A Web-Delivered, Clinician-Led Group Exercise Intervention for Older Adults With Type 2 Diabetes: Single-Arm Pre-Post Intervention.

BACKGROUND: The COVID-19 pandemic created unprecedented shifts in the way health programs and services are delivered. A national lockdown to prevent the spread of COVID-19 in Australia was introduced in March 2020. This lockdown included the closure of exercise clinics, fitness centers, and other community spaces, which, before the pandemic, were used to deliver Beat It. Beat It is an 8-week in-person, community-based, and clinician-led group exercise and education program for adults self-managing diabetes. To continue offering Beat It, it was adapted from an in-person program to a fully web-based supervised group exercise program for adults with type 2 diabetes (T2DM). OBJECTIVE: This study aims to assess whether the Beat It Online program produced comparable health outcomes to the Beat It in-person program in terms of improving physical fitness (muscular strength and power, aerobic endurance, balance, and flexibility) and waist circumference in older adults with T2DM. METHODS: Australians with T2DM who were aged ≥60 years were included. They were enrolled in Beat It Online, a twice-weekly supervised group exercise and education program conducted via videoconference over 8 weeks. Anthropometric measurements and physical fitness parameters were assessed at baseline and completion. The adaptations to Beat It are reported using the Model for Adaptation, Design, and Impact, including the type of changes (what, where, when, and for whom), the criteria for making those changes (why and how), and the intended and unintended outcomes. The intended outcomes were comparable functional fitness as well as physical and mental health improvements across demographics and socioeconomic status. RESULTS: A total of 171 adults (mean 71, SD 5.6 years; n=54, 31.6% male) with T2DM were included in the study, with 40.4% (n=69) residing in lower socioeconomic areas. On the completion of the 8-week program, significant improvements in waist circumference, aerobic capacity, muscular strength, flexibility, and balance were observed in both male and female participants (all P<.001). The Model for Adaptation, Design, and Impact reports on 9 clinical, practical, and technical aspects of Beat It that were adapted for web-based delivery. CONCLUSIONS: This study found that Beat It Online was just as effective as the in-person program. This adapted program produced comparable health benefits across demographics and socioeconomic status. This study offers important findings for practitioners and policy makers seeking to maintain independence of older people with T2DM, reversing frailty and maximizing functional and physical fitness, while improving overall quality of life. Beat It Online offers a flexible and inclusive solution with significant physical and mental health benefits to individuals. Further evaluation of Beat It (both in-person and Online) adapted for culturally and linguistically diverse communities will provide greater insights into the efficacy of this promising program.

Interrogating the Relationship Between Schizotypy, the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism, and Neuronal Oscillatory Activity.

The COMT Val158Met polymorphism affects the availability of synaptic dopamine in the prefrontal cortex and has been widely studied as a genetic risk factor for psychosis. Schizotypy is associated with an increased risk of psychosis, with some studies implicating similar neurobiological mechanisms to schizophrenia. The present study sought to interrogate the link between the COMT Val158Met polymorphism and schizotypy using electroencephalogram (EEG) to identify neurophysiological mechanisms underpinning psychosis risk. Neurotypical (N = 91) adults were genotyped for the COMT Val158Met polymorphism, completed the Schizotypal Personality Questionnaire (SPQ), and had eyes open resting-state EEG recorded for 4 min. SPQ suspiciousness subscale scores were higher for individuals homozygous for Val/Val and Met/Met versus Val/Met genotypes. Delta, theta, alpha-2, beta-1, and beta-2 amplitudes were lower for Val/Val than Met/Met individuals. Lower theta amplitudes were correlated with higher total SPQ scores (P = 0.050), and multiple regression revealed that higher delta, and lower theta and beta-2 amplitudes (but not COMT genotype) best predicted total SPQ scores (P = 0.014). This study demonstrates the importance of COMT genotype in determining trait suspiciousness and EEG oscillatory activity. It also highlights relationships between dopaminergic alterations, EEG and schizotypy that are dissimilar to those observed in schizophrenia.

Comparing DNA methylation profiles in saliva and intestinal mucosa.

BACKGROUND: Altered epigenetic profiles are a feature of intestinal diseases, including ulcerative colitis and Crohn's disease. DNA methylation studies in these diseases have utilised intestinal mucosal tissue or blood which can be difficult to collect, particularly for large-scale research studies. Saliva is an attractive alternative for epigenetic studies as it is easy to collect and provides high quality methylation profiles. The aim of the study was to determine the utility of saliva as an alternative for DNA methylation studies of intestinal disorders. RESULTS: DNA methylation in saliva and intestinal mucosa samples were compared in individuals (n = 10) undergoing endoscopies using the Illumina Infinium Methylation 450 K Beadchip array. We found that DNA methylation was correlated between tissue types within an individual (Pearson correlation co-efficient r = 0.92 to 0.95, p < 0.001). Of the 48,541 probes (approximately 11% of CpG sites) that were differentially methylated between saliva and intestinal mucosa (adjusted p < 0.001, |Δß| ≥ 20%), these mapped to genes involved in tissue-specific pathways, including the apelin signalling and oxytocin pathways which are important in gastrointestinal cytoprotection and motility. CONCLUSIONS: This study suggests that saliva has the potential to be used as an alternate DNA source to invasive intestinal mucosa for DNA methylation research into intestinal conditions.

DNA methylation profiles in preeclampsia and healthy control placentas.

Preeclampsia is a hypertensive disorder of pregnancy that affects 3-5% of all pregnancies. There is evidence to suggest that epigenetic mechanisms, such as DNA methylation, play a role in placental development and function. This study compared DNA methylation profiles of placentas from preeclampsia-affected pregnancies with placentas from healthy pregnancies to identify gene-specific changes in DNA methylation that may contribute to the development of preeclampsia. The methylation status of eight placental biopsies taken from preeclampsia-affected and 16 healthy pregnancies was analyzed using the Illumina Infinium Methylation 450 BeadChip array. Bisulfite pyrosequencing was used to confirm regions found to be differentially methylated between preeclampsia and healthy placentas. A total of 303 differentially methylated regions, 214 hypermethylated and 89 hypomethylated, between preeclampsia cases and controls were identified, after adjusting for gestational age (adjusted P < 0.05). Functional annotation found cell adhesion, wingless type MMTV Integration Site family member 2 (Wnt) signaling pathway, and regulation of transcription were significantly enriched in these gene regions. Hypermethylation of WNT2, sperm equatorial segment protein (SPESP1), NADPH oxidase 5 (NOX5), and activated leukocyte cell adhesion molecule (ALCAM) in preeclampsia placentas was confirmed with pyrosequencing. This study found differences in methylation in gene regions involved in cell signaling (WNT2), fertilization and implantation (SPESP1), reactive oxygen species signaling (NOX5), and cell adhesion (ALCAM). These results build on recently published studies that have reported significant differences in DNA methylation in preeclampsia placentas.

Does Telomere Shortening Precede the Onset of Hypertension in Spontaneously Hypertensive Mice?

Telomere length is widely considered as a marker of biological aging. Clinical studies have reported associations between reduced telomere length and hypertension. The aim of this study was to compare telomere length in hypertensive and normotensive mice at pre-disease and established disease time points to determine whether telomere length differs between the strains before and after the onset of disease. Genomic DNA was extracted from kidney and heart tissues of 4-, 12-, and 20-week-old male hypertensive (BPH/2J) and normotensive (BPN/3J) mice. Relative telomere length (T/S) was measured using quantitative PCR. Age was inversely correlated with telomere length in both strains. In 4-week-old pre-hypertensive animals, no difference in T/S was observed between BPH/2J and BPN/3J animals in kidney or heart tissue (kidney p = 0.14, heart p = 0.06). Once the animals had established disease, at 12 and 20 weeks, BPH/2J mice had significantly shorter telomeres when compared to their age-matched controls in both kidney (12 weeks p < 0.001 and 20 weeks p = 0.004) and heart tissues (12 weeks p < 0.001 and 20 weeks p < 0.001). This is the first study to show that differences in telomere lengths between BPH/2J and BPN/3J mice occur after the development of hypertension and do not cause hypertension in the BPH/2J mice.

Past oral contraceptive use and self-reported high blood pressure in postmenopausal women.

BACKGROUND: Studies have reported current hormonal contraceptive use is associated with adverse cardiovascular outcomes, including high blood pressure. The aim of this study was to determine the association between past hormonal contraception use and high blood pressure in Australian postmenopausal women. METHODS: Women were recruited from the 45 and Up Study, an observational cross-sectional study, conducted from February 2006 to December 2009, NSW Australia. All of the variables used in this study were derived from self-reported data. These women reported being postmenopausal, having an intact uterus, and had given birth to one or more children. Odds ratios and 99% confidence intervals for the association between past hormonal contraceptive use and current treatment for high blood pressure, stratified by current age (<58 yrs, 58-66 yrs, and ≥67 yrs) were estimated using logistic regression, adjusted for income, country of origin, BMI, smoking, alcohol, exercise, family history of high blood pressure, menopausal hormone therapy use, number of children, whether they breastfed, and age of menopause. RESULTS: A total of 34,289 women were included in the study. No association between past hormonal contraception use and odds of having high blood pressure were seen in any of the age groups (<58 yrs: odds ratio (OR) 1.1, 99% confidence interval (CI) 0.8 to 1.5, p = 0.36; 58-66 yrs: OR 0.9, 99% CI 0.7 to 1.1, p = 0.11; and ≥67 yrs: OR 0.9, 99% CI 0.8 to 1.0. p = 0.06). In women with a history of hormonal contraception use, no association between duration of hormonal contraception use and high blood pressure was observed. CONCLUSIONS: Past hormonal contraception use and duration of use is not associated with high blood pressure in postmenopausal women.

Identification of genes with altered expression in male and female Schlager hypertensive mice.

BACKGROUND: Numerous studies have shown sex differences in the onset and severity of hypertension. Despite these sex-differences the majority of animal studies are carried out in males. This study investigated expression changes in both male and female hypertensive mouse kidneys to identify common mechanisms that may be involved in the development of hypertension. METHODS: The Schlager hypertensive mouse model (BPH/2J) and its normotensive control (BPN/3J) were used in this study. Radiotelemetry was performed on 12 to 13 week old BPH/2J and BPN/3J male and female animals. Affymetrix GeneChip Mouse Gene 1.0 ST Arrays were performed in kidney tissue from 12 week old BPH/2J and BPN/3J male and female mice (n = 6/group). Genes that were differentially expressed in both male and female datasets were validated using qPCR. RESULTS: Systolic arterial pressure and heart rate was significantly higher in BPH/2J mice compared with BPN/3J mice in both males and females. Microarray analysis identified 153 differentially expressed genes that were common between males and females (70 upregulated and 83 downregulated). We validated 15 genes by qPCR. Genes involved in sympathetic activity (Hdc, Cndp2), vascular ageing (Edn3), and telomere maintenance (Mcm6) were identified as being differentially expressed between BPH/2J and BPN/3J comparisons. Many of these genes also exhibited expression differences between males and females within a strain. CONCLUSIONS: This study utilised data from both male and female animals to identify a number of genes that may be involved in the development of hypertension. We show that female data can be used to refine candidate genes and pathways, as well as highlight potential mechanisms to explain the differences in prevalence and severity of disease between men and women.

Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).

BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major regulator of both physiological and pathological angiogenesis. Associations between polymorphisms in VEGFA and complex disease have been inconsistent. The parent from whom the allele was inherited may account for these inconsistencies. This study examined the parent of origin effect on the expression of murine Vegfa. METHODS: Two homozygous, inbred mouse strains A/J (AJ) and 129x1/SvJ (129) were crossed to produce reciprocal AJ129 and 129AJ offspring, respectively. RNA was extracted from cardiac tissue of 6 week old male (n = 8) and female (n = 8) parental, and male and female F1 offspring mice (AJ129 n = 8 and 129AJ n = 8). Vegfa and Hif1a expression levels were measured by qPCR and compared between the F1 offspring from the reciprocal crosses. RESULTS: We found significant differences in the expression of Vegfa in F1 offspring (AJ129 and 129AJ mice) of the reciprocal crosses between AJ and 129 mice. Offspring of male AJ mice had significantly higher expression of Vegfa than offspring of male 129 mice (p = 0.006). This difference in expression was not the result of preferential allele expression (allelic imbalance). Expression of Hif1a, a transcriptional regulator of Vegfa expression, was also higher in F1 offspring of an AJ father (p = 0.004). CONCLUSION: Differences in Vegfa and Hif1a gene expression are likely the result of an upstream angiogenic regulator gene that is influenced by the parent of origin. These results highlight the importance of including inheritance information, such as parent of origin, when undertaking allelic association studies.

Association between parity and breastfeeding with maternal high blood pressure.

OBJECTIVE: The objective of this study was to determine how parity and breastfeeding were associated with maternal high blood pressure, and how age modifies this association. STUDY DESIGN: Baseline data for 74,785 women were sourced from the 45 and Up Study, Australia. These women were 45 years of age or older, had an intact uterus, and had not been diagnosed with high blood pressure before pregnancy. Odds ratios (ORs) and 99% confidence intervals (CIs) for the association between giving birth, breastfeeding, lifetime breastfeeding duration, and average breastfeeding per child with high blood pressure were estimated using logistic regression. RESULTS: The combination of parity and breastfeeding was associated with lower odds of having high blood pressure (adjusted OR, 0.89; 99% CI, 0.82-0.97; P < .001), compared with nulliparous women, whereas there was no significant difference between mothers who did not breastfeed and nulliparous women (adjusted OR, 1.06; 99% CI, 0.95-1.18; P = .20). Women who breastfed for longer than 6 months in their lifetime, or greater than 3 months per child, on average, had significantly lower odds of having high blood pressure when compared with parous women who never breastfed. The odds were lower with longer breastfeeding durations and were no longer significant in the majority of women over the age of 64 years. CONCLUSION: Women should be encouraged to breastfeed for as long as possible and a woman's breastfeeding history should be taken into account when assessing her likelihood of high blood pressure in later life.

A randomized, double-blind, placebo-controlled, parallel-group 12-week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment.

INTRODUCTION: This study primarily aimed to evaluate the efficacy and safety of SaiLuoTong (SLT) on cognition in mild cognitive impairment (MCI). METHODS: Community-dwelling people with MCI aged ≥60 years were randomly assigned to 180 mg/day SLT or placebo for 12 weeks. RESULTS: Thirty-nine participants were randomized to each group (N = 78); 65 were included in the final analysis. After 12 weeks, the between-groups difference in Logical Memory delayed recall scores was 1.40 (95% confidence interval [CI]: 0.22 to 2.58; P = 0.010); Delis-Kaplan Executive Function System Trail Making Test Condition 4 switching and contrast scaled scores were 1.42 (95% CI: -0.15 to 2.99; P = 0.038) and 1.56 (95% CI: -0.09 to 3.20; P = 0.032), respectively; Rey Auditory Verbal Learning Test delayed recall was 1.37 (95% CI: -0.10 to 2.84; P = 0.034); and Functional Activities Questionnaire was 1.21 (95% CI: -0.21 to 2.63; P = 0.047; P < 0.001 after controlling for baseline scores). DISCUSSION: SLT is well tolerated and may be useful in supporting aspects of memory retrieval and executive function in people with MCI. Highlights: SaiLuoTong (SLT) improves delayed memory retrieval and executive function in people with mild cognitive impairment (MCI).SLT is well tolerated in people ≥ 60 years.The sample of community dwellers with MCI was well characterized and homogeneous.

A hypertension gene: are we there yet?

Cardiovascular diseases are the leading cause of death worldwide. Essential hypertension is a major risk factor for the development of other cardiovascular diseases and is caused by a combination of environmental and genetic factors, with up to 50% of blood pressure variance currently attributed to an individual's genetic makeup. By studying genes that cause monogenic forms of hypertension and pathways relevant to blood pressure control, a number of polymorphisms have been identified that increase an individual's risk of developing high blood pressure. We report on candidate gene association studies and genome-wide association studies that have been performed to date in the field of hypertension research. It is becoming clear that for the majority of people there is no single gene polymorphism that causes hypertension, but rather a number of common genetic variants, each having a small effect. Using pharmacogenomics to personalize the treatment of hypertension holds promise for achieving and sustaining normotensive pressures quickly, while minimizing the risk of adverse reactions and unwanted side-effects. This will decrease the risk of stroke and myocardial infarction in individuals and lead to a reduced burden of disease upon society as a whole.

