A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization.

Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial-targeting sequence was sufficient for this process. Membrane permeabilization was inhibited by nonselective channel blockers or by N-(n-nonyl)deoxynojirimycin (NN-DNJ), a viroporin inhibitor. Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.

Effects of acute lipopolysaccharide-induced toxemia model on some neglected blood parameters.

The presence of lipopolysaccharide (LPS) in blood induces an inflammatory response which leads to multiple organ dysfunction and numerous metabolic disorders. Uncontrolled, improper or late intervention may lead to tissue hypoxia, anaerobic glycolysis and a disturbance in the acid -base balance. The effects of LPS-induced toxemia on biological and immunological markers were well studied. However, parameters such as base excess, ions, and acid-base balance were not fully investigated. Therefore, the objective of this study was to examine these blood parameters collectively in LPS-induced inflammatory toxemia in rat's model. After induction of toxemia by injecting LPS at a rate of 5 mg/kg body weight intravenously, blood was collected from the tail vein of twenty rats and immediately analyzed. After 24 hours, the animals were sacrificed and the blood was collected from the caudal vena cava. The results revealed that the levels of pH, bicar- bonate, partial pressure of oxygen, oxygen saturation, Alveolar oxygen, hemoglobin, hematocrit, magnesium (Mg2+), and calcium (Ca2+) were significantly decreased. On the other side, the levels of Base excess blood, Base excess extracellular fluid, partial pressure of carbon dioxide, lactate, Ca2+/Mg2+, potassium, and chloride were significantly increased compared to those found pre toxemia induction. However, sodium level showed no significant change. In conclusion, Acute LPS-toxemia model disturbs acid-base balance, blood gases, and ions. These parameters can be used to monitor human and animal toxemic inflammatory response induced by bacterial LPS conditions to assist in the management of the diagnosed cases.

A multicenter study on anaphylaxis caused by peanut, tree nuts, and seeds in children and adolescents.

Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013). One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA /l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.

Prevalence and prognosis of hypoglycaemia in patients receiving maintenance dialysis.

BACKGROUND: End-stage renal disease is a common predisposing condition for the development of hypoglycaemia. AIM: To determine the effect of hypoglycaemia on the mortality of patients undergoing maintenance dialysis. METHODS: Retrospective and descriptive analyses were performed in five dialysis centres in the Republic of Korea between June 2002 and August 2008. We enrolled 1685 patients who had undergone dialysis for at least 1 month. RESULTS: We identified 453 episodes of hypoglycaemia in 256 of 1685 patients (15.2%); 189 patients (73.8%) had diabetes, whereas the other patients did not. The occurrence of hypoglycaemia in patients receiving dialysis appeared to be a life-threatening complication because 27.0% of patients died within two days of the onset of a hypoglycaemic episode. Older age, low serum albumin levels and infections were independent risk factors for total mortality in these patients. Furthermore, the absence of diabetes, age and serum glucose levels were independent factors associated with early mortality within two days of the development of hypoglycaemia. CONCLUSION: Although several factors were associated with mortality, the degree of hypoglycaemia, absence of diabetes and old age were associated with early mortality. Elderly hypoglycaemic patients, especially those without diabetes, should be closely monitored.

Tannerella forsythia BspA increases the risk factors for atherosclerosis in ApoE(-/-) mice.

OBJECTIVE: The aim of this study was to evaluate the effects of Tannerella forsythia and its major surface virulence factor, BspA, on the progression of atherosclerosis in ApoE(-/-) mice and the expression of lipid metabolism-related genes. METHODS: PMA-differentiated THP-1 cells were treated with BspA to detect foam cell formation. The proximal aortas of ApoE(-/-) mice injected with T. forsythia or BspA were stained with oil red O to examine lipid deposition. The serum levels of CRP, HDL, and LDL were detected by ELISA. The liver tissue of T. forsythia- or BspA-injected ApoE(-/-) mice was examined for mRNA expression of lipid metabolism-related genes, such as liver X receptors (LXRα and LXRß) and ATP-binding cassette transporter A1 (ABCA1). RESULTS: Tannerella forsythia and BspA induced foam cell formation in THP-1 cells and accelerated the progression of atherosclerotic lesions in ApoE(-/-) mice. Mouse serum levels of CRP and LDL were increased, and HDL was decreased by T. forsythia and BspA. The expression levels of LXRα and LXRß, and ABCA1 in liver tissue were decreased by T. forsythia and BspA. CONCLUSIONS: Tannerella forsythia and BspA augmented atherosclerotic lesion progression in ApoE(-/-) mice. This process may be associated with downregulation of lipid metabolism-related gene expression.

Reading nutrition labels is associated with a lower risk of metabolic syndrome in Korean adults: the 2007-2008 Korean NHANES.

BACKGROUND AND AIMS: Several studies demonstrated that reading nutrition labels was associated with healthier food choices, despite some controversy. This study investigated the association between the use of nutrition labels and metabolic syndrome (MetS) in Korean adults. METHODS AND RESULTS: This cross-sectional study included 7756 individuals who participated in the 2007-2009 Korean National Health and Nutrition Examination Survey (KNHANES). A self-reported questionnaire was used to determine participant's awareness of nutrition labels. Modified Asian criteria based on a harmonizing definition of MetS were adopted. Individuals in the group that read nutrition labels (the Reading Group) were youngest and leanest, but their daily caloric intake fell between that of the group that did not read nutrition labels (the Non-Reading Group) and the group that did not know about them (the Not-Knowing Group). The prevalence of MetS was 16.8% in the Reading Group, 27.2% in the Non-Reading Group, and 47.3% in the Not-Knowing Group. In comparison to participants in the Reading Group, the odds ratios (95% confidence interval) for MetS in the participants in the Non-Reading Group and Not-Knowing Group were 1.85 (1.60-2.14) and 4.44 (3.79-5.20), respectively, when not adjusted. The relationship between the use of nutrition labels and MetS remained statistically significant even after adjusting for covariates such as age, sex and socioeconomic status including household income and education level [1.27 (1.05-1.53) in the Non-Reading Group and 1.34 (1.05-1.70) in the Not-Knowing Group]. CONCLUSION: Reading nutrition labels appeared to be associated with a lower prevalence of MetS in a nationally representative sample of Korean adults.

An outbreak of lymphomas in a layer chicken flock previously infected with fowlpox virus containing integrated reticuloendotheliosis virus.

Visceral lymphomas occurred in a 236-day-old layer flock previously diagnosed with reticuloendotheliosis virus (REV)-integrated fowlpox virus (FPV) infection at the age of 77 days. Common pathologic lesions were multiple neoplastic nodules of homogeneous lymphocytes in the livers and spleens of all submitted chickens. All neoplastic tissues were positive for the REV envelope (env) gene by PCR. In a retrospective molecular study of FPV-infected 77-day-old chickens from the same flock, we identified nearly full-length REV provirus integrated into the genome of FPV as well as the REV env gene in trachea samples, whereas only the REV LTR region was present in the FPV strain used to vaccinate this flock. The 622-bp REV env gene nucleotide sequence derived from the trachea and neoplastic tissues was identical. Commercial ELISA of serum samples revealed that all chickens aged between 17 and 263 days in this flock were positive for REV but not for avian leukosis virus. Taken together, the evidence suggests that the visceral lymphomas were caused by a REV-integrated FPV field strain. FPV infections of commercial chickens should be followed up by careful monitoring for manifestations of REV infection, including lymphomas and immune depression, considering the ease with which the REV provirus appears to be able to integrate into the FPV genome.

Molecular survey of enteric viruses in commercial chicken farms in Korea with a history of enteritis.

Several enteric viruses have increasingly received attention as potential causative agents of runting-stunting syndrome (RSS) in chickens. A molecular survey was performed to determine the presence of a broad range of enteric viruses, namely chicken astrovirus (CAstV), avian nephritis virus (ANV), chicken parvovirus (ChPV), infectious bronchitis virus (IBV), avian rotavirus (AvRV), avian reovirus (ARV), and fowl adenovirus (FAdV), in intestinal samples derived from 34 commercial chicken flocks that experienced enteritis outbreaks between 2010 and 2012. Using techniques such as PCR and reverse-transcription PCR, enteric viruses were identified in a total of 85.3% of investigated commercial chicken flocks in Korea. Furthermore, diverse combinations of 2 or more enteric viruses were simultaneously identified in 51.7% of chicken farms positive for enteric viruses. The rank order of positivity for enteric viruses was as follows: ANV (44.1%), CAstV (38.2%), ChPV (26.5%), IBV (20.6%), ARV (8.8%), AvRV (5.9%), and FAdV (2.9%). Additionally, other pathogens such as Escherichia coli, Salmonella spp., Eimeria spp., and FAdV were detected in 79% of chicken flocks positive for enteric viruses using PCR, bacterial isolation, and microscopic examination. The results of our study indicate the presence of several enteric viruses with various combinations in commercial chicken farms that experienced enteritis outbreaks. Experimental studies are required to further understand the roles of enteric viruses in RSS in commercial chickens.

Understanding the socioeconomic heterogeneity in healthcare in US counties: the effect of population density, education and poverty on H1N1 pandemic mortality.

The recent outbreak of H1N1 has provided the scientific community with a sad but timely opportunity to understand the influence of socioeconomic determinants on H1N1 pandemic mortality. To this end, we have used data collected from 341 US counties to model H1N1 deaths/1000 using 12 socioeconomic predictors to discover why certain counties reported fewer H1N1 deaths compared to other counties. These predictors were then used to build a decision tree. The decision tree developed was then used to predict H1N1 mortality for the whole of the USA. Our estimate of 7667 H1N1 deaths are in accord with the lower bound of the CDC estimate of 8870 deaths. In addition to the H1N1 death estimates, we have listed possible counties to be targeted for health-related interventions. The respective state/county authorities can use these results as the basis to target and optimize the distribution of public health resources.

Relationship between non-alcoholic fatty liver disease and pulmonary function.

BACKGROUND: It has been observed that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease and insulin resistance. Pulmonary function is also known to be related with cardiovascular disease and metabolic syndrome. AIMS: The objective of this study was to investigate the association between NAFLD and pulmonary function. METHODS: We performed a cross-sectional study to examine the association of NAFLD based on abdominal sonographic findings and pulmonary function in 2119 Korean men between the ages of 30 and 75. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) were compared according to the presence of NAFLD. Univariate and multivariate logistic regression analyses were conducted to evaluate the relationship of NAFLD with FVC and FEV(1) as pulmonary function tests. RESULTS: The subjects with NAFLD had lower FVC and FEV(1) than their non-steatotic counterparts, and FVC and FEV(1) gradually decreased according to the grade of hepatic steatosis. After adjusting for age, body mass index, smoking status, blood pressure, fasting plasma glucose, total cholesterol, hypertension, diabetes, triglyceride and high-density lipoprotein cholesterol, the FVC and FEV(1) were found to be inversely associated with the presence of NAFLD. CONCLUSION: NAFLD was independently associated with reduced pulmonary function, and the severity of NAFLD was inversely correlated with pulmonary function.

Effect of dietary zinc proteinate supplementation on growth performance, and skin and meat quality of male and female broiler chicks.

1. An experiment was conducted to evaluate the effect of dietary zinc proteinate (ZP) supplementation on growth performance and on skin and meat quality of male and female broiler chicks. 2. A total of 240 1-d-old male and 240 1-d-old female broiler chicks were randomly distributed into 24 floor pens (12 replicate pens/sex; 20 birds/pen) and were given either 0 (Control diet) or 40 mg/kg ZP (ZP 40), resulting in a 2 × 2 factorial arrangement of treatments. 3. The growth performance of male and female broiler chicks was not affected by the ZP supplementation, but the males showed significantly higher growth performance than did females. 4. ZP supplementation increased the total thickness of skin in both sexes, and males had thicker skin than females. It also increased the collagen content of skin, but not that of meat. Males had higher skin collagen contents than did females, but no sex difference was found in the meat collagen contents. 5. ZP supplementation did not affect the shear force values of skin and meat; however, males had higher shear force values of back skin than females. ZP supplementation increased the zinc contents of thigh meat and plasma in both sexes. Males had higher zinc contents in back skin than females. 6. It is concluded that dietary ZP supplementation could increase the skin quality of broiler chicks in both sexes, particularly in female broilers, without any effect on growth performance. Male broilers have better growth performance and skin quality than females.

Supplementation of graded levels of organic zinc in the diets of female broilers: effects on performance and carcase quality.

Zinc is an essential trace element. The objective of this research was to investigate the effects of various levels of organic zinc (OZ) supplementation on growth performance and carcase quality of female broiler chickens. A total of 3200 1-d-old female broiler chicks were randomly allotted to 16 floor pens with 200 birds per pen. A maize-wheat-soyabean meal basal diet (Control) was formulated and 20 mg/kg OZ (20 OZ), 40 mg/kg OZ (40 OZ), and 80 mg/kg OZ (80 OZ) were added to the basal diet to form 4 dietary treatments with 4 replicates per treatment. The OZ source was zinc proteinate which contained 15% zinc. Results showed no significant difference between the treatments in growth performance. A significant increase in thigh skin epidermis and dermis thickness was shown in the OZ supplementation groups; however, no effect was found on the thickness of back skin epidermis and dermis. Collagen contents in breast and thigh meats were not influenced by OZ supplementation but a significant increase in collagen content was found in the back and thigh skin. This increase in collagen content was significantly greater in the back and thigh skin of OZ 80 than with OZ 20. Shear force value and zinc concentration in skins and meat were not significantly influenced by supplementation with OZ. It is concluded that dietary OZ does not improve growth performance of broilers; however, it could increase skin thickness by increasing collagen content in skin, thereby improving carcase quality.

Metabolic syndrome and its association with white blood cell count in children and adolescents in Korea: the 2005 Korean National Health and Nutrition Examination Survey.

BACKGROUND AND AIMS: To estimate the prevalence of metabolic syndrome (MS) and determine its association with white blood cell (WBC) count as a marker of low-grade systemic inflammation in children and adolescents in Korea. METHODS AND RESULTS: We investigated the prevalence of MS and its association with WBC count in 928 children and adolescents. MS was defined as having 3 or more conditions based on the modified criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). The odds ratios (ORs) for MS were also calculated using multivariate logistic regression analysis across WBC count quartiles (Q1, <5200; Q2, 5200-6100; Q3, 6200-7200; and Q4, >or=7300 cells/microL for boys; Q1, <5200; Q2, 5200-6000; Q3, 6100-7000; and Q4, >or=7100 cells/microL for girls). The prevalence of MS in children and adolescents in Korea was 6.7% (8.5% in boys, 4.5% in girls, P<0.001). MS was more prevalent in overweight and obese children and adolescents in both boys and girls. The mean WBC counts continuously increased with each additional component of MS in both boys and girls. The ORs (95% CIs) for MS in each WBC quartile were 1.00, 1.56 (0.43-5.67), 4.47 (1.42-14.07), and 5.25 (1.71-16.07) in boys and 1.00, 1.05 (0.15-7.61), 2.89 (0.55-15.17), and 7.47 (1.61-36.67) in girls after adjusting for age, household income, and residential area. CONCLUSION: In summary, this study shows that a substantial number of children and adolescents in Korea have MS, and elevated WBC count may be a surrogate marker for MS.

Temperature-resilient solid-state organic artificial synapses for neuromorphic computing.

Devices with tunable resistance are highly sought after for neuromorphic computing. Conventional resistive memories, however, suffer from nonlinear and asymmetric resistance tuning and excessive write noise, degrading artificial neural network (ANN) accelerator performance. Emerging electrochemical random-access memories (ECRAMs) display write linearity, which enables substantially faster ANN training by array programing in parallel. However, state-of-the-art ECRAMs have not yet demonstrated stable and efficient operation at temperatures required for packaged electronic devices (~90°C). Here, we show that (semi)conducting polymers combined with ion gel electrolyte films enable solid-state ECRAMs with stable and nearly temperature-independent operation up to 90°C. These ECRAMs show linear resistance tuning over a >2× dynamic range, 20-nanosecond switching, submicrosecond write-read cycling, low noise, and low-voltage (±1 volt) and low-energy (~80 femtojoules per write) operation combined with excellent endurance (>109 write-read operations at 90°C). Demonstration of these high-performance ECRAMs is a fundamental step toward their implementation in hardware ANNs.

Assessing cancer treatment related information online: unintended retrieval of complementary and alternative medicine web sites.

The aims of this study were to determine the number of Complementary and Alternative Medicine (CAM) web sites retrieved form Korean search engines, and to evaluate the quality of online CAM content. We evaluated results retrieved by the use of the key word 'anticancer treatment' on six common search engines in Korea. Among a total of 651 web sites, 226 web sites (35%) related to CAM were identified. The quality and risk of these sites were assessed for 97 web sites after removing duplicate and dysfunctional web sites. We evaluated the quality of the sites using Sandvik score. Scores in this study varied between 5 and 12 points, with a maximum of 14 points. We categorized the risk score for each web site based on the following criteria: (1) the site discourages the use of conventional medicine (23%: 22/97); (2) the site discourages adherence to the advice of a clinician (15%:15/97); (3) the site either provides opinions and experiences, or factual details (26%: 25/97); and (4) the site provides commercial details (46%: 45/97). The most popular web sites in Korea that relate to CAM for cancer offer information of extremely variable quality. Clinicians should be aware of the risks of inaccurate online information and attempt to protect their patients from those.

