Anatomy of the Facial Nerve at the Condylar Area: Measurement Study and Clinical Implications

The aim of this study was to elucidate the detailed anatomy of the facial nerve (FN) at the condylar area to helping physicians preventing the iatrogenic trauma on the nerve. We dissected 25 specimens of the embalmed Korean cadavers (13 males and 2 females; mean age 76.9 years). The FN course at the condylar was examined, and the location of the FN branches was measured with superficial standards. The trunks of the FN emerged in the condylar area as one trunk, two trunks, and a loop or plexiform in 36%, 12%, and 52% areas, respectively. The zygomatic branch (Zbr) of FN passed over the tragus-alar line 23 mm anterior to the tragus (Tg) in most of the cases. The Zbr passed over the vertical line 2 cm anterior to the Tg through the area about 6 to 20 mm inferior to the Tg. Regardless of careful approach techniques to the condylar area, the FN could be damaged by a careless manipulation. Any reference landmarks could not guarantee the safety during the approach to the condylar area because more than half of the cases present the complicated branching type in the front of the Tg

Identification of a novel human Rad51 variant that promotes DNA strand exchange

Rad51 plays a key role in the repair of DNA double-strand breaks through homologous recombination, which is the central process in the maintenance of genomic integrity. Five paralogs of the human Rad51 gene (hRad51) have been identified to date, including hRad51B, hRad51C, hRad51D, Xrcc2 and Xrcc3. In searches of additional hRad51 paralogs, we identified a novel hRad51 variant that lacked the sequence corresponding to exon 9 (hRad51-Δex9). The expected amino acid sequence of hRad51-Δex9 showed a frame-shift at codon 259, which resulted in a truncated C-terminus. RT-PCR analysis revealed that both hRad51 and hRad51-Δex9 were prominently expressed in the testis, but that there were subtle differences in tissue specificity. The hRad51-Δex9 protein was detected as a 31-kDa protein in the testis and localized at the nucleus. In addition, the hRad51-Δex9 protein showed a DNA-strand exchange activity comparable to that of hRad51. Taken together, these results indicate that hRad51-Δex9 promotes homologous pairing and DNA strand exchange in the nucleus, suggesting that alternative pathways in hRad51- or hRad51-Δex9-dependent manners exist for DNA recombination and repair

One-pot Enzymatic Synthesis of Deoxy-thymidine-diphosphate (TDP)-2-deoxy-∝-d-glucose Using Phosphomannomutase

Production of deoxy-thymidine-diphosphate (TDP)-sugars as substrates of glycosyltransferases, has been one of main hurdles for combinatorial antibiotic biosynthesis, which combines sugar moiety with aglycon of various antibiotics. Here, we report the one-pot enzymatic synthesis of TDP-2-deoxy-glucose employing high efficient TMP kinase (TMK; E.C. 2.7.2.12), acetate kinase (ACK; E.C. 2.7.1.21), and TDP-glucose synthase (TGS; E.C. 2.7.7.24) with phosphomannomutase (PMM; E.C. 5.4.2.8). In this study, replacing phosphoglucomutase (PGM; E.C. 5.4.2) by PMM from Escherichia coli gave four times higher specific activity on 2-deoxy-6-phosphate glucose, suggesting that the activity on 2-deoxy-glucose-6-phosphate was mainly affected by PMM activity, not PGM activity. Using an in vitro system starting from TMP and 2-deoxy-glucose-6-phosphate glucose, TDP-2-deoxy-glucose (63% yield) was successfully synthesized. Considering low productivity of NDP-sugars from cheap starting materials, this paper showed how production of NDP-sugars could be enhanced by controlling mutase activity

The Effect of Pretreatment with Thiopental on Reducing Pain Induced by Rocuronium Injection

We examined whether pretreatment with a small dose of thiopental was effective in reducing pain induced by the intravenous injection of rocuronium. Withdrawal movement was used to assess pain reduction. Ninety patients were randomly assigned to one of two groups: patients in the control group were pretreated with 2 mL saline, and those in the thiopental group were pretreated with 2 mL (50 mg) thiopental. Thiopental 5 mg/kg was injected intravenously. After a loss of consciousness, the upper arm was compressed with a rubber tourniquet, and the pretreatment drugs were administered. Thirty seconds later the tourniquet was removed and 0.6 mg/kg rocuronium was administered. Withdrawal movement was assessed using a four-grade scale: no movement, movement limited to the wrist, to the elbow or to the shoulder. The frequency of withdrawal movement in the group pretreated with thiopental was lower than in the control group (34 vs. 13, p < 0.05). We concluded that pretreatment with 2 mL (50 mg) thiopental is effective in reducing pain caused by the intravenous injection of rocuronium

Activation of PERK Signaling Attenuates Aβ-Mediated ER Stress

Alzheimer's disease (AD) is characterized by the deposition of aggregated beta-amyloid (Aβ), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of ER stress-mediated Aβ neurotoxicity still remain unknown. Here, we show that treatment of Aβ triggers the UPR in the SK-N-SH human neuroblastoma cells. Aβ mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2α pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Aβ neurotoxicity through reducing the activation of eIF2α and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2α pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Aβ treated neurons. These results indicate that PERK-eIF2α pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD

An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT

Easy Diagnosis of Asthma: Computer-Assisted, Symptom-Based Diagnosis

Diagnosis of asthma is often challenging in primary-care physicians due to lack of tools measuring airway obstruction and variability. Symptom-based diagnosis of asthma utilizing objective diagnostic parameters and appropriate software would be useful in clinical practice. A total of 302 adult patients with respiratory symptoms responded to a questionnaire regarding asthma symptoms and provoking factors. Questions were asked and recorded by physicians into a computer program. A definite diagnosis of asthma was made based on a positive response to methacholine bronchial provocation or bronchodilator response (BDR) testing. Multivariate logistic regression analysis was used to evaluate the significance of questionnaire responses in terms of discriminating asthmatics. Asthmatic patients showed higher total symptom scores than non-asthmatics (mean 5.93 vs. 4.93; p<0.01). Multivariate logistic regression analysis identified that response to questions concerning the following significantly discriminated asthmatics; wheezing with dyspnea, which is aggravated at night, and by exercise, cold air, and upper respiratory infection. Moreover, the presence of these symptoms was found to agree significantly with definite diagnosis of asthma (by kappa statistics). Receiver-operating characteristic curve analysis revealed that the diagnostic accuracy of symptom-based diagnosis was high with an area under the curve of 0.647±0.033. Using a computer-assisted symptom-based diagnosis program, it is possible to increase the accuracy of diagnosing asthma in general practice, when the facilities required to evaluate airway hyperresponsiveness or BDR are unavailable

Dual oxidase 1 and NADPH oxidase 2 exert favorable effects in cervical cancer patients by activating immune response

Background Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) not only can promote cancer progression, but also they have recently emerged as mediators of the mucosal immune system. However, the roles and clinical relevance of the collective or individual NADPH oxidase (NOX) family genes in cervical cancer have not been studied. Methods We investigated the clinical significance of the NOX family genes using data from 307 patients with cervical cancer obtained from The Cancer Genome Atlas. Bioinformatics and experimental analyses were performed to examine NOX family genes in cervical cancer patients. Results Dual Oxidase1 (DUOX1) and Dual Oxidase 2 (DUOX2) mRNA levels were upregulated 57.9- and 67.5-fold, respectively, in cervical cancer patients. The protein expression of DUOX1, DUOX2, and NOX2 also identified in cervical squamous cell carcinoma tissues. Especially, DUOX1 and DUOX2 mRNA levels were significantly increased in patients infected with human papillomavirus (HPV) 16. Moreover, high DUOX1 mRNA levels were significantly associated with both favorable overall survival and disease-free survival in cervical cancer patients. High NOX2 mRNA levels was significantly associated with favorable overall survival. Gene set enrichment analyses revealed that high DUOX1 and NOX2 expression was significantly correlated with the enrichment of immune pathways related to interferon (IFN)-alpha, IFN-gamma, and natural killer (NK) cell signaling. Cell-type identification by estimating relative subsets of known RNA transcript analyses indicated that the fraction of innate immune cells, including NK cells, monocytes, dendritic cells, and mast cells, was elevated in patients with high DUOX1 expression. Conclusions DUOX1 and NOX2 expression are associated with mucosal immunity activated in cervical squamous cell carcinoma and predicts a favorable prognosis in cervical cancer patients.This work was supported by a grant from Korea Institute of Oriental Medicine (K18123), National Research Foundation of Korea funded by the Korean government (NRF-2017R1C1B1004924) and Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government (NRF-2019M3E5D1A02068557). The funding bodies had no involvement in the design of the study, collection, analysis, and interpretation of data and in writing the manuscript