Maternal nanoplastic ingestion induces an increase in offspring body weight through altered lipid species and microbiota.

The rapidly increasing prevalence of obesity and overweight, especially in children and adolescents, has become a serious societal issue. Although various genetic and environmental risk factors for pediatric obesity and overweight have been identified, the problem has not been solved. In this study, we examined whether environmental nanoplastic (NP) pollutants can act as environmental obesogens using mouse models exposed to NPs derived from polystyrene and polypropylene, which are abundant in the environment. We found abnormal weight gain in the progeny until 6 weeks of age following the oral administration of NPs to the mother during gestation and lactation. Through a series of experiments involving multi-omic analyses, we have demonstrated that NP-induced weight gain is caused by alterations in the lipid composition (lysophosphatidylcholine/phosphatidylcholine ratio) of maternal breast milk and he gut microbiota distribution of the progeny. These data indicate that environmental NPs can act as obesogens in childhood.

Two Unrecorded Apiospora Species Isolated from Marine Substrates in Korea with Eight New Combinations (A. piptatheri and A. rasikravindrae)

Although Apiospora Sacc. has previously been considered a sexual morph of Arthrinium species on the basis of phylogenetic, morphological, and ecological diagnoses, a recent study delimited these as different species. Recently, 14 species, including eight new species, of marine Arthrinium have been reported from Korea. Six known species have previously been renamed as species in the genus Apiospora (A. arundinis, A. marii, A. piptatheri, A. rasikravindrae, A. sacchari, and A. saccharicola). However, the eight new species of marine Arthrinium (Ar. agari, Ar. arctoscopi, Ar. fermenti, Ar. koreanum, Ar. marinum, Ar. pusillispermum, Ar. sargassi, and Ar. taeanense) are yet to be studied, and thus the taxonomic status of these species remains to be clarified. In this study, we conducted phylogenetic analyses using the internal transcribed spacer, 28S large subunit ribosomal RNA gene, translation elongation factor 1-alpha, and beta-tubulin regions to confirm the phylogenetic position of these eight species. Based on these analyses, we re-identified the eight Arthrinium species as new combinations in Apiospora. Additionally, among the six known Apiospora species, two (A. piptatheriand A. rasikravindrae) have not previously been recorded in Korea. On the basis of morphological and molecular analyses, we report these as new species in Korea. Herein, we present scanning electron micrographs detailing the morphologies of these species, along with phylogenetic trees and detailed descriptions.

Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis.

BACKGROUND: Obesity can influence on carcinogenesis through alterations in adipokines and subsequent inflammatory changes. This meta-analysis was aimed to comprehensively assess the association between circulating adipokines and risk of obesity-related cancers. METHODS: Pubmed and Embase were searched up to October 2017 for observational studies investigating the relationship between adipokines and cancers. Pooled odds ratio and the corresponding 95% confidence interval was estimated through the meta-analysis using a random-effects model. Findings A total of 93 observational studies (adiponectin = 60, high molecular weight adiponectin = 9, leptin = 39, IL-6 = 16, TNF-α = 10, and resistin = 17) were included. Adiponectin was significantly associated with decreased risk of cancer (pooled OR 0.70, 95% CI 0.60-0.80; I2 = 71.9%; Pheterogeneity <0.01). Leptin was significantly associated with increased risk of cancer (1.26, 1.05-1.51; I2 = 65.7%; Pheterogeneity <0.01). For each 5 µg/ml increase in adiponectin and 5 ng/ml increase in leptin, the pooled OR was 0.88 (0.83-0.93; I2 = 80.2%; Pheterogeneity <0.01) and 1.05 (1.01-1.09; I2 = 67.9%; Pheterogeneity<0.01)), respectively. There was nonlinear dose-response association (Pnonlinearity for adiponectin = 0.01; Pnonlinearity for leptin = 0.003).IL-6 (1.09, 0.94-1.25), TNF- α (1.65, 0.99-2.74), and resistin (1.28, 0.78-2.11) was not associated with risk of cancer. By cancer site and type, highest category of adiponectin was associated with decreased risk of breast (OR 0.74, 0.60-0.91), colorectal (0.74, 0.60-0.91), and endometrial cancer (0.49, 0.34-0.72). Higher leptin was associated with increased risk of endometrial (1.88, 1.24-2.87) and kidney cancer (2.07, 1.51-2.83). CONCLUSION: Our study suggests that adiponectin and leptin may play a role in the etiology of cancer.

Intraoperative Management to Prevent Cardiac Collapse in a Patient With a Recurrent, Large-volume Pericardial Effusion and Paroxysmal Atrial Fibrillation During Liver Transplantation: A Case Report.

BACKGROUND: Pericardial effusion is a common feature of end-stage liver disease. In this case report we describe the intraoperative management of recurrent pericardial effusion, without re-pericardiocentesis, to prevent circulatory collapse during a critical surgical time-point; that is, during manipulation of the major vessels and graft reperfusion. METHODS: A 47-year-old woman with hepatitis B was scheduled to undergo deceased donor liver transplantation (LT). A large pericardial effusion was preoperatively identified using transthoracic echocardiography (TTE). The patient also had paroxysmal atrial fibrillation. Two days before surgery, preemptive pericardiocentesis was performed and the 1150-mL effusion was drained. Intraoperatively, recurrence of the large pericardial effusion was identified using transesophageal echocardiography (TEE). During inferior vena cava manipulation, the surgeon consulted the anesthesiologist to evaluate the hemodynamic changes in the patient. After 3 attempts, the transplant team was able to determine the most appropriate anastomosis site, defined as that with the least impact on cardiac function. To prevent the development of severe postreperfusion syndrome, 10% MgSO4 (2 g) was gradually infused 20 minutes before portal vein declamping, and immediately before graft reperfusion a 100-µg bolus of epinephrine was administered. RESULTS: During graft reperfusion, there was no evidence of heart chamber collapse or flow disturbance, as seen on the TEE findings. Postoperatively, the patient recovered completely and was discharged from the hospital. Six months after surgery, there was no sign of pericardial effusion on follow-up TTE. CONCLUSION: Our intraoperative strategy may prevent cardiac collapse in patients with pericardial effusion detected during LT. Intraoperative TEE plays an important role in guiding hemodynamic management.

Eating alone and metabolic syndrome: A population-based Korean National Health and Nutrition Examination Survey 2013-2014.

Eating alone has been an emerging social concern in modern life. However, there is little research on the association between eating alone and Metabolic syndrome (MetS). We aimed to assess the association between eating alone and the MetS and to identify whether sociodemographic factors modify this association. This study included 7725 adults (≥19 years) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) 2013-2014. Multivariable logistic regression analysis was used for assessing the association of eating alone (none, 1 time/day, and ≥2 times/day) with MetS. The percentages of subjects with MetS were 30.4% in men and 24.2% in women. 20.8% of men and 29.2% of women ate alone ≥2 times/day. Individuals who ate alone 2 or more times per day showed higher frequency of living alone, having no spouse, skip meals, and less eating out (p<0.05). Women with eating alone ≥2 times/day had a crude OR of 1.29 (95% CI:1.08-1.53, p-trend=0.001) for MetS compared with women without eating alone. However, this association was no longer significant after adjustments for confounding factors. Eating alone ≥2 times/day was significantly associated with increase abdominal obesity (OR, 95% CI:1.45, 1.10-1.91, p-trend=0.039) and MetS (1.64, 1.28-2.10, p-trend=0.004) in men. Eating alone was associated with a higher likelihood of having a MetS in men without spouse as compared with those with spouse (OR for men without spouse 3.02, 95% CI:1.50-6.11 and OR for men with spouse 1.48, 95% CI:1.22-1.7, p-interaction=0.027). Our results indicate that eating alone may be a potential risk factor for MetS.

Loss of skeletal muscle mass in patients with chronic liver disease is related to decrease in bone mineral density and exercise tolerance.

AIM: This study aimed to identify the relationship between loss of skeletal muscle mass and clinical factors such as osteoporosis in patients with chronic liver disease. METHODS: The subjects were 112 patients (85 men and 27 women) with hepatocellular carcinoma who were scheduled to undergo hepatectomy. Skeletal muscle reduction was diagnosed according to the cut-off level of the skeletal mass index (SMI) for Asians (men <7.0 kg/m2 , women <5.4 kg/m2 ). Osteoporosis was diagnosed according to T-score ≤-2.5 standard deviation. The SMI and T-score were assessed using the results of dual-energy X-ray absorption. Peak oxygen consumption (PeakVO2 ), an index of exercise tolerance, was evaluated using the cardiopulmonary exercise test. The characteristics of patients with low SMI (low SMI group) were compared with those of patients whose SMI was not low (control group). Outcomes are presented as median (interquartile range). RESULTS: The T-score was significantly lower in the low SMI group (control vs. low SMI -1.1 [1.8] vs. -1.6 [1.9], P = 0.049). T-score positively correlated with SMI (r = 0.409, P < 0.0001). PeakVO2 was significantly decreased in the low SMI group (17.7 [6.3] vs. 14.4 [4.5], P = 0.006). In multivariate logistic regression analysis, T-score (odds ratio [OR], 3.508; 95% confidence interval [CI], 1.074-11.456; P = 0.038) and PeakVO2 (OR, 3.512; 95% CI, 1.114-11.066; P = 0.032) were significantly related to SMI, independent of age and sex. CONCLUSIONS: Skeletal muscle reduction in chronic liver disease is closely related to exercise tolerance and osteoporosis, and these factors are believed to be associated with physical inactivity in daily life.

A comparative proteomic analysis of blood serum for developmental stages in pigs.

This study aimed to differentiate genes at developmental stages of pigs from 0 to 150 days of age, to build up a protein database and to find candidate genetic markers for growth traits. The analysis of two-dimensional electrophoresis and matrix-assisted laser-desorption/ionization mass spectrometry separated 252 protein segments. After successfully blasting the peptide sequences, the analysis confirmed 37 differentially expressed proteins that increased from birth to 150 days of age (type A), whereas the type B proteins presented the inverse pattern. The type C proteins included proteins that were expressed continuously throughout the developmental periods. A total of 319 primer sets for 33 genes were designed to find genetic variants using pooled DNA samples of Yorkshire pigs. Amplification products for all primer sets produced approximately 20 000 clones that were sequenced, and 48 candidate SNP sites were finalized for genotyping. A total of 475 animals were used for high throughput genotyping analysis. Among these, phenotype data of all 475 animals were collected for average daily gain, backfat thickness and days to 90 kg, whereas feed conversion data were collected for 300 animals and body measurement traits (starting weight, ending weight, body length, wither height and chest depth) were collected for 209 animals. Association analysis found significant statistical differences between the animals having genotypes of 13 SNPs (g.78935883C>T, g.147629986C>T, g.98266037T>C, g.214707340G>A, g.88350299C>T, g.17180956C>T, g.17181024C>T, g.2350283A>G, g.138361311C>T, g.44996379C>T, g.44996247A>C, g.107715245C>T, g.4149631C>T) for the various measured traits. The identified genetic polymorphisms, of which one was novel (g.214707340G>A), may serve as candidate molecular markers to change population means for the targeted growth traits.

Structural equation modelling for the effect of physical exercise on excessive daytime sleepiness.

OBJECTIVES: The present study aimed to examine the effect of physical exercise on excessive daytime sleepiness (EDS) which is a significant public health problem. STUDY DESIGN: This is a population-based cohort study. METHODS: We hypothesized that those who engage in regular exercise would have lower chances of dozing in the daytime and examined causal relationships between EDS and known risk factors for EDS using structural equation model (SEM). RESULTS: We found that causal relationships from both depression and sleep quality to EDS were relatively weaker in those who regularly engage in physical exercise, which resulted in lower chances of having EDS. CONCLUSION: Regular exercise may play a protective role in EDS prevention.

Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment.

The multi-kinase inhibitor sorafenib is clinically approved for the treatment of patients with advanced hepatocellular carcinoma (HCC). We previously reported that fibroblast growth factor 3 and 4 (FGF3/FGF4) amplification is a predictor of a response to sorafenib. This study aims to analyze the relationship between FGF-FGF receptor (FGFR) genetic alterations and the response to sorafenib. Formalin-fixed, paraffin-embedded tissue specimens from HCC patients who had achieved a complete response (CR, N=6) or non-CR (N=39) to sorafenib were collected and were examined for FGF-FGFR gene alterations using next generation sequencing and copy number assay. FGFR mutations were detected in 5 of 45 (11.1%) cases. There was no significant association between FGFR mutation status and the response to sorafenib. We detected no increase in the FGF3/FGF4 copy number in CR cases. An FGF19 copy number gain was detected more frequently among CR cases (2/6, 33.3%) than among non-CR cases (2/39, 5.1%) (P = 0.024, Chi-squared test). In conclusion, a copy number gain for FGF19 may be a predictor of a response to sorafenib, in addition to FGF3/FGF4 amplification.

Posttraumatic myositis ossificans of the hand : A locally aggressive malignancy-mimicking tumor.

Posttraumatic myositis ossificans (PTMO) is the most common form of myositis ossificans, but it rarely affects the hand. Due to the aggressive behavior of this unusual tumor, it is commonly misdiagnosed as malignancy or local infection. This report describes a case of PTMO of the hand in a 25-year-old women, and reviews the clinical, radiologic, and histologic characteristics. By understanding the disease characteristics and maturation process, physicians can avoid a misdiagnosis that may lead to functional impairment or improper treatment.

Grade B pancreatic fistulas do not affect survival after pancreatectomy for pancreatic cancer: A multicenter observational study.

BACKGROUND: Several studies have demonstrated that postoperative complications after pancreatectomy for pancreatic cancer adversely affect survival. The impact on survival of a pancreatic fistula according to the classification of the International Study Group for Pancreatic Surgery has not been fully evaluated. The aim of this multicenter, observational study was to evaluate the impact of pancreatic fistula on pancreatic cancer patients who had undergone pancreatectomy. METHODS: Between 2001 and 2012, 1,397 patients who underwent pancreatectomy for pancreatic cancer at 7 high-volume centers in Japan were reviewed retrospectively. The impact of pancreatic fistula on survival was evaluated by univariate and multivariate analysis. RESULTS: Pancreatic fistula occurred in 327 of 1,397 patients (23.4%) and was classified based on the International Study Group for Pancreatic Surgery as follows: grade A in 9.9%, grade B in 10.6%, and grade C in 2.9% of the patients. Median survival time in no fistula/grade A, grade B, and grade C were 23.6, 26.0, and 9.0 months, respectively. There was no significant difference in overall survival between patients with no fistula/grade A and those with grade B (P = .403); in contrast, overall survival in patients with grade C was worse than in patients without grade C (P < .001). The multivariate Cox proportional hazard analysis demonstrated that grade C pancreatic fistula was an independent prognostic factor (hazard ratio 1.59; 95% confidence interval, 1.03-2.45; P = .035). CONCLUSION: Grade B pancreatic fistula after pancreatectomy does not adversely affect long-term survival, but a grade C pancreatic fistula has a negative impact on long-term survival of patients with pancreatic cancer.

Clinical adherence to thrombophilia screening guidelines at a major tertiary care hospital.

