Determinants of Health-Related Quality of Life (HRQoL) in the Multiethnic Singapore Population - A National Cohort Study

Background: HRQoL is an important outcome to guide and promote healthcare. Clinical and socioeconomic factors may influence HRQoL according to ethnicity. Methodology: A multiethnic cross-sectional national cohort (N = 7198) of the Singapore general population consisting of Chinese (N = 4873), Malay (N = 1167) and Indian (N = 1158) adults were evaluated using measures of HRQoL (SF-36 version 2), family functioning, health behaviours and clinical/laboratory assessments. Multiple regression analyses were performed to identify determinants of physical and mental HRQoL in the overall population and their potential differential effects by ethnicity. No a priori hypotheses were formulated so all interaction effects were explored. Principal Findings: HRQoL levels differed between ethnic groups. Chinese respondents had higher physical HRQoL (PCS) than Indian and Malay participants (p<0.001) whereas mental HRQoL (MCS) was higher in Malay relative to Chinese participants (p<0.001). Regressions models explained 17.1% and 14.6% of variance in PCS and MCS respectively with comorbid burden, income and employment being associated with lower HRQoL. Age and family were associated only with MCS. The effects of gender, stroke and musculoskeletal conditions on PCS varied by ethnicity, suggesting non-uniform patterns of association for Chinese, Malay and Indian individuals. Conclusions: Differences in HRQoL levels and determinants of HRQoL among ethnic groups underscore the need to better or differentially target population segments to promote well-being. More work is needed to explore HRQoL and wellness in relation to ethnicity

Preventing mood and anxiety disorders in youth: a multi-centre RCT in the high risk offspring of depressed and anxious patients

<p>Abstract</p> <p>Background</p> <p>Anxiety and mood disorders are highly prevalent and pose a huge burden on patients. Their offspring is at increased risk of developing these disorders as well, indicating a clear need for prevention of psychopathology in this group. Given high comorbidity and non-specificity of intergenerational transmission of disorders, prevention programs should target both anxiety and depression. Further, while the indication for preventive interventions is often elevated symptoms, offspring with other high risk profiles may also benefit from resilience-based prevention programs.</p> <p>Method/design</p> <p>The current STERK-study (Screening and Training: Enhancing Resilience in Kids) is a randomized controlled clinical trial combining selected and indicated prevention: it is targeted at both high risk individuals without symptoms and at those with subsyndromal symptoms. Individuals without symptoms meet two of three criteria of the High Risk Index (HRI; female gender, both parents affected, history of a parental suicide (attempt). This index was developed in an earlier study and corresponds with elevated risk in offspring of depressed patients. Children aged 8–17 years (n = 204) with subthreshold symptoms or meeting the criteria on the HRI are randomised to one of two treatment conditions, namely (a) 10 weekly individual child CBT sessions and 2 parent sessions or (b) minimal information. Assessments are held at pre-test, post-test and at 12 and 24 months follow-up. Primary outcome is the time to onset of a mood or anxiety disorder in the offspring. Secondary outcome measures include number of days with depression or anxiety, child and parent symptom levels, quality of life, and cost-effectiveness. Based on models of aetiology of mood and anxiety disorders as well as mechanisms of change during interventions, we selected potential mediators and moderators of treatment outcome, namely coping, parent–child interaction, self-associations, optimism/pessimism, temperament, and emotion processing.</p> <p>Discussion</p> <p>The current intervention trial aims to significantly reduce the risk of intergenerational transmission of mood and anxiety disorders with a short and well targeted intervention that is directed at strengthening the resilience in potentially vulnerable children. We plan to evaluate the effectiveness and cost-effectiveness of such an intervention and to identify mechanisms of change.</p> <p>Trial registration</p> <p>NTR2888</p

Predictors of health-related quality of life in type II diabetic patients in Greece

<p>Abstract</p> <p>Background</p> <p>Diabetes Mellitus (DM) is a major cause of morbidity and mortality affecting millions of people worldwide, while placing a noteworthy strain on public health funding. The aim of this study was to assess health-related quality of life (HRQOL) of Greek Type II DM patients and to identify significant predictors of the disease in this patient population.</p> <p>Methods</p> <p>The sample (N = 229, 52.8% female, 70.0 years mean age) lived in a rural community of Lesvos, an island in the northeast of the Aegean Archipelagos. The generic SF-36 instrument, administered by trainee physicians, was used to measure HRQOL. Scale scores were compared with non-parametric Mann-Whitney and Kruskal-Wallis tests and multivariate stepwise linear regression analyses were used to investigate the effect of sociodemographic and diabetes-related variables on HRQOL.</p> <p>Results</p> <p>The most important predictors of impaired HRQOL were female gender, diabetic complications, non-diabetic comorbidity and years with diabetes. Older age, lower education, being unmarried, obesity, hypertension and hyperlipidaemia were also associated with impaired HRQOL in at least one SF-36 subscale. Multivariate regression analyses produced models explaining significant portions of the variance in SF-36 subscales, especially physical functioning (R²= 42%), and also showed that diabetes-related indicators were more important disease predictors, compared to sociodemographic variables.</p> <p>Conclusion</p> <p>The findings could have implications for health promotion in rural medical practice in Greece. In order to preserve a good HRQOL, it is obviously important to prevent diabetes complications and properly manage concomitant chronic diseases. Furthermore, the gender difference is interesting and requires further elucidation. Modifying screening methods and medical interventions or formulating educational programs for the local population appear to be steps in the correct direction.</p

A Nutrition and Conditioning Intervention for Natural Bodybuilding Contest Preparation: Case Study.

Bodybuilding competitions are becoming increasingly popular. Competitors are judged on their aesthetic appearance and usually exhibit a high level of muscularity and symmetry and low levels of body fat. Commonly used techniques to improve physique during the preparation phase before competitions include dehydration, periods of prolonged fasting, severe caloric restriction, excessive cardiovascular exercise and inappropriate use of diuretics and anabolic steroids. In contrast, this case study documents a structured nutrition and conditioning intervention followed by a 21 year-old amateur bodybuilding competitor to improve body composition, resting and exercise fat oxidation, and muscular strength that does not involve use of any of the above mentioned methods. Over a 14-week period, the Athlete was provided with a scientifically designed nutrition and conditioning plan that encouraged him to (i) consume a variety of foods; (ii) not neglect any macronutrient groups; (iii) exercise regularly but not excessively and; (iv) incorporate rest days into his conditioning regime. This strategy resulted in a body mass loss of 11.7 kg’s, corresponding to a 6.7 kg reduction in fat mass and a 5.0 kg reduction in fat-free mass. Resting metabolic rate decreased from 1993 kcal/d to 1814 kcal/d, whereas resting fat oxidation increased from 0.04 g/min to 0.06 g/min. His capacity to oxidize fat during exercise increased more than two-fold from 0.24 g/min to 0.59 g/min, while there was a near 3-fold increase in the corresponding exercise intensity that elicited the maximal rate of fat oxidation; 21% V̇ O2max to 60% V̇ O2max. Hamstring concentric peak torque decreased (1.7 to 1.5 Nm/kg), whereas hamstring eccentric (2.0 Nm/kg to 2.9 Nm/kg), quadriceps concentric (3.4 Nm/kg to 3.7 Nm/kg) and quadriceps eccentric (4.9 Nm/kg to 5.7 Nm/kg) peak torque all increased. Psychological mood-state (BRUMS scale) was not negatively influenced by the intervention and all values relating to the Athlete’s mood-state remained below average over the course of study. This intervention shows that a structured and scientifically supported nutrition strategy can be implemented to improve parameters relevant to bodybuilding competition and importantly the health of competitors, therefore questioning the conventional practices of bodybuilding preparation

CSN-mediated deneddylation differentially modulates Ci155 proteolysis to promote Hedgehog signalling responses

The Hedgehog (Hh) morphogen directs distinct cell responses according to its distinct signalling levels. Hh signalling stabilizes transcription factor cubitus interruptus (Ci) by prohibiting SCFSlimb-dependent ubiquitylation and proteolysis of Ci. How graded Hh signalling confers differential SCFSlimb-mediated Ci proteolysis in responding cells remains unclear. Here, we show that in COP9 signalosome (CSN) mutants, in which deneddylation of SCFSlimb is inactivated, Ci is destabilized in low-to-intermediate Hh signalling cells. As a consequence, expression of the low-threshold Hh target gene dpp is disrupted, highlighting the critical role of CSN deneddylation on low-to-intermediate Hh signalling response. The status of Ci phosphorylation and the level of E1 ubiquitin-activating enzyme are tightly coupled to this CSN regulation. We propose that the affinity of substrate–E3 interaction, ligase activity and E1 activity are three major determinants for substrate ubiquitylation and thereby substrate degradation in vivo

Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells

INTRODUCTION: Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage response pathways. METHODS: The human breast carcinoma cell line MCF-7, the adriamycin-resistant MCF-7 (Adr/MCF-7) cell line, as well as normal human mammary epithelial (NME) cells were treated with DNA oligonucleotides homologous to the telomere 3' overhang (T-oligos). SCID mice received intravenous injections of MCF-7 cells followed by intravenous administration of T-oligos. RESULTS: Acting through ataxia telangiectasia mutated (ATM) and its downstream effectors, T-oligos induced apoptosis and senescence of MCF-7 cells but not NME cells, in which these signaling pathways were induced to a far lesser extent. In MCF-7 cells, experimental telomere loop disruption caused identical responses, consistent with the hypothesis that T-oligos act by mimicking telomere overhang exposure. In vivo, T-oligos greatly prolonged survival of SCID mice following intravenous injection of human breast carcinoma cells. CONCLUSION: By inducing DNA damage-like responses in MCF-7 cells, T-oligos provide insight into innate cancer avoidance mechanisms and may offer a novel approach to treatment of breast cancer and other malignancies

The Lysosome and Intracellular Signalling.

In addition to being the terminal degradative compartment of the cell's endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell's response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB). Under conditions in which mTORC1 is inhibited including starvation, TFEB becomes dephosphorylated and translocates to the nucleus where it functions as a master regulator of lysosome biogenesis. The signalling role of lysosomes is not limited to this pathway. They act as an intracellular Ca2+ store, which can release Ca2+ into the cytosol for both local effects on membrane fusion and pleiotropic effects within the cell. The relationship and crosstalk between the lysosomal and endoplasmic reticulum (ER) Ca2+ stores play a role in shaping intracellular Ca2+ signalling. Lysosomes also perform other signalling functions, which are discussed. Current views of the lysosomal compartment recognize its dynamic nature. It includes endolysosomes, autolysosome and storage lysosomes that are constantly engaged in fusion/fission events and lysosome regeneration. How signalling is affected by individual lysosomal organelles being at different stages of these processes and/or at different sites within the cell is poorly understood, but is discussed

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base

Pest control and resistance management through release of insects carrying a male-selecting transgene

Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis (‘Bt crops’) emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations