Identification of Two Homozygous Sequence Variants in the COL7A1 Gene Underlying Dystrophic Epidermolysis Bullosa by Whole-Exome Analysis in a Consanguineous Family.

Dystrophic epidermolysis bullosa (DEB) is an inherited skin disorder with variable severity and heterogeneous genetic involvement. Diagnostic approaches for this condition include clinical evaluations and electron microscopy of patients' skin biopsies, followed by Sanger sequencing (SS) of a large gene (118 exons) that encodes the alpha chain of type VII collagen (COL7A1) located on Chromosome 3p21.1. However, the use of SS may hinder diagnostic efficiency and lead to delays because it is costly and time-consuming. We evaluated a 5-generation consanguineous family with 3 affected individuals presenting the severe generalised DEB phenotype. Human whole-exome sequencing (WES) revealed 2 homozygous sequence variants: the previously reported variant p.Arg578* in exon 13 and a novel variant p.Arg2063Gln in exon 74 of the COL7A1 gene. Validation by SS, performed on all family members, confirmed the cosegregation of the 2 variants with the disease phenotype. To the best of our knowledge, 2 homozygous COL7A1 variants have never been simultaneously reported in DEB patients; however, the upstream protein truncation variant is more likely to be disease-causing than the novel missense variant. WES can be used as an efficient molecular diagnostic tool for evaluating autosomal recessive forms of DEB.

Quality of life in children with Down syndrome and its association with parent and child demographic characteristics: Parent-reported measures.

BACKGROUND: This study aims to explore the association between the quality of life (QoL) in children with Down syndrome (DS) and its relationship with demographic characteristics of both parents and children. The investigation encompasses five domains: physical and psychological well-being, autonomy and parental relationship, social well-being, and peers, as well as school and the learning environment. METHOD: An online questionnaire, the KIDSCREEN-27, was used to measure the QoL of 112 families with DS in Saudi Arabia, referred to as "Parent-Reported Measures." Descriptive statistics were analyzed using the Statistical Package for Social Sciences. RESULTS: The study found that the QoL of children with DS showed high scores in the psychological well-being, autonomy, parental relations, school, and learning environment domains. However, the physical and social well-being and peer domains had lower scores, although still considered "good scores." Family income had a positively significant influence on all QoL domains. Specifically, higher family income was associated with better QoL outcomes, except for social well-being. Parental age was found to influence psychological well-being, while parental education and the relationship between the parent and child influenced social well-being. Lastly, the child's gender was found to have an impact on the school and learning environment domain. CONCLUSION: The study highlights the importance of understanding the impact of the demographic variability of children with DS and their parents on the QoL of their children. It emphasizes the need to address the needs of families with lower incomes and the importance of parental education and relationships with their children in improving social well-being. The findings could aid policymakers and healthcare providers in improving the QoL for families with children who have DS.

Three-dimensional reconstruction of fracture callus morphogenesis.

Rat and mouse femur and tibia fracture calluses were collected over various time increments of healing. Serial sections were produced at spatial segments across the fracture callus. Standard histological methods and in situ hybridization to col1a1 and col2a1 mRNAs were used to define areas of cartilage and bone formation as well as tissue areas undergoing remodeling. Computer-assisted reconstructions of histological sections were used to generate three-dimensional images of the spatial morphogenesis of the fracture calluses. Endochondral bone formation occurred in an asymmetrical manner in both the femur and tibia, with cartilage tissues seen primarily proximal or distal to the fractures in the respective calluses of these bones. Remodeling of the calcified cartilage proceeded from the edges of the callus inward toward the fracture producing an inner-supporting trabecular structure over which a thin outer cortical shell forms. These data suggest that the specific developmental mechanisms that control the asymmetrical pattern of endochondral bone formation in fracture healing recapitulated the original asymmetry of development of a given bone because femur and tibia grow predominantly from their respective distal and proximal physis. These data further show that remodeling of the calcified cartilage produces a trabecular bone structure unique to fracture healing that provides the rapid regain in weight-bearing capacity to the injured bone.

Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34).