UNLABELLED: Essentials Thrombophilia screening has significantly increased but has limited clinical utility. We evaluated the positive rate of thrombophilia screening and adherence to published guidelines. Both the positive rate for thrombophilia screening and the adherence to guidelines were low. Guidance implementation is essential to improve current thrombophilia screening practice. SUMMARY: Background Thrombophilia screening is widely performed but provides limited clinical utility in managing patients predisposed to venous thromboembolism. Although guidelines to limit testing have been published, adherence to those guidelines in the outpatient clinical setting has not been assessed. Objective To evaluate outpatient thrombophilia screening practices at a tertiary academic medical center. Methods We performed a retrospective review of the electronic medical records and a computational analysis of thrombophilia tests collected during a 3-year period (August 2010 to June 2013) at a large teaching hospital. Our primary outcome measures were positive diagnostic yield for thrombophilia and clinician adherence to published thrombophilia screening guidelines in the outpatient setting. Results and Conclusions We found a positive diagnostic yield of 13.8% (95% confidence interval 12.3% to 15.3%) for outpatient thrombophilia screening at our institution. Of the screening tests requiring a second confirmatory assay for definitive diagnosis, only 12% (95% confidence interval 10.3% to 13.7%) were appropriately obtained. We also observed that 73% of patients in our electronic medical record review were inappropriately tested based on existing screening guideline criteria. When parsed by specialty, we identified that hematologists had a higher adherence rate to guideline criteria than do physicians from other specialties. Our study confirms low adherence to thrombophilia screening guidelines across disciplines and indicates the need for continued clinician education.

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis.

The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information were also reviewed to investigate the mutational gene- or domain-specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin-binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS.

Mutational spectrum of Korean patients with corneal dystrophy.

Corneal dystrophy typically refers to a group of rare hereditary disorders with a heterogeneous genetic background. A comprehensive molecular genetic analysis was performed to characterize the genetic spectrum of corneal dystrophies in Korean patients. Patients with various corneal dystrophies underwent thorough ophthalmic examination, histopathologic examination, and Sanger sequencing. A total of 120 probands were included, with a mean age of 50 years (SD = 18 years) and 70% were female. A total of 26 mutations in five genes (14 clearly pathogenic and 12 likely pathogenic) were identified in 49 probands (41%). Epithelial-stromal TGFBI dystrophies, macular corneal dystrophy and Schnyder corneal dystrophy (SCD) showed 100% mutation detection rates, while endothelial corneal dystrophies showed lower detection rates of 3%. Twenty six non-duplicate mutations including eight novel mutations were identified and mutations associated with SCD were identified genetically for the first time in this population. This study provides a comprehensive characterization of the genetic aberrations in Korean patients and also highlights the diagnostic value of molecular genetic analysis in corneal dystrophies.

Evaluation of the efficacy of daikenchuto (TJ -100) for the prevention of paralytic ileus after pancreaticoduodenectomy: A multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: We assessed the efficacy of TJ-100 taken perioperatively to recovery among patients with periampullary tumor or tumor of the head of the pancreas who underwent pancreaticoduodenectomy (PD). PATIENTS AND METHODS: In this multicenter, randomized, double-blinded, placebo-controlled, phase II trial (JAPAN-PD Study), patients were assigned randomly in a 1:1 ratio to receive TJ-100 or placebo. The coprimary endpoints were (1) incidence of postoperative paralytic ileus lasting >72 hours after surgery and (2) time to occurrence of postoperative paralytic ileus. This trial is registered at the UMIN Clinical Trials Registry (000007975) and at ClinicalTrials.gov (NCT01607307). RESULTS: From August 2012 through July 2013, we assessed 273 patients for eligibility, and 224 underwent randomization; 112 patients received TJ-100, and 112 patients received placebo. The population for analysis consisted of 104 patients who received TJ-100 and 103 who received placebo. Paralytic ileus occurred 35 (33.7%) in the TJ-100 group and 38 (36.9%) in the placebo group (P = .626). Time to first flatus was 2.25 (2.00-2.50) days in the TJ-100 group and 2.50 (1.50-2.50) days in the placebo group (P = .343). Among 23 patients who underwent a pylorus ring-preserving PD, time to first flatus was lower in the TJ-100 group than in the placebo group: 0.50 (0.50-1.00) days versus 1.50 (0.50-3.00) days (P = .034). CONCLUSION: Our findings suggest that use of TJ-100 did not improve recovery from paralytic ileus after PD, and may preclude the routine use of TJ-100 in clinical practice after PD operation.

Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia.

KIT exon 17 mutation is a poor prognostic factor in core-binding factor acute myeloid leukemia. However, the mutation detection method used for risk assessment is not assigned. It is necessary to verify the analytical and clinical performance before applying new methods. Herein, we firstly applied a highly sensitive allele-specific, real-time quantitative PCR (AS-qPCR) assay to analyze KIT mutations, which demonstrated excellent sensitivity and specificity. Much higher incidence of KIT mutations (62.2%, 69/111) and prevalence of multiple mutations (43.5%, 30/69) were observed using AS-qPCR, which meant the existence of multiple KIT mutant subclones. The relative KIT mutant level was variable (median, 0.3 per control allele 100 copies, 0.002-532.7) and was divided into two groups: high (⩾10, n=26) and low (<10) mutant level. Interestingly, rather than mutation positivity, mutant level was found to be associated with clinical outcome. High mutant level showed significantly inferior overall survival (P=0.005) and event-free survival (P=0.03), whereas low level did not influence the prognosis. The follow-up data showed that the mutant level were along with fusion transcripts in the majority (n=29), but moved separately in some cases, including the loss of mutations (n=5) and selective proliferation of minor clones (n=2) at relapse. This study highlighted that the KIT mutation should be analyzed using sensitive and quantitative techniques and set a cutoff level for identifying the risk group.

Identification and Characterization of Lineage(-)CD45(-)Sca-1(+) VSEL Phenotypic Cells Residing in Adult Mouse Bone Tissue.

Murine bone marrow (BM)-derived very small embryonic-like stem cells (BM VSELs), defined by a lineage-negative (Lin(-)), CD45-negative (CD45(-)), Sca-1-positive (Sca-1(+)) immunophenotype, were previously reported as postnatal pluripotent stem cells (SCs). We developed a highly efficient method for isolating Lin(-)CD45(-)Sca-1(+) small cells using enzymatic treatment of murine bone. We designated these cells as bone-derived VSELs (BD VSELs). The incidences of BM VSELs in the BM-derived nucleated cells and that of BD VSELs in bone-derived nucleated cells were 0.002% and 0.15%, respectively. These BD VSELs expressed a variety of hematopoietic stem cell (HSC), mesenchymal stem cell (MSC), and endothelial cell markers. The gene expression profile of the BD VSELs was clearly distinct from those of HSCs, MSCs, and ES cells. In the steady state, the BD VSELs proliferated slowly, however, the number of BD VSELs significantly increased in the bone after acute liver injury. Moreover, green fluorescent protein-mouse derived BD VSELs transplanted via tail vein injection after acute liver injury were detected in the liver parenchyma of recipient mice. Immunohistological analyses suggested that these BD VSELs might transdifferentiate into hepatocytes. This study demonstrated that the majority of the Lin(-)CD45(-)Sca-1(+) VSEL phenotypic cells reside in the bone rather than the BM. However, the immunophenotype and the gene expression profile of BD VSELs were clearly different from those of other types of SCs, including BM VSELs, MSCs, HSCs, and ES cells. Further studies will therefore be required to elucidate their cellular and/or SC characteristics and the potential relationship between BD VSELs and BM VSELs.

Successful Multidisciplinary Therapy for Small Cell Carcinomas Arising from the Extrahepatic Bile Duct.

A 74-year-old man was diagnosed with small cell carcinoma arising from the extrahepatic bile duct according to a histological examination of the biopsy specimen obtained during endoscopic retrograde cholangiopancreatography. Additionally, bulky hilar lymphadenopathy was observed, and the patient was treated with the combination of radiation and chemotherapy (cisplatin and irinotecan). Post-therapy, he underwent pancreaticoduodenectomy. The histological examination of the resected specimen revealed no residual cancer cells in the bile duct wall and a small amount of cancer cells in only a single lymph node. Due to this multidisciplinary therapy, the patient showed no signs of recurrence 12 months postoperatively.