Single‐nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine

Pemphigus vulgaris (PV) is a rare autoimmune blistering disorder, which could affect both skin and mucosal surfaces. There is increasing evidence that genetics plays a critical role in PV development, severity and prognosis. Single‐nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people and have been widely evaluated in most diseases. However, there are few studies regarding the roles of SNPs in the PV. Here, we reviewed both pathogenic and protective roles of the SNPs in non‐HLA genes regarding the PV. Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population‐specific manner. Moreover, SNPs in glucocorticoid receptor, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, including rs11745958, rs17209237, rs33388, rs7701443 as well as rs116855232 at NUDT15, seem to be associated with therapeutic outcomes in PV patients. Additionally, variations in the other genes involved in the drugs' metabolisms, pharmacokinetics and pharmacodynamics such as rs396991 in FCGR3A gene could be used for the prediction of clinical response to drugs and side effects. Taken together, SNPs seem to be valuable tools for better management of PV patients. Further studies need to be conducted to evaluate SNPs in genes that control immune responses and apoptosis.     

Fracture strength of machined ceramic crowns as a function of tooth preparation design and the elastic modulus of the cement

Objectives

To determine, by means of static fracture testing the effect of the tooth preparation design and the elastic modulus of the cement on the structural integrity of the cemented machined ceramic crown-tooth complex.

Methods

Human maxillary extracted premolar teeth were prepared for all-ceramic crowns using two preparation designs; a standard preparation in accordance with established protocols and a novel design with a flat occlusal design. All-ceramic feldspathic (Vita MK II) crowns were milled for all the preparations using a CAD/CAM system (CEREC-3). The machined all-ceramic crowns were resin bonded to the tooth structure using one of three cements with different elastic moduli: Super-Bond C&B, Rely X Unicem and Panavia F 2.0. The specimens were subjected to compressive force through a 4 mm diameter steel ball at a crosshead speed of 1 mm/min using a universal test machine (Loyds Instrument Model LRX.). The load at the fracture point was recorded for each specimen in Newtons (N). These values were compared to a control group of unprepared/unrestored teeth.

Results

There was a significant difference between the control group, with higher fracture strength, and the cemented samples regardless of the occlusal design and the type of resin cement. There was no significant difference in mean fracture load between the two designs of occlusal preparation using Super-Bond C&B. For the Rely X Unicem and Panavia F 2.0 cements, the proposed preparation design with a flat occlusal morphology provides a system with increased fracture strength.

Significance

The proposed novel flat design showed less dependency on the resin cement selection in relation to the fracture strength of the restored tooth. The choice of the cement resin, with respect to its modulus of elasticity, is more important in the anatomic design than in the flat design.     

Investigating the role of endogenous opioid system in chloroquine-induced phospholipidosis in rat liver by morphological,biochemical and molecular modelling studies

Drug-induced phospholipidosis (DIPL) is characterized by phospholipid storage in the lysosomes of affected tissues. Many severe effects and toxicities have been linked to DIPL. The aim of this study was to determine whether the endogenous opioid system is involved in chloroquine-induced phospholipidosis. The effect of naltrexone as an antagonist of opioid receptors in chloroquine-induced phospholipidosis in rat liver was investigated by morphological, biochemical, and molecular modelling studies. Transmission electron microscopy (TEM) showed that morphological characteristic changes of rat liver, including the number of lamellar bodies, grade of vacuolization and cell steatosis, were markedly attenuated in rats treated with naltrexone alone or in combination with chloroquine, in comparison with chloroquine-treated rats. The results of liquid chromatography mass spectrometry (LC/MS) showed that the concentrations of phenylacetylglycine (PAG) and hippuric acid (HA) were significantly decreased and increased, respectively, in target groups. Besides, the concentration ratio of PAG/HA was significantly decreased. Spectrophotometry resulted in a notable decrease in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in target groups. The results from the molecular docking and molecular dynamic simulation studies demonstrated clear chloroquine interaction with the active site cavity of the µ opioid receptor. These data suggest that administration of naltrexone alone, or in combination with chloroquine, notably attenuates the side effects of chloroquine-induced phospholipidosis, as well as demonstrating an increased probability of the endogenous opioid system involvement in chloroquine-induced phospholipidosis in rat liver.     

Multicomponent gas separation and purification using advanced 2D carbonaceous nanomaterials

Multicomponent gas separation and purification is an important pre- or post-processing step in industry. Herein, we employed a multiscale computational approach to investigate the possibility of multicomponent low-weight gas (H₂, O₂, N₂, CO₂, CH₄) separation and purification using novel porous 2D carbonaceous nanomaterials, namely Graphdiyne (GD), Graphenylene (GN), and Rhombic-Graphyne (RG). The dispersion-corrected plane-wave density functional theory (DFT) calculation combined with the Climbing Image Nudged Elastic Band (CI-NEB) method was employed to study the gas/membrane interaction energy and diffusion barrier of different gases passing through the geometrically optimized membranes. The results from CI-NEB calculations were then fitted to the Morse potential function to construct a bridge between quantum mechanics calculations and non-equilibrium molecular dynamics (NEMD) simulation. The selectivity of each membrane for all binary mixtures was calculated using the estimated diffusion energy barriers based on the Arrhenius equation. Finally, a series of extensive NEMD simulations were carried out to evaluate the real word and time dependent separation process. According to the results, CH₄ molecules can be completely separated from the other gases using a GD membrane, O₂ molecules from CH₄, N₂, and CO₂ by a GN membrane, and H₂ molecules from all other gases using a RG membrane.

Multicomponent gas separation and purification is an important pre- or post-processing step in industry.     

Embolization of immediate release transcatheter patch for atrial septal defect occlusion: the causes and the pitfalls to avoid

We report embolization of a bioabsorbable immediate-release patch for closure of atrial septal defect into left atrium with forward movement into and out of the mitral valve during each cardiac cycle. The dislodged device was ultimately explanted by a surgical operation and the defect was closed. We discuss causes and recommend tips to prevent such a serious potential complication. We also suggest some modifications to the device for making it more safe and effective.     

Primary hepatic malignant fibrous histiocytoma: clinicopathologic characteristics and prognostic value of ezrin expression

Primary hepatic malignant fibrous histiocytoma (MFH) is a rare entity with ill-defined clinicopathologic characteristics. We present the largest series to date (7 cases) of primary hepatic MFH, a systematic review of 27 cases published in the English literature, and an analysis of prognostic factors including ezrin expression. The 2 men and 5 women in our series were 34 to 80 years old (average 61 y) and presented with abdominal pain (6/7), systemic symptoms of low-grade fever, malaise, anorexia and weight loss (4/7), and spiking fever (1/7). One case was an incidental finding. Computed tomography and ultrasound revealed a well-demarcated solitary heterogeneous low-density mass ranging from 5.5 to 20 cm (average 12 cm) in largest dimension (5/7), or multiple small nodules up to 2 cm in diameter (1/7) or a 10 cm multiloculated cystic lesion owing to extensive necrosis (1/7). Histologically, a storiform-pleomorphic pattern with variable degrees of necrosis predominated (6/7). A myxoid pattern was seen in only 1 case and this case lacked necrosis. Lymphoplasmacytic infiltration was seen in 3/7 of the cases. Tumors were grade I (1/7), grade II (2/7), grade III (4/7), stage pT1 (4/7), pT2 (1/7), pT4 (1/7), and pT4, cM1 (1/7) at diagnosis. Three patients with tumor cell ezrin immunoreactivity score >or=1 died of tumor within 1 year. Two patients with tumor cell ezrin immunoreactivity score <1 survived >4 years after surgery. Combined analysis of our series and previously reported cases suggest that primary hepatic MFH possess certain characteristic clinicopathologic features that may help in making the diagnosis and in differentiating it from other more common neoplasms in the liver. The prognosis of hepatic MFH depends primarily on tumor size and stage at the time of diagnosis. Ezrin expression in tumor cells can provide additional prognostic information and may be a potential target for new adjuvant therapies.