Dietary fiber, potassium, magnesium and calcium in relation to the risk of preeclampsia

To explore the relation between preeclampsia risk and maternal intake of dietary fiber, potassium, magnesium and calcium. STUDY DESIGN: We conducted a case-control study of 172 preeclamptics and 339 normotensive controls. Maternal dietary intake was assessed using a food frequency questionnaire. Logistic regression procedures were used to estimate the association between each dietary factor and preeclampsia risk. RESULTS: Fiber intake was inversely associated with the risk of preeclampsia. When extreme quartiles of total fiber intake were compared, the odds ratio (OR) for preeclampsia was 0.46 (95% confidence interval [CI] 0.23-0.92). The multivariate OR for preeclampsia for women in the top quartile of potassium intake (>4.1 g/d) versus the lowest quartile (<2.4 g/d) was 0.49 (95% CI 0.24-0.99). There was some evidence of a reduced risk of preeclampsia with a high intake of magnesium and calcium, though these results were not statistically significant. Intake of fruits and vegetables, low-fat dairy products, total cereal and dark bread were each associated with a reduced risk of preeclampsia. CONCLUSION: Our results support previous reports that suggest that diets high in fiber and potassium are associated with a reduced risk of hypertension. Maternal intake of recommended amounts of foods rich in fiber, potassium and other nutrients may reduce the risk of preeclampsia.

Is adiposity an under-recognized risk factor for tendinopathy? A systematic review

Objective : Tendon injuries have been reported to occur more frequently in individuals with increased adiposity. Treatment also appears to have poorer outcomes among these individuals. Our objective was to examine the extent and consistency of associations between adiposity and tendinopathy.

Methods : A systematic review of observational studies was conducted. Eight electronic databases were searched (Allied and Complementary Medicine, Biological Abstracts, CINAHL, Current Contents, EMBase, Medline, SPORTDiscus, and Web of Science) and citation tracking was performed on included reports. Studies were included if they compared adiposity between subjects with and without tendon injury or examined adiposity as a predictor of conservative treatment success.

Results : Four longitudinal cohorts, 14 cross-sectional studies, 8 case-control studies, and 2 interventional studies (28 in total) met the inclusion criteria, providing a total of 19,949 individuals. Forty-two subpopulations were identified, 18 of which showed elevated adiposity to be associated with tendon injury (43%). Sensitivity analyses indicated a clustering of positive findings among studies that included clinical patients (81% positive) and among case-control studies (77% positive).

Conclusion : Elevated adiposity is frequently associated with tendon injury. Published reports suggest that elevated adiposity is a risk factor for tendon injury, although this association appears to vary depending on aspects of study design and measurement. Adiposity is of particular interest in tendon research because, unlike a number of other reported risk factors for tendon injury, it is somewhat preventable and modifiable. Further research is required to determine if reducing adiposity will reduce the risk of tendon injury or improve the results of treatment.

Exposure estimation, uncertainty and variability in occupational hygiene retrospective assessment

This thesis reports on a quantitative exposure assessment and on an analysis of the attributes of the data used in the estimations, in particular distinguishing between its uncertainty and variability. A retrospective assessment of exposure to benzene was carried out for a case control study of leukaemia in the Australian petroleum industry. The study used the mean of personal task-based measurements (Base Estimates) in a deterministic algorithm and applied factors to model back to places, times etc for which no exposure measurements were available. Mean daily exposures were estimated, on an individual subject basis, by summing the task-based exposures. These mean exposures were multiplied by the years spent on each job to provide exposure estimates in ppm-years. These were summed to provide a Cumulative Estimate for each subject. Validation was completed for the model and key inputs. Exposures were low, most jobs were below TWA of 5 ppm benzene. Exposures in terminals were generally higher than at refineries. Cumulative Estimates ranged from 0.005 to 50.9 ppm-years, with 84 percent less than 10 ppm-years. Exposure probability distributions were developed for tanker drivers using Monte Carlo simulation of the exposure estimation algorithm. The outcome was a lognormal distribution of exposure for each driver. These provide the basis for alternative risk assessment metrics e.g. the frequency of short but intense exposures which provided only a minimal contribution to the long-term average exposure but may increase risk of leukaemia. The effect of different inputs to the model were examined and their significance assessed using Monte Carlo simulation. The Base Estimates were the most important determinant of exposure in the model. The sources of variability in the measured data were examined, including the effect of having censored data and the between and within-worker variability. The sources of uncertainty in the exposure estimates were analysed and consequential improvements in exposure assessment identified. Monte Carlo sampling was also used to examine the uncertainties and variability associated with the tanker drivers' exposure assessment, to derive an estimate of the range and to put confidence intervals on the daily mean exposures. The identified uncertainty was less than the variability associated with the estimates. The traditional approach to exposure estimation typically derives only point estimates of mean exposure. The approach developed here allows a range of exposure estimates to be made and provides a more flexible and improved basis for risk assessment.