Abnormal expression of TIMP-2, SOD, vimentin and PAI proteins in cloned bovine placentae.

Cloned mammals suffer from high rates of placental abnormality and foetal loss during pregnancy. We previously used 2-D gel electrophoresis and mass spectrometry for global proteomic analysis of cloned and normal bovine placentae to identify differential protein expression patterns. Here, we used Western blot analysis to confirm the expression levels of several pregnancy-related proteins putatively identified as being differentially expressed in somatic cell nuclear transfer (SCNT) vs normal bovine placentae. The expression levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), its downstream protein, matrix metalloproteinase-2 (MMP-2), superoxide dismutase (SOD), vimentin and plasminogen activator inhibitor-1 (PAI) were analysed in the placentae of SCNT cloned Korean native cattle that died immediately after birth and in normal placentae obtained by AI. Our results revealed that TIMP-2 and SOD were up-regulated in SCNT placenta compared with normal placenta, whereas MMP-2 levels were comparable in cloned and normal placentae, and vimentin and PAI were significantly down-regulated in SCNT compared with normal placentae. Our results suggest that key proteins of placental development are abnormally expressed in SCNT cloned bovine placentae, probably resulting in abnormal placental function and clonal mortality.

New clinical grading system for chronic GVHD predicts duration of systemic immunosuppressive treatment and GVHD-specific and overall survival.

We investigated outcomes according to a new clinical grading system for chronic graft-versus-host disease (chronic GVHD) in 38 patients who developed chronic GVHD after an allogeneic hematopoietic stem cell transplantation. We categorized the patients into three grade groups, namely, grade I, grade II and grade III, according to the presence of three risk factors: extensive skin involvement, thrombocytopenia (TP) and progressive type of onset. Sixteen patients were classified into grade 1, 19 into grade II and three into grade III. The probability of withdrawal of systemic immunosuppression (IST) at 1, 2 and 3 years was 61, 76 and 87%, respectively. Patients with grades 2 or 3 chronic GVHD had prolonged duration of systemic IST compared to grade 1 (P=0.043). The probability of GVHD-specific survival (GSS) at 5 years was 52%. Twenty-two of 38 patients with chronic GVHD were still alive and the estimated 3-year overall survival (OS) rate was 60%, whereas that for the group with chronic GVHD grade I and grade II+III was 64 and 48% (P<0.05). Multivariate analysis showed that prior occurrence of acute GVHD, chronic GVHD grade, serum bilirubin over 1.5 mg/dl, date of diagnosis of chronic GVHD (day 150) and transplantation-risk factor were independent prognostic factors for GSS and OS.

Prevalence of non-tuberculous mycobacteria in a hospital environment.

In recent years, non-tuberculous mycobacteria (NTM) have emerged as an important cause of opportunistic nosocomial infections but there is little known about the isolation and identification of NTM in Korea. The aim of this study was to assess the prevalence of NTM in the hospital environment and identify the species. A total of 150 samples were collected from different parts of the hospital. NTM were isolated and identified by restriction fragment length polymorphism analysis of the gene encoding rpoB and partial sequencing analysis of hsp65 and rpoB. In this study, 60 strains of NTM were isolated from 50 of the 150 samples. Half of the tap water samples (50 of 100) were positive for mycobacteria. An estimated 73.3% of the isolates were saprophytic, 21.7% were potentially pathogenic and 5% were unidentified. The presence of NTM in hospital tap water is not uncommon. Such water isolates might cause true nosocomial infection in immunocompromised patients, in addition to the risk of false-positive culture results.

Tannerella forsythia GroEL induces inflammatory bone resorption and synergizes with interleukin-17.

Tannerella forsythia is a major periodontal pathogen, and T. forsythia GroEL is a molecular chaperone homologous to human heat-shock protein 60. Interleukin-17 (IL-17) has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase-2 (COX-2) and concentrations of IL-6, IL-8, and prostaglandin E2 (PGE2 ) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. Tannerella forsythia GroEL induced IL-6 and IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. Both T. forsythia GroEL and IL-17 synergistically increased PGE2 production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. forsythia GroEL injection, and simultaneous injection of T. forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption.