New players in high fat diet-induced obesity: LETM1 and CTMP

Objective

Obesity contributes to insulin resistance and is a risk factor for diabetes. C-terminal modulator protein (CTMP) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) have been reported to influence the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) signaling pathway via the modulation of PKB activity, a key player for insulin signaling. However, it remains unclear whether CTMP and LETM1 are associated with PI3K/PKB signaling in mouse models of obesity.

Materials/Methods

To address this question, we used two different mouse models of obesity, including high-fat diet (HFD)-induced diabetic mice and genetically modified obese mice (ob/ob mice). The levels of insulin-signaling molecules in these mice were determined by immunohistochemical and Western blot analyses. The involvement of CTMP and LETM1 in PI3K/PKB signaling was investigated in HEK293 cells by transient transfection and adenovirus-mediated infection.

Results

We found that the levels of insulin receptor, phosphorylated PKB, and LETM1 were lower and the level of CTMP was higher in the adipose tissue of obese mice on an HFD compared to lean mice on a chow diet. Similar results were obtained in ob/ob mice. In HEK293 cells, the activation of PKB increased the LETM1 level, and inhibition of PKB increased the CTMP level. The overexpression of CTMP suppressed the insulin-induced increase in PKB phosphorylation, which was abrogated by co-overexpression with LETM1.

Conclusion

These results suggest that CTMP and LETM1 may participate in impaired insulin signaling in the adipose tissue of obese mice, raising the possibility that these parameters may serve as new candidate biomarkers or targets in the development of new therapeutic approaches for diabetes.     

The prevalence of fabella and its association with the osteoarthritic severity of the knee in Korea

Clinical Rheumatology - The clinical relevance of the fabella, a sesamoid bone, has recently been investigated. Although many studies have documented the prevalence of the fabella, few large-scale...     

IgG4-related disease presenting as otogenic skull base osteomyelitis

IgG4-related disease (IgG4-RD) is an emerging clinical disease entity characterized by tumefactive lesions at multiple sites with a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells. Although almost any organ can be affected, IgG4-RD is most likely to involve the submandibular, lacrimal, or parotid glands in the head and neck region. However, skull base involvement presenting as otogenic skull base osteomyelitis (SBO) is rare. We encountered a 70-year-old male with IgG4-RD presenting primarily with severe otalgia and otorrhea. He had uncontrolled diabetes mellitus and showed clinical manifestations of otogenic SBO. Tissue immunostaining revealed typical features of increased IgG4-positive plasma cells, and hematological examination showed elevated serum IgG4 concentrations. Treatment with corticosteroids significantly improved well-being and partially resolved the lesion based on computed tomography (CT) scan.     

Sample size determination for longitudinal designs with binary response

In this article, we develop appropriate statistical methods for determining the required sample size while comparing the efficacy of an intervention to a control with repeated binary response outcomes. Our proposed methodology incorporates the complexity of the hierarchical nature of underlying designs and provides solutions when varying attrition rates are present over time. We explore how the between‐subject variability and attrition rates jointly influence the computation of sample size formula. Our procedure also shows how efficient estimation methods play a crucial role in power analysis. A practical guideline is provided when information regarding individual variance component is unavailable. The validity of our methods is established by extensive simulation studies. Results are illustrated with the help of two randomized clinical trials in the areas of contraception and insomnia. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

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.     

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.     

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.