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Background: Understanding the genetic basis of human diseases has become integral to drug development and precision medicine. Recent advancements have enabled the identification of molecular pathways driving diseases, leading to targeted treatment strategies. The increasing investment in rare diseases by the biotech industry underscores the importance of genetic evidence in drug discovery and approval processes. Here we studied a monogenic Mendelian kidney disease, TRPC6-associated podocytopathy (TRPC6-AP), to present its natural history, genetic spectrum, and clinicopathological associations in a large cohort of patients with causal variants in TRPC6, in order to help define the specific features of disease and further facilitate drug development and clinical trials design., Methods: the study involved 64 individuals from 39 families with TRPC6 causal missense variants. Clinical data, including age of onset, laboratory results, response to treatment, kidney biopsy findings, and genetic information, were collected from multiple centers nationally and internationally. Exome or targeted sequencing was performed and variant classification was based on strict criteria. Structural and functional analyses of TRPC6 variants were conducted to understand their impact on protein function. In depth re-analysis of light and electron microscopy specimens for 9 available kidney biopsies was conducted to identify pathological features and correlates of TRPC6-AP., Results: Large-scale sequencing data did not support causality for TRPC6 protein-truncating variants. We identified 21 unique TRPC6 missense variants, clustering in three distinct regions of the protein, and with different effects on TRPC6 3D protein structure. Kidney biopsy analysis revealed FSGS patterns of injury in most cases, along with distinctive podocyte features including diffuse foot process effacement and swollen cell bodies. The majority of patients presented in adolescence or early adulthood but with ample variation (average 22, SD ± 14 years), with frequent progression to kidney failure but with variability in time between presentation and ESKD., Conclusions: This study provides insights into the genetic spectrum, clinicopathological associations, and natural history of TRPC6-AP., (Copyright © 2024 by the American Society of Nephrology.)

Objective: The study aimed to assess the prevalence of dental malocclusion, orthodontic parameters, and parafunctional habits in children with developmental dyslexia (DD)., Methods: Forty pediatric patients (67.5% boys and 32.5% girls, mean age: 11.02 ± 2.53 years, range: 6-15 years) with DD were compared with 40 age- and sex-matched healthy participants for prevalence of dental malocclusion, orthodontic parameters, and parafunctional habits. Dental examinations were performed by an orthodontist., Results: Pediatric patients with DD exhibited a significantly higher prevalence of Angle Class III malocclusion (22.5% vs. 5.0%, P = 0.024), deep bite (27.5% vs. 7.5%, P = 0.019), midline deviation (55.0% vs. 7.5%, P < 0.0001), midline diastemas (32.5% vs. 7.5%, P = 0.010), wear facets (92.5% vs. 15.0%, P < 0.0001), self-reported nocturnal teeth grinding (82.5% vs. 7.5%, P < 0.0001), nail biting (35.0% vs. 0.0%, P < 0.0001), and atypical swallowing (85.0% vs. 17.5%, P < 0.0001) compared to that in healthy controls., Conclusions: Pediatric patients with DD showed a higher prevalence of Class III malocclusion, greater orthodontic vertical and transverse discrepancies, and incidence of parafunctional activities. Clinicians and dentists should be aware of the vulnerability of children with dyslexia for exhibiting malocclusion and encourage early assessment and multidisciplinary intervention.

Objectives: Literature presents conflicting results regarding malocclusions, Obstructive Sleep Apnea (OSA) and sleep bruxism in children with ADHD. Aim of this study was to evaluate the prevalence of these parameters., Methods: A prospective study was conducted on 40 consecutive ADHD children referred to the Paediatric Dentistry Unit of Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome. All subjects underwent an orthodontic examination and were screened for OSA and sleep bruxism. Data were compared to a sex- and aged-matched control group., Results: Prevalence of high risk of OSA in children with ADHD was 62.5% compared to 10% in the control group ( p  < .00001). No differences were found in any of the occlusal variables examined between children with ADHD and controls ( p  > .05). An increased prevalence of sleep bruxism was observed in ADHD children (40%) compared to controls (7.5%) ( p  < .001)., Conclusions: A higher prevalence of OSA risk and probable sleep bruxism were observed in ADHD patients compared with controls. No significant differences were observed in malocclusions d., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The effectiveness of clear aligners in correcting malocclusions is closely linked to the properties of the materials used to make them. The polymers used in the manufacture of clear aligners have well-established properties. However, the process of manufacturing clear aligners, known as thermoforming, involves thermal and mechanical shocks that may alter these properties. The objective of this study was to evaluate the effects of thermoforming on the mechanical, optical, chemical, and morphological properties of sixty PET-G specimens. The study compared the thickness, weight, absorbance, chemical structure, surface roughness, elastic modulus, yield strength, and breaking load of thirty thermoformed specimens with thirty non-thermoformed specimens. The study introduces a new approach by using standardized samples to analyze both chemical and physical properties. The results showed statistically significant differences in thickness (-15%), weight (-11%), and surface roughness (+1233% in roughness average; +1129% in RMS roughness) of the material. Additionally, a correlation was found between reduction in thickness and increase in opalescence. There was no significant change in the functionality of the aligners after thermoforming, as no significant mechanical changes were found. However, the increase in surface roughness may lead to plaque and fluid accumulation and worsen the fit of the aligners.