Physiological effects of anterior repositioning splint on temporomandibular joint disc displacement: a quantitative analysis

Anterior repositioning splints (ARS) are used primarily for the management of temporomandibular joint (TMJ) anterior disc displacement with reduction (ADDwR). However, the exact physiological effects of ARS are still unclear. This study investigated the short and long‐term effects of ARS on disc and condyle angles/positions by metric analysis. Twenty‐two subjects diagnosed with ADDwR were recruited. Maxillary full‐coverage ARS were fabricated, and MRI of TMJs was obtained before splint treatment, immediate post‐insertion and 6 months after splint treatment. Disc–condyle relationship was determined by disc–condyle angle measurement. Disc and condyle positions were described as X‐Y coordinates with the summit of glenoid fossa as the origin of the coordinates. Thirty‐two TMJs were classified as ADDwR and 12 were normal. Upon ARS insertion, all TMJs with ADDwR got normal disc–condyle relationships. The condyles moved significantly forward and downward, while the discs moved significantly backward and upward. MRI at 6 months after treatment (without ARS insertion) indicated that only 40·6% (13/32) of the joints were maintained in the normal disc–condyle relationship. The majority of condyles returned to their pre‐treatment positions, while the discs generally moved anteriorly again. The use of ARS resulted in forward and downward condyle movement, and a concurrent backward movement of the disc resulting in ideal spatial disc–condyle relationship. The stability of this relationship, however, could not be maintained in the majority of TMJs upon ARS removal. Findings explain the good short‐term clinical outcomes with ARS and their relatively lower efficacy in the long term.     

A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome

We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype–phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy‐six non‐related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation‐dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild‐type probands. There were non‐significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.     

Opportunistische filamentöse Mykosen: Aspergillose,Mukormykose, Phäohypho‐ und Hyalohyphomykose

Opportunistic filamentous mycoses are widely distributed all over the world. They are rarely observed in Europe but are common in developing countries. The most common are the aspergilloses (due to Aspergillus spp.) mostly in neutropenia and immunosuppression; the mucormycoses characterized by rapid progression in patients with diabetic ketoacidosis; the phaeohyphomycoses due to pigmented fungi causing either a mild superficial or a very serious deep disease and the hyalohyphomycoses due to hyaline filamentous fungi (Fusarium spp., Pseudallescheria spp., Scopulariopsis spp.). Cutaneous manifestations are usually secondary to dissemination from pulmonary or visceral disease; primary cases are less frequent and due to direct inoculation into the skin. We review epidemiological, clinical, diagnostic, and therapeutic data on the four most important opportunistic filamentous mycoses: aspergillosis, mucormycosis, phaeohyphomycosis and hyalohyphomycosis.     

Hypoxic inactivation of glycogen synthase kinase‐3β promotes gastric tumor growth and angiogenesis by facilitating hypoxia‐inducible factor‐1 signaling

Since the molecular mechanism of hypoxic adaptation in cancer cells is cell‐type specific, we investigated whether glycogen synthase kinase‐3β (GSK‐3β) activation is involved in hypoxia‐induced gastric tumor promotion. Stable gastric cancer cell lines (SNU‐638, SNU‐484, MKN1, and MKN45) were cultured under hypoxic conditions. Cells overexpressing wild‐type GSK‐3β (WT‐GSK‐3β) or kinase‐dead mutant of GSK‐3β (KD‐GSK‐3β) were generated and used for cell culture and animal studies. In cell culture experiments, hypoxia decreased GSK‐3β activation in gastric cancer cells. Cell viability and the expressions of HIF‐1α protein and VEGF mRNA in gastric cancer cells were higher in KD‐GSK‐3β transfectants than in WT‐GSK‐3β transfectants under hypoxic conditions, but not under normoxic conditions. Gastric cancer xenografts showed that tumor growth, microvessel area, HIF‐1α activation, and VEGF expression were higher in KD‐GSK‐3β tumors than in WT‐GSK‐3β tumors in vivo. In addition, the expression of hypoxia‐induced HIF‐1α protein was regulated by GSK‐3β at the translational level. Our data suggest that GSK‐3β is involved in hypoxic adaptation of gastric cancer cells as an inhibitory upstream regulator of the HIF‐1α/VEGF signaling pathway.     

The Logistic Regression Model for Gene–Environment Interactions Using Both Case‐Parent Trios and Unrelated Case–Controls

One of the greatest challenges in genetic studies is the determination of gene–environment interactions due to underlying complications and inadequate statistical power. With the increased sample size gained by using case‐parent trios and unrelated cases and controls, the performance may be much improved. Focusing on a dichotomous trait, a two‐stage approach was previously proposed to deal with gene–environment interaction when utilizing mixed study samples. Theoretically, the two‐stage association analysis uses likelihood functions such that the computational algorithms may not converge in the maximum likelihood estimation with small study samples. In an effort to avoid such convergence issues, we propose a logistic regression framework model, based on the combined haplotype relative risk (CHRR) method, which intuitively pools the case‐parent trios and unrelated subjects in a two by two table. A positive feature of the logistic regression model is the effortless adjustment for either discrete or continuous covariates. According to computer simulations, under the circumstances in which the two‐stage test converges in larger sample sizes, we discovered that the performances of the two tests were quite similar; the two‐stage test is more powerful under the dominant and additive disease models, but the extended CHRR is more powerful under the recessive disease model.