BACKGROUND: Recombinant human parathyroid hormone (PTH [1-34]; teriparatide) is a new treatment for postmenopausal osteoporosis that can be systemically administered for the primary purpose of increasing bone formation. Because several studies have described the enhancement of fracture-healing and osteointegration in animals after use of PTH, we sought to critically analyze this skeletal effect. METHODS: Two hundred and seventy male Sprague-Dawley rats underwent standard, closed femoral fractures and were divided into three groups that were administered daily subcutaneous injections of 5 or 30 mug/kg of PTH (1-34) or vehicle (control). The dosing was administered for up to thirty-five days. Groups were further divided into three subgroups and were killed on day 21, 35, or 84 after the fracture. The bones were subjected to mechanical torsion testing, histomorphometric analysis, or microquantitative computed tomography. RESULTS: By day 21, calluses from the group treated with 30 mug of PTH showed significant increases over the controls with respect to torsional strength, stiffness, bone mineral content, bone mineral density, and cartilage volume. By day 35, both groups treated with PTH showed significant increases in bone mineral content and density and total osseous tissue volume, and they demonstrated significant decreases in void space and cartilage volume (p < 0.05). Torsional strength was significantly increased at this time-point in the group treated with 30 mug of PTH (p < 0.05). While dosing was discontinued on day 35, analyses performed after eighty-four days in the group treated with 30 mug of PTH showed sustained increases over the controls with respect to torsional strength and bone mineral density. No change was noted in osteoclast density at the time-points measured, suggesting that treatment with PTH enhanced bone formation but did not induce bone resorption. CONCLUSIONS: These data show that daily systemic administration of PTH (1-34) enhances fracture-healing by increasing bone mineral content and density and strength, and it produces a sustained anabolic effect throughout the remodeling phase of fracture-healing.

Effect of lip position and gingival display on smile and esthetics as perceived by college students with different educational backgrounds.

AIM: The aim of this study was to evaluate the influence of education on the perception of female college students on the effect of lip position and gingival display upon smiling and esthetics. METHODS: A photograph of a smiling subject was altered to show varying degrees of gingival display. Female students, who were studying in different colleges, assessed a total of five images, using a numerical rating scale. RESULTS: A total of 440 college students from eight educational faculties (dentistry, dental assistants, medicine, medical technology, nursing, science, arts, and pharmacology) participated in this study. There was no difference found between students' ratings of the altered images (P<0.05). The perception of a gummy smile was found to be similar among the participants. There was agreement between all participants that 2 mm of gingival display was the most attractive smile, while a 4 mm covering of the teeth by the upper lip was the least attractive. CONCLUSION: Educational influence did not have an effect of the perception of a gummy smile.

Effects of acid hydrolysis and mechanical polishing on surface residual stresses of low-fusing dental ceramics.

STATEMENT OF PROBLEM: Cracks may arise in a ceramic restorative material over time, resulting in sudden fractures at stresses well below the yield stress. PURPOSE: This study evaluated by means of indentation technique the effects of acid hydrolysis and mechanical polishing on the surface residual stresses of low-fusing ceramic materials. MATERIAL AND METHODS: A total of 64 ceramic bars were formed to produce 4 groups of 16 bars each for 4 ceramic materials (Duceram-LFC Dentin, Duceram-LFC Enamel, Finesse Dentin, and Finesse Enamel). Four surface-treatment groups (n=4) were then formed for each of the 4 materials. The 4 surface treatments were control (autoglaze), hydrolysis, glaze/polish, and polish/glaze. A Vickers indenter contacted the Duceram-LFC specimens with a 5-N load and the Finesse specimens with a 3-N load for 10 seconds. Scanning electron microscope (SEM) was used to study surface texture before and after hydrolysis and polishing. Differences in mean crack lengths were analyzed with 1-way analysis of variance and least significant difference test (alpha=.05.) RESULTS: SEM showed obvious surface flaws as a result of hydrolysis on Duceram-LFC Enamel and Dentin specimens. However, statistical analysis of the resulting crack lengths revealed no significant differences between values for the control groups (58.16 +/- 3.88) (53.53 +/- 2.67) and hydrolysis groups (57.11 +/- 4.09) (54.54 +/- 3.15) for Enamel (P=.081) and Dentin (P=.093) respectively. When comparing polished groups and nonpolished groups, the mean crack lengths were significantly shorter for polished specimens of Duceram-LFC Enamel (53.76 +/- 3.17), Finesse Enamel (40.56 +/- 3.31), and Finesse Dentin (39.76 +/- 3.81) porcelains compared with their control groups (58.16 +/- 3.88) (43.54 +/- 4.12) (41.19 +/- 3.47), respectively (P<.0001). The mean crack lengths were significantly longer for polished specimens of Duceram-LFC Dentin (59.16 +/- 3.52) porcelain compared with the control group (53.53 +/- 2.67) (P<.0001). CONCLUSION: Within the limitations of this study, hydrolysis did not improve surface residual stresses of Duceram-LFC and Finesse ceramic materials. Mechanical polishing improved surface residual stresses of all materials tested, except Duceram-LFC Dentin porcelain.