Pulmonary and upper limbs function in children with early stage Duchenne muscular dystrophy compared to their healthy peers

BackgroundPulmonary and upper limbs function of children with Duchenne muscular dystrophy (DMD) are known to deteriorate throughout the disease process. However, there is a lack of information on the extent of impairments in the early stages of DMD when compared to healthy peers.ObjectiveTo investigate to what extent pulmonary and upper limbs function of children with early stage DMD are impaired.MethodsSixty-one children participated in the study: 31 with Grade 1 DMD (study group) according to the Brooke Upper and Lower Extremity Functional Classification Systems, and 30 age matched healthy peers (control group). Pulmonary function was determined with pulmonary function tests. The Performance of Upper Limb test was used to evaluate the upper limbs function.ResultsStudy and control groups were homogenous in terms of physical characteristics (p > 0.05). Pulmonary and upper limbs function of children with DMD were about 85% and 93% of healthy peers, respectively.ConclusionThis study provides evidence for deterioration of pulmonary and upper limbs function in children with early stage DMD. Better knowledge of deterioration rate over time may help therapists to better plan and update their plan of care.     

A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine

BackgroundVaccines are urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the safety and immunogenicity of vaccine candidate mRNA-1273, encoding the prefusion-stabilized spike protein of SARS-CoV-2.MethodsThis phase 2, randomized, observer-blind, placebo-controlled trial was conducted at 8 sites in the USA, in healthy adults aged ≥18 years with no known history or risk of SARS-CoV-2 infection, and had not previously received an investigational CoV vaccine or treatment. Participants were stratified into two age cohorts (≥18-<55 and ≥55) and were randomly assigned (1:1:1) to either 50 or 100 µg of mRNA-1273, or placebo administered as two intramuscular injections 28 days apart. The primary outcomes were safety, reactogenicity, and immunogenicity assessed by anti-SARS-CoV-2-spike binding antibody level (bAb). Secondary outcome was immunogenicity assessed by SARS-CoV-2 neutralizing antibody (nAb) response.ResultsBetween 29 May and 8 July 2020, 600 participants were randomized, 300 per age cohort. The most common solicited adverse reactions were pain at injection site, headache, and fatigue following each vaccination in both age cohorts. One serious adverse event deemed unrelated by the site investigator occurred 33 days post-vaccination one. mRNA-1273 induced bAb and nAb by 28 days post-vaccination one that were higher at the 100 µg dose relative to the 50 µg dose; this difference was less apparent post-vaccination two. Binding antibodies and nAb increased substantially by 14 days following the second vaccination (day 43) to levels exceeding those of convalescent sera and remained elevated through day 57.ConclusionsVaccination with mRNA-1273 resulted in significant immune responses to SARS-CoV-2 in participants 18 years and older, with an acceptable safety profile, confirming the safety and immunogenicity of 50 and 100 µg mRNA-1273 given as a 2 dose-regimen.ClinicalTrials.gov; NCT04405076.     

Effectiveness of Anma massage therapy in alleviating physical symptoms in outpatients with Parkinson's disease: A before-after study

We aimed to confirm the physical effects of a single Anma massage session and continuous Anma massage therapy for outpatients with Parkinson's disease (PD). Twenty-one PD outpatients (mean age, 64.43 ± 8.39 [SD] years; Hoehn and Yahr stage I–IV) received a single 40-min Anma massage session involving upper and lower limb exercises and some subsequently received seven weekly Anma massage sessions. After a single session, visual analogue scale scores were significantly lower for muscle stiffness, movement difficulties, pain, and fatigue; gait speed and pegboard test time were significantly shortened; stride length was significantly lengthened; and shoulder flexion and abduction were significantly improved. No significant changes occurred in controls. After continuous sessions, we found general improvements in the same outcomes. In conclusion, Anma massage might effectively alleviate various physical PD symptoms; furthermore, because it is given through clothing, Anma massage is accessible for PD patients with movement difficulties.     

Validity and reliability of the Disabilities of Arm,Shoulder, and Hand scale in dental students: A transnational study

This study aimed to evaluate the validity and reliability of the Disabilities of Arm, Shoulder, and Hand (DASH) scale in Brazilian and American dental students and assess the influence of demographic variables on disability in them. A cross-sectional observational study was conducted with a nonprobabilistic sample. The sample was composed of students of both genders from the School of Dentistry of Araraquara, State University of São Paulo (UNESP) (n = 288), and students from Stony Brook University, New York, NY, USA (n = 149). The disabilities of the upper limbs were estimated using the DASH scale. The samples were characterized by collecting information on gender, academic year, and sports and work activities. The refined bifactorial model presented goodness-of-fit indices for both countries. There was a significant effect of the variables gender and academic year for the Brazilian sample and the variable sports practices for the American sample. The refined bifactorial model was valid and reliable for the Brazilian and American populations. In this model, the removal of item 17 for the Brazilian sample and items 3, 13, and 23 for the American sample was necessary. Demographic variables such as gender, academic year, and sports practice contributed significantly to the level of disability in the study populations.     

Genetic interactions between Ror2 and Wnt9a,Ror1 and Wnt9a and Ror2 and Ror1: Phenotypic analysis of the limb skeleton and palate in compound mutants

Mutations in the human receptor tyrosine kinase ROR2 are associated with Robinow syndrome (RRS) and brachydactyly type B1. Amongst others, the shortened limb phenotype associated with RRS is recapitulated in Ror2^?/? mutant mice. In contrast, Ror1^?/? mutant mice are viable and show no limb phenotype. Ror1^?/?;Ror2^?/? double mutants are embryonic lethal, whereas double mutants containing a hypomorphic Ror1 allele (Ror1^hyp) survive up to birth and display a more severe shortened limb phenotype. Both orphan receptors have been shown to act as possible Wnt coreceptors and to mediate the Wnt5a signal. Here, we analyzed genetic interactions between the Wnt ligand, Wnt9a, and Ror2 or Ror1, as Wnt9a has also been implicated in skeletal development. Wnt9a^?/? single mutants display a mild shortening of the long bones, whereas these are severely shortened in Ror2^?/? mutants. Ror2^?/?;Wnt9a^?/? double mutants displayed even more severely shortened long bones, and intermediate phenotypes were observed in compound Ror2;Wnt9a mutants. Long bones were also shorter in Ror1^hyp/hyp;Wnt9a^?/? double mutants. In addition, Ror1^hyp/hyp;Wnt9a^?/? double mutants displayed a secondary palate cleft phenotype, which was not present in the respective single mutants. Interestingly, 50% of compound mutant pups heterozygous for Ror2 and homozygous mutant for Ror1 also developed a secondary palate cleft phenotype.