New anatomical profile of the nasal musculature: dilator naris vestibularis, dilator naris anterior, and alar part of the nasalis

The aim of this study was to clarify the morphology and topography of the dilator naris vestibularis, dilator naris anterior, and alar part of the nasalis. Anatomical variations in the topographic relationships are also described to provide critical data for understanding nasal muscular functions. Anatomical and histological examinations were performed on 40 specimens of embalmed Korean adult cadavers. The dilator naris vestibularis muscle (named by the present authors) was located between the external and vestibular skin of the alar lobule. The muscle fibers radiated along the dome-shaped nasal vestibule. The dilator naris anterior muscle originated from the frontal surfaces of the lateral half of the lateral crus and the accessory alar cartilage adjacent to the lateral crus. The extent of the lower insertion of the dilator naris anterior muscle was at the alar groove. The alar part of the nasalis originated with the transverse part of nasalis from the maxilla. It ascended to attach to the alar crease and the adjacent deep surface of external skin of the alar lobule. These findings may provide anatomical knowledge required to understand the structure and function of these nasal muscles such as during rhinoplasty or other surgery of the face.     

CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells

Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule is expressed only in germinal center B cells, specifically, in a subpopulation of centroblasts and centrocytes. In the present study, we investigated the apoptosis induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40 ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL cell lines, we found that cellular signaling by CM1 induces apoptosis and decreases cell viability, in BL cell lines cultured for 24 hours with protein-G agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells. Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95 was downregulated and CD40 was slightly upregulated in Raji cells. The engagement of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization was observed only in Raji cells. Moreover, the effector caspase inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found that CM1-induced apoptosis is achieved via different initiation pathways, which are cell-type dependent.     

Aromatherapy for stress reduction in healthy adults: a systematic review and meta-analysis of randomized clinical trials

The aim of this review was to systematically assess the effectiveness of aromatherapy for stress management. Seven databases were searched from their inception through April 2014. RCTs testing aromatherapy against any type of controls in healthy human person that assessed stress level and cortisol level were considered. Two reviewers independently performed the selection of the studies, data abstraction and validations. The risk of bias was assessed using Cochrane criteria. Five RCTs met our inclusion criteria, and most of them had high risk of bias. Four RCTs tested the effects of aroma inhalation compared with no treatment, no aroma, and no odour oil. The meta-analysis suggested that aroma inhalation has favourable effects on stress management (n = 80; standard mean difference (SMD), −0.96; 95% CI, −1.44 to −0.48; P < 0.0001; I² = 0%). Three of included RCTs tested aroma inhalation on saliva or serum cortisol level compared with control and meta-analysis failed to show significant difference between two groups (n = 88, SMDs −0.62; 95% CIs −1.26 to 0.02, P = 0.06, I² = 46%). In conclusion, there is limited evidence suggesting that aroma inhalation may be effective in controlling stress. However, the number, size and quality of the RCTs are too low to draw firm conclusions.     

Alleviation of capsular formations on silicone implants in rats using biomembrane-mimicking coatings

Despite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including capsular contracture – an excessive foreign body reaction that forms a tight and hard fibrous capsule around the implant. This study examines the effects of using biomembrane-mimicking surface coatings to prevent capsular formations on silicone implants. The covalently attached biomembrane-mimicking polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), prevented nonspecific protein adsorption and fibroblast adhesion on the silicone surface. More importantly, in vivo capsule formations around PMPC-grafted silicone implants in rats were significantly thinner and exhibited lower collagen densities and more regular collagen alignments than bare silicone implants. The observed decrease in α-smooth muscle actin also supported the alleviation of capsular formations by the biomembrane-mimicking coating. Decreases in inflammation-related cells, myeloperoxidase and transforming growth factor-β resulted in reduced inflammation in the capsular tissue. The biomembrane-mimicking coatings used on these silicone implants demonstrate great potential for preventing capsular contracture and developing biocompatible materials for various biomedical applications.     

Effects of Transglutaminase 2 Inhibition on Ventilator-Induced Lung Injury

This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-κB (NF-κB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-κB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.

Graphical Abstract

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Varicella and Varicella Vaccination in South Korea

With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea.     

Circumferential Resection Margin Involvement in Stage III Rectal Cancer Patients Treated with Curative Resection Followed by Chemoradiotherapy: A Surrogate Marker for Local Recurrence?

Purpose

Circumferential resection margin (CRM) involvement is a well-known predictor for poor prognosis in rectal cancer. However, the significance is controversial in some studies. Accordingly, this study attempted to examine the prognostic impact of CRM involvement in stage III rectal cancer.

Materials and Methods

Between January 1990 and December 2007, a total of 449 patients who underwent curative resection followed by complete adjuvant chemoradiotherapy for stage III rectal cancer located within 12 cm from the anal verge were selected. Patients were divided into a CRM-positive group (n=79, 17.6%) and a CRM-negative group (n=370, 82.4%).

Results

With a median follow-up of 56.6 months, recurrent disease was seen in 53.2 and 43.5% of the CRM-positive and CRM-negative group, respectively. CRM involvement was an independent prognostic factor for 5-year systemic recurrence-free survival (HR: 1.5, CI: 1.0-2.2, p=0.017). However, no significant difference was observed for local recurrence rate between the two groups (13.0 and 13.5%, respectively, p=0.677).

Conclusion

In this study, local recurrence rate did not differ according to CRM involvement status in stage III rectal cancer patients, although CRM involvement was shown to be an independent poor prognostic factor. Accordingly, validation of the results of this study by further large prospective randomized trials is warranted.     

MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC

The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T-cell activities leading to poor clinical outcomes. First, we verified PMN-MDSCs, monocytic-MDSCs (M-MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T-cell activities and induced T-cell exhaustion. The analysis of NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low PMN-MDSCs, M-MDSCs, and CD39⁺CD8⁺ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN-MDSCs, M-MDSCs, and CD39⁺CD8⁺ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.     

Diagnosis of occult thyroid carcinoma by ultrasonography

The increased sensitivity of many imaging devices has increased the identification of asymptomatic nodules in the thyroid gland. In this study we investigated the actual incidence of nonpalpable thyroid nodules and occult carcinoma in women. Between January and June 2003, among the women who were scheduled to undergo breast ultrasonography, 697 without palpable thyroid nodules were screened for thyroid nodules. They were classified into four categories according to ultrasonographic findings: negative, benign, indeterminate and malignant. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was carried out for all malignant lesions and for some of the benign and indeterminate ones. The nodule detection and malignancy rates were determined and the effectiveness of ultrasonography as a diagnostic tool was also investigated. Out of the 697 subjects, 246 (35.3%) were found to have thyroid nodules. The malignancy detection rate based on the FNAB results, including both suspicious and malignant groups, was 3.6% (25/697) for all subjects. In addition, 3.0% (21/697) of all the women were confirmed to have thyroid cancer by surgery. The sensitivity of sonographic classification was increased from 80% to 100% when the indeterminate class was added to the malignant one, although this decreased the specificity from 91.7% to 33.3%. In conclusion, high-resolution ultrasonography detected a high percentage of malignant nodules. Ultrasonography can augment its value by guiding FNAB, in addition to providing diagnostic images.     

Clinical benefit of low molecular weight heparin for ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitor

The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH.