A study on health-related quality of life of patients with Colorectal Neoplasm and cost-effectiveness analysis of Colorectal Cancer Screening in Hong Kong

Conference Theme: Translating Health Research into Policy and Practice for Health of the PopulationPoster Presentation - Delivery of Health Services: abstract no. P41-Ab0005BACKGROUND: Colorectal cancer (CRC) is the most common cancer in Hong Kong. Health-related quality of life (HRQOL) is an important health outcome of CRC survivors. Screening for CRC has the potential of preventing CRC death but there was uncertainty on its impact on HRQOL and the cost-effectiveness of different screening strategies ...postprin

Health-related quality of life in patients with colorectal neoplasm and cost-effectiveness of colorectal cancer screening in Hong Kong

Key Messages 1. Compared with the Hong Kong general population norm, Chinese patients with colorectal neoplasm (CRN) reported worse physical health-related quality of life (HRQOL) but better mental HRQOL and comparable health preference scores. 2. The CRN stage at diagnosis was the most significant determinant of HRQOL. Colorectal cancer was associated with worse physical HRQOL and health preference scores. 3. Immunochemical faecal occult blood testing every 2 years is the most cost-effective colorectal cancer screening strategy, with an incremental cost-effectiveness ratio of HK$43 660 per quality-adjusted life year gained.published_or_final_versio

Effect of a qigong intervention program on telomerase activity and psychological stress in abused Chinese women: a randomized, wait-list controlled trial

BACKGROUND: Abused women, who suffer from chronic psychological stress, have been shown to have shorter telomeres than never abused women. Telomere shortening is associated with increased risk of cell death, and it is believed that adopting health-promoting behaviors can help to increase the activity of telomerase, an enzyme that counters telomere shortening. Qigong is an ancient Chinese mind-body integration, health-oriented practice designed to enhance the function of qi, an energy that sustains well-being. Therefore, an assessor-blind, randomized, wait-list controlled trial was developed to evaluate the effect of a qigong intervention on telomerase activity (primary objective) and proinflammatory cytokines, perceived stress, perceived coping, and depressive symptoms (secondary objectives) in abused Chinese women. METHODS/DESIGN: A total of 240 Chinese women, aged >/= 18 years, who have been abused by an intimate partner within the past three years will be recruited from a community setting in Hong Kong and randomized to receive either a qigong intervention or wait-list control condition as follows: the qigong intervention will comprise (i) a 2-hour group qigong training session twice a week for 6 weeks, (ii) a 1-hour follow-up group qigong exercise session once a week for 4 months, and (iii) a 30-minute self-practice qigong exercise session once a day for 5.5 months. The wait-list control group will receive qigong training after the intervention group completes the program. Upon completion of the qigong intervention program, it is expected that abused Chinese women in the intervention group will have higher levels of telomerase activity and perceived coping and lower levels of proinflammatory cytokines, perceived stress, and depressive symptoms than will abused Chinese women in the wait-list control group. DISCUSSION: This study will provide information about the effect of qigong exercise on telomerase activity and chronic psychological stress in abused Chinese women. The findings will inform the design of interventions to relieve the effects of IPV-related psychological stress on health. Also, the concept that health-promoting behaviors could slow down cellular aging might even motivate abused women to change their lifestyles. TRIAL REGISTRATION: Current Controlled Trials NCT02060123. Registered February 6, 2014.published_or_final_versio

PARP inhibitors and the treatment of breast cancer: beyond BRCA1/2?

