Isoflavones in treating watchful waiting benign prostate hyperplasia: a double-blinded, randomized controlled trial

OBJECTIVES: This study aims to determine the efficacy and safety of soy isoflavones in controlling the symptoms and signs of lower urinary tract symptoms due to benign prostate hyperplasia (BPH). DESIGN: This was a prospective, randomized, double-blind, placebo-controlled pilot study. SETTING: This trial was conducted at two hospitals in Hong Kong between May 2006 and September 2007. PARTICIPANTS: One hundred and seventy-six (176) participants diagnosed with BPH were recruited from outpatient clinics. Participants with lower urinary tract symptoms were recruited through newspaper and radio interviews, posters placed at government outpatient clinics, and a public seminar offered by the investigators. INTERVENTIONS: Participants were randomly assigned to either intervention (40 mg of isoflavones daily from Soylife 40) or placebo groups in a double-blind fashion. MAIN OUTCOME MEASURES: The primary outcome parameter of peak urine flow rate and the second outcome parameters of postresidual urine volume, lower urinary tract symptoms, testosterone, prostate-specific antigen, quality of life, diet, and safety profile (liver and renal function) were collected. All parameters were assessed at baseline, 6 months, and 12 months in a 12-month study period except testosterone, prostate-specific antigen, and safety profile, which were assessed at baseline and at 12 months. RESULTS: The peak urine flow rate (Qmax), postresidual urine volume, International Prostate Symptoms Scores (IPSS), and 36-Item Short Form Health Survey (SF-36) significantly improved from baseline to the 12th month within both groups. However, when compared between groups, Qmax (p=0.055) and incomplete emptying subscore in IPSS (p=0.05) were marginally/statistically different between the two groups from the 6th to the 12th months, in addition to the general health domain of SF-36 from the baseline to 12th month (p=0.02) and from the 6th month to the 12th month (p=0.055). Isoflavones were generally safe and well tolerated. CONCLUSIONS: This randomized control pilot study showed only slight superiority of isoflavones over placebo over 12 months with otherwise surprising beneficial effects in both groups. Tolerability of isoflavones was excellent; thus it has laid foundations for further studies of isoflavones in BPH with focus on dosage and possible specificity of the effect.published_or_final_versio

β-spline estimation in a semiparametric regression model with nonlinear time series errors

2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Blending using ODE swept surfaces with shape control and C1 continuity

Surface blending with tangential continuity is most widely applied in computer aided design, manufacturing systems, and geometric modeling. In this paper, we propose a new blending method to effectively control the shape of blending surfaces, which can also satisfy the blending constraints of tangent continuity exactly. This new blending method is based on the concept of swept surfaces controlled by a vector-valued fourth order ordinary differential equation (ODE). It creates blending surfaces by sweeping a generator along two trimlines and making the generator exactly satisfy the tangential constraints at the trimlines. The shape of blending surfaces is controlled by manipulating the generator with the solution to a vector-valued fourth order ODE. This new blending methods have the following advantages: 1). exact satisfaction of 1C continuous blending boundary constraints, 2). effective shape control of blending surfaces, 3). high computing efficiency due to explicit mathematical representation of blending surfaces, and 4). ability to blend multiple (more than two) primary surfaces

Inhibition of CK2α Down-Regulates Hedgehog/Gli Signaling Leading to a Reduction of a Stem-Like Side Population in Human Lung Cancer Cells

Protein kinase CK2 is frequently elevated in a variety of human cancers. The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance, and its aberrant activation has been indicated in several types of cancer, including lung cancer. In this study, we show that CK2 is positively involved in Hh/Gli signaling in lung cancer cell lines A549 and H1299. First, we found a correlation between CK2α and Gli1 mRNA levels in 100 primary lung cancer tissues. Down-regulation of Gli1 expression and transcriptional activity were demonstrated after the silencing of CK2α in lung cancer cells. In addition, CK2α siRNA down-regulated the expression of Hh target genes. Furthermore, two small-molecule CK2α inhibitors led to a dose-dependent inhibition of Gli1 expression and transcriptional activity in lung cancer cells. Reversely, forced over-expression of CK2α resulted in an increase both in Gli1 expression and transcriptional activity in A549 cells. Finally, the inhibition of Hh/Gli by CK2α siRNA led to a reduction of a cancer stem cell-like side population that shows higher ABCG2 expression level. Thus, we report that the inhibition of CK2α down-regulates Hh/Gli signaling and subsequently reduces stem-like side population in human lung cancer cells

Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

Specific cortical and subcortical grey matter regions are associated with insomnia severity

BACKGROUND: There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen. METHODS: 120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed. RESULTS: ISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh of the right orbitofrontal, right superior and caudal middle frontal areas, right temporo-parietal junction and left anterior cingulate cortex (p<0.001, uncorrected FWE). When adjusting by GDS, right ventral orbitofrontal and temporo-parietal junction remained significant, and left insula became significant (p<0.001, uncorrected FWE). Conversely, BA showed no effect. The results were no longer significant following FWE multiple comparisons. Regarding subcortical areas, higher putamen volumes were associated with higher ISI (p<0.01). CONCLUSIONS: Our findings highlight a relationship between insomnia severity and brain health, even with relatively mild insomnia, and independent of depression and likelihood of sleep apnea. The results extend the previous literature showing the association of specific GM areas (i.e, orbitofrontal, insular and temporo-parietal junction) not just with the presence of insomnia, but across the spectrum of severity itself. Moreover, our results suggest subcortical structures (i.e., putamen) are involved as well. Longitudinal studies are needed to clarify how these insomnia-related brain changes in healthy subjects align with an increased risk of dementia

Clothing insulation and temperature, layer and mass of clothing under comfortable environmental conditions

This study was designed to investigate the relationship between the microclimate temperature and clothing insulation (Icl) under comfortable environmental conditions. In total, 20 subjects (13 women, 7 men) took part in this study. Four environmental temperatures were chosen: 14??C (to represent March/April), 25??C (May/June), 29??C (July/August), and 23??C (September/October). Wind speed (0.14ms-1) and humidity (45%) were held constant. Clothing microclimate temperatures were measured at the chest (Tchest) and on the interscapular region (Tscapular). Clothing temperature of the innermost layer (Tinnermost) was measured on this layer 30 mm above the centre of the left breast. Subjects were free to choose the clothing that offered them thermal comfort under each environmental condition. We found the following results. 1) All clothing factors except the number of lower clothing layers (Llower), showed differences between the different environmental conditions (P&lt;0.05). The ranges of Tchest were 31.6 to 33.5??C and 32.2 to 33.4??C in Tscapular. The range of Tinnermost was 28.6 to 32.0??C. The range of the upper clothing layers (Lupper) and total clothing mass (Mtotal) was 1.1 to 3.2 layers and 473 to 1659 g respectively. The range of Icl was 0.78 to 2.10 clo. 2) Post hoc analyses showed that analysis of Tinnermost produced the same results as for that of Icl. Likewise, the analysis of Lupper produced the same result as the analysis of the number of total layers (Ltotal) within an outfit. 3) Air temperature (ta) had positive relationships with Tchest and Tscapular and with Tinnermost but had inverse correlations with Icl, Mtotal, Lupper and Ltotal. Tchest, Tscapular, and Tinnermost increased as ta rose. 4) Icl had inverse relationships with Tchest and Tinnermost, but positive relationships with Mtotal, Lupper and Ltotal. Icl could be estimated by Mtotal, Lupper, and Tscapular using a multivariate linear regression model. 5) Lupper had positive relationships with Icl and Mtotal, but Llower did not. Subjects hardly changed Llower under environmental comfort conditions between March and October. This indicates that each of the Tchest, Mtotal, and Lupper was a factor in predicting Icl. Tinnermost might also be a more influential factor than the clothing microclimate temperature.open1

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the Delta dblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+) T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1 beta. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.open111815sciescopu

QTL Mapping of Combining Ability and Heterosis of Agronomic Traits in Rice Backcross Recombinant Inbred Lines and Hybrid Crosses

BACKGROUND: Combining ability effects are very effective genetic parameters in deciding the next phase of breeding programs. Although some breeding strategies on the basis of evaluating combining ability have been utilized extensively in hybrid breeding, little is known about the genetic basis of combining ability. Combining ability is a complex trait that is controlled by polygenes. With the advent and development of molecular markers, it is feasible to evaluate the genetic bases of combining ability and heterosis of elite rice hybrids through QTL analysis. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we first developed a QTL-mapping method for dissecting combining ability and heterosis of agronomic traits. With three testcross populations and a BCRIL population in rice, biometric and QTL analyses were conducted for ten agronomic traits. The significance of general combining ability and special combining ability for most of the traits indicated the importance of both additive and non-additive effects on expression levels. A large number of additive effect QTLs associated with performance per se of BCRIL and general combining ability, and dominant effect QTLs associated with special combining ability and heterosis were identified for the ten traits. CONCLUSIONS/SIGNIFICANCE: The combining ability of agronomic traits could be analyzed by the QTL mapping method. The characteristics revealed by the QTLs for combining ability of agronomic traits were similar with those by multitudinous QTLs for agronomic traits with performance per se of BCRIL. Several QTLs (1-6 in this study) were identified for each trait for combining ability. It demonstrated that some of the QTLs were pleiotropic or linked tightly with each other. The identification of QTLs responsible for combining ability and heterosis in the present study provides valuable information for dissecting genetic basis of combining ability