Regressive logistic and proportional hazards disease models for within-family analyses of measured genotypes, with application to a CYP17 polymorphism and breast cancer

Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population-based case families in which a mutation is known to be segregating. Here we extend the method to a common polymorphism, and use a regressive logistic approach to model familial aggregation by conditioning each individual on their mother's breast cancer history. We considered three models: 1) class A regressive logistic model; 2) age-of-onset regressive logistic model; and 3) proportional hazards familial model. Maximum likelihood estimates were calculated using the software MENDEL. We applied these methods to data from the Australian Breast Cancer Family Study on the CYP17 5UTR TC MspA1 polymorphism measured for 1,447 case probands, 787 controls, and 213 relatives of case probands found to have the CC genotype. Breast cancer data for first- and second-degree relatives of case probands were used. The three methods gave consistent estimates. The best-fitting model involved a recessive inheritance, with homozygotes being at an increased risk of 47% (95% CI, 28-68%). The cumulative risk of the disease up to age 70 years was estimated to be 10% or 22% for a CYP17 homozygote whose mother was unaffected or affected, respectively. This analytical approach is well-suited to the data that arise from population-based case-control-family studies, in which cases, controls and relatives are studied, and genotype is measured for some but not all subjects.

Genome - wide association study identifies novel breast cancer susceptibility loci

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r² > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10^-7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia)

OBJECTIVE: We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. METHODS: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. RESULTS: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. CONCLUSIONS: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women

Background: Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population.
Methods: In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders.Habitual physical activity,measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded.
Results: Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32–0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association.
Conclusion: This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.

Association between abnormal psychosocial situations in childhood, generalised anxiety disorder and oppositional defiant disorder

Objective: Psychosocial stressors are important in the pathogenesis of most mental disorders. However, little is known about the way psychosocial stressors uniquely combine to create risk for different expressions of child and adolescent psychopathology. The purpose of this study was to determine whether core dimensions of stressful psychosocial situations are differentially associated with childhood generalized anxiety disorder and oppositional defi ant disorder.

Method: A case-control design conducted in Trondheim (Norway) from 2002 to 2004 comparing exposure to ICD-10-defi ned abnormal psychosocial situations (Z-codes) among 21 children with oppositional defi ant disorder (ODD) and 22 children with generalized anxiety disorder (GAD) recruited from a university outpatient clinic with 42 non-patient school controls.

Results: Multigroup discriminant analysis extracted two signifi cant dimensions within the psychosocial variables assessed. Function 1 was characterized by overprotection, parental pressures and acute life events and was associated with GAD. Function 2 was characterized by parental abuse/hostility and interpersonal stress and was associated with ODD. Both dimensions were able to correctly classify 89.7% of the cases, compared to 35.9% by chance.

Conclusions: The results indicate that specifi c psychosocial dimensions are differentially related to childhood GAD and ODD. This may be useful in targeting at-risk populations for preventive intervention as well as informing more accurate alignment of psychosocial resources for treatment.

The association between urban or rural locality and hip fracture in community-based adults : a systematic review

Urban or rural locality has been suggested to influence musculoskeletal health, with lower bone mineral density (BMD) and greater prevalence of fracture identified in urban residents. A computer-aided search of Medline, EMBASE, CINAHL and PsychINFO, January 1966 to November 2007 was conducted to identify studies investigating the relationship between urban or rural locality and the occurrence of hip fracture. The methodological quality of studies was assessed, and a best-evidence synthesis was used to summarise the results. Fourteen cohort studies and one case-control study were identified for inclusion in this review, indicating a lack of literature in the field. Best-evidence analysis identified moderate evidence for residents of rural regions to have lower risk of hip fracture compared to urban residents. Examining principal mechanisms for the observed relationship between urban/rural locality and hip fracture, such as factors at the person or area level, may help to identify modifiable risk factors and inform appropriate prevention strategies.

Application of epidemiology to change health policy : defining age-related thresholds of bone mineral density for primary prevention of fracture

In Australia, benefits for antifracture therapies have been available for patients with osteoporosis and a prior fracture. No benefits were available to those with no prior fracture. We aimed to define, in women with no prior fracture, age-related thresholds of bone mineral density (BMD) associated with fracture risk equivalent to that of women with prior fracture and osteoporosis. A case-control study of women (≥50 yr) was conducted, including 291 fracture cases and 823 controls. BMD was measured at the proximal femur and posterior anterior (PA) spine. A fracture risk score (FRS) for the group with no prior fracture was calculated with discriminant analysis. The thresholds for equivalent fracture risk between those with no prior fracture and those with prior fracture were assessed using logistic regression. Increasing the FRS to +0.98 in women with no prior fracture resulted in equivalent odds of sustaining a fracture to those with prior fracture and osteoporosis. The corresponding T-score thresholds at the spine were −4.6 at 50 yr, −3.9 at 60 yr, −3.1 at 70 yr, and −2.4 at 80 yr. The femoral neck T-score thresholds were lower by 0.5 standard deviation. The high-risk individuals defined by this study should be considered for primary fracture prevention therapy.

β-Adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density : Geelong Osteoporosis Study

This population-based study documented β-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with β-blocker use was 0.68 (95%CI, 0.49–0.96). β-Blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. β-Blocker use is associated with reduced fracture risk and higher BMD.

Introduction: Animal data suggests that bone formation is under β-adrenergic control and that β-blockers stimulate bone formation and/or inhibit bone resorption.

Materials and Methods: We evaluated the association between β-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. β-Blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire.

Results: Odds ratio for fracture associated with β-blocker use was 0.68 (95% CI, 0.49–0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. β-Blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use.

Conclusion: β-Blockers are associated with a reduction in fracture risk and higher BMD.

Risk factors for Mycobacterium ulcerans infection, southeastern Australia

Buruli/Bairnsdale ulcer (BU) is a severe skin and soft tissue disease caused by Mycobacterium ulcerans. To better understand how BU is acquired, we conducted a case-control study during a sustained outbreak in temperate southeastern Australia. We recruited 49 adult patients with BU and 609 control participants from a newly recognized BU-endemic area in southeastern Australia. Participants were asked about their lifestyle and insect exposure. Odds ratios were calculated by using logistic regression and were adjusted for age and location of residence. Odds of having BU were at least halved for those who frequently used insect repellent, wore long trousers outdoors, and immediately washed minor skin wounds; odds were at least doubled for those who received mosquito bites on the lower legs or lower arms. This study provides new circumstantial evidence that implicates mosquitoes in the transmission of M. ulcerans in southeastern Australia.

Acute rheumatic fever associated with household crowding in a developed country

Background: Acute rheumatic fever (ARF) and its sequelae, chronic rheumatic heart disease, remain important causes of morbidity and mortality worldwide, but there is little recent information about risk factors. The aim of this study was to examine the association between ARF and household crowding in New Zealand between 1996 and 2005.

Methods: This ecologic study used hospitalization data and census data to calculate incidence rates by census area unit (CAU). Rates of ARF were examined in relation to individual factors (age, ethnicity) and area factors based on the CAU of home address (household crowding, New Zealand deprivation index, household income, and proportion of children aged 5–14 years). The multivariate relationship between ARF incidence and CAU-based variables was assessed using a zero-inflated negative binomial model.

Results: This study included 1249 new cases of ARF between 1996 and 2005. At the univariate level, ARF rates were associated with household crowding across all age groups and ethnicities. ARF rates were significantly and positively related to household crowding after controlling for age, ethnicity, household income, and the density of children in the neighborhood. The incidence rate ratio was 1.065 (95% confidence interval, 1.052–1.079) for the total population.

Conclusions: In New Zealand, ARF rates are associated with household crowding at the CAU level. This finding supports action to reduce household crowding to improve health and reduce health inequalities. Our conclusion could be further investigated using a case-control study.

B-cell loss and B-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition

Amyloid deposition and reduced β-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased β-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased β-cell area quantified on histological sections is correlated with increased β-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 ± 2 and 70 ± 4 islets/subject, respectively). Amyloid and β cells were visualized by thioflavin S and insulin immunolabeling. Apoptotic β cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased -cell area, and increased β-cell βapoptosis, as expected. There was a strong inverse correlation between β-cell area and amyloid deposition (r=0.42, P < 0.001). β-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had β-cell area equivalent to islets from control subjects. Increased amyloid deposition was associated with β-cell apoptosis (r= 0.56, P < 0.01). Thus, islet amyloid is associated with decreased β-cell area and increased β-cell apoptosis, suggesting that islet myloid deposition contributes to the decreased β-cell mass that characterizes type 2 diabetes.

Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach

Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized.

An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched.