Wasabi (Eutrema japonicum) Reduces Obesity and Blood Pressure in Diet-Induced Metabolic Syndrome in Rats.

6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) has several biological functions. The present study aimed to evaluate the composition of hydroponically grown Tasmanian wasabi (Eutrema japonicum (Miq.) Koidz.) for 6-MSITC in all plant tissues and investigate the influence of wasabi (rhizome and stem blend) in high-carbohydrate, high-fat (H) diet-fed rats. Male Wistar rats were fed either a corn starch (C) or H diet. After the initial 8 weeks, half of the animals on the C and H diets were given 5% (w/w) wasabi powder in their respective diets for an 8-week duration (CW and HW). The control animals received diets without supplementation throughout the 16-week experiment. Our findings demonstrated that wasabi grown under hydroponic conditions contained 6-MSITC in all parts of the plant such as the stem, leaf and flower, as well as the commonly used rhizome, albeit at lower concentrations. Rats treated with wasabi showed reductions in body weight (H, 460.0 ± 9.5; HW, 416.0 ± 3.6 g), fat mass (H, 178 ± 14; HW, 120 ± 23 g), plasma triglycerides (H, 1.7 ± 0.3; HW, 0.9 ± 0.3 mmol/L) and total cholesterol (H, 1.5 ± 0.1; HW, 1.0 ± 0.04 mmol/L), and the plasma activities of aspartate transaminase. Systolic blood pressure and the area under the curve of blood glucose concentration were decreased by wasabi treatment. Thus, wasabi may be a novel alternative treatment to assist in the management of obesity and related metabolic disorders.

Evaluation of polymyxin B in combination with 13 other antibiotics against carbapenemase-producing Klebsiella pneumoniae in time-lapse microscopy and time-kill experiments.

OBJECTIVES: This study aimed to explore the interactions of polymyxin B in combination with 13 other antibiotics against carbapenemase-producing Klebsiella pneumoniae. METHODS: Five clinical isolates of multidrug-resistant K. pneumoniae producing KPC-2, KPC-3, NDM-1, OXA-48 and VIM-1 carbapenemases were used. Polymyxin B was tested alone and in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, linezolid, meropenem, minocycline, rifampicin, temocillin, thiamphenicol and trimethoprim. Inhibition of growth during antibiotic exposure was evaluated in 24-hr automated time-lapse microscopy experiments. Combinations that showed positive interactions were subsequently evaluated in static time-kill experiments. RESULTS: All strains carried multiple (≥9) resistance genes as determined by whole-genome sequencing. In the initial screening the combination of polymyxin B and minocycline was most active with enhanced activity compared with the single antibiotics detected against all strains. Positive interactions were also observed with polymyxin B in combination with rifampicin and fosfomycin against four of five strains and less frequently with other antibiotics. Time-kill experiments demonstrated an additive or synergistic activity (1-2 log10 or ≥2 log10 CFU/mL reduction, respectively, compared with the most potent single antibiotic) with 21 of 23 tested combinations. However, because of regrowth, only 13 combinations were synergistic at 24 hr. Combinations with minocycline or rifampicin were most active, each showing synergy and bacteriostatic or bactericidal effects resulting in 1.93-3.97 and 2.55-5.91 log10 CFU/mL reductions, respectively, after 24 hr against four strains. DISCUSSION: Polymyxin B in combination with minocycline, rifampicin or fosfomycin could be of potential clinical interest. Time-lapse microscopy showed some discrepancy in results compared with the time-kill data but was useful for screening purposes.

Basimarols A, B, and C, Highly Oxygenated Pimarane Diterpenoids from Basilicum polystachyon.

The highly oxygenated pimarane diterpenoids basimarols A, B, and C (3-5) were isolated from the plant species Basilicum polystachyon, which was collected within the Australian arid zone. Structure elucidation was performed using a suite of spectroscopic techniques, including X-ray crystallography. Anticancer and anti-DENV activity of 3-5 was explored, but only limited activity was observed. More extensive antiviral evaluation of stachyonic acid A (1), which was also isolated from B. polystachyon, revealed broad spectrum antiviral activity against West Nile virus (Kunjin strain, WNVKun) and human influenza viruses H1N1 and H3N2.

Stachyonic Acid: A Dengue Virus Inhibitor from Basilicum polystachyon.

Stachyonic acid A, arising from the first in-depth phytochemical investigation of the herb Basilicum polystachyon, was found to display potent inhibitory activity against dengue virus, with limited cytotoxicity. Andrographolide, a known dengue virus inhibitor and closely related labdane-type diterpene, is structurally more complex but displayed poor antiviral activity in the PRNT assay, and increased cytotoxicity in comparison. Furthermore, a Diels-Alder reaction with PTAD identified the active pharmacophore of stachyonic acid to be the conjugated diene.

Furofuran lignans from the Simpson Desert species Eremophila macdonnellii.

The Eremophila plant family, which occurs in the arid zones of Australia, have witnessed extensive investigation, mostly inspired by Aboriginal traditional medicine. A wide and varied biological and phytochemical profile has been reported for over 18 individual species of Australian Eremophila, although E. macdonnellii from the Simpson Desert has not yet been investigated. Isolation and elucidation of one new and six known furofuran lignans are reported. The new lignan, epimethoxypiperitol, displayed moderate anti-cancer activity against the breast cancer cell line (MCF-7).

Laboratory parameter-based machine learning model for excluding non-alcoholic fatty liver disease (NAFLD) in the general population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 20%-40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Electronic medical records facilitate large-scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. AIM: To develop and validate a laboratory parameter-based machine learning model to detect NAFLD for the general population. METHODS: We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton-magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver-operating characteristic curve (AUROC) of models in validation group were compared. RESULTS: Six predictors including alanine aminotransferase, high-density lipoprotein cholesterol, triglyceride, haemoglobin A1c , white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83-0.90) and 0.88 (0.84-0.91) in the training and validation groups respectively. Using dual cut-offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%-96%) sensitivity and 90% (86%-93%) specificity with corresponding negative and positive predictive values of 96% (91%-98%) and 69% (59%-78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate. CONCLUSIONS: NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.

Urine Exosomes: An Emerging Trove of Biomarkers.

Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies.

Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB). DESIGN: Retrospective cohort study. SETTING: One-stop PMB clinic in a Hong Kong teaching hospital. POPULATION: A cohort of 4383 women with PMB. METHODS: Transvaginal ultrasonic measurement of ET and endometrial biopsies were obtained in women presenting with PMB between 2002 and 2013. Endometrial histology was used as the reference standard to calculate accuracy estimates. MAIN OUTCOME MEASURES: Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. RESULTS: Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%). CONCLUSIONS: Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

A cost-effectiveness analysis of teledietetics in short-, intermediate-, and long-term weight reduction.

INTRODUCTION: To evaluate the effectiveness of teledietetics in weight loss for 24 weeks and the cost-effectiveness of weight loss between face-to-face and teledietetics services. METHODS: The study was conducted at a community health center and a community dietetics clinic. The study was a quasiexperimental design. Fifty adults aged 20-50 with a BMI ≥23 participated in the study. The face-to-face (FD) group received 12 dietary counselling sessions and recorded their diet in a log book. The teledietetics (TD) group attended three group nutrition seminars and recorded their diet on a Web-based platform. Changes in variables were compared using an independent t-test. Direct and indirect costs were applied to compute cost-effectiveness ratios. RESULTS: At week 6, the FD group showed greater reductions in all variables than did the TD group. At week 12, the effects reversed. At week 24, the accumulated reductions in weight and fat in the TD group were significantly higher than those in the FD group (all at p < 0.0001). The observed direct costs for 1% weight loss and 1% fat loss were USD 28.24 and USD17.09, respectively. DISCUSSION: A dietetic service delivered as a teledietetics model is more cost-effective than the face-to-face dietetics model in weight reduction.

Development and validation of a lifetime exposure questionnaire for use among Chinese populations.

The sunlight exposure questionnaire for use in the Chinese population was constructed based on extensive literature review and item suitability for measuring life-time exposure. The content validity index (CVI) was derived from ratings by, an expert panel to assess the item content and relevance. 650 population-based Chinese women completed the sunlight exposure questionnaire through telephone interview. To assess the questionnaire reliability, 94 women were re-interviewed after 2 weeks. 98.4% of the sunlight exposure questionnaire items were found to have valid CVI (>0.83). The Scree plot and the Principal Components Factor Analysis showed a two-factor construct was appropriate and no questionnaire item needed to be excluded. The questionnaire also had a good test-retest reliability (ICC: 0.59-0.93; k: 0.51-100). This sunlight exposure questionnaire was found to be adequate for measurement of life-time sunlight exposure among Hong Kong Chinese women.

Fast-track ventilation strategy to cater for pandemic patient isolation surges.

BACKGROUND: The shortage of isolation facilities in hospitals was highlighted during the severe acute respiratory syndrome (SARS) pandemic in 2003. Yet, as the nature and scale of future pandemics cannot be adequately estimated, it is difficult to justify construction of sufficient isolation facilities. A fast-track and cost-effective ventilation strategy for the retrofitting of existing general wards could help hospitals deal with patient surges. AIM: This article reviews the effectiveness of a fast-track, makeshift isolation approach employed during the SARS outbreak which involved installing simple window-mounted exhaust fans to create negative-pressure airflow in hospital general wards. METHODS: Computational fluid dynamics (CFD) was used to assess by simulation whether the approach adopted meets US Centers for Disease and Control and Prevention requirements for properly constructed isolation wards. FINDINGS: CFD simulation revealed that this makeshift approach could match the ventilation standards of isolation rooms. The approach was certainly effective as no secondary infections were reported in hospitals that used it during SARS. CONCLUSIONS: When there is a shortfall in isolation facilities to accommodate a surge in patients, the proposed ventilation set-up could be quickly and widely implemented by existing general wards.

