Preoperative considerations and benefits of neoadjuvant chemotherapy: insights from a 12-year review of the Hong Kong Breast Cancer Registry.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) was initially used for locally advanced or inoperable breast cancers. Its extension to early disease has facilitated breast-conserving surgery (BCS). This study investigated the use of NAC in patients registered with the Hong Kong Breast Cancer Registry (HKBCR); it also assessed NAC effectiveness according to rates of pathological complete response (pCR) and BCS. METHODS: Records were retrieved from the HKBCR regarding 13 435 women who had been diagnosed with invasive breast cancer during the period of 2006 to 2017, including 1084 patients who received NAC. RESULTS: The proportion of patients treated with NAC nearly doubled from 5.6% in 2006-2011 to 10.3% in 2012-2017. The increase was most pronounced among patients with stage II or III disease. In terms of biological subtype, substantial increases in the receipt of NAC were evident among patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive (non-luminal) tumours. The best rates of pCR were observed in patients with HER2-positive (non-luminal) [46.0%] tumours, followed by patients with luminal B (HER2-positive) [29.4%] and triple-negative (29.3%) tumours. After NAC, the rate of BCS was 53.9% in patients with clinical stage IIA disease, compared with 38.2% in patients with pathological stage IIA disease who did not receive NAC. CONCLUSION: The use of NAC in Hong Kong increased from 2006 to 2017. The findings regarding rates of pCR and BCS indicate that NAC is an effective treatment; it should be considered in patients with stage ≥II disease, as well as patients with HER2- positive (non-luminal) or triple-negative breast cancers.

Association between mortality risk and the number, location, and sequence of subsequent fractures in the elderly.

The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk. INTRODUCTION: It is unclear whether subsequent fractures or a certain location and sequence of subsequent fractures are associated with mortality risk in the elderly. We aimed to investigate the relationship between subsequent fractures and mortality risk. METHODS: Using the Korean National Health Insurance Research Database, we analyzed the cohort data of 24,756 patients aged > 60 years who sustained fractures between 2002 and 2013. Cox regression was used to assess the mortality risk associated with the number, locations, and sequences of subsequent fractures. RESULTS: Mortality hazard ratios (HRs) for women and men were shown to be associated with the number of subsequent fractures (one, 1.63 (95% confidence interval [CI], 1.48-1.80) and 1.42 (95% CI, 1.28-1.58); two, 1.75 (95% CI, 1.47-2.08) and 2.03 (95% CI, 1.69-2.43); three or more, 2.46(95% CI, 1.92-3.15) and 1.92 (95% CI, 1.34-2.74), respectively). For women, the mortality risk was high when hip (HR, 2.49; 95% CI, 1.80-3.44) or vertebral (HR, 1.40; 95% CI, 1.03-1.90) fracture occurred as a second fracture. Compared with a single hip fracture, there was a high mortality risk in the group with hip fracture after the first vertebral fracture (HR, 2.90; 95% CI, 1.86-4.54), followed by vertebral fracture after the first hip fracture (HR, 1.90; 95% CI, 1.12-3.22). CONCLUSION: The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.

A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects.

BACKGROUND AND OBJECTIVE: Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24. MATERIAL AND METHODS: Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA. RESULTS: Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive levels of inducible MMPs to near-normal levels, but appeared to have no significant effect on the constitutive MMPs required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically, CMC 2.24 also favorably affected extra-oral connective tissues, skin and skeletal bone. CONCLUSION: This study supports our hypothesis that CMC 2.24 is a potential therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia- and bacteria-induced connective tissue destruction.

Relationship between dyslipidaemia and glycaemic status in patients with Type 2 diabetes mellitus.

The risk of coronary heart disease (CHD) is dramatically increased in diabetic patients due to their atherogenic lipid profile. The severity of CHD in diabetic patients has been found to be directly associated with glycated haemoglobin (HbA1c). According to the Malaysian Clinical Practice Guidelines on diabetes mellitus (DM), HbA1c level less than 6.5% reduces the risk of microvascular and macrovascular complications. Hence, this study aimed to determine the relationship between dyslipidaemia and glycaemic status in patients with type 2 DM (T2DM) patients in Hospital Putrajaya, a tertiary endocrine centre in Malaysia. This was a cross sectional, retrospective study of 214 T2DM patients with dyslipidaemia who had visited the endocrine clinic between January 2009 and December 2012. Significant correlations were found between fasting blood glucose (FBG) and HbA1c with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), non-high density lipoprotein cholesterol (non-HDL), LDL/HDL ratio and TC/HDL ratio; greater correlation being with HbA1c than FBG. In patients with HbA1c ≥ 6.5%, TC, TG, non-HDL and TC/HDL ratio were significantly higher than in patients with HbA1c < 6.5%. Non-HDL, LDL/HDL ratio, TC/HDL ratio and HbA1c were significantly lower in patients on statin treatment than nontreated patients (p<0.05). This significant association between glycaemic status and dyslipidaemia emphasises the additional possible use of HbA1c as a biomarker for dyslipidaemia as well as a potential indirect predictor of cardiovascular disease (CVD) risk in T2DM patients.

Non-linear relationship between birthweight and cardiometabolic risk factors in Chinese adolescents and adults.

AIM: To investigate the relationship between birthweight and cardiometabolic traits in two cohorts: one of Chinese adolescents and one of Chinese adults. METHODS: Birthweight and clinical data, including anthropometric traits, fasting plasma glucose and fasting plasma insulin levels, blood pressure and lipid profiles were collected from 2035 adolescents and 456 adults. A subset of 735 subjects underwent an oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min. RESULTS: Among adolescents, birthweight showed U-shaped relationships with larger body size, obesity, abdominal obesity in girls, insulin resistance and worse lipid profiles (0.0013 < P(quadratic) < 0.0499), as well as an inverse association with fasting plasma glucose (P(linear) = 0.0368). After further adjustment for adiposity, decreasing birthweight was associated with elevated fasting plasma glucose levels, greater insulin resistance and worse lipid profiles (3.1 × 10⁻5 < P(linear) < 0.0058). Among adults, high birthweight was associated with larger body size and abdominal obesity in men, while low birthweight was associated with elevated glucose levels at 15, 30, 60 and 120 min and a greater area under the curve at 0-120 min, as well as with ß-cell dysfunction (6.5 × 10⁻5 < P(linear) < 0.0437). Adjustment for adult adiposity did not substantially change the relationships. There was significant interaction between birthweight and abdominal obesity in elevating fasting plasma insulin and homeostasis model assessment of insulin resistance (P > 0.05), with abdominally obese adolescents in the lowest birthweight category (≤ 2.5 kg) having the highest risk of insulin resistance. CONCLUSIONS: Both high and low birthweights are associated with an increased risk of cardiometabolic abnormalities including obesity, abdominal obesity, hyperglycaemia, dyslipidaemia and insulin resistance, as well as with ß-cell dysfunction.

Early gene-diet interaction between glucokinase regulatory protein (GCKR) polymorphism, vegetable and fish intakes in modulating triglyceride levels in healthy adolescents.

BACKGROUND AND AIMS: The benefits of dietary vegetable and fish consumptions on improving glucose and lipid metabolism have been well established. Recently, the T-allele of a common genetic variant rs780094 at glucokinase regulatory protein (GCKR) was reported to be associated with elevated triglyceride (TG) levels but reduced fasting plasma glucose (FPG) and type 2 diabetes risk. However, the dietary modulation on genetic risk is not clearly understood. METHODS AND RESULTS: A cohort of 2095 Chinese adolescents (mean age 15.6 ± 2.0 years, 45.3% male) recruited from a population-based school survey for cardiovascular risk factor assessment, with dietary data including weekly vegetable and fish consumptions as well as clinical data were genotyped for the GCKR rs780094 polymorphism. In the linear regression analysis with adjustment for sex, age, body mass index, and socioeconomic status (school banding, paternal and maternal education levels), the frequency of vegetable intake per week was inversely associated with FPG (P = 0.044). Individuals with low fish intake generally had elevated TG levels but reduced TC, HDL-C and LDL-C (0.006 < P < 0.029). We also observed significant associations of the minor T-allele of GCKR rs780094 with decreased FPG (P = 0.013) and increased TG levels (P = 2.7 × 10(-8)). There were significant gene-diet interactions between rs780094 and vegetable consumption (P(interaction) = 0.009), and between rs780094 and fish consumption (P(interaction) = 0.031) in modulating TG levels. The T-allele of GCKR locus was associated with higher TG levels amongst individuals with ≥7 vegetable meals per week (P = 6.4 × 10(-9)), and among individuals with <7 fish meals per week (P = 0.020 and 7.0 × 10(-7) for 4-6 and ≤3 meals per week, respectively). High intake of vegetable exerted a reduction in TG levels only among CC genotype carriers (Ptrend = 0.020), while high intake of fish was associated with reduced TG levels only among TT genotype carriers (Ptrend = 0.026). CONCLUSIONS: In summary, our data indicated that the favorable associations of higher vegetable and fish intakes on TG levels are dependent on the genetic background of an individual. In particular, at-risk TT- genotype carriers of the GCKR variant may derive more benefits from a high fish intake, while the CC-genotype carriers may find further benefits from a high consumption of vegetable.

Five-minute parameter of thromboelastometry is sufficient to detect thrombocytopenia and hypofibrinogenaemia in patients undergoing liver transplantation.

BACKGROUND: Early detection of coagulopathy is important to prevent bleeding during liver transplantation (LT). Rotation thromboelastometry (ROTEM(®)) provides the earliest parameter of clot amplitudes at 5 min (A5). We evaluated whether A5 correlates with platelet count (PLT) and fibrinogen concentration (Fib) and can predict thrombocytopenia and hypofibrinogenaemia in hypocoagulable patients undergoing living-donor LT (LDLT). METHODS: A total of 3446 retrospective ROTEM(®) measurements, including 1139 EXTEM, 1182 INTEM, and 1125 FIBTEM, with simultaneously measured PLT and Fib, were analysed during LDLT in 239 patients. The correlations between A5 and maximum clot firmness (MCF) index, PLT, and Fib were calculated. Receiver operating characteristic analysis with area under the curve (AUC) was used to assess A5 thresholds predictive of PLT and Fib. RESULTS: The median PLT was 47 000 mm(-3) and the median Fib was 100 mg dl(-1) during LDLT. The A5 parameters of EXTEM (A5EXTEM) and INTEM (A5INTEM) were highly correlated with MCF (r=0.96 and r=0.95, respectively), PLT (r=0.76 and r=0.77, respectively), and Fib (r=0.63 and r=0.64, respectively). A5 of FIBTEM (A5FIBTEM) was also correlated with MCF (r=0.91) and Fib (r=0.75). A5EXTEM thresholds of 15 and 19 mm predicted PLT<30 000 mm(-3) (AUC=0.90) and <50 000 mm(-3) (AUC=0.87), respectively, whereas A5FIBTEM 4 mm predicted Fib<100 mg dl(-1) (AUC=0.86). Biases from A5EXTEM and A5FIBTEM to their MCFs were 16.4 and 1.3 mm, respectively. CONCLUSIONS: A5 as an early variable of clot firmness is effective in detecting critically low PLT and Fib. A5 can therefore be a reliable fast index guiding transfusion therapy in hypocoagulable patients undergoing LDLT.

Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians. METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations. RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10(-5) from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p meta = 2.6 × 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p meta = 2.3 × 10(-10)) and a population of European descent (p = 8.6 × 10(-3)). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians. CONCLUSIONS/INTERPRETATION: Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.

Erythrocyte sedimentation rate and anaemia are independent predictors of survival in patients with clear cell renal cell carcinoma.

BACKGROUND: The 1997 international consensus conference on renal cell cancer (RCC) prognosis suggested erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and anaemia as prognostic biomarkers, but most studies reviewed were limited by small sample sizes. METHODS: The Cox proportional hazards model was used to evaluate whether ESR, ALP, haemoglobin (Hb), and haematocrit (Hct) could predict survival outcomes in 1307 patients with clear cell RCC (ccRCC) who underwent nephrectomy during 1994-2008. RESULTS: During a median follow-up of 43 months, we found that the patients with preoperative high levels of ESR, had a 2.10-fold (95% confidence interval (CI): 1.21-3.67) greater risk of dying from RCC compared with patients with low levels (normal range). Patients with preoperative anaemia, assessed by Hb and Hct, had a 3.11-fold (95% CI: 1.17-8.25) and 6.20-fold (95% CI: 2.30-16.72) greater risk of dying from other illnesses, respectively, compared with patients without anaemia. ALP levels were not associated with ccRCC patients' survival. These associations for ESR and anaemia were more pronounced in patients with body mass index (BMI) <25 compared with patients with BMI ≥ 25 kg m(-2). CONCLUSION: Preoperative high ESR, but not ALP, was a significant predictor for cancer-specific survival among ccRCC patients. Anaemia increases the risk of death from other illness.

Activation of TLR4 induces VEGF expression via Akt pathway in nasal polyps.

BACKGROUND: Nasal polyposis is characterized by tissue remodelling and oedematous nasal mucosa. Vascular endothelial growth factor (VEGF) plays a significant role in the regulation of remodelling in nasal polyps. TLR4 activation is associated with VEGF expression in murine macrophages and odontoblasts. OBJECTIVE: This study aimed to evaluate whether lipopolysaccharide (LPS), an inducer of TLR4, stimulates VEGF expression and to determine the mechanism underlying VEGF production in nasal polyps. METHODS: Nasal polyp-derived fibroblasts (NPDFs) were isolated from 10 patients with nasal polyps and exposed to LPS. LPS from Rhodobacter sphaeroides (LRS) was used to inhibit the expression levels of TLR4, MyD88 and VEGF. Messenger RNA (mRNA) expression levels of TLRs, MyD88 and VEGF were determined by gene expression microarray and semiquantitative reverse transcription-PCR. Protein expression levels of TLR4 and VEGF were analysed using western blot, immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Activation of MAPKs (ERK, p38, and JNK) and Akt was examined using western blot analysis. The expression level of VEGF was measured by ELISA and western blot analysis in ex vivo nasal polyp organ culture. RESULTS: The protein expression level of VEGF was increased in nasal polyp tissues compared with inferior turbinate tissues. LRS inhibited the mRNA and protein expression of TLR4, MyD88 and VEGF in LPS-stimulated NPDFs. LPS-activated MAPKs and Akt signals, whereas MAPK inhibitors did not inhibit VEGF expression, and only Akt inhibitor blocked VEGF production. LRS reduced the production of VEGF in LPS-stimulated ex vivo organ culture. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that LPS stimulates the production of VEGF through the TLR4-Akt signalling pathway in nasal polyps. LPS may be involved in the pathogenesis of nasal polyp remodelling.

Anti-adhesive effect of a thermosensitive poloxamer applied after the removal of nasal packing in endoscopic sinus surgery: a randomised multicentre clinical trial.

OBJECTIVE: To compare the efficacies of a thermosensitive poloxamer (TPX) and Merogel in preventing adhesion applied after the removal of nasal packing in endoscopic sinus surgery as a non-inferiority trial. DESIGN: Randomised, multicentre, single-blind, active-controlled, matched-pair study. SETTING: Yonsei University Gangnam Severance Hospital, Korea University Guro Hospital. PARTICIPANTS: A total of 70 patients were enroled and underwent endoscopic sinus surgeries. Four of the patients did not complete their follow-up. Analysis of the 66 enroled patients having completed postoperative assessment was performed. The severity of rhinosinusitis was graded with a Lund-McKay CT score, and only those with bilateral disease and a CT score difference ≤2 between sinuses were included. MAIN OUTCOME MEASURES: An independent rhinologist from a third institution through a blinded assessment with digital photoendoscopy of the middle meati bilaterally taken postoperatively. RESULTS: In the blinded assessment, thermosensitive poloxamer (anti-adhesion rate: 92%) was similar to Merogel (anti-adhesion rate: 89%). Evaluation of the presence and grade of adhesion, oedema, and infection in the middle meatus revealed no significant differences between the thermosensitive poloxamer group and the Merogel group at all postoperative periods. CONCLUSION: Anti-adhesive effects of thermosensitive poloxamer are similar to those of Merogel. Therefore, thermosensitive poloxamer can be considered a safe alternative to Merogel for preventing adhesion in patients undergoing endoscopic sinus surgeries, and further evaluation of thermosensitive poloxamer as an anti-adhesive and primary packing material compared with the control using no packing is needed.

α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 (SIRT1) and activation of AMP-activated protein kinase.

AIMS/HYPOTHESIS: Sirtuin 1 (SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether α-lipoic acid (ALA) exerts a lipid-lowering effect through regulation of SIRT1 activation and production in C(2)C(12) myotubes. METHODS: ALA-stimulated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), adipose triacylglycerol lipase (ATGL) and fatty acid synthase (FAS) production, as well as intracellular triacylglycerol accumulation and fatty acid ß-oxidation were analysed in the absence or presence of a SIRT1 inhibitor (nicotinamide), SIRT1 small interfering (si) RNA and an AMPK inhibitor (compound C) in C(2)C(12) myotubes. Mice with streptozotocin/nicotinamide-induced diabetes and db/db mice fed on a high-fat diet were used to study the ALA-mediated lipid-lowering effects in vivo. RESULTS: ALA increased the NAD(+)/NADH ratio to enhance SIRT1 activity and production in C(2)C(12) myotubes. ALA subsequently increased AMPK and ACC phosphorylation, leading to increased palmitate ß-oxidation and decreased intracellular triacylglycerol accumulation in C(2)C(12) myotubes. In cells treated with nicotinamide or transfected with SIRT1 siRNA, ALA-mediated AMPK/ACC phosphorylation, intracellular triacylglycerol accumulation and palmitate ß-oxidation were reduced, suggesting that SIRT1 is an upstream regulator of AMPK. ALA increased ATGL and suppressed FAS protein production in C(2)C(12) myotubes. Oral administration of ALA in diabetic mice fed on a high-fat diet and db/db mice dramatically reduced the body weight and visceral fat content. CONCLUSIONS/INTERPRETATION: ALA activates both SIRT1 and AMPK, which leads to lipid-lowering effects in vitro and in vivo. These findings suggest that ALA may have beneficial effects in the treatment of dyslipidaemia and obesity.

Epigenetic regulation of myofibroblast differentiation and extracellular matrix production in nasal polyp-derived fibroblasts.

BACKGROUND: Nasal polyposis is a multi-factorial disease associated with chronic inflammatory condition of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) accumulation are involved in the pathogenesis of nasal polyposis. OBJECTIVE: The aim of this study was to study the effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on transforming growth factor (TGF)-ß1-induced myofibroblast differentiation and ECM accumulation in nasal polyp-derived fibroblasts (NPDFs). METHODS: Nasal polyp-derived fibroblasts were isolated from nasal polyps of patients who have chronic rhinosinusitis with nasal polyp. TSA was treated in TGF-ß1-induced NPDFs. Expression levels of HDAC2, α-smooth muscle actin (SMA), TGF-ß1, collagen type I, acetylated Histone H3, acetylated Histone H4, phosphorylated Smad2/3 and Smad7 were determined by RT-PCR, western blot and/or immunofluorescent staining. The total collagen amount production was analysed by Sircol soluble collagen assay and contractile activity was measured by collagen gel contraction assay. HDAC2 inhibition by TSA or HDAC2 silencing was established by RT-PCR and western blot. The epigenetic effect on α-SMA gene inactivation was examined by chromatin immunoprecipitation assay. Proliferation was determined by Ki67-positive cell staining and cytotoxicity was assessed by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: The expression levels of HDAC2, α-SMA and TGF-ß1 were increased in nasal polyp tissues compared to normal inferior turbinate tissues. TSA and HDAC2 silencing inhibited expression levels α-SMA, collagen and HDAC2. TSA induced hyperacetylation of histone and suppressed opening of α-SMA gene promoter in TGF-ß1-induced NPDFs. TSA inhibited TGF-ß1-induced Smad 2/3 and rescued TGF-ß1-suppressed Smad7 signalling pathway. Finally, TSA blocked proliferation in TGF-ß1-induced NPDFs and has no cytotoxic effect in NPDFs. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that HDAC inhibition is associated with myofibroblast differentiation and extracelluar matrix accumulation in nasal polyposis. TSA may be useful as an inhibitor of nasal polyp growth, and thus has potential to be used as a novel treatment option for nasal polyposis.

Radioactive impact in South Korea from the damaged nuclear reactors in Fukushima: evidence of long and short range transport.

Traces of long-lived fallout-derived radioisotopes ((134)Cs and (137)Cs) were found in wet and dry deposition samples collected from the west and east coasts of South Korea from March to May 2011 following the release of radionuclides from the damaged nuclear power plants in Fukushima, Japan. The analysis of air mass back trajectory and atmospheric pressure systems indicated that the Fukushima-derived radiocaesium had predominantly reached South Korea from the west by surface westerlies from 11 March to 5 April; however, after 6 April, air masses arrived from Japan directly due to a high pressure system that developed to the east of Japan. Spatial variation of deposition fluxes of radiocaesium in South Korea was partly attributed to the presence of local longitudinal orography.

Impact of intravenous lidocaine on myocardial injury after off-pump coronary artery surgery.

BACKGROUND: Lidocaine has been demonstrated to exert cardioprotective effects against myocardial ischaemia and reperfusion injury. We evaluated whether a continuous i.v. infusion of lidocaine reduced myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB). METHODS: In this randomized, double-blinded trial, 99 patients received i.v. lidocaine 2% (i.e. a 1.5 mg kg(-1) bolus at induction of anaesthesia followed by a 2.0 mg kg(-1) h(-1) infusion intraoperatively) or an equal volume of saline. Serum creatine kinase-myocardial band (CK-MB) and troponin I (TnI) concentrations were measured before surgery, upon arrival in the intensive care unit, and at 6, 24, 48, and 72 h after surgery. Cardiac enzymes, other biological markers, and rate of postoperative adverse events were compared between the groups. RESULTS: The median (25-75% inter-quartile range) TnI [0.90 (0.43-1.81) vs 1.71 (0.88-3.02) ng ml(-1), P=0.027] and CK-MB [6.5 (3.9-12.3) vs 9.8 (6.0-18.6) ng ml(-1), P=0.005] concentrations 24 h after surgery were significantly lower in the lidocaine group than in the control group. Moreover, lidocaine infusion reduced the total area under the curve of TnI and CK-MB release after surgery by 42% and 27%, respectively, compared with control. CONCLUSIONS: Continuous i.v. infusion of lidocaine during surgery reduces myocardial injury in patients undergoing OPCAB.

Seasonal variation of patulous Eustachian tube diagnoses using climatic and national health insurance data.

OBJECTIVES: This study aimed to analyse if there were any associations between patulous Eustachian tube occurrence and climatic factors and seasonality. METHODS: The correlation between the monthly average number of patients diagnosed with patulous Eustachian tube and climatic factors in Seoul, Korea, from January 2010 to December 2016, was statistically analysed using national data sets. RESULTS: The relative risk for patulous Eustachian tube occurrence according to season was significantly higher in summer and autumn, and lower in winter than in spring (relative risk (95 per cent confidence interval): 1.334 (1.267-1.404), 1.219 (1.157-1.285) and 0.889 (0.840-0.941) for summer, autumn and winter, respectively). Temperature, atmospheric pressure and relative humidity had a moderate positive (r = 0.648), negative (r = -0.601) and positive (r = 0.492) correlation with the number of patulous Eustachian tube cases, respectively. CONCLUSION: The number of patulous Eustachian tube cases was highest in summer and increased in proportion to changes in temperature and humidity, which could be due to physiological changes caused by climatic factors or diet trends.

Forced vital capacity paired with Framingham Risk Score for prediction of all-cause mortality.

Forced vital capacity (FVC) measures lung function and predicts coronary heart disease (CHD); whether it provides additive prediction over CHD risk factors has not been established. We examined whether FVC adds to the prediction of all-cause mortality provided by Framingham Risk Score (FRS) alone. We examined 5,485 (61.1 million projected) nonsmoking adults from the USA who were aged 20-79 yrs. Subjects were from the Third National Health and Nutrition Examination Survey, were without obstructive lung disease, had FVC measurements and had ≤ 12 yrs (mean 8.8 yrs) mortality follow-up. We performed Cox regression analysis to examine whether FVC and forced expiratory volume in 1 s (FEV(1)) (categorised as low ≤ 85% predicted, borderline 86-94% predicted and normal ≥ 95% predicted) within FRS groups (10-yr risk of cardiovascular disease low <10%, intermediate 10-20%, high 20%) predict mortality. Receiver operator characteristic analysis examined whether FVC and FEV(1) added to the prediction provided by FRS. Low-, intermediate- and high-risk FRS groups had 79.5% (n = 4,361), 10.1% (n = 555) and 10.4% (n = 569) persons, respectively. Only the intermediate FRS group showed a graded increase in mortality (10.7, 18.2 and 42.8% per 1,000 person-yrs from highest to lowest FVC categories, respectively); those with low FVC had an almost three-fold greater risk of mortality (hazard ratio 2.64; p<0.01) than those with normal FVC. FVC provided incremental additive value for predicting mortality in addition to FRS for only this group (area under curve 0.65 versus 0.58; p<0.05). Similar results were obtained for FEV(1). Evaluation of lung function may be useful to improve risk stratification in persons with intermediate CHD risk where it adds to prediction of mortality over global risk assessment.

Remodelling of nasal mucosa in mild and severe persistent allergic rhinitis with special reference to the distribution of collagen, proteoglycans, and lymphatic vessels.

BACKGROUND: Small leucine-rich repeat proteoglycans (decorin, biglycan, and lumican), collagen, and lymphangiogenesis are involved in tissue remodelling of various organs with inflammatory diseases. OBJECTIVE: We determined the expression level and the distribution pattern of small leucine-rich repeat proteoglycans (decorin, biglycan, and lumican), collagen and lymphatic vessels in healthy, mild, and severe persistent allergic nasal mucosa. METHODS: The distribution pattern of collagen, proteoglycans, and lymphatic vessels in healthy, mild, and severe persistent allergic nasal mucosa was evaluated by the van Gieson staining, immunohistochemistry, RT-PCR, and Western blotting. Quantitative analyses of collagen deposition were calculated as the median of the total percentage area in the tissue specimen. For the evaluation of proteoglycans, the percentage area stained and median optical density were measured for each image. Lymphatic vessels were identified by D2-40 antibody and calculated using the lymphatic vessel density and endothelial length density in tissue specimens. The expression of MMP 2 and 9, TIMP1 and 2 was evaluated with RT-PCR and Western blotting. RESULTS: In mild and severe persistent allergic nasal mucosa, compared with healthy nasal mucosa, collagen showed more intense staining in the superficial and submucosal layer. In healthy and allergic nasal mucosa, decorin was lightly stained without significant differences in the percentage area and optical density of staining. However, lumican and biglycan showed strong immunoreactivity in mild and severe persistent allergic nasal mucosa, which was verified by Western blotting. The number and endothelial length density of lymphatic vessels were increased in mild and severe persistent allergic nasal mucosa compared with healthy nasal mucosa. The expression of MMP 9 was increased in severe persistent allergic rhinitis. CONCLUSION AND CLINICAL RELEVANCE: These results suggest that the altered distribution pattern of collagen, proteoglycans, and lymphatic vessels could potentially modulate the remodelling of nasal mucosa in mild and severe persistent allergic nasal mucosa.