The HLA-A*33:110 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*33:110 differs from HLA-A*33:03:01:01 in a codon 149 in exon 3.

The HLA-B*46:67 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*46:67 differs from HLA-B*46:01:01 in codons 94, 95, and 103 in exon 3.

The HLA-B*54:35 and -B*54:38 identified in volunteer donors for hematopoietic stem cell transplant.

HLA-B*54:35 and -B*54:38 differ from HLA-B*54:01:01 in codons in exons 2 and 3.

The HLA-B*15:400N allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*15:400N differs from HLA-B*15:01:01:01 by nucleotide deletions from position 328 to 331 in exon 3.

The HLA-B*58:01:20 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*58:01:20 differs from HLA-B*58:01:01:01 by a single synonymous nucleotide exchange at position 297 in exon 3.

The HLA-A*26:132 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*26:132 differs from HLA-A*26:01:01:01 at nucleotides 269 and 346 in exons 2 and 3.

Isolated Acute Appendicitis Caused by Aspergillus in a Patient Who Underwent Lung Transplantation: A Case Report.

Invasive aspergillosis is an important cause of morbidity and mortality in patients who have undergone lung transplantation. Aspergillus infections usually involve the respiratory tract, with vascular invasion and subsequent dissemination. However, acute appendicitis associated with localized aspergillosis is rare, especially among patients who have undergone prophylaxis with voriconazole. We present a case of primary Aspergillus appendicitis diagnosed by histologic examination in a patient who underwent lung transplantation. A 51-year-old woman with dermatomyositis underwent lung transplantation for acute interstitial pneumonitis. According to our institution's protocol, the patient was treated with immunosuppressive therapy and prophylaxis with voriconazole, ganciclovir, and trimethoprim sulfamethoxazole during the post-transplantation period. Twenty-eight days after transplantation, the patient developed mild abdominal pain and paralytic ileus. There was no apparent infection sign. Abdominal computerized tomography indicated a wall defect of the appendix with multifocal fluid collection, mesenteric leave thickening, and pneumoperitoneum. These findings were consistent with perforated appendicitis, and the patient underwent an appendectomy. The histopathology examination of the resected appendix showed inflammation and abscess. Periodic acid-Schiff-positive and Grocott-Gomori methenamine silver-positive fungal hyphae with acute-angle branching were observed, demonstrating muscular invasion. A galactomannan antigen test obtained on the same day had negative results. The trough level of voriconazole was well maintained and was subsequently adjusted through monitoring of circulating drug concentration. Simultaneously, other potential sites of disseminated Aspergillus were considered and examined, but no other site of systemic Aspergillus infection was detected. Voriconazole treatment was maintained for 3 months, and no aspergillosis relapse or other invasive fungal infections were observed.

Dietary total, animal, vegetable calcium and type 2 diabetes incidence among Korean adults: The Korean Multi-Rural Communities Cohort (MRCohort).

BACKGROUND AND AIMS: Although a possible mechanism for developing type 2 diabetes in relation to calcium intake has been suggested, there is currently little epidemiological evidence on the association between dietary calcium and type 2 diabetes (T2D). This study aimed to evaluate the prospective association between dietary calcium and T2D incidence among adults 40 years of age or over, from the Multi-rural Communities Cohort (MRCohort), South Korea. METHODS AND RESULTS: In total, 8313 participants (3033 men and 5280 women) who did not have diabetes at baseline were recruited between 2005 and 2013. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During follow-up (31,570 person-years), 322 T2D cases were newly diagnosed. Dietary calcium (total and vegetable calcium) were inversely associated with the risk of T2D incidence among women (IRR = 0.61, 95% CI = 0.43-0.86, P for trend = 0.007 in third tertile of baseline total calcium intake comparing to the first tertile; IRR = 0.57, 95% CI = 0.39-0.84, P for trend = 0.006 for baseline vegetable calcium intake), not for men. The tendency of those inverse associations remained in both the normal fasting blood glucose group and the impaired fasting blood glucose group and were independent of obesity, smoking, and magnesium intake. CONCLUSIONS: Total and vegetable calcium may be inversely associated with T2D incidence among women, regardless of impaired fasting blood glucose group or normal group. The associations may be potentially dose-responsive. Moderate dietary calcium may be related to lower risk of T2D incidence comparing to low intake group among women.

LSD1 demethylates HIF1α to inhibit hydroxylation and ubiquitin-mediated degradation in tumor angiogenesis.

Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis. LSD1 demethylates HIF1α at lysine (K) 391, which protects HIF1α against ubiquitin-mediated protein degradation. LSD1 also directly suppresses PHD2-induced HIF1α hydroxylation, which has a mutually dependent interplay with Set9-mediated HIF1α methylation. Moreover, the HIF1α acetylation that occurs in a HIF1α methylation-dependent manner is inhibited by the LSD1/NuRD complex. HIF1α stabilized by LSD1 cooperates with CBP and MTA1 to enhance vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. Thus, LSD1 is a key regulator of HIF1α/VEGF-mediated tumor angiogenesis by antagonizing the crosstalk between PTMs involving HIF1α protein degradation.

A Case of Ectopic Paragonimiasis in a 17th Century Korean Mummy.

Archaeoparasitological studies on fossilized feces obtained from Joseon Dynasty (1392-1910 CE) mummies have provided invaluable data on the patterns of parasitic infection in pre-modern Korean societies. In our recent radiological investigation of a 17th century Joseon mummy discovered in Cheongdo (South Korea), we located a liver mass just below the diaphragm. Anatomical dissection confirmed the presence of a mass of unknown etiology. A subsequent parasitological examination of a sample of the mass revealed a large number of ancient Paragonimus sp. eggs, making the current report the first archaeoparasitological case of liver abscess caused by ectopic paragonimiasis.

The effect of low-volatile organic compounds, water-based paint on aggravation of allergic disease in schoolchildren.

Whether indoor painting aggravates preexisting allergic diseases remains unclear. We aimed to evaluate the impact of new classroom painting on aggravation of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) in children. Studied school was previously painted with conventional water-based paint 20 years ago and had natural ventilation system. We identified a total of 172 children aged 10-12 years with allergic diseases in 17 classrooms, which were allocated to newly painted rooms with low-volatile organic compounds (VOC), water-based paint, or existing rooms. After painting, there was no intervention or internal airflow to influence indoor air environment in both classrooms. We prospectively assessed the symptom severity and serious events of allergic diseases between both classrooms at baseline and after one and eight weeks after painting. At one and eight weeks, there were no significant changes in the Childhood Asthma Control Test scores, the fractional nitric oxide levels, lung function in asthmatic children in either classroom. There were also no significant changes in the severity score of AR or AD, or serious events in all allergic diseases. These findings suggest classroom painting with this new paint at the levels encountered in this study might not be a major aggravating factor for school-aged children with allergic diseases.

Measurement of levels of fractional exhaled nitric oxide in patients with pulmonary tuberculosis.

SETTING: The role of fractional exhaled nitric oxide (FeNO) in the diagnosis and treatment of pulmonary tuberculosis (PTB) is uncertain. OBJECTIVE: To examine the value of FeNO as a biomarker for PTB. DESIGN: Baseline FeNO levels were compared in 69 PTB patients and 118 healthy controls. The correlation between baseline FeNO levels and clinical variables of tuberculosis were studied. FeNO levels were checked twice in the PTB group, at diagnosis and after 2 months of anti-tuberculosis medication, and factors affecting changes in FeNO levels after treatment were analysed. RESULTS: FeNO levels were not significantly different in the PTB group and controls (mean ± standard deviation 27.7 ± 17.6 parts per billion [ppb] vs. 27.0 ± 10.8 ppb, P = 0.531). In a multivariate regression analysis, no variable was shown to affect FeNO levels at diagnosis. FeNO levels did not significantly change after 2 months of treatment (26.8 ± 18.3 ppb vs. 24.0 ± 10.7 ppb, P = 0.257). Only PTB with a high FeNO level (>25 ppb) was related to a decline in FeNO levels after 2 months of treatment. CONCLUSION: FeNO levels do not appear to be affected in PTB patients.

PPARγ neddylation essential for adipogenesis is a potential target for treating obesity.

