Katrina King

Hematologic and Urinary Excretion Anomalies in Patients with Chronic Fatigue Syndrome

Patients with chronic fatigue syndrome (CFS) have a broad and variable spectrum of signs and symptoms with variable onsets. This report outlines the results of a single-blind, cross-sectional research project that extensively investigated a large cohort of 100 CFS patients and 82 nonfatigued control subjects with the aim of performing a case-control evaluation of alterations in standard blood parameters and urinary amino and organic acid excretion profiles. Blood biochemistry and full blood counts were unremarkable and fell within normal laboratory ranges. However, the case-control comparison of the blood cell data revealed that CFS patients had a significant decrease in red cell distribution width and increases in mean platelet volume, neutrophil counts, and the neutrophil-lymphocyte ratio. Evaluation of the urine excretion parameters also revealed a number of anomalies. The overnight urine output and rate of amino acid excretion were both reduced in the CFS group (P < 0.01). Significant decreases in the urinary excretion of asparagine (P < 0.0001), phenylalanine (P < 0.003), the branch chain amino acids (P < 0.005), and succinic acid (P < 0.0001), as well as increases in 3-methylhistidine (P < 0.05) and tyrosine (P < 0.05) were observed. It was concluded that the urinary excretion and blood parameters data supported the hypothesis that alterations in physiologic homeostasis exist in CFS patients.

Folate status, folate-related genes and serum miR-21 expression: implications for miR-21 as a biomarker

Background Free circulating microRNA (miRNA) in serum may be valuable biomarkers for disease diagnosis and prognosis. miR-21, the archetypal oncogenic miRNA, has been proposed as a biomarker for colorectal cancer and its benign precursor, adenomatous polyps. However, it is now becoming clear that circulating miRNA profiles may be sensitive to lifestyle and environmental influences. Dietary components involved in one-carbon metabolism are particularly well placed to modulate miRNA expression through an influence on DNA methylation pathways. Methods We investigated the role of methyl group donors (folate, B12, cysteine, homocysteine), polymorphisms of the enzymes of one-carbon metabolism, and serum miR-21 expression in a primary case–control cohort (colonoscopy confirmed adenomatous colon polyps vs controls; n = 253) and a secondary cross-sectional cohort (over 65s; n = 649). The relationships between these parameters and serum miR-21 levels were assessed, stratified by gender. Conclusions Serum miR-21 expression was related to occurrence of adenomatous polyps in females, but not males. Folate levels and MTHFR-C677T genotype was associated with miR-21 expression in both genders. Additionally, DHFR-19 del and MSR-A66G were associated with miR-21 expression in females and males, respectively. Stimulation with excess folate increased expression of miR-21 in colon cancer cell lines. General significance This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.

Association between omega-3 index and blood lipids in older Australians

Management of hyperlipidaemia remains a cornerstone therapy for the prevention of cardiovascular disease (CVD). Dietary supplementation with n-3 polyunsaturated fatty acid (PUFA) has been shown to modulate blood lipid profiles and reduce the risk of developing CVD. However, studies relating objective measures of long-term dietary n-3 PUFA intake and circulating lipid levels in older adults are limited. Thus, we aimed to determine whether there is an association between erythrocyte n-3 PUFA status (omega-3 index, O3I) and blood lipid profiles in older adults. A sample of adults aged 65-95 years who participated in the Retirement Health and Lifestyle Study was evaluated. Outcome measures included O3I (% eicosapentaenoic acid+% docosahexaenoic acid) and fasting blood lipid profiles [total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and triglyceride (TG)]. Two hundred and seventy-six subjects were included in the analyses. The mean±SD age was 77.6±7.4 years, and 40.9% were males. O3I was significantly higher in females compared to males. O3I was inversely associated with plasma TG (P<.001) and TC/HDL-cholesterol ratio (P<.05), and positively associated with HDL-cholesterol (P<.05), in all subjects. Associations between O3I and TG were evident in both females (r=-0.250, P<.01) and males (r=-0.225, P<.05). In females only, the odds of being hypertriglyceridaemic were highest in those with lowest O3I (P=.006). Trends for hypercholesterolaemia and elevated LDL risk were converse between males and females. Long-term n-3 PUFA status is associated with blood lipid profiles in older Australians. Our findings support the development and implementation of age-specific dietary strategies to reduce the risk of CVD via improving the O3I.

