Music-Based Intervention Ameliorates Mecp2-Loss-Mediated Sociability Repression in Mice through the Prefrontal Cortex FNDC5/BDNF Pathway.

Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investigate the mechanism by which music-based interventions compromise sociability impairments in mecp2 null/y mice as an experimental RTT model. Male mecp2 null/y mice and wild-type mice (24 days old) were randomly divided into control, noise, and music-based intervention groups. Mice were exposed to music or noise for 6 h/day for 3 consecutive weeks. Behavioral patterns, including anxiety, spontaneous exploration, and sociability, were characterized using open-field and three-chamber tests. BDNF, TrkB receptor motif, and FNDC5 expression in the prefrontal cortex (PFC), hippocampus, basal ganglia, and amygdala were probed using RT-PCR or immunoblotting. mecp2 null/y mice showed less locomotion in an open field than wild-type mice. The social novelty rather than the sociability of these animals increased following a music-based intervention, suggesting that music influenced the mecp2-deletion-induced social interaction repression rather than motor deficit. Mechanically, the loss of BDNF signaling in the prefrontal cortex and hippocampal regions, but not in the basal ganglia and amygdala, was compromised following the music-based intervention in mecp2 null/y mice, whereas TrkB signaling was not significantly changed in either region. FNDC5 expression in the prefrontal cortex region in mecp2 null/y mice also increased following the music-based intervention. Collective evidence reveals that music-based interventions improve mecp2-loss-induced social dysfunction. BDNF and FNDC5 signaling in the prefrontal cortex region mediates the music-based-intervention promotion of social interactions. This study gives new insight into the mechanisms underlying the improvement of social behaviors in mice suffering from experimental Rett syndrome following a music-based intervention.

Comparative Effectiveness of Different Nonsurgical Treatments for Patellar Tendinopathy: A Systematic Review and Network Meta-analysis.

PURPOSE: To investigate the functional improvement and pain reduction of different nonsurgical treatments for patellar tendinopathy (PT), a systematic review with network meta-analysis was performed. METHODS: Studies were comprehensively searched for without language restrictions in the CENTRAL, MEDLINE, EMBASE, Web of Science, Physiotherapy Evidence Database, and SPORTDiscus databases from inception to May 2018. Randomized controlled trials about nonsurgical treatments for PT were included. The outcome measurements were the Victorian Institute of Sports Assessment (VISA) scale and pain scores (such as the visual analog scale or Numerical Rating Scale). Study quality was evaluated using the Physiotherapy Evidence Database score. Direct comparisons were performed using pairwise meta-analysis, whereas network meta-analysis was performed using a frequentist method in a multivariate random-effects model. RESULTS: Eleven studies with 430 affected patellar tendons were included in the systematic review. The summary mean difference of improvement in the VISA scale versus the control group for corticosteroid injection was -23.00 (95% confidence interval [CI] -36.73 to -9.27), for leukocyte-rich platelet-rich plasma (LR-PRP) was 13.22 (95% CI 2.37-24.07), for focused extracorporeal shockwave therapy (ESWT) was -1.28 (95% CI -6.25 to 3.68), for radial ESWT was -6.68 (95% CI -20.20 to 6.84), for ultrasound was -0.70 (95% CI -11.23 to 9.83), for autologous blood injection was -0.60 (95% CI -9.30 to 8.10), for dry needling was 17.51 (95% CI -2.57 to 37.60), for topical glyceryl trinitrate was -0.90 (95% CI -13.07 to 11.27), and for skin-derived tendon-like cells was 10.40 (95% CI -1.59 to 22.39). LR-PRP (Surface Under the Cumulative Ranking curve [SUCRA] = 87.5%) or dry needling (SUCRA = 90.5%) was most likely to be ranked the best in terms of improvement on the VISA scale. Compared with the control group, the summary mean difference of the change in pain score for corticosteroid injection was 0.80 (95% CI -3.48 to 5.08), for LR-PRP was -1.87 (95% CI -3.28 to -0.46), for focused ESWT was 0.13 (95% CI -0.68 to 0.93), for radial ESWT was 0.03 (95% CI -1.92 to 1.98), for ultrasound was -0.20 (95% CI -1.49 to 1.09), for autologous blood injection was 0.60 (95% CI -0.73 to 1.93), for dry needling was -0.37 (95% CI -2.71 to 1.97), and for topical glyceryl trinitrate was -0.50 (95% CI -2.55 to 1.55). The treatment most likely to be ranked the best in terms of change in pain score was LR-PRP (SUCRA = 94.9%). CONCLUSIONS: The network meta-analysis demonstrated that LR-PRP has the greatest functional improvement and pain reduction for PT compared with other treatment options. However, the treatment effect estimates can be biased by the possible intransitivity and should not be overestimated. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I studies.

The effectiveness of music therapy for individuals with Rett syndrome and their families.

BACKGROUND: Patients with Rett syndrome (RTT) present characteristic regression in communication and hand skills, which eventually leads to intellectual and physical disability. Moreover, caregivers of patients with RTT face stressors related to patients' medical and developmental concerns. Given the indications from case reports, this pilot study investigated the effectiveness of music therapy on RTT patients, as well as on parental stress for families of children with RTT. METHODS: Families in the study group were enrolled in a twice-weekly 120-minute music therapy program for 24 weeks (n = 11), whereas families in the control group did not receive music therapy (n = 12). Participants were administered the Vineland Adaptive Behavior Scales, Rett Syndrome Clinical Severity Scale, Rett Syndrome Motor Behavioral Assessment, and Parenting Stress Index for caregivers of RTT children before and after the music therapy program. RESULTS: Music therapy improved receptive language, verbal and non-verbal communication skills, and social interaction for RTT patients. In addition, purposeful hand function, breathing patterns, and eye contact were significantly improved. Of note, music therapy also decreased the frequency of epileptic seizures. Lastly, caregivers in the study group exhibited significantly lower stress following the program. CONCLUSION: The 24-week music therapy program was effective in improving social interaction, communication skills, eye contact, hand function, and reducing seizure frequency among RTT patients. Additionally, music therapy was effective in relieving parenting stress, which may help healthcare providers initiate early intervention strategies that can prevent parenting stress and reduce the risk of depression.