Community-Based Exercise and Lifestyle Program Improves Health Outcomes in Older Adults with Type 2 Diabetes.

BACKGROUND: The aim of this study was to assess the efficacy of Beat It-a community-based exercise and lifestyle intervention-in improving anthropometric and physical fitness outcomes in older adults with type 2 diabetes mellitus (T2DM). METHODS: Australians with T2DM who were aged 60 years or older were included. These individuals were enrolled in Beat It, a twice-weekly supervised group exercise and education program conducted over 8 weeks. Anthropometric measurements and physical fitness parameters were assessed at baseline and completion. Physical fitness measures were then compared to validated criterion standards of fitness levels required by older adults to remain physically independent into later life. RESULTS: A total of 588 individuals were included in the study. At baseline, a substantial proportion of the cohort had physical fitness measures that were below the standard for healthy independent living for their gender and age. Significant improvements in waist circumference and physical fitness were observed post program and resulted in an increase in the number of participants who met the standard for healthy independent living. CONCLUSIONS: Participation in Beat It improved important health outcomes in older adults with T2DM. A longer-term follow-up is needed to determine whether these positive changes were maintained beyond the delivery of the program.

Comparison of DNA methylation profiles from saliva in Coeliac disease and non-coeliac disease individuals.

BACKGROUND: Coeliac disease (CD) is a autoimmune disease characterised by mucosal inflammation in the small intestine in response to dietary gluten. Genetic factors play a key role with CD individuals carrying either the HLA-DQ2 or HLA-DQ8 haplotype, however these haplotypes are present in half the general population making them necessary but insufficient to cause CD. Epigenetic modifications, including DNA methylation that can change in response to environmental exposure could help to explain how interactions between genes and environmental factors combine to trigger disease development. Identifying changes in DNA methylation profiles in individuals with CD could help discover novel genomic regions involved in the onset and development of CD. METHODS: The Illumina InfiniumMethylation450 Beadchip array (HM450) was used to compare DNA methylation profiles in saliva, in CD and non-CD affected individuals. CD individuals who had been diagnosed at least 2 years previously; were on a GFD; and who were currently asymptomatic; were compared to age and sex-matched non-CD affected healthy controls. Bisulphite pyrosequencing was used to validate regions found to be differentially methylated. These regions were also validated in a second larger cohort of CD and non-CD affected individuals. RESULTS: Methylation differences within the HLA region at HLA-DQB1 were identified on HM450 but could not be confirmed with pyrosequencing. Significant methylation differences near the SLC17A3 gene were confirmed on pyrosequencing in the initial pilot cohort. Interestingly pyrosequencing sequencing of these same sites within a second cohort of CD and non-CD affected controls produced significant methylation differences in the opposite direction. CONCLUSION: Altered DNA methylation profiles appear to be present in saliva in CD individuals. Further work to confirm whether these differences are truly associated with CD is needed.

Electrophysiological correlates of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism.

The brain-derived neurotrophic factor (BDNF) protein is essential for neuronal development. Val66Met (rs6265) is a functional polymorphism at codon 66 of the BDNF gene that affects neuroplasticity and has been associated with cognition, brain structure and function. The aim of this study was to clarify the relationship between BDNF Val66Met polymorphism and neuronal oscillatory activity, using the electroencephalogram (EEG), in a normative cohort. Neurotypical (N = 92) young adults were genotyped for the BDNF Val66Met polymorphism and had eyes open resting-state EEG recorded for four minutes. Focal increases in right fronto-parietal delta, and decreases in alpha-1 and right hemispheric alpha-2 amplitudes were observed for the Met/Met genotype group compared to Val/Val and Val/Met groups. Stronger frontal topographies were demonstrated for beta-1 and beta-2 in the Val/Met group versus the Val/Val group. Findings highlight BDNF Val66Met genotypic differences in EEG spectral amplitudes, with increased cortical excitability implications for Met allele carriers.

Development of a Risk Score for Extraintestinal Manifestations of Coeliac Disease.

The aim of this study was to identify indicators of coeliac disease (CD) in an Australian cohort, beyond the known gastrointestinal symptoms. Individuals were recruited from the general population and at the 2014 Gluten Free Expo in Sydney and in Melbourne, Australia. Data on their current health status including medical history, diagnosis for CD, and family history were collected. Multivariable logistic regression was used to identify independent predictors of CD. A weighted risk score system was then generated for the independent predictors, and a risk score was calculated for each individual. A total of 301 individuals were included in the study. We found an association between CD and having a family history of CD (odds ratio [OR] 7.6, 95%confidence interval [CI] 3.7-15.6), an autoimmune disorder (OR 2.1, 95%CI 1.1-4.1), anemia (OR 5.8, 95%CI 2.8-11.9), lactose intolerance (OR 4.5, 95%CI 1.2-17.7), and depression (OR 4.8, 95%CI 1.9-11.6). Risk score analysis found individuals in the medium (OR 4.8, 95%CI 2.5 to 9.3) and high-risk (OR 36.6, 95%CI 16.4 to 81.6) groups were significantly more likely to report having CD compared with those in the low-risk group. This study identifies a set of factors more commonly observed in individuals with CD, beyond the traditional gastrointestinal complaints. These include a family history of CD, the presence of another autoimmune disorder, anemia, lactose intolerance, and depression. A risk score was developed (Coeliac Risk COMPARE) which scores individuals based on the presence or absence of these additional symptoms and provides an additional screening tool when assessing whether the patient requires follow-up testing for CD.

A Cross-Sectional Study of Ageing and Cardiovascular Function over the Baboon Lifespan.

BACKGROUND: Ageing is associated with changes at the molecular and cellular level that can alter cardiovascular function and ultimately lead to disease. The baboon is an ideal model for studying ageing due to the similarities in genetic, anatomical, physiological and biochemical characteristics with humans. The aim of this cross-sectional study was to investigate the changes in cardiovascular profile of baboons over the course of their lifespan. METHODS: Data were collected from 109 healthy baboons (Papio hamadryas) at the Australian National Baboon Colony. A linear regression model, adjusting for sex, was used to analyse the association between age and markers of ageing with P < 0.01 considered significant. RESULTS: Male (n = 49, 1.5-28.5 years) and female (n = 60, 1.8-24.6 years) baboons were included in the study. Age was significantly correlated with systolic (R2 = 0.23, P < 0.001) and diastolic blood pressure (R2 = 0.44, P < 0.001), with blood pressure increasing with age. Age was also highly correlated with core augmentation index (R2 = 0.17, P < 0.001) and core pulse pressure (R2 = 0.30, P < 0.001). Creatinine and urea were significantly higher in older animals compared to young animals (P < 0.001 for both). Older animals (>12 years) had significantly shorter telomeres when compared to younger (<3 years) baboons (P = 0.001). CONCLUSION: This study is the first to demonstrate that cardiovascular function alters with age in the baboon. This research identifies similarities within cardiovascular parameters between humans and baboon even though the length of life differs between the two species.

Association Between a Woman's Age at First Birth and High Blood Pressure.

The aim of this article is to determine whether the age of a woman at first birth is associated with treatment for high blood pressure (HBP) later in life.Baseline data for 62,914 women were sourced from the "45 and Up Study," an observational cohort study of healthy aging in Australia. These women had given first birth between the ages of 18 and 45 years. Odds ratios and 95% confidence intervals for the association between age that a woman gave first birth and treatment for HBP were estimated using logistic regression. Data were stratified by current age (<60 and ≥60 years) and adjusted for demographic and lifestyle factors.There was a significant association between age at first birth and present day HBP. Older age at first birth was associated with a lower likelihood of HBP in women aged 25 to <35 years and 35 to 45 years at first birth (in women currently <60 years) and 35 to 45 years at first birth (in women currently ≥60 years of age), compared with women aged 18 to <25 years at first birth, adjusting for demographic and lifestyle factors.Women who were older when they gave first birth had lower odds of treatment for HBP compared with women who were younger when they gave birth to their first child. The contribution of a woman's pregnancy history, including her age at first birth, should be discussed with a patient when assessing her risk of HBP.

Variability in mRNA expression of fms-like tyrosine kinase-1 variants in normal and preeclamptic placenta.

BACKGROUND: Preeclampsia is a complication of pregnancy characterised by gestational hypertension and proteinuria and is a leading cause of morbidity and mortality in both mothers and infants. Certain anti-angiogenic factors have long been implicated in the pathogenesis of preeclampsia and the placental expression of factors such as soluble fms-like tyrosine kinase-1 (sFLT-1) are often reported in studies of normal and diseased placentae. Despite evidence showing significant differences in placental gene expression by collection site, many studies fail to provide sufficient details on sample selection and collection. FINDINGS: With ourselves and others investigating and reporting on the expression of FLT-1 variants and other genes in the placenta of normotensive and preeclamptic patients, we felt it prudent to examine the variation in expression of FLT-1 variants across human placenta. We examined the differential expression of FLT-1 variants in samples obtained from 12 sites on normal and preeclamptic placentae and found expression to be highly variable between sites. We therefore developed an algorithim to calculate the mean expression for any number of these sites collected and in any combination. The coefficient of variation for all combinations of sites was then used to determine the minimum number of sites required to reduce coefficient of variation to below an acceptable 10%. We found that 10 and 11 sites had to be sampled in the normal and preeclamptic placentae respectively to ensure a representative expression pattern for all FLT-1 variants for an individual placenta. CONCLUSIONS: These findings demonstrate significant variation in expression levels of several commonly investigated genes across sites in both normal and preeclamptic placenta. This highlights both the importance of adequate sampling of human placenta for expression studies and the effective communication of sample selection and collection methods, for data interpretation and to ensure the reproducibility and reliability of results and conclusions drawn.

Menopausal hormone therapy: examining cardiovascular and clinical impacts of treatment.

Postmenopausal women have reduced levels of female sex hormones and this may play a significant role in the onset of cardiovascular disease. Menopausal hormone therapy (MHT), which is primarily prescribed for the treatment of perimenopausal symptoms, has been associated with risk of coronary heart disease, hypertension and stroke in women. This review will summarize the outcomes of observational studies and randomized clinical trials that have investigated the influence of MHT use on the cardiovascular system. In addition, it will explore how the timing of MHT prescription relative to menopause, dosage and route of administration may alter the impact of MHT on cardiovascular health.

Changes in retinal microvascular caliber precede the clinical onset of preeclampsia.

Preeclampsia is a leading cause of maternal morbidity and mortality. The degree of maternal cardiovascular dysfunction that precedes the onset of preeclampsia is largely unknown. This prospective cohort study aimed to characterize differences in vivo in retinal microvascular caliber and blood pressure throughout pregnancy in relation to preeclampsia development. Women were recruited from Royal Prince Alfred Hospital, Sydney, Australia, of which 92 women were included in the study. Retinal images and blood pressures were collected at 13, 19, 29, and 38 weeks of gestation. Retinal vessels were analyzed as the central retinal arteriolar equivalent corrected for mean arterial blood pressure and the central retinal venular equivalent corrected for mean arterial blood pressure, using generalized linear models adjusted for age and body mass index. The preeclampsia group were significantly older (P=0.002) and had a significantly higher mean body mass index (P=0.005). The central retinal arteriolar equivalent corrected for mean arterial blood pressure was significantly reduced at 13 (P=0.03), 19 (P=0.007), and 38 (P=0.03) weeks of gestation in the preeclampsia group. The central retinal venular equivalent corrected for mean arterial blood pressure was also significantly lower at 13 (P=0.04) and 19 (P=0.001) weeks of gestation in the women who progressed to preeclampsia. This study directly documents increased peripheral resistance in vivo, observed as the combination of constricted retinal arterioles or venules and elevated blood pressure, in women who later developed preeclampsia. This difference preceded the clinical signs of preeclampsia.