The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator-activated receptor gamma (PPARγ) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARγ is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARγ, leading to PPARγ stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARγ signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARγ.

Intracavernous delivery of clonal mesenchymal stem cells rescues erectile function in the streptozotocin-induced diabetic mouse.

The major hurdle for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes. The aim of this study was to examine the effectiveness of mouse clonal bone marrow-derived stem cells (BMSCs) obtained from a single colony by using subfractionation culturing method for erectile function in diabetic animals. Twelve-week-old C57BL/6J mice were divided into four groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of PBS (20 µL) or clonal BMSCs (3 × 10(5) cells/20 µL). Clonal BMSCs were isolated from 5-week-old C3H mice. Two weeks after treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was stained with antibodies to PECAM-1, smooth muscle α-actin, neuronal nitric oxide synthase (nNOS), neurofilament, and phosphorylated endothelial NOS (phospho-eNOS). We also performed Western blot for phospho-eNOS, and eNOS in the corpus cavernosum tissue. Local delivery of clonal BMSCs significantly restored cavernous endothelial and smooth muscle cell contents, and penile nNOS and neurofilament contents, and induced eNOS phosphorylation (Ser1177) in diabetic mice. Intracavernous injection of clonal BMSCs induced significant recovery of erectile function, which reached 80-90% of the control values. Clonal BMSCs successfully restored erectile function through dual angiogenic and neurotrophic effects in diabetic mice. The homogenous nature of clonal mesenchymal stem cells may allow their clinical applications and open a new avenue through which to treat diabetic erectile dysfunction.

Abatement of fluorinated compounds using a 2.45GHz microwave plasma torch with a reverse vortex plasma reactor.

Abatement of fluorinated compounds (FCs) used in semiconductor and display industries has received an attention due to the increasingly stricter regulation on their emission. We have developed a 2.45GHz microwave plasma torch with reverse vortex reactor (RVR). In order to design a reverse vortex plasma reactor, we calculated a volume fraction and temperature distribution of discharge gas and waste gas in RVR by ANSYS CFX of computational fluid dynamics (CFD) simulation code. Abatement experiments have been performed with respect to SF6, NF3 by varying plasma power and N2 flow rates, and FCs concentration. Detailed experiments were conducted on the abatement of NF3 and SF6 in terms of destruction and removal efficiency (DRE) using Fourier transform infrared (FTIR). The DRE of 99.9% for NF3 was achieved without an additive gas at the N2 flow rate of 150 liter per minute (L/min) by applying a microwave power of 6kW with RVR. Also, a DRE of SF6 was 99.99% at the N2 flow rate of 60 L/min using an applied microwave power of 6kW. The performance of reverse vortex reactor increased about 43% of NF3 and 29% of SF6 abatements results definition by decomposition energy per liter more than conventional vortex reactor.

Association of interleukin-10 promoter region polymorphisms with risk factors of Atherosclerosis.

Atherosclerosis is considered as an inflammatory disease, and carotid artery intima-media thickness (IMT) and carotid plaque are generally used as intermediated phenotype of atherosclerosis. The aim of this study was to investigate whether carotid IMT and plaque are associated with promoter region polymorphisms of interleukin 10 (IL-10) gene. We recruited 135 subjects from a rural area of south-eastern part of South Korea. Three polymorphisms in the promoter region of IL-10 (-1082 A/G, -819 T/C and -592 A/C) were genotyped by pyrosequencing. Carotid IMT was measured at common carotid arteries, and carotid bulbs and cardiovascular risk factors such as cholesterol, blood pressure, uric acid and homocysteine were measured using blood samples. Subjects with the minor allele (C) of -819 T/C or the minor allele (C) of -592 A/C showed lower values in carotid IMT than those with major allele homozygote of each polymorphism (P = 0.018 and P = 0.031, respectively). Subjects with carotid plaque were significantly older and showed higher values in carotid IMT, uric acid and homocysteine than those without plaque (P < 0.01, respectively). In conclusion, the promoter region polymorphisms of IL-10 gene associate with carotid IMT and plaque. Further studies with larger samples are needed to provide stronger evidence to justify anti-atheromatous properties of IL-10.