Poly(ADP-ribose) polymerase (PARP) inhibitors have been explored as therapeutic agents for the treatment of hereditary breast and ovarian cancers harboring mutations in BRCA1 or BRCA2. In a new study, Inbar-Rozensal and colleagues show that phenanthridine-derived PARP inhibitors promote cell cycle arrest and cell death in breast cancer cells lacking BRCA1 and BRCA2 mutations and prevent the growth of tumors from xenografts of these cells in immunocompromised mice. These results suggest a potential broader utility of PARP-1 inhibitors in the treatment of breast cancer, although further mechanistic studies are needed

Impact of the "Tobacco control law" on exposure to environmental tobacco smoke in Spain

<p>Abstract</p> <p>Background</p> <p>The initial evaluations of the introduction of legislation that regulates smoking in enclosed public places in European countries, describe an important effect in the control of exposure to environmental tobacco smoke. However, the evidence is still limited. The objective of this study is to estimate the short-term effects of the comprehensive "Tobacco control law" introduced in Spain on January 2006, which includes a total ban of smoking in workplaces and a partial limitation of smoking in bars and restaurants.</p> <p>Methods</p> <p>Cross-sectional, population-based study. The self-reported exposure to environmental tobacco smoke at home, at work, in bars and restaurants of the population aged 18 to 64 years in the Madrid Region during a period prior to the law (October and November 2005; n = 1750) was compared to that of the period immediately after the law came into force (January-July 2006; n = 1252). Adjusted odds ratios (OR) were calculated using logistic regression models.</p> <p>Results</p> <p>Passive exposure to tobacco smoke at home has hardly changed. However, at indoor workplaces there has been a considerable reduction: after the law came into force the OR for daily exposure > 0–3 hours versus non-exposure was 0.11 (95% CI: 0.07 to 0.17) and for more than 3 hours, 0.12 (95% CI: 0.09 to 0.18). For fairly high exposure in bars and restaurants versus non-exposure, the OR in the former was 0.30 (95% CI: 0.20 to 0.44) and in the latter was 0.24 (95% CI: 0.18 to 0.32); for very high exposure versus non-exposure they were 0.16 (95% CI: 0.10 to 0.24) and 0.11 (95% CI: 0.07 to 0.19), respectively. These results were similar for the smoking and non-smoking populations.</p> <p>Conclusion</p> <p>A considerable reduction in exposure to environmental tobacco smoke in the workplace and, to a lesser extent, in bars and restaurants, is related to the implementation of the "Tobacco control law". Although only initial figures, these results already demonstrate the effectiveness of strategies that establish control measures to guarantee smoke-free places.</p

Body circumferences: clinical implications emerging from a new geometric model

<p>Abstract</p> <p>Background</p> <p>Body volume expands with the positive energy balance associated with the development of adult human obesity and this "growth" is captured by two widely used clinical metrics, waist circumference and body mass index (BMI). Empirical correlations between circumferences, BMI, and related body compartments are frequently reported but fail to provide an important common conceptual foundation that can be related to key clinical observations. A two-phase program was designed to fill this important gap: a geometric model linking body volume with circumferences and BMI was developed and validated in cross-sectional cohorts; and the model was applied to the evaluation of longitudinally monitored subjects during periods of voluntary weight loss. Concepts emerging from the developed model were then used to examine the relations between the evaluated clinical measures and body composition.</p> <p>Methods</p> <p>Two groups of healthy adults (n = 494 and 1499) were included in the cross-sectional model development/testing phase and subjects in two previous weight loss studies were included in the longitudinal model evaluation phase. Five circumferences (arm, waist, hip, thigh, and calf; average of sum, C), height (H), BMI, body volume (V; underwater weighing), and the volumes of major body compartments (whole-body magnetic resonance imaging) were measured.</p> <p>Results</p> <p>The evaluation of a humanoid geometric model based a cylinder confirmed that V derived from C and H was highly correlated with measured V [R²both males and females, 0.97; p < 0.001). Developed allometric models confirmed model predictions that C and BMI (represented as V/H) are directly linked as, C = (V/H)^0.5. The scaling of individual circumferences to V/H varied, with waist the highest (V/H^~0.6) and calf the lowest (V/H^~0.3), indicating that the largest and smallest between-subject "growth" with greater body volume occurs in the abdominal area and lower extremities, respectively. A stepwise linear regression model including all five circumferences²showed that each contributed independently to V/H. These cross-sectional observations were generally confirmed by analysis of the two longitudinal weight loss studies. The scaling of circumference ratios (e.g., waist/hip) to V/H conformed to models developed on the scaling of individual circumferences to V/H, indicating their relations to BMI are predictable <it>a priori</it>. Waist, hip, and arm/calf circumferences had the highest associations with whole-body visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle volumes, respectively.</p> <p>Conclusion</p> <p>These observations provide a simple geometric model relating circumferences with body size and composition, introduce a conceptual foundation explaining previous empirical observations, and reveal new clinical insights.</p

A five-year retrospective study of the epidemiological characteristics and visual outcomes of patients hospitalized for ocular trauma in a Mediterranean area

<p>Abstract</p> <p>Background</p> <p>To determine the epidemiological characteristics and visual outcome of ocular trauma in southern Italy.</p> <p>Methods</p> <p>All cases of ocular trauma admitted to Department of Ophthalmology of Palermo University, Italy, from January 2001–December 2005 were retrospectively reviewed for open- or closed-globe injury (OGI or CGI). Data extracted included age, sex, residence, initial and final visual acuity (VA), cause and treatment of injury, hospitalization. The injuries were classified by Ocular Trauma Classification System (OTCS) and Birmingham Eye Trauma Terminology (BETT). We also referred to the Ocular Trauma Score (OTS) in evaluating the final visual outcome.</p> <p>Results</p> <p>Of the 298 eyes, there were 146 OGI and 152 CGI. Fifty eyes (16.8%) had an intraocular foreign body (IOFB). The annual incidence of eye injuries was 4.9 per 100,000. Most injuries occurred in men (84.6%, p < 0.0005), with an average age of 33.0 vs. 49.9 for women (p = 0.005). Cause of injury differed significantly by gender (p = 0.001) and urban vs. rural location (p = 0.009). The most frequent causes in men were outdoor activities related injuries (30.9%), work-related (25.4%), and sport-related (17.5%), and in women were home-related (52.2%) and outdoor activities related injuries (30.4%). In urban areas, road accidents were more frequent; in rural areas, work-related injuries were more frequent with a greater rate of IOFBs than in urban areas (p = 0.002).</p> <p>The incidence of OGI and CGI differed in work-related injuries (p < 0.0005), sport-related injuries (p < 0.0005), and assaults (p = 0.033). The final visual acuity was 20/40 (6/12) or better in 144 eyes (48.3%), 20/40–20/200 (6/12–6/60) in 90 eyes (30.2%), and <20/200 (6/60) or less in 46 eyes (15.5%). Eighteen eyes (6%) had a final acuity of no light perception. Of those eyes that presented with hand motion vision or better, 220 (86.6%) had a final vision of better than 20/200 (6/60). Initial visual acuity was found to be correlated with final visual acuity (Spearman's correlation coefficient = 0.658; p < 0.001). The likelihood of the final visual acuities in the OTS categories was correlated to that of the OTS study group in 12 of 14 cases (85.7%).</p> <p>Conclusion</p> <p>This analysis provides insight into the epidemiology of patients hospitalized for ocular trauma. The findings indicate that ocular trauma is a significant cause of visual loss in this population.</p

Identification of metabolic engineering targets through analysis of optimal and sub-optimal routes

Identification of optimal genetic manipulation strategies for redirecting substrate uptake towards a desired product is a challenging task owing to the complexity of metabolic networks, esp. in terms of large number of routes leading to the desired product. Algorithms that can exploit the whole range of optimal and suboptimal routes for product formation while respecting the biological objective of the cell are therefore much needed. Towards addressing this need, we here introduce the notion of structural flux, which is derived from the enumeration of all pathways in the metabolic network in question and accounts for the contribution towards a given biological objective function. We show that the theoretically estimated structural fluxes are good predictors of experimentally measured intra-cellular fluxes in two model organisms, namely, Escherichia coli and Saccharomyces cerevisiae. For a small number of fluxes for which the predictions were poor, the corresponding enzyme-coding transcripts were also found to be distinctly regulated, showing the ability of structural fluxes in capturing the underlying regulatory principles. Exploiting the observed correspondence between in vivo fluxes and structural fluxes, we propose an in silico metabolic engineering approach, iStruF, which enables the identification of gene deletion strategies that couple the cellular biological objective with the product flux while considering optimal as well as sub-optimal routes and their efficiency.This work was supported by the Portuguese Science Foundation [grant numbers MIT-Pt/BS-BB/0082/2008, SFRH/BPD/44180/2008 to ZS] (http://www.fct.pt/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Additional Serine/Threonine Phosphorylation Reduces Binding Affinity but Preserves Interface Topography of Substrate Proteins to the c-Cbl TKB Domain

