Subclinical thyroid dysfunction, bone mineral density, and osteoporosis in a middle-aged Korean population.

Thyroid dysfunction is associated with the loss of bone density (osteoporosis). However, the connection between subclinical thyroid dysfunction and osteoporosis remains controversial. This study found no apparent association between subclinical hypothyroidism or subclinical hyperthyroidism and bone mineral density (BMD) in the lumbar spine and femur. INTRODUCTION: The present study examined the relationship between subclinical thyroid dysfunction and BMD in healthy middle-aged adults. METHODS: A total of 25,510 healthy Koreans with normal free thyroxine levels were enrolled from January 2011 to December 2016, and 91% of subjects visited only once. The average age of the 15,761 women was 45, and the average age of the 9749 men was 48. Levels of thyroid-stimulating hormone (TSH) and BMD were recorded in all subjects. BMD was measured using dual-energy X-ray absorptiometry. RESULTS: No apparent association was found between subclinical thyroid dysfunction and BMD in the lumbar spine, femur-neck, and proximal femur sites compared with a euthyroid group. Age, body mass index (BMI), and postmenopausal status affected BMD in women, and only BMI affected BMD in men. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis (odds ratio 0.657, 95% confidence interval 0.464-0.930) in 4710 postmenopausal women. CONCLUSIONS: No apparent association was found between subclinical hypothyroidism or subclinical hyperthyroidism defined on single TSH measurement and BMD at the lumbar spine and femur in a large cohort of middle-aged men and women. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis in postmenopausal women.

Switching to tenofovir vs continuing entecavir for hepatitis B virus with partial virologic response to entecavir: a randomized controlled trial.

Entecavir 0.5 mg (ETV) is widely used among treatment-naïve chronic hepatitis B (CHB) patients. However, 10%-30% of patients show partial virologic response (PVR) to the drug. If the hepatitis B virus (HBV) continues to replicate, the underlying liver disease may progress. Herein, we compared the efficacy of switching to tenofovir disoproxil fumarate (TDF) with that of continuing ETV in CHB patients with PVR to ETV. This was an open-label randomized controlled trial including CHB patients who had been receiving 0.5 mg of ETV for >12 months, but who still had detectable HBV DNA levels of >60 IU/mL without known resistance to ETV. Sixty patients were enrolled and 45 qualified for the study: Twenty-two patients were randomly assigned into the TDF group and 23 into the ETV group. After 12 months of treatment, the virologic response rate (HBV DNA <20 IU/mL) was significantly higher in the TDF group than in the ETV group, as measured using per-protocol analysis (55% vs 20%; P = .022) and intention-to-treat analysis (50% vs 17.4%; P = .020). The reduction in HBV DNA was greater (-1.13 vs -0.67 log10 IU/mL; P = .024), and the mean HBV DNA level was lower (1.54 vs 2.01 log10 IU/mL; P = .011) in the TDF group than in the ETV group. In conclusion, to achieve optimal response in CHB patients with PVR to ETV, switching to TDF would be a better strategy than continuing ETV. Appropriate modification of therapy would further improve the outcome of chronic HBV infection.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.

The efficacy of a nested polymerase chain reaction in detecting the cytochrome c oxidase subunit 1 gene of Sarcoptes scabiei var. hominis for diagnosing scabies.

BACKGROUND: A widespread scabies infestation, associated with long-term residence in nursing homes, is becoming an issue in high-income countries. Mineral oil examination is regarded as the gold standard in diagnosing scabies, but the sensitivity of this method is generally low - approximately 50%. Molecular techniques may contribute to enhancing the sensitivity of current tests for laboratory diagnosis of human scabies. OBJECTIVES: To develop new primers for a nested polymerase chain reaction (PCR) for the cytochrome c oxidase subunit 1 (cox1) gene of Sarcoptes scabiei var. hominis to increase the sensitivity of a previously developed conventional PCR. METHODS: Patients with clinically suspected scabies underwent dermoscopy-guided skin scraping with microscopic examination. The diagnosis was positive for scabies when mites or eggs were found under the microscope, and patients were then designated as 'microscopy positive'. Patients who presented with negative microscopic results were placed in the 'microscopy-negative' group. Skin scrapings were collected from both groups for PCR. RESULTS: Of the total 63 samples, 28 were microscopy positive and 35 were negative with no differences in sex and age between the two groups. All microscopically proven cases of scabies were positive using the cox1 nested PCR. Among microscopy-negative samples, S. scabieiDNA was detected in nine. If sensitivity of the cox1 nested PCR is considered 100% [95% confidence interval (CI) 90·5-100], then sensitivity of microscopy is 75·7% (95% CI 58·8-88·2; P = 0·004). CONCLUSIONS: Nested PCR can be successfully used as an alternative method for diagnosing suspected scabies. Therefore, infection control measures and treatments can be initiated before significant transmission occurs, minimizing the risk of outbreaks.

Sleep duration and progression to diabetes in people with prediabetes defined by HbA1c concentration.

AIMS: To evaluate the association between sleep duration and the risk of progression to diabetes among people with prediabetes, defined by HbA1c values. METHODS: We conducted a cohort study in 17 983 adults who underwent health check-up examinations, including assessments of sleep duration and quality. Diabetes was defined as either HbA1c ≥48 mmol/mol (6.5%), or the use of antidiabetic medication. Time-dependent proportional hazards models were used to evaluate the association between sleep duration and the risk of progression to diabetes. RESULTS: During 31,582 person-years of follow-up, 664 incident cases of diabetes were identified; the incidence rate was 21.0 per 1000 person-years. The multivariate adjusted hazard ratios for progression to diabetes in people with sleep durations of ≤5, 6 and ≥8 h compared with 7 h were 1.68 (95% CI 1.30-2.16), 1.44 (95% CI 1.17-1.76) and 1.23 (95% CI 0.85-1.78), respectively (P for quadratic trend <0.001). This association was partially mediated by biomarkers of adiposity, fatty liver and insulin resistance. CONCLUSION: In this large study in young and middle-aged adults with prediabetes, we found an association between short sleep duration and the risk of progression to diabetes. Our findings suggest that sufficient sleep duration is important for delaying or preventing the progression of prediabetes to diabetes.

Anti-heparan sulfate antibody and functional loss of glomerular heparan sulfate proteoglycans in lupus nephritis.

Background The purpose of this study was to evaluate the features of heparan sulfate proteoglycans (HSPGs) as agrins of the glomerular basement membrane (GBM) and circulating anti-heparan sulfate (HS) antibodies in lupus nephritis, comparing titers among the following groups: lupus nephritis (LN), non-renal lupus, non-lupus nephritis, and healthy controls. Methods The stage of nephritis was determined based on the kidney biopsy. Alcian blue staining and immunohistochemical (IHC) staining for agrin were performed for histological evaluation of GBM HSPGs in normal glomeruli, non-lupus membranous glomerulonephritis (MGN), and lupus MGN. The results were used for measurement of the serum anti-HS antibody titers using an enzyme-linked immunosorbent assay (ELISA) in the following groups: 38 healthy controls, 38 non-lupus nephritis, 37 non-renal lupus, and 38 LN. Results Glomerulus HSPGs were stained bluish-green along the GBM with Alcian blue. However, IHC staining against agrin was almost completely negative in the lupus MGN group compared with the normal and non-lupus MGN groups, which showed brown staining of GBM. A higher level of anti-HS IgG was detected in LN compared with other groups, respectively. Higher titers were associated with the presence of SLE and nephritis. A higher degree of proteinuria normalized to glomerular filtration rate (eGFR) was observed in association with higher anti-HS antibody titers in LN. Conclusion This study demonstrated a functional loss of GBM HSPGs and higher levels of circulating anti-HS antibodies as a characteristic feature of lupus nephritis, suggesting their involvement in the pathogenesis of lupus nephritis and proteinuria.

Atopic dermatitis is inversely associated with hepatitis B antigen positivity: a population-based cohort study.

BACKGROUND: No clear association between hepatitis B virus (HBV) infection and atopic dermatitis (AD) has been established. Some studies have reported that subjects with HBV had an increased risk of atopy; other studies reported an inverse association between HBV seropositivity and allergic diseases. OBJECTIVE: We evaluated the association between AD and hepatitis B antigen (HBsAg) positivity using Korean National Health and Nutrition Examination Survey data. METHODS: In total, 14 776 participants aged >19 years were included in the analysis. Multiple logistic regression analyses were used to evaluate the odds ratio of HBsAg positivity in association with AD and asthma. RESULTS: The prevalence of HBsAg positivity was lower in individuals with AD than in those without AD (mean [SE], 0.7% [0.4] vs. 3.7% [0.2]; P < 0.001). However, HBsAg positivity was not significantly associated with asthma (3.7% [0.2] vs. 2.8% [0.8]; P < 0.001). HBsAg positivity decreased the risk of AD significantly (OR = 0.223; 95% CI = 0.069-0.72). CONCLUSIONS: This study demonstrates an inverse association between AD and HBsAg positivity using a nationwide, population-based, cross-sectional health examination and survey.

Effects of cell death-inducing DFF45-like effector B on meat quality traits in Berkshire pigs.

Cell death-inducing DFF45-like effector (CIDE) B is a member of the CIDE family of apoptosis-inducing factors. In the present study, we detected a single nucleotide polymorphism (SNP), c.414G>A, which corresponds to the synonymous SNP 414Arg, in CIDE-B in the Berkshire pigs. We also analyzed the relationships between the CIDE-B SNP and various meat quality traits. The SNP was significantly associated with post-mortem pH24h, water-holding capacity (WHC), fat content, protein content, drip loss, post-mortem temperature at 12 h (T12) and 24 h (T24) in a co-dominant model (P < 0.05). A significant association was detected between the SNP and post-mortem pH24h, fat content, protein content, drip loss, shear force, and T24 in gilts; and color parameter b*, WHC, and T24 in barrows (P < 0.05). The SNP was significantly correlated with the fat content, and CIDE-B mRNA expression was significantly upregulated during the early stage of adipogenesis, suggesting that CIDE-B may contribute towards initiation of adipogenesis (P < 0.05). Furthermore, CIDE-B mRNA was strongly expressed in the liver, kidney, large intestine, and small intestine, and weakly expressed in the stomach, lung, spleen, and white adipose tissue. These results indicate that the CIDE-B SNP is closely associated with meat quality traits and may be a useful DNA marker for improving pork quality.

Late anastomotic leakage after low anterior resection in rectal cancer patients: clinical characteristics and predisposing factors.

AIM: The purpose was to examine the clinical characteristics and predisposing factors of late anastomotic leakage following low anterior resection for rectal cancer. METHOD: We retrospectively evaluated the clinicopathological features of patients who experienced anastomotic leakage after low anterior resection for rectal cancer. Patients were divided into two groups according to the time to leakage: early leakage (within 30 days postoperatively) and late leakage (after 30 days postoperatively). Clinicopathological characteristics were compared between the two groups. RESULTS: Anastomotic leakage occurred in 141 patients. Anastomotic leakage was diagnosed at a median of 17 (range 0-886) days postoperatively; 85 (60.3%) and 56 (39.7%) were categorized as the early and late leakage groups, respectively. Radiotherapy (hazard ratio 5.007; 95% CI 2.208-11.354; P < 0.0001) was the only significant independent predisposing factor for late leakage. Diverting stoma did not protect against late leakage. The late leakage group more frequently had the fistula type (46.4% vs. 10.6%; P < 0.001) and less frequently needed laparotomy (55.4% vs. 78.8%; P = 0.001). The rate of long-term stoma over 1 year was greater in the late leakage than the early leakage group (51.8% vs. 29.4%; P = 0.009). CONCLUSION: Late anastomotic leakages that develop after 30 days following low anterior resection are not uncommon and may be associated with the use of radiotherapy. Late leakage should be a different entity from early leakage in terms of the type of leakage, methods of management and subsequent sequelae.

Blue Emitters Based on Aryl End-Capped Pyrene Groups for OLEDs.

We have synthesized four pyrene-derived blue emitting materials using Suzuki cross coupling reactions. All OLED devices using these materials as emitting materials showed efficient blue electroluminescence (EL). Particularly, a device using 1,1'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis-pyrene (1) showed best EL properties with the luminous efficiency of 4.32 cd/A, the power efficiency of 3.98 lm/W and the external quantum efficiency of 2.48% at 500 cd/m2.

Association between a non-synonymous HSD17B4 single nucleotide polymorphism and meat-quality traits in Berkshire pigs.

Single nucleotide polymorphisms (SNPs) are useful genetic markers that allow correlation of genetic sequences with phenotypic traits. It is shown here that HSD17B4, a bifunctional enzyme mediating dehydrogenation and anhydration during ß-oxidation of long-chain fatty acids, contains a non-synonymous SNP (nsSNP) of chr2:128,825,976A>G, c.2137A>G, I690V, within the sterol carrier protein-2 domain of the HSD17B4 gene, by RNA-Seq of liver RNA. The HSD17B4 mRNA was highly expressed in the kidney and liver among various other tissues in four pig breeds, namely, Berkshire, Duroc, Landrace, and Yorkshire. The nsSNP was significantly associated with carcass weight, backfat thickness, and drip loss (P < 0.05). Furthermore, HSD17B4 may play a crucial role during the early stages of myogenesis when expression of its mRNA was significantly high. In conclusion, HSD17B4 may serve as a possible regulator of muscle development, and its identification should help to select for improved economic traits of Berkshire pigs such as carcass weight, backfat thickness, and drip loss.

Comparison of mechanical artificial shrinkage methods in mouse blastocyst vitrification.

PURPOSE OF INVESTIGATION: This study was designed to determine which mechanical artificial shrinkage (AS) method, conducted by puncture, pipetting, or aspiration, was effective in increasing the re-expansion rate of mouse blastocysts. MATERIALS AND METHODS: In each group, 30 mouse blastocysts were used. Before vitrification, the blastocoelic cavity was collapsed by puncture with a micro-needle, pipetting with a micro-glass pipette, and direct aspiration with an ICSI pipette. After thawing, the re-expansion rate of blastocysts was examined for each AS method. Re-expansion rate was checked at three, five, and seven hours after thawing. RESULTS: The number of re-expanded mouse blastocysts at five hours after thawing was 12 in the puncture with a micro-needle group, 11 in the pipetting with a micro-glass pipette group, and 24 in the direct aspiration with an ICSI pipette group. The cumulative number of re-expanded mouse blastocysts at seven hours after thawing was 20 in the puncture with a micro-needle group, 20 in the pipetting with a micro-glass pipette group, and 28 in the direct aspiration with an ICSI pipette group. There were statistically significant differences in the cumulative number of re-expanded mouse blastocysts between five and seven hours after thawing (p = 0.001 and 0.021, respectively). CONCLUSIONS: Direct aspiration with an ICSI pipette resulted in a higher re-expansion rate than the puncture and pipetting methods. It can be considered that the direct aspiration method is more convenient and simpler than the other two methods.

Evaluation of in vivo antitumor effects of ANT2 shRNA delivered using PEI and ultrasound with microbubbles.

Gene therapy using RNA interference can be directed against tumors through various strategies, but has been hindered owing to the inefficiency of non-viral delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2 (ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the polyethylenimine (PEI) and an ultrasound gene delivery method, human breast carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL-2Rγ(null)) mice. The results showed greater tumor regression (*P<0.05) as well as an increased survival rate in the group receiving ANT2 shRNA+two types of enhancer relative to the groups receiving ANT2 shRNA without enhancer. These findings demonstrate that the introduction of PEI and ultrasound with SonoVue exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI and ultrasound provided the best results with respect to tumor regression, the antitumor effects from the individual enhancers were approximately equivalent. In addition, we confirmed that there was no toxicity on aspartate aminotransferase and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen or creatine kinase levels in the kidney following the various gene delivery methods.

Ferritin is associated with neural differentiation of bone marrow-derived mesenchymal stem cells under extremely low-frequency electromagnetic field.

Extremely low-frequency electromagnetic field (ELFEF) is a well-known mechanical stimulation that induces neural differentiation. It is potentially an effective treatment for neurodegenerative diseases. In a previous study, ferritin light chain was upregulated in ELFEF-exposed human bone marrow-derived mesenchymal stem cells (BM-MSCs). Ferritin light chain is a component of ferritin, a highly conserved iron-binding protein. In this study, to identify molecules associated with ferritin during neural differentiation of BM-MSCs, we performed reverse transcription polymerase chain reaction (RT-PCR), western blotting, and ATP analysis. Our data indicated that ELFEF triggers the upregulation of ferritin light chain (FLC) and ferritin heavy chain (FHC) in BM-MSCs. The elevated levels of FLC and FHC correlated positively with the differentiation of BM-MSCs into neural cells. Moreover ELFEF induced the activation of iron regulatory protein-1 (IRP-1) and cofilin, which are downstream targets of ferritin. These results suggest that ELFEF induces neural differentiation through activation of a ferritin-regulated mechanism.

Use of vertebral body units to locate the cavoatrial junction for optimum central venous catheter tip positioning.

BACKGROUND: Central venous catheter (CVC) placement plays an important role in clinical practice; however, optimal positioning of the CVC tip remains a controversial issue. The objective of this study was to evaluate the use of vertebral body unit (VBUs), to locate the cavoatrial junction (CAJ), for optimal CVC tip placement based on chest radiography (CXR) using the carina as a landmark. METHODS: 524 patients who underwent coronary computed tomographic angiography (CTA) and CXR were included. The position of the CAJ was identified using VBUs, and the efficacy of VBUs for locating the CAJ with the carina as a landmark was analysed using multiple regression analysis. A VBU was defined as the distance between two adjacent vertebral bodies, including the inter-vertebral disk space. RESULTS: The mean (sd) distance from the carina to the superior CAJ was 54.3 (9.7) mm on CTA; the mean distance in VBUs at the level of the carina was 21.4 (1.7) mm on CTA and 22.6 (2.1) mm on CXR. The mean CAJ position was 2.5 VBUs below the carina on CTA and 2.4 VBUs below on CXR with 95% limits of agreement between -0.6 and +0.3. CONCLUSIONS: The position of the CVC tip in relation to the carina can be described using the thoracic spine as an internal ruler, and the position of the CAJ in adults was reliably estimated to be 2.4 VBUs below the carina. CLINICAL TRIAL REGISTRATION: KCT0001319.

Clinical implications of mucinous components correlated with microsatellite instability in patients with colorectal cancer.

AIM: Colorectal cancer (CRC) with microsatellite instability (MSI) is characterized by frequent poor differentiation or mucinous histology. The purpose of this study was to evaluate the association of MSI with clinicopathological features and the oncological outcome in patients with a mucinous component. METHOD: CRC tissue samples were analysed for histology and MSI. Patients were grouped according to the mucinous content of the tumour, as follows: > 50%, mucinous adenocarcinoma (MA); ≤ 50%, adenocarcinoma with mucinous component (AMC); none, nonmucinous adenocarcinoma (NMA). Clinicopathological parameters and survival were compared between patient groups. RESULTS: Of 2025 patients, 84 (4%) had MA and 124 (6%) had AMC. In addition, 202 (10%) had MSI. Patients with MA and AMC tended to have a younger age of onset, right-colon predilection, large-sized tumour and high frequency of MSI compared with those with NMA (P < 0.001). MA and AMC patients with MSI showed a trend towards right-colon predilection and infrequent lymph-node metastasis compared with those with microsatellite stability (MSS; P = 0.005-0.03). There were no survival differences between the three groups, but patients with MSI-MA demonstrated lower 4-year recurrence and better overall survival rates than those with MSS-MA (P = 0.018 and P = 0.046, respectively). CONCLUSION: Clinicopathological features of AMC and MA were similar and closely associated with MSI status. Although the prognoses of AMC and MA were no different from that of NMA, survival of patients with an MSI-MA tumour was significantly better than for those with MSS-MA tumours.

Efficacy and safety of a lindane 1% treatment regimen for scabies, confirmed by dermoscopy-guided skin scraping with microscopic examination.

BACKGROUND: This is the first study investigating scabies treatment since 1992 to involve examination of patients with microscopically confirmed scabies. AIM: To assess the efficacy of 1% lindane cream in treating microscopically confirmed scabies, and to determine the utility of dermoscopy-guided skin scraping with microscopic examination (DSGSS-ME) in evaluating the efficacy of scabies treatment. METHODS: This retrospective study analysed patients treated for scabies between January 2012 and December 2013. From the hospital database, 287 cases of scabies were identified and 50 were enrolled in the study. Patients were treated with 1% lindane cream twice weekly (days 0 and 1) and were evaluated with DSGSS-ME on day 7. Treatment and evaluations were repeated once weekly until a negative DSGSS-ME result was obtained. RESULTS: The cumulative efficacy of lindane 1% cream was 40% (20/50) after 1 week, 88% (44/50) after 2 weeks and 98% (49/50) after 3 weeks of treatment. There was a statistically significant difference between the 1- and 2-week (P = 0.03), and 1- and 3-week (P = 0.02) treatments. A total of 90 post-treatment DSGSS-MEs were performed, with a sensitivity of 97.3% (95% CI 85.8-99.9) and a negative predictive value of 98.2% (95% CI 90.1-100). Specificity and positive predictive value were 100%, as this procedure cannot yield false-positive results, because it relies on finding mites, eggs or faeces. CONCLUSIONS: We suggest that a twice-weekly schedule (on consecutive days) of 1% lindane treatment lasting at least 2 weeks is required to clear scabies. DSGSS-ME appears to be a good method to evaluate the efficacy of scabies treatment. This study introduces a safe and effective method to treat scabies, and to accurately monitor infestation status in patients.