Improved methods for selective cryolipolysis results in subcutaneous fat layer reduction in a porcine model.

BACKGROUND/AIMS: Cryolipolysis is a noninvasive method for the selective reduction of localized fat tissues. It has demonstrated efficacy in both clinical and preclinical trials; however, despite its popularity, its mechanisms of action and evaluation methods are not yet fully defined. The purpose of this study was to improved methods for cryolipolysis using a porcine model. METHODS: The abdomens of female PWG micro-pigs were treated with a cooling device (CRYOLIPO II(™)), and we examined the treatment effects using photography, three-dimensional photography, ultrasound, gross, and microscopic pathology, and serum lipid level analyses in order to determine the mechanism of action, efficacy, and safety of CRYOLIPO II(™). RESULTS: CRYOLIPO II(™) successfully reduced abdominal fat in our porcine model. Gross and microscopic histological results confirmed the noninvasive cold-induced selective subcutaneous fat destruction, and showed increases in pre-adipocyte differentiation and in the activation of lipid catabolism. In particular, we found that CRYOLIPO II(™) may increase PPARδ (delta) levels in adipose tissue at 30-60 days post-treatment. CONCLUSION: Fat reduction by cryolipolysis was successfully achieved in our porcine model. Thus, our findings indicate that CRYOLIPO II(™) may be a promising fat reduction device for body contouring and fat reduction in humans, and that cryolipolysis exerts its effects, at least partly, by targeting the PPARδ signaling pathway. These results show that both investigative and diagnostic potentials capacity.

Harmful and beneficial relationships between alcohol consumption and subclinical atherosclerosis.

BACKGROUND AND AIMS: Arterial stiffness and increased intima-media wall thickness are two of the main predictors of cardiovascular disease (CVD). We evaluated whether brachial-ankle pulse wave velocity (baPWV) and common carotid artery intima-media wall thickness (CCA-IMT) are correlated with alcohol consumption in a cross-sectional study among Korean men and women aged 40 years and over. METHODS AND RESULTS: All 5539 subjects (2121 men and 3418 women) were participants in the Multi-Rural Communities cohort (MRcohort) study, a part of the Korean Genome Epidemiology Study (KoGES). The baPWV was positively correlated with alcohol consumption in men (p for trend <0.0001). Age (middle-aged versus elderly) modified the effect of alcohol consumption on PWV. On the other hand CCA-IMT decreased with alcohol consumption in men. There was no favorable zone of alcohol consumption in terms of baPWV and CCA-IMT. Adjustment for lipid profiles substantially attenuated the relationship between alcohol consumption and CCA-IMT. There was no clear relation between alcohol consumption and baPWV/CCA-IMT in women. CONCLUSIONS: Along with a linear harmful relationship between alcohol consumption and arterial stiffness in men there may also be a beneficial relationship between alcohol consumption and carotid intima-wall thickness. The effect of alcohol on arterial stiffness may be slightly stronger in elderly men, and the effect of alcohol on CCA-IMT may be mediated by lipid factors.

Preferential location for arterial dissection presenting as golf-related stroke.

SUMMARY: Golf-related stroke has not been systematically reviewed. The purpose of our study was to describe in detail this particular stroke syndrome. Seven patients were analyzed at a university hospital and 7 patients were reviewed from MEDLINE literature. General demographics, symptom onset, neurologic signs, radiologic findings, and outcome were investigated. A total of 14 patients including 7 patients from the MEDLINE search were analyzed; all were men, with a mean age of 46.9 ± 12.8 years. Symptom onset was classified as during the golf swing (n = 9), unknown (n = 3), and after playing golf (n = 2). Most patients (n = 12) showed involvement of the vertebral artery and 2 patients showed involvement of the internal carotid artery (P = .008). Nine dissections were found on the right side, 3 on the left side, and 2 were bilateral (P = .046). Twelve patients had extracranial involvement and 2 patients had intracranial involvement (P = .008). Seven patients returned to normal, 5 returned to independence, 1 had unknown status, and 1 died. The anatomic preference of golf-related craniocervical arterial dissection is associated with the extracranial and vertebrobasilar system with a right-sided tendency as the result of stereotypical rotational movement during a golf swing.