The E3-ubiquitin ligase, c-Cbl, is a multi-functional scaffolding protein that plays a pivotal role in controlling cell phenotype. As part of the ubiquitination and downregulation process, c-Cbl recognizes targets, such as tyrosine kinases and the Sprouty proteins, by binding to a conserved (NX/R)pY(S/T)XXP motif via its uniquely embedded SH2 domain (TKB domain). We previously outlined the mode of binding between the TKB domain and various substrate peptide motifs, including epidermal growth factor receptor (EGFR) and Sprouty2 (Spry2), and demonstrated that an intrapetidyl hydrogen bond forms between the (pY-1) arginine or (pY-2) asparagine and the phosphorylated tyrosine, which is crucial for binding. Recent reports demonstrated that, under certain types of stimulation, the serine/threonine residues at the pY+1 and/or pY+2 positions within this recognition motif of EGFR and Sprouty2 may be endogenously phosphorylated. Using structural and binding studies, we sought to determine whether this additional phosphorylation could affect the binding of the TKB domain to these peptides and consequently, whether the type of stimulation can dictate the degree to which substrates bind to c-Cbl. Here, we show that additional phosphorylation significantly reduces the binding affinity between the TKB domain and its target proteins, EGFR and Sprouty2, as compared to peptides bearing a single tyrosine phosphorylation. The crystal structure indicates that this is accomplished with minimal changes to the essential intrapeptidyl bond and that the reduced strength of the interaction is due to the charge repulsion between c-Cbl and the additional phosphate group. This obvious reduction in binding affinity, however, indicates that Cbl's interactions with its TKB-centered binding partners may be more favorable in the absence of Ser/Thr phosphorylation, which is stimulation and context specific in vivo. These results demonstrate the importance of understanding the environment in which certain residues are phosphorylated, and the necessity of including this in structural investigations

Hospitalizations for acetaminophen overdose: a Canadian population-based study from 1995 to 2004

<p>Abstract</p> <p>Background</p> <p>Acetaminophen overdose (AO) is the most common cause of acute liver failure. We examined temporal trends and sociodemographic risk factors for AO in a large Canadian health region.</p> <p>Methods</p> <p>1,543 patients hospitalized for AO in the Calgary Health Region (population ~1.1 million) between 1995 and 2004 were identified using administrative data.</p> <p>Results</p> <p>The age/sex-adjusted hospitalization rate decreased by 41% from 19.6 per 100,000 population in 1995 to 12.1 per 100,000 in 2004 (<it>P </it>< 0.0005). This decline was greater in females than males (46% vs. 29%). Whereas rates fell 46% in individuals under 50 years, a 50% increase was seen in those ≥ 50 years. Hospitalization rates for intentional overdoses fell from 16.6 per 100,000 in 1995 to 8.6 per 100,000 in 2004 (2004 vs. 1995: rate ratio [RR] 0.49; <it>P </it>< 0.0005). Accidental overdoses decreased between 1995 and 2002, but increased to above baseline levels by 2004 (2004 vs. 1995: RR 1.24;<it>P </it>< 0.0005). Risk factors for AO included female sex (RR 2.19; <it>P </it>< 0.0005), Aboriginal status (RR 4.04; <it>P </it>< 0.0005), and receipt of social assistance (RR 5.15; <it>P </it>< 0.0005).</p> <p>Conclusion</p> <p>Hospitalization rates for AO, particularly intentional ingestions, have fallen in our Canadian health region between 1995 and 2004. Young patients, especially females, Aboriginals, and recipients of social assistance, are at highest risk.</p