A model for malaria treatment evaluation in the presence of multiple species.

Plasmodium falciparum and P. vivax are the two most common causes of malaria. While the majority of deaths and severe morbidity are due to P. falciparum, P. vivax poses a greater challenge to eliminating malaria outside of Africa due to its ability to form latent liver stage parasites (hypnozoites), which can cause relapsing episodes within an individual patient. In areas where P. falciparum and P. vivax are co-endemic, individuals can carry parasites of both species simultaneously. These mixed infections complicate dynamics in several ways: treatment of mixed infections will simultaneously affect both species, P. falciparum can mask the detection of P. vivax, and it has been hypothesised that clearing P. falciparum may trigger a relapse of dormant P. vivax. When mixed infections are treated for only blood-stage parasites, patients are at risk of relapse infections due to P. vivax hypnozoites. We present a stochastic mathematical model that captures interactions between P. falciparum and P. vivax, and incorporates both standard schizonticidal treatment (which targets blood-stage parasites) and radical cure treatment (which additionally targets liver-stage parasites). We apply this model via a hypothetical simulation study to assess the implications of different treatment coverages of radical cure for mixed and P. vivax infections and a "unified radical cure" treatment strategy where P. falciparum, P. vivax, and mixed infections all receive radical cure after screening glucose-6-phosphate dehydrogenase (G6PD) normal. In addition, we investigated the impact of mass drug administration (MDA) of blood-stage treatment. We find that a unified radical cure strategy leads to a substantially lower incidence of malaria cases and deaths overall. MDA with schizonticidal treatment was found to decrease P. falciparum with little effect on P. vivax. We perform a univariate sensitivity analysis to highlight important model parameters.

River Plume Liftoff Dynamics and Surface Expressions.

The water surface expression of liftoff and its dependence on discharge are examined using numerical simulations with the Regional Ocean Modeling System (ROMS). Liftoff is the process by which buoyant river water separates from the bed and flows over denser saltwater. During low-discharge conditions liftoff occurs in the river and is accompanied by a change in the surface slope. During high-discharge conditions liftoff occurs outside the mouth and generates a ridge on the water surface. The location and height of the ridge can be described by analytical equations in terms of discharge, shelf slope, and river mouth aspect ratio. The offshore distance and height of the ridge are proportional to the river discharge and vary inversely with river mouth aspect ratio. For steep shelf slopes liftoff occurs close to the river mouth and generates a large ridge. The ridge is modified, but not eliminated, by the presence of tides. The water surface slope change at the ridge peak is large enough to be detected by the upcoming Surface Water and Ocean Topography (SWOT) altimeter and can be used to identify the liftoff location during high discharge. However, during low discharge the water surface slope change at the liftoff location is too small to be detected by SWOT. These results indicate that remote measurements of the presence or absence of the ridge may be useful to distinguish between low and high flows, and remote measurements of the ridge location or height could be used to estimate freshwater discharge.

Barriers and enablers in the implementation of a standardised process for nutrition care: findings from a multinational survey of dietetic professionals in 10 countries.

BACKGROUND: To explore the barriers and enablers experienced by nutrition and dietetic professionals in the implementation of the standardised Nutrition Care Process (NCP) across 10 different countries. NCP related beliefs, motivations and values were investigated and compared. METHODS: A validated online survey was disseminated to nutrition and dietetics professionals in 10 countries in the local language during 2017. Cross-sectional associations and differences between countries were explored for level of implementation, barriers/enablers and attitudes/motivation among the respondents. RESULTS: Higher NCP implementation was associated with greater occurrence of enabling aspects, as well as fewer occurrences of barriers. The most common enabler was 'recommendation by the national dietetic association' (69%) and the most common barrier was 'lack of time' (39%). A longer experience of NCP use was associated with a more positive attitude towards all NCP aspects. Differences between countries were identified, regarding both the occurrence of barriers/enablers and attitudes/motivations. CONCLUSIONS: Implementation efforts need to be tailored to country-specific contexts when implementing a new standard of care framework among nutrition and dietetic professionals. Additional research is needed to further assess the management and workplace strategies to support the development of nutrition and dietetics professionals in multidisciplinary healthcare organisations.

Association of pretreatment neutrophil-lymphocyte ratio and outcome in emergency colorectal cancer care.

Introduction The association between the neutrophil-lymphocyte ratio (NLR) and outcome in elective colorectal cancer surgery is well established; the relationship between NLR and the emergency colorectal cancer patient is, as yet, unexplored. This paper evaluates the predictive quality of the NLR for outcome in the emergency colorectal cancer patient. Materials and Methods A total of 187 consecutive patients who underwent emergency surgery for colorectal cancer were included in the study. NLR was calculated from the haematological tests done on admission. Receiver operating characteristic analyses were used to determine the most suitable cut-off for NLR. Outcomes were assessed by mortality at 30 and 90 days using stepwise Cox proportional hazards regression. Results An NLR cut-off of 5 was found to have the highest sensitivity and specificity. At 30 days, age and time from admission to surgery were associated with increased mortality; a high NLR was associated with an increased risk of mortality in univariate but not multivariate analysis. At 90 days, age, NLR, time from admission to surgery and nodal status were all significantly associated with increased mortality on multivariate analysis. Conclusions Pre-operative NLR is a cheap, easily performed and useful clinical tool to aid prediction of outcome in the emergency colorectal cancer patient.

Tailored Nutrition Education in the Elderly Can Lead to Sustained Dietary Behaviour Change.

OBJECTIVES: Evaluate a 4-week dementia specific nutrition education intervention to determine long term knowledge and healthy dietary behaviour changes in 72 elderly men and women. DESIGN: A mixed method design used qualitative findings to triangulate quantitative within-subject changes to determine efficacy and sustained dietary behaviour change. SETTING: Community. PARTICIPANTS: 72 independently-living individuals. INTERVENTION: 4-week dementia specific nutrition education intervention. MEASUREMENTS: Change in participant attitude, confidence, dietary patterns, cooking behaviour, and knowledge were analysed within-subjects using non-parametric repeated-measures procedures. Significance level was set at 5% (α = 0.05). Effect size (ES) was reported and identified as small (S), medium (M) or large (L) if a significant change was observed. RESULTS: Compared to before the nutrition education intervention participants had an increase in total knowledge (p < 0.001, ES = 0.972 (L)), consumed a greater variety of vegetables (p = 0.007, ES = 0.35 (M)), used less salt (p = 0.006, ES = -0.42 (M-L)) and increased spice use (p < 0.001, ES = 0.40 (M-L)). Participants overcame barriers to enable sustained change, held a positive view on healthy living and believed government should invest in this sector of the community. Sharing and socialisation emerged as important themes that increased program satisfaction. CONCLUSION: The dementia specific nutrition program produced a large effect in knowledge improvement from pre to post, which was retained at follow up, consolidated observational and participatory learning which produced a moderate increase in healthy dietary behaviours which participants valued and sustained.

Investigation of the relationship between low environmental exposure to metals and bone mineral density, bone resorption and renal function.

Environmental exposure to metals has been linked to adverse health outcomes. Exposure to cadmium has been associated with decreased bone density, an increased risk of osteoporotic fracture and possible renal dysfunction. Older women are a group at risk of renal and bone density impacts and exposure to metals may be an important risk factor for these health outcomes. This study was a cross sectional study of 77 women aged 50 years and above examining the relationship between metals exposure and renal and bone health. Urinary and blood metals concentrations, plasma creatinine, iron, ferritin and transferrin were measured in these subjects. Bone biomarkers assessed included the pyridinium crosslinks, pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was assessed using DEXA. Blood and urinary metals concentrations were generally low in the subjects, with a median urinary cadmium concentration of 0.26 µg/g creatinine (range <0.065-1.03 µg/g). Urinary cadmium was found to be a significant predictor of bone mineral density at whole body, lumber spine, total hip and femoral neck, with increasing urinary Cd concentrations associated with decreased bone density. Urinary cadmium and aluminium concentrations were positively correlated with bone resorption whilst blood zinc and mercury concentrations were negatively correlated. Urinary aluminium was positively correlated with KIM-1 concentrations, a marker of early kidney damage, however blood zinc concentrations were significantly negatively correlated with this biomarker. This study provides additional support for low cadmium exposure being of concern for the health of older women. Further investigation into the role of exposure to other metals on bone and renal health is warranted.

Consumption of a whey protein-enriched diet may prevent hepatic steatosis associated with weight gain in elderly women.