Rethinking hospital general ward ventilation design using computational fluid dynamics.

Indoor ventilation with good air quality control minimises the spread of airborne respiratory and other infections in hospitals. This article considers the role of ventilation in preventing and controlling infection in hospital general wards and identifies a simple and cost-effective ventilation design capable of reducing the chances of cross-infection. Computational fluid dynamic (CFD) analysis is used to simulate and compare the removal of microbes using a number of different ventilation systems. Instead of the conventional corridor air return arrangement used in most general wards, air return is rearranged so that ventilation is controlled from inside the ward cubicle. In addition to boosting the air ventilation rate, the CFD results reveal that ventilation performance and the removal of microbes can be significantly improved. These improvements are capable of matching the standards maintained in a properly constructed isolation room, though at much lower cost. It is recommended that the newly identified ventilation parameters be widely adopted in the design of new hospital general wards to minimise cross-infection. The proposed ventilation system can also be retrofitted in existing hospital general wards with far less disruption and cost than a full-scale refurbishment.

Exosomes from human saliva as a source of microRNA biomarkers.

OBJECTIVE: The aim of this study was to examine the presence of microRNAs (miRNAs) within exosomes isolated from human saliva and to optimize and test methods for successful downstream applications. DESIGN: Exosomes isolated from fresh and frozen glandular and whole human saliva were used as a source of miRNAs. The presence of miRNAs was validated with TaqMan quantitative PCR and miRNA microarrays. RESULTS: We successfully isolated exosomes from human saliva from healthy controls and a patient with Sjögren's syndrome. microRNAs extracted from the exosomal fraction were sufficient for quantitative PCR and microarray profiling. CONCLUSIONS: The isolation of miRNAs from easily and non-invasively obtained salivary exosomes with subsequent characterization of the miRNA expression patterns is promising for the development of future biomarkers of the diagnosis and prognosis of various salivary gland pathologies.

Heyde's syndrome: diagnosis and management by the novel single-balloon enteroscopy.

We present a case of obscure gastro-intestinal bleeding due to small bowel angiodysplasia in a 68-year-old woman with severe aortic valve stenosis. The diagnosis was confirmed and subsequently managed using single-balloon enteroscopy.

Menstrual problems and health-seeking behaviour in Hong Kong Chinese girls.

OBJECTIVE: To ascertain the prevalence of menstrual problems in adolescent girls and their health-seeking behaviour. DESIGN: Questionnaire survey on menstruation, menstrual problems, medical consultation, and factors influencing girls seeking medical care. SETTING: Secondary schools in the catchment area of a tertiary teaching hospital in Hong Kong. PARTICIPANTS: A total of 5609 girls from 10 secondary schools. MAIN OUTCOME MEASURES: Prevalence of menstrual problems and health-seeking behaviour of adolescent girls. RESULTS: The mean age of the girls and their mean age at menarche were 15.1 (standard deviation, 2.0) years and 12.3 (1.1) years, respectively. The prevalence of menorrhagia, dysmenorrhoea, and menstrual symptoms were 17.9% (95% confidence interval, 16.9-19.1%), 68.7% (67.7-70.3%), and 37.7% (36.7-39.3%), respectively. The prevalence of menstrual symptoms (P<0.001) and dysmenorrhoea (P<0.001) increased with gynaecological age (calendar age minus age at menarche), whilst the proportion having short or long cycles decreased (P=0.002 and P=0.009). One in eight girls reported having been absent from school, whilst only 6.4% had sought medical care because of menses. Multivariate analysis indicated that seeking medical care for menorrhagia was dependent on the opinion of a family member (P=0.005), and for dysmenorrhoea on its severity (P=0.046) and anxiety about embarrassing questions (P=0.039). CONCLUSIONS: The prevalence of menstrual problems in Hong Kong Chinese girls is high and causes significant disruption to their school and daily activities. However, only a minority seek medical advice.

Setting the stage for acute-on-chronic kidney injury.

Acute-on-chronic kidney disease will be familiar to many nephrologists. Hsu et al. quantify the risk of acute-on-chronic disease across the stages of preexisting chronic kidney disease. Their study demonstrates the valuable insights that large epidemiological studies can bring to the field of acute kidney injury.

AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality.

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. alpha-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new alpha-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 h after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-alpha and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-kappaB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis.

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women.

OBJECTIVE: To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen. DESIGN: Randomised controlled trial. SETTING: A tertiary teaching hospital. POPULATION: One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy. METHODS: Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen. MAIN OUTCOME MEASURES: De novo endometrial pathology at 1 year of tamoxifen. RESULTS: Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year. CONCLUSION: LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.