A founder truncating variant in GDF1 causes autosomal‐recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds

The genetic basis of congenital heart malformations associated with disruption of left–right (L–R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left–right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab‐Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left–right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.     

Occupation as a potential contributing factor for temporomandibular disorders,bruxism, and cervical muscle pain: a controlled comparative study

The aim of the study was to compare the prevalence of cervical muscle pain (CMP) and myogenic temporomandibular disorders (MFP) among female dentists, high‐tech workers, and a group of subjects employed in other occupations; to investigate the associations among CMP, MFP, and bruxism in those groups; and to evaluate the influence of work‐related stress on MFP and CMP. Evaluation was based on clinical examinations of MFP and CMP and self‐reported questionnaires concerning pain and stress. The diagnosis of sleep bruxism was adapted using the validated diagnostic criteria of the American Academy of Sleep Medicine (International Classification of Sleep Disorders (ICSD‐2), 2005, Westchester, IL), whilst the diagnosis of awake bruxism was made on the basis of a questionnaire. The odds of a subject with MFP experiencing concurrent CMP or bruxism (sleep and/or awake) ranged from 2.603 to 3.077. These results suggest that high‐tech workers and dentists are at greater risk for developing temporomandibular disorders (TMDs) and CMP when compared with general occupation workers, as defined in this study. Furthermore, the associations shown here between TMDs and CMP highlight the importance of palpating neck musculature as part of any routine examination of TMD.     

Two-stage reconstruction of the severely deficient alveolar ridge: bone graft followed by alveolar distraction osteogenesis

Distraction osteogenesis for the augmentation of severe alveolar bone deficiency has gained popularity during the past two decades. In cases where the vertical bone height is not sufficient to create a stable transport segment, performing alveolar distraction osteogenesis (ADO) is not possible. In these severe cases, a two-stage treatment protocol is suggested: onlay bone grafting followed by ADO. An iliac crest onlay bone graft followed by ADO was performed in 13 patients: seven in the mandible and six in the maxilla. Following ADO, endosseous implants and prosthetic restorations were placed. In all cases, the onlay bone graft resulted in inadequate height for implant placement, but allowed ADO to be performed. ADO was performed to a mean total vertical augmentation of 13.7 mm. Fifty-two endosseous implants were placed. During a mean follow-up of 4.85 years, two implants failed, both during the first 6 months; the survival rate was 96.15%. In severe cases lacking the required bone for ADO, using an onlay bone graft as a first stage treatment increases the bone height thus allowing ADO to be performed. This article describes a safe and stable two-stage treatment modality for severely atrophic cases, resulting in sufficient bone for implant placement and correction of the inter-maxillary vertical relationship.     

Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas aeruginosa Virulence Factors

We investigated the efficacy and safety of liposomal clarithromycin formulations with different surface charges against clinical isolates of Pseudomonas aeruginosa from the lungs of cystic fibrosis (CF) patients. The liposomal clarithromycin formulations were prepared by the dehydration-rehydration method, and their sizes were measured using the dynamic-light-scattering technique. Encapsulation efficiency was determined by microbiological assay, and the stabilities of the formulations in biological fluid were evaluated for a period of 48 h. The MICs and minimum bactericidal concentrations (MBCs) of free and liposomal formulations were determined with P. aeruginosa strains isolated from CF patients. Liposomal clarithromycin activity against biofilm-forming P. aeruginosa was compared to that of free antibiotic using the Calgary Biofilm Device (CBD). The effects of subinhibitory concentrations of free and liposomal clarithromycin on bacterial virulence factors and motility on agar were investigated on clinical isolates of P. aeruginosa. The cytotoxicities of the liposome preparations and free drug were evaluated on a pulmonary epithelial cell line (A549). The average diameter of the formulations was >222 nm, with encapsulation efficiencies ranging from 5.7% to 30.4%. The liposomes retained more than 70% of their drug content during the 48-h time period. The highly resistant strains of P. aeruginosa became susceptible to liposome-encapsulated clarithromycin (MIC, 256 mg/liter versus 8 mg/liter; P < 0.001). Liposomal clarithromycin reduced the bacterial growth within the biofilm by 3 to 4 log units (P < 0.001), significantly attenuated virulence factor production, and reduced bacterial twitching, swarming, and swimming motilities. The clarithromycin-entrapped liposomes were less cytotoxic than the free drug (P < 0.001). These data indicate that our novel formulations could be a useful strategy to enhance the efficacy of clarithromycin against resistant P. aeruginosa strains that commonly affect individuals with cystic fibrosis.     

Association between posterior crossbite and/or deep bite and temporomandibular disorders among Palestinian adolescents: A sex comparison

ABSTRACT

Objective: To assess the prevalence of temporomandibular disorders (TMDs) and posterior crossbite and/or deep bite and any possible association between them.

Methods: One thousand-nineteen adolescents responded to a questionnaire regarding oral habits and TMD symptoms. Afterwards, they were diagnosed according to the Axis I of the DC/TMD and underwent a dental examination. The chi-square test was used for statistical analysis.

Results: A significant association was found between posterior crossbite and some TMD diagnosis, but no association was found between deep bite and TMD, nor between occlusal diagnosis and bruxism. TMDs were more prevalent in girls. There was a significant sex difference (more among females) in the prevalence of painful TMDs.

Conclusion: Posterior crossbite in the adolescent population analyzed may be related to TMDs, in contrary to deep-bite. The presence of posterior crossbite may have different impact on TMD findings between the sexes.