BACKGROUND AND AIMS: Protein consumption has been associated with cardio-metabolic benefits, including weight loss and improved insulin sensitivity, and may have potential benefits for individuals with fatty liver disease (FLD). We investigated the effect of increasing dietary protein intake from whey relative to carbohydrate on hepatic steatosis. METHODS AND RESULTS: A two-year randomized, double-blind, placebo-controlled trial of 30 g/day whey protein-supplemented beverage (protein) or an energy-matched low-protein high-carbohydrate beverage (control) for cardio-metabolic and bone health in 219 healthy elderly women, recruited from the Western Australian general population. Hepatic steatosis was quantified using computed tomographic liver-to-spleen (L/S) ratio. FLD was defined as liver-to-spleen difference <10 Hounsfield units. At baseline, FLD prevalence was 11.4%. Control and protein groups were similar in body mass index (BMI), insulin resistance, L/S ratio and FLD prevalence at baseline. At two-years, dietary protein increased by 20 g in the protein, but not the control, group. Total energy intake and physical activity remained similar between groups. At two-years, BMI and FLD prevalence increased in both groups, with no between group differences. L/S ratio increased in control, but not protein, group at two-years, with no between group differences. In a within group comparison, change in BMI correlated with changes in L/S ratio in control (r = 0.37, P = 0.0007), but not with protein group (r = 0.04, P = 0.73). CONCLUSION: Increasing dietary protein intake from whey relative to carbohydrate does not reduce weight, hepatic steatosis or the prevalence of FLD in elderly women. However, it may prevent worsening of hepatic steatosis associated with weight gain. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (Registration no. ACTRN012607000163404).

Dairy product consumption, dietary nutrient and energy density and associations with obesity in Australian adolescents.

BACKGROUND: Dairy intake is likely to influence dietary energy density (ED) and nutrient density (ND), which are factors representing aspects of dietary quality. Although evidence suggests dairy intake is unlikely to contribute to obesity, intake tends to decrease over adolescence, potentially as a result of concerns around weight gain. We examined associations between dairy intake, ED and ND, and investigated relationships with obesity in adolescents. METHODS: The present study comprised a cross-sectional study of 1613 14-year-olds in the Western Australian Pregnancy Cohort (Raine) Study. Adolescents completed a 212-item food frequency questionnaire. Nutrient Rich Food index 9.3 (NRF9.3) was used to estimate ND. Age-specific body mass index (BMI) and waist-height cut-offs were used to categorise obesity risk. RESULTS: Mean (SD) dairy intake was: 2.62 (1.51) servings daily; ED was 4.53 (0.83) (food and beverage) and 6.28 (1.33) (food only); ND was 373 (109). Dairy intake was inversely associated with ED and positively associated with ND. The odds of being overweight (as assessed by BMI) increased by 1.24 (95% confidence interval = 1.09-1.42) with each 100-point increase in ND, after adjustment for potential confounders and energy intake. ED measures and dairy intake were inversely associated with obesity after adjustment for confounders; associations became nonsignificant after energy adjustment. CONCLUSIONS: The NRF9.3 was originally designed to assess foods, not diets. Further research in other cohorts to determine whether similar findings exist, or investigations into alternate measures of dietary ND, may prove useful. Our findings may be the result of factors such as an excess consumption of refined but fortified foods. Although higher dairy intakes were associated with higher ND, intakes were not associated with higher obesity risk.

Exercise for depression in care home residents: a randomised controlled trial with cost-effectiveness analysis (OPERA).

BACKGROUND: Many older people living in care homes (long term residential care or nursing homes) are depressed. Exercise is a promising non-drug intervention for preventing and treating depression in this population. OBJECTIVE: To evaluate the impact of a 'whole-home' intervention, consisting of training for residential and nursing home staff backed up with a twice-weekly, physiotherapist-led exercise class on depressive symptoms in care home residents. DESIGN: A cluster randomised controlled trial with a cost-effectiveness analysis to compare (1) the prevalence of depression in intervention homes with that in control homes in all residents contributing data 12 months after homes were randomised (cross-sectional analysis); (2) the number of depressive symptoms at 6 months between intervention and control homes in residents who were depressed at pre-randomisation baseline assessment (depressed cohort comparison); and (3) the number of depressive symptoms at 12 months between intervention and control homes in all residents who were present at pre-randomisation baseline assessment (cohort comparison). SETTING: Seventy-eight care homes in Coventry and Warwickshire and north-east London. PARTICIPANTS: Care home residents aged ≥ 65 years. INTERVENTIONS: Control intervention: Depression awareness training programme for care home staff. Active intervention: A 'whole-home' exercise intervention, consisting of training for care home staff backed up with a twice-weekly, physiotherapist-led exercise group. MAIN OUTCOME MEASURES: Geriatric Depression Scale-15, proxy European Quality of Life-5 Dimensions (EQ-5D), cost-effectiveness from an National Health Service perspective, peripheral fractures and death. RESULTS: We recruited a total of 1054 participants. Cross-sectional analysis: We obtained 595 Geriatric Depression Scale-15 scores and 724 proxy EQ-5D scores. For the cohort analyses we obtained 765 baseline Geriatric Depression Scale-15 scores and 776 proxy EQ-5D scores. Of the 781 who we assessed prior to randomisation, 765 provided a Geriatric Depression Scale-15 score. Of these 374 (49%) were depressed and constitute our depressed cohort. Resource-use and quality-adjusted life-year data, based on proxy EQ-5D, were available for 798 residents recruited prior to randomisation. We delivered 3191 group exercise sessions with 31,705 person attendances and an average group size of 10 (5.3 study participants and 4.6 non-study participants). On average, our participants attended around half of the possible sessions. No serious adverse events occurred during the group exercise sessions. In the cross-sectional analysis the odds for being depressed were 0.76 [95% confidence interval (CI) 0.53 to 1.09] lower in the intervention group at 12 months. The point estimates for benefit for both the cohort analysis (0.13, 95% CI -0.33 to 0.60) and depressed cohort (0.22, 95% CI -0.52 to 0.95) favoured the control intervention. There was no evidence of differences in fracture rates or mortality (odds ratio 1.07, 95% CI 0.79 to 1.48) between the two groups. There was no evidence of differences in the other outcomes between the two groups. Economic analysis: The additional National Health Service cost of the OPERA intervention was £374 per participant (95% CI -£655 to £1404); the mean difference in quality-adjusted life-year was -0.0014 (95% CI -0.0728 to 0.0699). The active intervention was thus dominated by the control intervention, which was more effective and less costly. CONCLUSION: The results do not support the use of a whole-home physical activity and moderate-intensity exercise programme to reduce depression in care home residents. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43769277. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 18. See the Health Technology Assessment programme website for further project information.

Under-reporting of energy intake in elderly Australian women is associated with a higher body mass index.

OBJECTIVES: Identify the extent of under-reporting of energy intake and the characteristics associated with implausible intakes in elderly women. DESIGN: Dietary intake was assessed using a 3-day weighed food record. Protein intake was validated by 24-hour urinary nitrogen. To examine under-reporting, participants were grouped according to their energy intake and compared to the Goldberg cut-off equation. Logistic regression was performed to assess the influence of body mass index (BMI) and social-demographic factors on under-reporting. SETTING: Community dwelling elderly women from Perth, Western Australia. PARTICIPANTS: 217 elderly women aged 70-80 years. RESULTS: Under-reporters had a higher physical activity level (p<0.001) compared with acceptable-reporters. The under-reporters also had a higher body weight (p=0.006), body mass index (BMI) (p=0.001), waist (p=0.011), hip circumference (p<0.001), whole body fat mass (p<0.001) and percentage body fat (p<0.001) than acceptable-reporters. Under-reporters had a significantly lower intakes of protein, fat, carbohydrate and alcohol (p<0.001) and fewer reported food items, compared with acceptable reporters. However, 24-hour urinary nitrogen was only marginally different between the two groups (p=0.053). Participants with a higher BMI were more likely to under-report their energy intake (BMI=25-29.9: odds ratio=2.98[95% CI=1.46-6.09]; BMI≥30: 5.84[2.41-14.14]). CONCLUSION: Under-reporting energy intake in elderly women was associated with a higher BMI, body fat and higher self-reported physical activity levels. A higher BMI (≥25) appears to be most significant factor in determining if elderly women will underreport their food intake and may be related to body image. These results have implications for undertaking surveys of food intake in elderly women.

Adequacy and change in nutrient and food intakes with aging in a seven-year cohort study in elderly women.

OBJECTIVE: As women age total dietary intake falls which may increase the risk of dietary deficiencies in some individuals. The aims of this study were to investigate the changes in nutrient and dietary intakes that occurred with aging in a seven-year longitudinal study of elderly Australian women and to evaluate the adequacy of their dietary intakes. DESIGN: Longitudinal population based study on health with ageing. PARTICIPANTS AND SETTING: 911 free-living elderly women aged 70-85 years at baseline from a cohort of 1500 elderly women. MEASUREMENTS: At baseline, 60 and 84 months, self-reported Food Frequency Questionnaires (FFQ) and demographics were collected and anthropometry measured. RESULTS: During the 84 month subjects lost height (1.8 cm) and body weight (1.9 kg). Intakes of energy and macronutrients carbohydrate, fat and protein declined significantly over the 84 months. Mean energy derived from saturated fat was above, whereas energy derived from carbohydrate was below, recommended levels of intake at all time points. Intakes of vitamins and minerals all declined with age and subjects had suboptimal intakes of folate, vitamin E and calcium at all time points. The serve sizes for potato and meat and the consumption of milk, bread and variety of vegetables declined significantly over time reflecting changes in nutrient intake. CONCLUSIONS: Ageing is associated with reduced food intake resulting in inadequate intakes in energy, and some nutrients. Nutrition policy for elderly women should include advice to maintain or increase intakes of carbohydrate, milk, vegetables and fruit whilst continuing to reduce fat intake.

Effects of antibiotics and oil on microbial profiles and fermentation in mixed cultures of ruminal microorganisms.

Ionophores and supplemental fat are fed to lactating cows to improve feed efficiency. Their effect on rumen fermentation is similar, but less is known about their impact on rumen microbes. The objective of this study was to determine the effects of monensin (M), bacitracin (B), and soybean oil (O) on microbial populations. Mixed cultures of rumen microbes were incubated in 5 dual-flow continuous fermentors and fed 13.8 g of alfalfa hay pellets daily (DM basis) for 16 d. All fermentors were allowed to stabilize for 4 d. From d 5 to 10, two fermentors received O (5% of diet DM), one fermentor received M (22 mg/kg), and one received B (22 mg/kg). From d 11 to 16, the 2 fermentors receiving O also received either M (OM) or B (OB) and O was included in the fermentors receiving M (MO) and B (BO). One fermentor served as the control and received 100% alfalfa pellets throughout the experiment. Each run was replicated 3 times. Samples were taken at 2 h after the morning feeding on d 4, 10, and 16 and were analyzed for bacterial populations using terminal restriction fragment length polymorphism. Volatile fatty acid concentration, methane production, and pH in the control cultures were not affected by time and remained similar during the entire experiment. The M and O treatments reduced molar concentration of acetate, increased concentration of propionate, and decreased methane production. Bacitracin did not alter acetate or propionate concentration, but reduced methane production. All 3 treatments (M, B, and O) altered the fragment patterns of microbial profiles. In contrast, treatments MO, OM, BO, and OB had little effect on culture fermentation despite differences in the patterns of microbial fragments. The terminal restriction fragment length polymorphism data suggest that microbial adaptation to the in vitro system in the control fermentor occurred within 4 d.

The effects of high potassium consumption on bone mineral density in a prospective cohort study of elderly postmenopausal women.

UNLABELLED: Few studies have investigated the long-term effects of potassium intake on BMD. In a cohort of 266 elderly women, we found that baseline potassium intake as reflected by 24-hour urine potassium excretion had positive association with BMD measured at 1 and/or 5 years later, suggesting a role of dietary potassium on osteoporosis prevention. INTRODUCTION: High dietary potassium intake has been suggested to be beneficial for bone structure, but few studies have investigated the long-term effects of potassium intake on BMD in elderly women. We examined the relationship between potassium intake as reflected by 24-hour urine potassium excretion and bone density in a cohort of elderly women. METHODS: The study subjects were 266 elderly postmenopausal women aged 70-80 years. Twenty-four-hour urinary potassium excretion was determined at baseline. At one year hip DXA BMD was measured, at 5 years hip and total body DXA BMD and distal radius and tibia pQCT vBMD were measured. The effects of potassium were evaluated by ANCOVA according to the quartile of baseline urinary potassium excretion. RESULTS: After adjustment for confounding factors, subjects in the highest quartile of urinary potassium excretion had significantly higher total hip BMD at 1 (5%) and 5 years (6%), and significantly higher total body BMD (4%) and 4% distal tibia total (7%) and trabecular vBMD (11%) at 5 years than those in the lowest quartile. CONCLUSIONS: Potassium intake shows positive association with bone density in elderly women, suggesting that increasing consumption of food rich in potassium may play a role in osteoporosis prevention.

The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women.

SUMMARY: Few studies have evaluated the effects of homocysteine and methylenetetrahydrofolate reductase (MTHFR) genotype on age-related bone loss. In our 5-year cohort study with 1,213 women aged 70-85 years, high homocysteine is associated with greater hip bone loss but not fracture risk. The effect of MTHFR genotype on bone density and fracture is weak. INTRODUCTION: Previous studies on the effects of homocysteine and MTHFR genotype on bone mineral density (BMD) and osteoporotic fracture risk have shown inconsistent results. Few studies have evaluated their effects on age-related bone loss. We evaluated the effects of homocysteine and MTHFR genotype variation on hip BMD and fracture risk over 5 years in a cohort of 1,213 community-dwelling women aged 70-85 years. METHODS: Nutritional intake and prevalent fracture status were assessed at baseline, plasma homocysteine was measured at year 1, and hip dual-energy X-ray absorptiometry (DXA) BMD was measured at years 1 and 5. Clinical incident osteoporotic fractures confirmed by radiographic report were collected throughout the study and the MTHFR gene C677T and A1298C polymorphisms genotyped. Data were analyzed using analysis of covariance and Cox proportional hazard regression. RESULTS: The highest tertile of homocysteine was associated with a greater hip BMD loss over 4 years (-2.8%) compared to the middle (-1.6%) and lowest tertiles (-1.2%) (P < 0.001). This effect remained after adjustment for covariates. There was no effect of homocysteine on fracture prevalence or incidence. MTHFR gene variation was only weakly related to one of the bone outcome measures. CONCLUSION: In this study population, high homocysteine is associated with greater hip bone loss but not fracture risk.

A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus.

OBJECTIVE: To determine the clinical effect of dietary supplementation with low-dose omega-3-polyunsaturated fatty acids on disease activity and endothelial function in patients with systemic lupus erythematosus. METHODS: A 24-week randomised double-blind placebo-controlled parallel trial of the effect of 3 g of omega-3-polyunsaturated fatty acids on 60 patients with systemic lupus erythematosus was performed. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and British Isles Lupus Assessment Group index of disease activity for systemic lupus erythematosus (BILAG), endothelial function using flow-mediated dilation (FMD) of the brachial artery, oxidative stress using platelet 8-isoprostanes and analysis of platelet membrane fatty acids were taken at baseline, 12 and 24 weeks. RESULTS: In the fish oil group there was a significant improvement at 24 weeks in SLAM-R (from 9.4 (SD 3.0) to 6.3 (2.5), p<0.001); in BILAG (from 13.6 (6.0) to 6.7 (3.8), p<0.001); in FMD (from 3.0% (-0.5 to 8.2) to 8.9% (1.3 to 16.9), p<0.001) and in platelet 8-isoprostanes (from 177 pg/mg protein (23-387) to 90 pg/mg protein (32-182), p = 0.007). CONCLUSIONS: Low-dose dietary supplementation with omega-3 fish oils in systemic lupus erythematosus not only has a therapeutic effect on disease activity but also improves endothelial function and reduces oxidative stress and may therefore confer cardiovascular benefits.

Bone structural effects of variation in the TNFRSF1B gene encoding the tumor necrosis factor receptor 2.

UNLABELLED: The 1p36 region of the human genome has been identified as containing a QTL for BMD in multiple studies. We analysed the TNFRSF1B gene from this region, which encodes the TNF receptor 2, in two large population-based cohorts. Our results suggest that variation in TNFRSF1B is associated with BMD. INTRODUCTION: The TNFRSF1B gene, encoding the TNF receptor 2, is a strong positional and functional candidate gene for impaired bone structure through the role that TNF has in bone cells. The aims of this study were to evaluate the role of variations in the TNFRSF1B gene on bone structure and osteoporotic fracture risk in postmenopausal women. METHODS: Six SNPs in TNFRSF1B were analysed in a cohort of 1,190 postmenopausal Australian women, three of which were also genotyped in an independent cohort of 811 UK postmenopausal women. Differences in phenotypic means for genotype groups were examined using one-way ANOVA and ANCOVA. RESULTS: Significant associations were seen for IVS1+5580A>G with BMD and QUS parameters in the Australian population (P = 0.008 - 0.034) and with hip BMD parameters in the UK population (P = 0.005 - 0.029). Significant associations were also observed between IVS1+6528G>A and hip BMD parameters in the UK cohort (P = 0.0002 - 0.003). We then combined the data from the two cohorts and observed significant associations between both IVS1+5580A>G and IVS1+6528G>A and hip BMD parameters (P = 0.002 - 0.033). CONCLUSIONS: Genetic variation in TNFRSF1B plays a role in the determination of bone structure in Caucasian postmenopausal women, possibly through effects on osteoblast and osteoclast differentiation.

Photofragment slice imaging studies of pyrrole and the Xe...pyrrole cluster.

The photolysis of pyrrole has been studied in a molecular beam at wavelengths of 250, 240, and 193.3 nm, using two different carrier gases, He and Xe. A broad bimodal distribution of H-atom fragment velocities has been observed at all wavelengths. Near threshold at both 240 and 250 nm, sharp features have been observed in the fast part of the H-atom distribution. Under appropriate molecular beam conditions, the entire H-atom loss signal from the photolysis of pyrrole at both 240 and 250 nm (including the sharp features) disappear when using Xe as opposed to He as the carrier gas. We attribute this phenomenon to cluster formation between Xe and pyrrole, and this assumption is supported by the observation of resonance enhanced multiphoton ionization spectra for the (Xe...pyrrole) cluster followed by photofragmentation of the nascent cation cluster. Ab initio calculations are presented for the ground states of the neutral and cationic (Xe...pyrrole) clusters as a means of understanding their structural and energetic properties.

A cohort study of the effect of endogenous estrogen on spine fracture risk and bone structure in elderly women and an assessment of its diagnostic usefulness.

The decline in endogenous estrogen concentration after menopause is associated with accelerated bone loss. However, effects in older women remain controversial and the usefulness of estrogen status as a predictor of spine fracture has not been assessed. Therefore, we undertook a prospective cohort study of 1350 women mean age 75 years in order to study the role of endogenous estrogen concentration on the risk of morphometric X-ray absorptiometry (MXA)-defined vertebral deformity and atraumatic clinical spine fracture and the association of endogenous estrogen with bone structure. At 5 years 70 patients (5.2%) had sustained > or = 1 incident spine fracture. The fracture group had significantly lower concentrations of baseline free estradiol index (FEI) median (IQ range) (0.38 (0.22-0.60) vs. 0.49 (0.29-0.84) pmol/nmol, p=0.009). The patients in the lowest tertile of FEI (FEI <0.35) had twice the risk of sustaining a clinical vertebral fracture compared to those subjects in the highest tertile (FEI >0.68) (HR 2.18: 95% CI 1.11-4.28). A low FEI was associated with an increased risk of a vertebral deformity over the 5-year study (OR 1.77: 95% CI 1.02-3.07) for the lowest compared to highest tertile. A low baseline FEI was associated with lower baseline QUS heel bone structure and DXA hip bone structure at 12 months and with deterioration in QUS heel bone structure 5 years later. The effect size of the FEI in predicting spine fracture was similar to the effect size for DXA BMD and heel QUS, probably because of the beneficial effect of the FEI on bone structure. The data suggest that the estrogen effect on reducing spine fracture is at least in part due to an effect on bone structure and its measurement does not significantly improve fracture prediction.

No associations between OPG gene polymorphisms or serum levels and measures of osteoporosis in elderly Australian women.

Bone mass is the single most important risk factor for osteoporotic fractures in the elderly and is mainly influenced by genetic factors accounting for 40-75% of the inter-individual variation. Critical for the bone remodeling process is the balance between the newly discovered members of the tumor necrosis factor ligand and receptor superfamilies, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand, which mediate the effects of many upstream regulators of bone metabolism. In the present study, we evaluated the impact of sequence variations in the OPG gene on bone mass, bone-related biochemistry including serum OPG and fracture frequency in elderly Australian women. A total of 1101 women were genotyped for 3 different single nucleotide polymorphisms (SNP) within the OPG gene (G1181C, T950C and A163G). The effects of these SNPs and serum OPG on calcaneal quantitative ultrasound measurements, osteodensitometry of the hip and bone-related biochemistry were examined. We found no significant relationship between sequence variations in the OPG gene or serum OPG and bone mass, bone-related biochemistry or fracture frequency. Our findings confirm some recent publications investigating the same SNPs but diverge from others, indicating that generalization of the relationships found in this type of study must be done with caution and signify the importance of determining associations between polymorphisms and osteoporosis in different ethnic groups.