Molecular diagnosis of congenital muscular dystrophies with defective glycosylation of alpha-dystroglycan using next-generation sequencing technology

Targeted resequencing using next-generation sequencing technology is being rapidly applied to the molecular diagnosis of human genetic diseases. The group of muscular dystrophies may be an appropriate candidate for this approach because these diseases exhibit genotype–phenotype heterogeneity. To perform a proof-of-concept study, we selected four patients with congenital muscular dystrophies with defective glycosylation of alpha-dystroglycan. A custom-solution-based target enrichment kit was designed to capture whole-genic regions of the 26 muscular-dystrophy-related genes, including six genes implicated in alpha-dystroglycanopathies. Although approximately 95% of both coding and noncoding regions were covered with at least 15-read depth, parts of the coding exons of FKRP and POMT2 were insufficiently covered. Homozygous and compound heterozygous POMGnT1 mutations were found in two patients. Two novel noncoding variants of FKTN were identified in one patient who had a retrotransposon insertion mutation of FKTN in only one allele. The current targeted resequencing strategy yielded promising results for the extension of this method to other muscular dystrophies. As suboptimal coverage in a small subset of coding regions may affect the sensitivity of the method, complementary Sanger sequencing may be required.     

Incidence Rate of Bee Venom Acupuncture Related Anaphylaxis: A Systematic Review

Background: Bee venom acupuncture (BVA) is an effective treatment method for various diseases. Bee venom, however, can cause adverse effects, even rarely including life-threatening anaphylaxis, so safety-related evidence is required. In this study, we systematically estimated the incidence rate of anaphylaxis in response to BVA. Methods: We searched eight databases (MEDLINE (Pubmed), EMBASE, Cochrane Central Register of Controlled, KISS, KMBASE, Koreamed, OASIS, and NDSL) and systematically reviewed the articles that met the inclusion/exclusion criteria. Results: Among 225 potentially relevant articles, 49 were selected for this study. The overall incidence rate of anaphylaxis in response to BVA was 0.045% (95% CI 0.028–0.062). Women (0.083%, 95% CI 0.010–0.157) showed a higher incidence rate than men (0.019%, 95% CI −0.018 to 0.055), while the incidence for patients who had a skin test conducted (0.041%, 95% CI 0.011–0.072) was not significantly different compared to that obtained for patients for which there was no information about a skin test (0.047%, 95% CI 0.026–0.067). The publication year affected the incidence rate: it was highest before 1999 (1.099%, 95% CI −1.043 to 3.241), lower between 2000 and 2009 (0.049%, 95% CI 0.025–0.073), and lowest between 2010 and 2021 (0.037% 95% CI 0.014–0.060). Conclusions: In this study, we provide reference data about risk size and factors of BVA-related anaphylaxis, which is essentially required for BVA application in clinics.     

Serial sections of atrophic acne scars help in the interpretation of microscopic findings and the selection of good therapeutic modalities

Background Acne scar causes problems cosmetically and psychologically. Although microscopic examination of acne scars is a necessity for understanding and treatment of them, and it is not easy to find a paper reporting the microscopic characterization of acne scars. Objective The aim of this study was to examine the microscopic findings of acne scars and to select a good therapeutic modality based on the findings. Methods Thirty‐one atrophic scars obtained from five patients for cosmesis and 18 serial sections were made from each atrophic scar. The sections were stained with H&E, Masson‐trichrome or Verhoeff van Gieson stains. Immunohistochemistry was done with antibodies against transforming growth factor‐β, metalloproteinase‐1 (MMP‐1), MMP‐2, MMP‐9 and MMP‐13. The stained sections were examined under the microscope. Results The epidermis of the acne scar was characterized by keratin plugging in the hair follicle orifice (32%) and multi‐channelled tracts (29%). The dermis of the acne scar had characteristics including a decrease in the dermal thickness and loss of pilosebaceous units. In addition, inflammatory cell infiltrates were seen in the dermis (77%), and insufficient dense collagen fibre deposition was found in the whole dermis (29%). Other findings such as calcium deposition and foreign body reaction were discovered. Conclusion We have found the characteristics of acne scar through the serial sections of several atrophic scars, and suggest that the treatment must reflect several considerations, including the understanding of histopathological findings and the use of combination therapy.     

