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.

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.

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.

Changes in the Ratio of T Helper 1 to T Helper 2 Signature Cytokines in Patients Undergoing Living Donor Liver Transplantation Surgery: A Prospective Controlled Study.

BACKGROUND: The balance between T helper 1 (Th1) and T helper 2 (Th2) signature cytokines plays a critical role in the immune response. The aim of this study was to evaluate the Th1 to Th2 cytokine ratio in healthy persons and patients with cirrhotic hepatitis and to investigate changes in the Th1 to Th2 cytokine ratio during living donor liver transplantation (LDLT) surgery. METHODS: Eighty patients were allocated to each of the donor and recipient groups. In the recipient group, signature cytokines-interferon gamma (IFN-γ) and tumor necrosis factor α (TNF-α) as Th1 and interleukin 6 (IL-6) and interleukin 10 (IL-10) as Th2-were quantified after induction of anesthesia (baseline, stage 1), 60 minutes after the start of the anhepatic phase (stage 2), and 60 minutes after reperfusion (stage 3). In the donor group, cytokine levels were analyzed only at stage 1. The Th1/Th2 cytokine ratios at baseline and over time during surgery in the recipient group were evaluated. RESULTS: At stage 1, the recipient group exhibited higher levels of all cytokines than the donor group. However, the IFN-γ/IL-6, IFN-γ/IL-10, TNF-α/IL-6, and TNF-α/IL-10 ratios of the groups were comparable. The levels of all cytokines, except IFN-γ, increased during LDLT. The IFN-γ/IL-6, IFN-γ/IL-10, TNF-α/IL-6, and TNF-α/IL-10 ratios declined significantly during LDLT. CONCLUSIONS: The preoperative Th1/Th2 cytokine ratios were similar in healthy persons and patients with cirrhotic hepatitis. During LDLT surgery, Th2 activity was enhanced, as indicated by a shift in the Th1/Th2 cytokine ratio toward Th2.

C-reactive protein binds to integrin α2 and Fcγ receptor I, leading to breast cell adhesion and breast cancer progression.

C-reactive protein (CRP) is an acute phase protein synthesized upon the inflammatory responses, associated with breast cancer. The process of tumor cell invasion and metastasis involves the adherence of cells to the extracellular matrix via integrin as a receptor for matrix molecules. The present study investigated the role of CRP in the adhesive phenotype of breast cells and the underlying mechanisms. Here, we first showed that CRP induces adhesion of MCF10A human breast epithelial cells through the activation of integrin α2 signaling. Expression of integrin α2 was induced by CRP in which transcription factors c-fos and SP1 may be involved. Binding of CRP with integrin α2 leads to the activation of focal adhesion kinase (FAK), paxillin and ERKs. CRP also binds to an Fcγ receptor Fcγ receptor I (FcγRI), and induces activation of paxillin, FAK and ERKs. Integrin α2 and FAK have crucial roles in the adhesive and invasive phenotypes as well as MMP-9 upregulation induced by CRP in MCF10A cells. Treatment with an inflammatory lipid sphingosine-1-phosphate induced CRP, which may be secreted and exert an autocrine effect by binding to FcγRI and integrin α2. Involvement of CRP in adhesion, invasion, anchorage-independent growth and upregulation of integrin α2, paxillin and FAK was observed in MDA-MB-231 triple-negative human breast cancer (TNBC) cells. Using an in vivo invasion model and an orthotopic mouse tumor model with MDA-MB-231 cells, we showed that CRP has an important role in intravasation and tumor growth in vivo, demonstrating the in vivo relevance of our in vitro results. The present study elucidates a critical molecular basis between CRP, integrin α2 and FcγRI pathways in MCF10A breast cells and MDA-MB-231 TNBC cells, thereby providing useful information on CRP-induced aggressiveness of breast cells in the inflammatory microenvironment.

Compensatory structural and functional adaptation after radical nephrectomy for renal cell carcinoma according to preoperative stage of chronic kidney disease. Choi DK, Jung SB, Park BH, Jeong BC, Seo SI, Jeon SS, Lee HM, Choi HY, Jeon HG.J Urol. 2015 Oct;194(4):910-5. [Epub 2015 Apr 28]. doi: 10.1016/j.juro.2015.04.093.

PURPOSE: We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. MATERIALS AND METHODS: We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease-glomerular filtration rate 90ml/min/1.73m2 or greater (230, 42.4%), chronic kidney disease stage II-glomerular filtration rate 60 to less than 90ml/min/1.73m2 (227, 41.8%), and chronic kidney disease stage III-glomerular filtration rate 30 to less than 60ml/min/1.73m2 (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. RESULTS: Among all patients (mean age = 56.0y) mean preoperative glomerular filtration rate, functional renal volume, and glomerular filtration rate/functional renal volume were 83.2ml/min/1.73m2, 340.6cm3, and 0.25ml/min/1.73m2/cm3, respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs. stage II 26.5% vs. stage III 12.8%, P<0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs. stage II 17.3% vs. stage III 16.5%, P = 0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs. stage II 20.1% vs. stage III 45.9%, P<0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (P = 0.012), diabetes mellitus (P = 0.023), hypertension (P = 0.015), and chronic kidney disease stage (P<0.001). CONCLUSIONS: Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration.

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.

210Po in the marine biota of Korean coastal waters and the effective dose from seafood consumption.

The activity concentrations of 210Po were determined in plankton and selected species of macroalgae, crustaceans, molluscs, and fish from Korean coastal waters to understand 210Po distribution in these trophic levels and to assess the effective dose of 210Po from seafood ingested by the average Korean. The activity concentration of 210Po in macroalgae, mixed plankton, anchovy (whole body), abalone muscle, and abalone viscera was 0.97-1.43, 32-137, 59-392, 2.93 ± 0.86, and 1495 ± 484 Bq kg-1 (w.w.), respectively. Polonium-210 concentration in the whole flesh of mussel and oyster were 47.8 ± 5.9 and 45.3 ± 7.1 Bq kg-1 (w.w.), respectively. Polonium-210 concentration in the muscle of the five tested species of fish other than anchovy ranged from 0.51 to 5.56 Bq kg-1 (w.w.), with the lowest amount in a demersal species. In fish, 210Po activity concentration was as much as three orders of magnitude higher in viscera than in muscle. The average annual effective 210Po dose per average Korean adult, who consumes 42.8 kg of seafood a year (excluding anchovy), was estimated to be 94 µSv y-1, with 42-71% of this attributed to shellfish. Further studies are required to assess the dose of 210Po from anchovy owing to its high activity concentration and the manner in which anchovy is consumed.

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.

Protective Effect of Eupatilin Pretreatment Against Hepatic Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and antiinflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice. MATERIALS AND METHODS: Partial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 90 minutes followed by reperfusion for 6 hours. Eupatilin (10 mg/kg body weight, oral) was administered 4 days before the IRI. RESULTS: Treatment with eupatilin significantly decreased serum alanine aminotransferase and serum aspartate aminotransferase as well as liver histologic changes. Eupatilin also prevented hepatic glutathione depletion and increased malondialdehyde levels induced by IRI. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein and B-cell lymphoma 2 protein, attenuated inducible nitric oxide synthase, and cleaved caspase-3 levels 6 hours after IRI. The expression of the Toll-like receptor 2/4, and phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor was significantly decreased in the eupatilin pretreatment group. CONCLUSIONS: Eupatilin improved the acute hepatic IRI by reducing inflammation and apoptosis. These findings suggest that eupatilin is a promising therapeutic agent against acute IR-induced hepatic damage.

Five-year decreased incidence of surgical site infections following gastrectomy and prosthetic joint replacement surgery through active surveillance by the Korean Nosocomial Infection Surveillance System.

BACKGROUND: Surveillance of healthcare-associated infection has been associated with a reduction in surgical site infection (SSI). AIM: To evaluate the Korean Nosocomial Infection Surveillance System (KONIS) in order to assess its effects on SSI since it was introduced. METHODS: SSI data after gastrectomy, total hip arthroplasty (THA), and total knee arthroplasty (TKA) between 2008 and 2012 were analysed. The pooled incidence of SSI was calculated for each year; the same analyses were also conducted from hospitals that had participated in KONIS for at least three consecutive years. Standardized SSI rates for each year were calculated by adjusting for SSI risk factors. SSI trends were analysed using the Cochran-Armitage test. FINDINGS: The SSI rate following gastrectomy was 3.12% (522/16,918). There was a significant trend of decreased crude SSI rates over five years. This trend was also evident in analysis of hospitals that had participated for more than three years. The SSI rate for THA was 2.05% (157/7656), which decreased significantly from 2008 to 2012. The risk factors for SSI after THA included the National Nosocomial Infections Surveillance risk index, trauma, reoperation, and age (60-69 years). The SSI rate for TKA was 1.90% (152/7648), which also decreased significantly during a period of five years. However, the risk-adjusted analysis of SSI did not show a significant decrease for all surgical procedures. CONCLUSION: The SSI incidence of gastrectomy and prosthetic joint replacement declined over five years as a result of active surveillance by KONIS.

The effects of prophylactic bolus phenylephrine on hypotension during low-dose spinal anesthesia for cesarean section.

BACKGROUND: Continuously infused phenylephrine is frequently used to reduce the incidence of hypotension in women undergoing cesarean section under spinal anesthesia, but less is known about the prophylactic bolus method. We evaluated three prophylactic bolus doses of phenylephrine during low-dose spinal anesthesia for cesarean section. METHODS: One-hundred-and-eighty-four patients were randomized to receive 0.9% saline 2mL (Control Group) or phenylephrine 1.0µg/kg (PHE1 Group), 1.5µg/kg (PHE1.5 Group), or 2.0µg/kg (PHE2 Group) immediately after induction of combined spinal-epidural anesthesia. Maternal blood pressure and heart rate were recorded at 1-min intervals until delivery. Hypotension, defined as systolic blood pressure <80% of baseline, was treated with rescue doses of phenylephrine 100µg at 1-min intervals until hypotension resolved. The incidence of nausea, vomiting, bradycardia, and hypertension, as well as Apgar scores and umbilical blood gases, were recorded. RESULTS: The incidence of hypotension was 71.7% (33/46) in the Control Group, 68.9% (31/45) in the PHE1 Group, 37.0% (17/46) in the PHE1.5 Group and 45.7% (21/46) in the PHE2 Group (P=0.001). The total rescue dose of phenylephrine was greater in the Control Group than those in the PHE1.5 Group (P<0.05) and PHE2 Group (P<0.05). The incidence of hypertension increased as the dose of prophylactic phenylephrine increased (P<0.001) and was highest in the PHE2 group (37%). Other variables did not differ among the four groups. CONCLUSIONS: Under the conditions of this study, prophylactic bolus injection of phenylephrine 1.5µg/kg was a suitable alternative method for reducing the incidence of hypotension during low-dose spinal anesthesia for cesarean section.

Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study.

BACKGROUND: Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection. AIM: To determine the safety and effectiveness of ETV in 'real-world' HBV patients in the United States (US). METHODS: Treatment-naïve HBV patients ≥18 years old who received ETV for ≥12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated. RESULTS: Of 841 patients, 658 [65% male, 83% Asian; median age 47 years] met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg- patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five-year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%. CONCLUSION: Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.

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.

Analysis of anonymized pooled urine in nine UK cities: variation in classical recreational drug, novel psychoactive substance and anabolic steroid use.

BACKGROUND: Analysis of anonymous pooled urine samples from street urinals has been used to demonstrate time-trends in the detection of classical recreational drugs and novel psychoactive substances (NPS). AIM: This study aimed to expand this to undertake a geographical trend analysis of classical recreational drugs/NPS across UK. METHODS: Samples of anonymous pooled urine were collected from street urinals that had been in place for one night in April 2014 in nine cities across the UK. Collected samples were then analysed for the presence of recreational drugs, NPS anabolic steroids using high-performance liquid chromatography coupled to high-resolution accurate mass full-scan mass spectrometry and gas chromatography coupled to electron impact ionization mass spectrometry operating in selected ion monitoring and full-scan modes. RESULTS: Ten classical recreational drugs, nine NPS and four anabolic steroids were detected across the nine cities; the range of detection was from 1 in Leeds to 14 in London. The most common classical drugs were cocaine (9 cities) and 3,4-methylenedioxy-methamphetamine (8 cities); the most common NPS was 4-methylmethcathinone (5 cities). In addition there was variation in the detection of NPS, with methylhexaneamine detected only in Bristol and London, piperazines (3-trifluoromethylphenylpiperazine and 1-benzylpiperazine) and pentedrone only detected in Birmingham and the cathinone methylone only detected in London. CONCLUSIONS: There is variability in the detection of classical recreational drugs, NPS and anabolic steroids across UK, likely reflecting variation in their use. This technique can be used to supplement drug use surveys to determine geographical and time trends in the use of these substances. This is important to ensure appropriate targeting of drug-related interventions.

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.