Effects of therapeutic and aerobic exercise programs in temporomandibular disorder-associated headaches

Objective: To assess the effects of three 8-week exercise programs on the frequency, intensity, and impact of headaches in patients with headache attributed to temporomandibular disorder (TMD). Methodology: Thirty-six patients diagnosed with headache attributed to TMD participated in the study and were divided into three groups of 12 patients: a therapeutic exercise program (G1, mean age: 26.3±5.6 years), a therapeutic and aerobic exercise program (G2, mean age: 26.0±4.6 years), and an aerobic exercise program (G3, 25.8±2.94 years). Headache frequency and intensity were evaluated using a headache diary, and the adverse headache impact was evaluated using the Headache Impact Test (HIT-6). The intensity was reported using the numerical pain rating scale. These parameters were evaluated twice at baseline (A01/A02), at the end of the 8-week intervention period (A1), and 8-12 weeks after the end of the intervention (A2). Results: At A1, none of the G2 patients reported having headaches, in G1, only two patients reported headaches, and in G3, ten patients reported headache. The headache intensity scores (0.3 [95% CI: -0.401, 1.068]), (0.0 [95% CI: -0.734, 0.734]) and HIT-6 (50.7 [95% CI: 38.008, 63.459]), (49.5 [95% CI: 36.808, 62.259]), significantly decreased in G1 and G2 at A1. At A2 headache intensity scores (0.5 [95% CI: -0.256, 1.256]), (0.0 [95% CI: -0.756, 0.756]) and HIT-6 (55.1 [95% CI: 42.998, 67.268]), (51.7 [95% CI: 39.532, 63.802]) in G1 and G2 haven't change significantly. The effects obtained immediately after the completion of the intervention programs were maintained until the final follow-up in all groups. Conclusion: The programs conducted by G1 (therapeutic exercises) and G2 (therapeutic and aerobic exercise) had significant results at A1 and A2.info:eu-repo/semantics/publishedVersio

Regulatory de novo mutations underlying intellectual disability

The genetic aetiology of a major fraction of patients with intellectual disability (ID) remains unknown. De novo mutations (DNMs) in protein-coding genes explain up to 40% of cases, but the potential role of regulatory DNMs is still poorly understood. We sequenced 63 whole genomes from 21 ID probands and their unaffected parents. In addition, we analysed 30 previously sequenced genomes from exome-negative ID probands. We found that regulatory DNMs were selectively enriched in fetal brain-specific enhancers as compared with adult brain enhancers. DNM-containing enhancers were associated with genes that show preferential expression in the prefrontal cortex. Furthermore, we identified recurrently mutated enhancer clusters that regulate genes involved in nervous system development (CSMD1, OLFM1, and POU3F3). Most of the DNMs from ID probands showed allele-specific enhancer activity when tested using luciferase assay. Using CRISPR-mediated mutation and editing of epigenomic marks, we show that DNMs at regulatory elements affect the expression of putative target genes. Our results, therefore, provide new evidence to indicate that DNMs in fetal brain-specific enhancers play an essential role in the aetiology of ID