Monocyte Aggregation and Multinucleated Giant-Cell Formation in Vitro in Crohn's Disease: The Effect of Cell Adhesion Molecules

Background: Helicobacter pylori     

Recalcitrant eosinophilic pustular folliculitis of Ofuji with palmoplantar pustulosis: dramatic response to narrowband UVB phototherapy

Eosinophilic pustular folliculitis of Ofuji is a recalcitrant disease typified by non‐infective eosinophilic spongiosis involving the infundibular region of the hair follicle. We present a case of a 49‐year‐old Chinese man with known palmoplantar pustulosis and acrodermatitis continua of Hallopeau which was promptly resolved with methotrexate therapy. He returned with an erythematous papulopustular eruption with coalescence to annular plaques, occurring over the face, chest and back with active palmoplantar pustulation. Histology from skin biopsy of the palmar lesion was in keeping with palmoplantar psoriasis, while biopsy of the facial and truncal lesions revealed florid perifollicular eosinophilic congregation diagnostic of eosinophilic pustular folliculitis of Ofuji. Indomethacin was initiated with partial improvement of lesions with cyclical flares. A trial of narrowband ultraviolet‐B phototherapy at a frequency of thrice weekly achieved sustained clearance of both eosinophilic pustular folliculitis and palmoplantar lesions. Indomethacin was tailed down and eventually discontinued with maintenance of narrowband ultraviolet‐B therapy; this achieved successful control of the disease.     

Role of Cholinergic and Cytokine Regulation of T Cell Function in Stimulation and Inhibition of Immune Reactions in Intoxication by Organophosphorus Compounds in Different Doses

Experiments on outbred albino rats showed that administration of acetylcholine and aceclidine in a dose of 0.1 LD₅₀ for 3 days and of dimethyl dichlorovinyl phosphate (organophosphorus compound) in a single dose of 0.05 LD₅₀ stimulated the function of Th1 and Th2 lymphocytes and cytokine production by these cells. Dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD₅₀ produced an opposite effect. Acetylcholine and aceclidine stimulated activity of acetylcholinesterase in T cells, while dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD₅₀ inhibited it. During acute intoxication, the organophosphorus compound, depending on the dose, can stimulate (acetylcholine effect) and inhibit the immune reactions (acetylcholinesterase inhibition of T cells).     

Deformability study of breast cancer cells using microfluidics

Cell deformability is an important biomarker which can be used to distinguish between healthy and diseased cells. In this study, microfluidics is used to probe the biorheological behaviour of breast cancer cells in an attempt to develop a method to distinguish between non-malignant and malignant cells. A microfabricated fluidic channel design consisting of a straight channel and two reservoirs was used to study the biorheological behaviour of benign breast epithelial cells (MCF-10A) and non-metastatic tumor breast cells (MCF-7). Quantitative parameters such as entry time (time taken for the cell to squeeze into the microchannel) and transit velocity (speed of the cell flowing through the microchannel) were defined and measured from these studies. Our results demonstrated that a simple microfluidic device can be used to distinguish the difference in stiffness between benign and cancerous breast cells. This work lays the foundation for the development of potential microfluidic devices which can subsequently be used in the detection of cancer cells. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Expression of the GLUT1 glucose transporter and p53 in carcinomas of the pancreatobiliary tract

Only few studies have evaluated the usefulness of the GLUT1 and p53 status of pancreatobiliary tract carcinomas in revealing tumorigenesis. We studied GLUT1 and p53 immunoexpression in a total of 355 cases of the pancreatobiliary carcinoma to determine the biological significance of GLUT1 and p53 expression. Positive expression of GLUT1 was identified in 38 out of 67 (57.7%) ampulla of Vater (AV) carcinomas, in 27 out of 52 (51.8%) pancreatic (PA) carcinomas, in 38 out of 121 (31.4%) extrahepatic bile duct (EBD) carcinomas, and in 53 out of 115 (46.5%) gallbladder (GB) carcinomas. GLUT1 expression in pancreatobiliary carcinomas showed some positive correlation with histological grade, T stage, N stage, TNM stage, and lymphatic invasion. However, p53 expression showed no correlation with any prognostic factors. In the Kaplan–Meier test, positive GLUT1 expression was a poor prognostic factor in the pancreatobiliary tract cancers; however, only GB cancers were statistically significant (P=0.002). Our results suggest that GLUT1 expression in the AV, EBD, and GB carcinomas is associated with some prognostic factors, and GLUT1 expression is associated with a worse prognosis in the patients with GB carcinomas.