Sex-dependent association between erythrocyte n -3 PUFA and type 2 diabetes in older overweight people

The association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46·3 % female; 76·7 (sd 5·9) years) and 466 non-diabetic (57·9 % female; 77·8 (sd 7·1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1·0 (reference), 0·82 (95 % CI 0·31, 2·18), 0·56 (95 % CI 0·21, 1·52) and 0·22 (95 % CI 0·06, 0·82) (P trend=0·015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences.

Retirement Health and Lifestyle Study: Australian Neighborhood Environments and Physical Activity in Older Adults:

The aim of this study was to compare the walkability of neighborhood environments of older adults (65 years and above) living in the general community and retirement village settings, and to describe associations between walkability and the physical activity of participants. The study was conducted in a coastal region of Australia largely characterized by urban sprawl. In 2011-2012, 292 participant neighborhoods (400 m radius around each home) were audited using the Irvine-Minnesota Inventory. Having validated a local adaptation of this tool, we compared neighborhood environments in the two settings. We found no association between walkability of the built environment and walking behavior of participants. Although retirement village residents lived in more highly walkable environments, they did not walk more and their overall levels of physical activity were lower than those of community residents.

InsuTAG: A novel physiologically relevant predictor for insulin resistance and metabolic syndrome

The aim of this study was to investigate whether a novel physiologically relevant marker, InsuTAG (fasting insulin × fasting triglycerides) can predict insulin resistance (IR) and metabolic syndrome (MetS). Data of 618 participants from the Retirement Health and Lifestyle Study (RHLS) were evaluated for the current study. IR was defined by homeostatic model assessment (HOMA-IR) scores. Pearson correlations were used to examine the associations of InsuTAG with HOMA-IR and other markers. Predictions of IR from InsuTAG were evaluated using multiple regression models. Receiver operating characteristic curves (ROC) were constructed to measure the sensitivity and specificity of InsuTAG values and to determine the optimum cut-off point for prediction of IR. InsuTAG was positively correlated with HOMA-IR (r = 0.86; p < 0.0001). InsuTAG is a strong predictor of IR accounting for 65.0% of the variation in HOMA-IR values after adjusting for potential confounders. Areas under the ROC curve showed that InsuTAG (0.93) has higher value than other known lipid markers for predicting IR, with a sensitivity and specificity of 84.15% and 86.88%. Prevalence of MetS was significantly (p < 0.0001) higher in subjects with InsuTAG values greater than optimal cut-off value of 11.2. Thus, InsuTAG appears to be a potential feasible marker of IR and metabolic syndrome.

Temperature profiles of antibiotic-containing elastomeric infusion devices used by ambulatory care patients

Purpose The temperature profiles of antibiotic‐containing elastomeric infusion devices used by ambulatory care patients under various environmental conditions were evaluated. Methods A prospective, descriptive survey of temperature exposure was conducted in 4 publically funded hospitals. Over a 12‐month period, electronic temperature‐recording devices were attached to the antibiotic infusion devices (infusers) of prospectively randomized hospital‐in‐the‐home (HITH) participants. Temperatures were recorded immediately after infuser connection and every 5 minutes thereafter for 24 hours. A structured data collection form was used to collect information on basic clinical and demographic characteristics and aspects of daily living (i.e., how and where the infuser was carried during the day, times the participant went to and arose from bed, location of the infuser while sleeping, and dates and times the infuser was connected and disconnected). Results A total of 115 patients successfully completed the study (17–91 years old, 55% males). A total of 31,298 temperature readings were collected. The storage location of the infuser did not influence daytime readings. However, the overnight storage location did have a significant impact on the temperatures recorded overnight. The mean temperatures of infusers stored on the bed or on the body overnight were significantly higher than those for infusers stored away from the bed. Diurnal and seasonal influences were also detected. Significantly warmer temperatures were recorded in afternoons and evenings and during the summer months. Conclusion Antibiotics administered to HITH patients via continuous infusion were frequently exposed to temperatures in excess of 25 °C. Specific patient behaviors and seasonal and chronological factors influenced temperatures. The findings challenge the validity of current fixed‐temperature models for testing stability, which do not reflect conditions found in clinical practice.