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1.
J Hum Nutr Diet ; 2020 Jan 07.
Article in English | MEDLINE | ID: mdl-31912581

ABSTRACT

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.

2.
Water Resour Res ; 56(7): e2019WR026475, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32999509

ABSTRACT

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.

3.
Nutr Metab Cardiovasc Dis ; 25(4): 388-95, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25638597

ABSTRACT

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).


Subject(s)
Diet , Fatty Liver/prevention & control , Weight Gain , Whey Proteins/administration & dosage , Aged , Aged, 80 and over , Blood Glucose/metabolism , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Double-Blind Method , Energy Intake , Female , Humans , Insulin/blood , Insulin Resistance , Motor Activity , New Zealand , Triglycerides/blood , Waist Circumference
4.
J Hum Nutr Diet ; 28(5): 452-64, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25157608

ABSTRACT

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.


Subject(s)
Body Mass Index , Dairy Products , Energy Intake , Feeding Behavior , Obesity/etiology , Adolescent , Australia , Cross-Sectional Studies , Diet , Female , Humans , Male , Weight Gain
5.
Epidemics ; 44: 100687, 2023 09.
Article in English | MEDLINE | ID: mdl-37348379

ABSTRACT

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.


Subject(s)
Coinfection , Malaria, Falciparum , Malaria, Vivax , Malaria , Humans , Plasmodium vivax , Malaria/drug therapy , Malaria/epidemiology , Malaria/parasitology , Malaria, Vivax/drug therapy , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Recurrence
6.
Osteoporos Int ; 20(2): 335-40, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18575949

ABSTRACT

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.


Subject(s)
Postmenopause/metabolism , Potassium, Dietary/administration & dosage , Absorptiometry, Photon , Aged , Aged, 80 and over , Analysis of Variance , Biomarkers/urine , Bone Density/drug effects , Female , Humans , Potassium/urine , Prospective Studies , Radius/diagnostic imaging , Tibia/diagnostic imaging , Tibia/physiology , Tomography, X-Ray Computed
7.
Osteoporos Int ; 20(7): 1183-91, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19037576

ABSTRACT

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.


Subject(s)
Fractures, Bone , Homocysteine/blood , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Osteoporosis, Postmenopausal , Polymorphism, Single Nucleotide , Absorptiometry, Photon , Aged , Aged, 80 and over , Bone Density , Female , Fractures, Bone/blood , Fractures, Bone/genetics , Hip Joint/diagnostic imaging , Humans , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/genetics , Prospective Studies , Western Australia
8.
J Dairy Sci ; 92(9): 4467-80, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19700708

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Fermentation/drug effects , Rumen/microbiology , Soybean Oil/pharmacology , Ammonia/metabolism , Animals , Bacteria/classification , Biodiversity , Bioreactors , Cattle , Fatty Acids, Volatile/metabolism , Female , Hydrogen-Ion Concentration , In Vitro Techniques , Methane/metabolism
9.
Ann Rheum Dis ; 67(6): 841-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-17875549

ABSTRACT

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.


Subject(s)
Endothelium, Vascular/physiopathology , Fatty Acids, Omega-3/administration & dosage , Lupus Erythematosus, Systemic/drug therapy , Adult , Biomarkers/blood , Brachial Artery/diagnostic imaging , Brachial Artery/drug effects , Brachial Artery/physiopathology , Cell Membrane/chemistry , Dietary Supplements , Dinoprost/analogs & derivatives , Dinoprost/blood , Docosahexaenoic Acids/analysis , Double-Blind Method , Eicosapentaenoic Acid , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Fatty Acids, Unsaturated/analysis , Female , Humans , Lupus Erythematosus, Systemic/metabolism , Male , Middle Aged , Nitroglycerin , Regional Blood Flow , Statistics, Nonparametric , Treatment Outcome , Ultrasonography, Doppler, Pulsed , Vasodilation , Vasodilator Agents
10.
Ann R Coll Surg Engl ; 100(4): 308-315, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29364006

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms/blood , Digestive System Surgical Procedures/statistics & numerical data , Emergency Treatment/statistics & numerical data , Lymphocytes , Neutrophils , Patient Selection , Age Factors , Aged , Aged, 80 and over , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Digestive System Surgical Procedures/adverse effects , Digestive System Surgical Procedures/methods , Emergency Treatment/methods , Female , Humans , Leukocyte Count , Lymphatic Metastasis , Male , Multivariate Analysis , Postoperative Period , Predictive Value of Tests , Preoperative Period , Prognosis , ROC Curve , Retrospective Studies , Survival Analysis , Time Factors , Treatment Outcome
11.
Bone ; 41(1): 33-8, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17482901

ABSTRACT

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.


Subject(s)
Bone and Bones/pathology , Estradiol/blood , Spinal Fractures/etiology , Absorptiometry, Photon , Aged , Bone Density , Cohort Studies , Female , Humans , Risk Factors , Sex Hormone-Binding Globulin/metabolism , Spinal Fractures/blood , Spinal Fractures/metabolism , Spinal Fractures/pathology
12.
Bone ; 40(1): 175-81, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16949901

ABSTRACT

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.


Subject(s)
Osteoporosis/blood , Osteoporosis/genetics , Osteoprotegerin/blood , Osteoprotegerin/genetics , Polymorphism, Single Nucleotide , Absorptiometry, Photon , Aged , Aged, 80 and over , Australia , Bone Density/genetics , Bone and Bones/diagnostic imaging , Bone and Bones/metabolism , Bone and Bones/ultrastructure , Cohort Studies , Female , Fractures, Spontaneous/blood , Fractures, Spontaneous/genetics , Gene Frequency , Haplotypes , Humans , Linkage Disequilibrium
14.
Cancer Res ; 61(1): 131-7, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11196150

ABSTRACT

R115777 [(B)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone] is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. In vitro, using isolated human farnesyl protein transferase, R115777 competitively inhibited the farnesylation of lamin B and K-RasB peptide substrates, with IC50s of 0.86 nM and 7.9 nM, respectively. In a panel of 53 human tumor cell lines tested for growth inhibition, approximately 75% were found to be sensitive to R115777. The majority of sensitive cell lines had a wild-type ras gene. Tumor cell lines bearing H-ras or N-ras mutations were among the most sensitive of the cell lines tested, with responses observed at nanomolar concentrations of R115777. Tumor cell lines bearing mutant K-ras genes required higher concentrations for inhibition of cell growth, with 50% of the cell lines resistant to R115777 up to concentrations of 500 nM. Inhibition of H-Ras, N-Ras, and lamin B protein processing was observed at concentrations of R115777 that inhibited cell proliferation. However, inhibition of K-RasB protein-processing could not be detected. Oral administration b.i.d. of R115777 to nude mice bearing s.c. tumors at doses ranging from 6.25-100 mg/kg inhibited the growth of tumors bearing mutant H-ras, mutant K-ras, and wild-type ras genes. Histological evaluations revealed heterogeneity in tumor responses to R115777. In LoVo human colon tumors, treatment with R115777 produced a prominent antiangiogenic response. In CAPAN-2 human pancreatic tumors, an antiproilferative response predominated, whereas in C32 human melanoma, marked induction of apoptosis was observed. The heterogeneity of histological changes associated with antitumor effects suggested that R115777, and possibly farnesyl protein transferase inhibitors as a class, alter processes of transformation related to tumor-host interactions in addition to inhibiting tumor-cell proliferation.


Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Quinolones/pharmacology , 3T3 Cells/cytology , 3T3 Cells/drug effects , Alkyl and Aryl Transferases/antagonists & inhibitors , Animals , Cell Line, Transformed , Female , Humans , Inhibitory Concentration 50 , Mice , Mice, Nude , Protein Prenylation/drug effects , Tumor Cells, Cultured/drug effects , Xenograft Model Antitumor Assays , ras Proteins/metabolism
15.
J Nutr Health Aging ; 20(1): 8-15, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26728927

ABSTRACT

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.


Subject(s)
Dementia , Diet , Feeding Behavior , Health Education/standards , Health Knowledge, Attitudes, Practice , Health Services for the Aged/standards , Aged , Cooking , Dementia/prevention & control , Female , Health Education/methods , Humans , Male , Nutritional Status , Personal Satisfaction , Residence Characteristics , Sodium Chloride, Dietary , Vegetables
16.
Bone ; 36(4): 599-606, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15777745

ABSTRACT

Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exon 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357 A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-up period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures.


Subject(s)
Fractures, Bone/genetics , LDL-Receptor Related Proteins/genetics , Organ Size , Polymorphism, Single Nucleotide , Absorptiometry, Photon , Aged , Aged, 80 and over , Australia , Bone Density , Cohort Studies , Female , Haplotypes , Heterozygote , Humans , Linkage Disequilibrium , Low Density Lipoprotein Receptor-Related Protein-5
17.
Bone ; 36(3): 555-61, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15777683

ABSTRACT

The pathogenesis of osteoporosis involves both genetic and environmental factors. On the basis of linkage data suggesting gene effects on bone density at chromosome 14q and data locating the BMP4 gene to 14q, we performed a positional candidate study to examine a possible association of BMP4 gene polymorphisms, hip bone density (n = 1012) and fracture rates (n = 1232) in postmenopausal women (mean age 75). On genotype analysis of the three selected single nucleotide polymorphisms (SNP), the 6007C > T polymorphism was associated with total and intertrochanteric hip BMD and BMD was lower in the 32% of subjects homozygous for the C allele. This polymorphism codes for a nonsynonymous amino acid change with the T allele coding for valine, while the C allele codes for alanine. The difference in BMD was 3.1% (TT vs. CC) and 2.3% (CT versus CC) for the total hip (P = 0.023), and 3.7% (TT vs. CC) and 2.8% (CT versus CC) for the intertrochanter site (P = 0.012). Haplotype analysis demonstrated 6 haplotypes of frequency greater than 2%. A major haplotype defined by G-C-T alleles in SNPs -5826G > A, 3564C > T and 6007C > T respectively, showed association with high bone mass. No SNP showed association with fracture rates. We conclude that a polymorphism found in the BMP4 gene, affecting amino acid sequence, is associated with hip bone density in postmenopausal women, presumably via regulation of anabolic effects on the skeleton.


Subject(s)
Alleles , Bone Density/genetics , Bone Morphogenetic Proteins/genetics , Osteoporosis, Postmenopausal/genetics , Polymorphism, Genetic/genetics , Aged , Aged, 80 and over , Bone Morphogenetic Protein 4 , Female , Humans
18.
Int J Hyg Environ Health ; 218(5): 444-51, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25857756

ABSTRACT

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.


Subject(s)
Bone Density/drug effects , Bone Resorption/etiology , Cadmium/adverse effects , Environmental Exposure/adverse effects , Kidney/drug effects , Metals/adverse effects , Aged , Aged, 80 and over , Aluminum/blood , Aluminum/urine , Biomarkers/blood , Biomarkers/urine , Cadmium/blood , Cadmium/urine , Creatinine/blood , Cross-Sectional Studies , Female , Glomerular Filtration Rate/drug effects , Hepatitis A Virus Cellular Receptor 1 , Humans , Kidney/metabolism , Kidney/physiopathology , Kidney Function Tests , Membrane Glycoproteins/blood , Mercury/blood , Metals/blood , Metals/urine , Middle Aged , Receptors, Virus/blood , Zinc/blood
19.
J Bone Miner Res ; 8(11): 1273-9, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8266819

ABSTRACT

There is general agreement that bone density falls with age and is higher in heavy people than light people. We have studied a variety of potential correlates of vertebral, ankle, and hip bone density to evaluate other potential influences on the skeleton. We recruited 196 healthy women who were more than 10 years past the menopause and collected a diet and activity record, a 24 h urine, and a fasting blood and urine specimen. These blood and urine samples were analyzed for factors related to calcium homeostasis. We then measured bone density at lumbar vertebrae 1-4 and the hip and the ankle bone density of the nondominant leg. Correlations between vertebral, hip, and ankle bone density and other measured variables were explored using the statistical package SPSS PC. At the vertebral site, in addition to correlations with age and body mass index (BMI), a negative correlation with a measure of bone resorption, the hydroxyproline creatinine ratio (OHPCR), was noted. At the ankle site, in addition to correlation with age, BMI, and OHPCR, a positive correlation with activity and a negative correlation with serum calcitriol were noted. At the hip site, as well as age, BMI, and OHPCR, significant correlations with GFR and dietary calcium intake were noted. These data suggest that even in women 10 years past the menopause bone resorption has a significant effect on bone density, that renal function may account for some of the variance in bone density at the hip, and that activity effects are more marked at sites of greater loading, namely the ankle.


Subject(s)
Ankle/physiology , Body Mass Index , Bone Density , Bone Resorption/urine , Hip/physiology , Lumbar Vertebrae/physiology , Postmenopause/urine , Aged , Calcitriol/blood , Creatinine/urine , Female , Humans , Hydroxyproline/urine , Middle Aged , Postmenopause/blood
20.
J Bone Miner Res ; 10(7): 1068-75, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7484282

ABSTRACT

The etiology of age-related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation. This 2-year randomized placebo-controlled study was designed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal. The subjects were randomized into one of 4 groups: placebo, milk powder containing 1 g of calcium, calcium tablets 1 g/night, and calcium tablets 1 g/night and an exercise regimen. The exercise group aimed to undertake 4 h of extra weight-bearing exercise per week and were undertaking 10% more activity than other groups at 2 years. Bone mineral density at the lumbar spine, three hip sites, and two sites of the tibia close to the ankle joint were measured at 6 month intervals. Dietary intake was evaluated by a weighed food record, exercise was evaluated by an exercise diary, and blood and urine samples were obtained to examine effects on calcium homeostasis. Individual data points were compared using repeated measures ANOVA and least squares regression. Calcium supplementation by either the calcium tablets or the milk powder resulted in cessation of bone loss at the intertrochanteric hip site (placebo, calcium tablets, calcium and exercise, milk powder -0.81, +0.17, +0.23, and +0.07% per year, respectively; p < 0.05 for all supplementation groups compared with placebo) with similar results at the trochanteric hip site. The calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone (placebo, calcium tablets, calcium and exercise, milk powder -0.67, -0.18, +0.28, and -0.18% per year, respectively; p < 0.05 for calcium and exercise compared with calcium alone). There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia (placebo, calcium tablets, calcium and exercise, milk powder -2.5, -1.6, -1.0, and -1.5% per year, respectively; p < 0.05 for all supplementation groups compared with placebo). There was no significant bone loss at the spine site in any group.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Bone Density/drug effects , Calcium, Dietary/therapeutic use , Calcium/therapeutic use , Exercise , Osteoporosis, Postmenopausal/physiopathology , Aged , Analysis of Variance , Animals , Biomarkers/blood , Biomarkers/urine , Bone Density/physiology , Calcium/blood , Calcium/urine , Calcium, Dietary/administration & dosage , Female , Hip Joint/drug effects , Hip Joint/physiology , Humans , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/physiology , Middle Aged , Milk , Osteoporosis, Postmenopausal/drug therapy , Tablets , Tibia/drug effects , Tibia/physiology , Weight-Bearing
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