extent 6 months later. No further lesions appeared at follow-up, and the 2-week post-marathon lesions showed signs of reversibility: 10 of 18 bone marrow oedema-like signals and 3 of 21 cartilage lesions decreased on MRI. CONCLUSION: The knees of novice runners achieved sustained improvement, for at least 6 months post-marathon, in the condition of their bone marrow and articular cartilage

Prevalence of abnormal findings in 230 knees of asymptomatic adults using 3.0 T MRI.

OBJECTIVE: To identify abnormalities in asymptomatic sedentary individuals using 3.0 Tesla high-resolution MRI. MATERIALS AND METHODS: The cohort comprised of 230 knees of 115 uninjured sedentary adults (51 males, 64 females; median age: 44 years). All participants had bilateral knee 3.0 T MRIs. Two senior musculoskeletal radiologists graded all intraarticular knee structures using validated scoring systems. Participants completed Knee Injury and Osteoarthritis Outcome Score questionnaires at the time of the MRI scan. RESULTS: MRI showed abnormalities in the majority (97%) of knees. Thirty percent knees had meniscal tears: horizontal (23%), complex (3%), vertical (2%), radial (2%) and bucket handle (1%). Cartilage and bone marrow abnormalities were prevalent at the patellofemoral joint (57% knees and 48% knees, respectively). Moderate and severe cartilage lesions were common, in 19% and 31% knees, respectively, while moderate and severe bone marrow oedema in 19% and 31% knees, respectively. Moderate-intensity lesion in tendons was found in 21% knees and high-grade tendonitis in 6% knees-the patellar (11% and 2%, respectively) and quadriceps (7% and 2%, respectively) tendons being most affected. Three percent partial ligamentous ruptures were found, especially of the anterior cruciate ligament (2%). CONCLUSION: Nearly all knees of asymptomatic adults showed abnormalities in at least one knee structure on MRI. Meniscal tears, cartilage and bone marrow lesions of the patellofemoral joint were the most common pathological findings. Bucket handle and complex meniscal tears were reported for the first time in asymptomatic knees

3.0 T MRI findings of 104 hips of asymptomatic adults: From non-runners to ultra-distance runners

OBJECTIVES: To determine and compare the health status of hip joints of individuals undertaking various lengths of long-distance running and of those who are not running. METHODS: Fifty-two asymptomatic volunteers underwent bilateral hip 3.0 Tesla MRI: (1) 8 inactive non-runners; (2) 28 moderately active runners (average half a marathon (21 km)/week) and (3) 16 highly active runners (≥ marathon (42 km)/week). Two musculoskeletal radiologists reported the hip MRI findings using validated scoring systems. Study participants completed a Hip disability and Osteoarthritis Outcome Score (HOOS) questionnaire to indicate their perceived hip function. RESULTS: The MRI findings show that there were no significant differences among inactive non-runners, moderately active runners and highly active runners in the amount of labral abnormalities (p=0.327), articular cartilage lesions (p=0.270), tendon abnormalities (p=0.141), ligament abnormalities (p=0.519). Bone marrow oedema was significantly more common in moderately active runners than in non-runners and highly active runners (p=0.025), while small subchondral cysts were more common in runners than in non-runners (p=0.017), but these were minor/of small size, asymptomatic and did not indicate specific exercise-related strain. Articular cartilage lesions and bone marrow oedema were not found in highly active runners. HOOS scores indicate no hip symptoms or functional problems among the three groups. CONCLUSION: The imaging findings were not significantly different among inactive non-runners, moderately active runners and highly active runners, in most hip structures, suggesting that long-distance running may not add further damage to the hip joints

A de novo dominant mutation in KIF1A associated with axonal neuropathy, spasticity and autism spectrum disorder

Mutations in the kinesin family member 1A (KIF1A) gene have been associated with a wide range of phenotypes including recessive mutations causing hereditary sensory neuropathy and hereditary spastic paraplegia and de novo dominant mutations causing a more complex neurological disorder affecting both the central and peripheral nervous system. We identified by exome sequencing a de novo dominant missense variant, (c.38G>A, p.R13H), within an ATP binding site of the kinesin motor domain in a patient manifesting a complex phenotype characterized by autism spectrum disorder (ASD), spastic paraplegia and axonal neuropathy. The presence of ASD distinguishes this case from previously reported patients with de novo dominant mutations in KIF1A

Can marathon running improve knee damage of middle-aged adults? A prospective cohort study.

Objectives: To evaluate the short-term impact of long-distance running on knee joints using MRI. Methods: 82 healthy adults participating in their first marathon underwent 3T (Tesla) MRI of both knees 6 months before and half a month after the marathon: 71 completed both the 4 month-long standardised training programme and the marathon; and 11 dropped-out during training and did not run the marathon. Two senior musculoskeletal radiologists graded the internal knee structures using validated scoring systems. Participants completed Knee Injury and Osteoarthritis Outcome Score questionnaires at each visit for self-reporting knee function. Results: Premarathon and pretraining MRI showed signs of damage, without symptoms, to several knee structures in the majority of the 82 middle-aged volunteers. However, after the marathon, MRI showed a reduction in the radiological score of damage in: subchondral bone marrow oedema in the condyles of the tibia (p=0.011) and femur (p=0.082). MRI did also show an increase in radiological scores to the following structures: cartilage of the lateral patella (p=0.0005); semimembranosus tendon (p=0.016); iliotibial band (p<0.0001) and the prepatellar bursa (p=0.016). Conclusion: Improvement to damaged subchondral bone of the tibial and femoral condyles was found following the marathon in novice runners, as well as worsening of the patella cartilage although asymptomatic. This is the most robust evidence to link marathon running with knee joint health and provides important information for those seeking to understand the link between long distance running and osteoarthritis of the main weight-bearing areas of the knee

Electronic and magnetic properties of Fe clusters inside finite zigzag single-wall carbon nanotubes

Density functional calculations of the electronic structure of the Fe12 cluster encapsulated inside finite singlewall zigzag carbon nanotubes of indices (11,0) and (10,0) have been performed. Several Fe12 isomers have been considered, including elongated shape isomers aimed to fit well inside the nanotubes, and the icosahedral minimum energy structure. We analyze the structural and magnetic properties of the combined systems, and how those properties change compared to the isolated systems. A strong ferromagnetic coupling between the Fe atoms occurs both for the free and the encapsulated Fe12 clusters, but there is a small reduction (3–7.4μB) of the spin magnetic moment of the encapsulated clusters with respect to that of the free ones (μ = 38μB). The reduction of the magnetic moment is mostly due to the internal redistribution of the spin charges in the iron cluster. In contrast, the spin magnetic moment of the carbon nanotubes, which is zero for the empty tubes, becomes nonzero (1–3μB) because of the interaction with the encapsulated cluster. We have also studied the encapsulation of atomic Fe and the growth of small Fen clusters (n = 2, 4, 8) encapsulated in a short (10,0) tube. The results suggest that the growth of nanowires formed by distorted tetrahedral Fe4 units will be favorable in (10,0) nanotubes and nanotubes of similar diameter

SIGMAR1 mutation associated with autosomal recessive Silver-like syndrome

OBJECTIVE: To describe the genetic and clinical features of a simplex patient with distal hereditary motor neuropathy (dHMN) and lower limb spasticity (Silver-like syndrome) due to a mutation in the sigma nonopioid intracellular receptor-1 gene (SIGMAR1) and review the phenotypic spectrum of mutations in this gene. METHODS: We used whole-exome sequencing to investigate the proband. The variants of interest were investigated for segregation in the family using Sanger sequencing. Subsequently, a larger cohort of 16 unrelated dHMN patients was specifically screened for SIGMAR1 mutations. RESULTS: In the proband, we identified a homozygous missense variant (c.194T>A, p.Leu65Gln) in exon 2 of SIGMAR1 as the probable causative mutation. Pathogenicity is supported by evolutionary conservation, in silico analyses, and the strong phenotypic similarities with previously reported cases carrying coding sequence mutations in SIGMAR1. No other mutations were identified in 16 additional patients with dHMN. CONCLUSIONS: We suggest that coding sequence mutations in SIGMAR1 present clinically with a combination of dHMN and pyramidal tract signs, with or without spasticity, in the lower limbs. Preferential involvement of extensor muscles of the upper limbs may be a distinctive feature of the disease. These observations should be confirmed in future studies

Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT

OBJECTIVE: To determine the prevalence and clinical and genetic characteristics of patients with X-linked Charcot-Marie-Tooth disease (CMT) due to mutations in noncoding regions of the gap junction β-1 gene (GJB1). METHODS: Mutations were identified by bidirectional Sanger sequence analysis of the 595 bases of the upstream promoter region, and 25 bases of the 3′ untranslated region (UTR) sequence in patients in whom mutations in the coding region had been excluded. Clinical and neurophysiologic data were retrospectively collected. RESULTS: Five mutations were detected in 25 individuals from 10 kindreds representing 11.4% of all cases of CMTX1 diagnosed in our neurogenetics laboratory between 1996 and 2016. Four pathogenic mutations, c.-17G>A, c.-17+1G>T, c.-103C>T, and c.-146-90_146-89insT were detected in the 5′UTR. A novel mutation, c.*15C>T, was detected in the 3′ UTR of GJB1 in 2 unrelated families with CMTX1 and is the first pathogenic mutation in the 3′UTR of any myelin-associated CMT gene. Mutations segregated with the phenotype, were at sites predicted to be pathogenic, and were not present in the normal population. CONCLUSIONS: Mutations in noncoding DNA are a major cause of CMTX1 and highlight the importance of mutations in noncoding DNA in human disease. Next-generation sequencing platforms for use in inherited neuropathy should therefore include coverage of these regions