Presynaptic inhibition decreases when estrogen level rises.

The objective was to determine estrogen's influence on control of a skeletal muscle through measurements of motorneuron excitability (H:M ratio) and presynaptic inhibition (PI). Estrogen serum concentrations were measured at menses and ovulation of female subjects and compared to male controls. Data were analyzed from 12 women and 13 men reporting no history of knee ligament injury. Women reported regular menstrual cycles and no hormone-based contraceptive use for the previous year. Women were tested at menses (Time1) and ovulation (Time2). Men were tested twice, approximately 14 days apart. Analysis indicated no difference in the H:M ratio between the sexes at either time point. A significant difference for the sexes was detected in the magnitude of estrogen change (∆EST) between observations. At Time1, the male and female estrogen concentrations were not different; however, they were different at Time2, primarily due to the large rise observed in the women. A significant difference between the sexes was also seen in the magnitude of change for PI (∆PI) between observations. As with EST, the levels of PI between the sexes at Time1 were not different; however, a difference existed at Time 2. Estrogen interacts with GABA at several nervous system locations affecting inhibition of synaptic transmission. This is the first study to investigate changes in PI of a skeletal muscle between times of low and high estrogen. Improving the understanding of estrogen's influence on skeletal muscles may provide answers to why noncontact anterior cruciate ligament injuries of the knee occur more frequently in women.

Walking, Sedentary Time and Health-Related Quality Life Among Kidney Transplant Recipients: An Exploratory Study.

OBJECTIVES: The primary objectives of this study were to: 1) establish walking and physical activity prevalence and sedentary time estimates; and 2) determine associations of health-related quality of life (HRQoL) with objectively assessed walking, self-reported physical activity, and sedentary time among kidney transplant recipients. METHODS: Using a cross-sectional design, kidney transplant recipients received a survey package containing measures of sedentary time, moderate-to-vigorous physical activity, and HRQoL, and a step pedometer. RESULTS: Thirty-two participants returned a completed survey, for a response rate of 82% (32 of 39 interested participants). The average steps per day were 9752 steps (SD = 3685) and 59% achieved public health guidelines of at least 150 minutes of moderate-to-vigorous physical activity per week. Total sedentary time during the week was 11.6 h/d whereas total sedentary time during the weekend was 8.9 h/d. Compared to those not achieving at least 10,000 steps/d, respondents who were achieving at least 10,000 steps/d had a significantly higher physical component score for HRQoL (Mdiff = 7.8, P = .018). Similar patterns emerged for meeting physical activity guidelines and sedentary time. CONCLUSION: For kidney transplant recipients, greater participation in walking, overall physical activity, and lower engagement in sedentary activity, was associated with better HRQoL.

Prompted awareness and use of Eating Well with Canada's Food Guide: a population-based study.

BACKGROUND: Little is known about the awareness of Canada's Food Guide (CFG). The present study aimed to report the general and specific awareness of CFG recommendations among adults in Alberta, Canada. METHODS: For this cross-sectional study, respondents (aged >18 years) from randomly selected households completed a telephone survey. Questions pertaining to CFG, physical activity, and vegetable and fruit consumption were included. Logistic regression determined associations between demographic characteristics and awareness of CFG. RESULTS: Thousand two hundred and ten Albertans (50% female, mean age 50.5 years) responded. Most [86.5%; 95% confidence interval (CI) = 84.6-88.4] indicated being generally aware of CFG when prompted and 82.5% were aware of specific CFG recommendations. There were no differences in age between those generally aware and unaware of CFG. Female sex [odds ratio (OR) = 3.6; 95%CI = 24-5.4], Caucasian ethnicity (OR = 3.7; 95% CI = 2.3-5.8), income ≥ Canadian $100 000 per annum (OR = 1.6; 95% CI = 1.1-2.3), reporting ≥5 vegetables and fruit per day (OR = 2.1; 95% CI = 1.4-3.2), exceeding recommended levels for physical activity (OR = 2.0; 95% CI = 1.3-2.9) and perception of current weight as healthy (OR = 1.8; 95% CI = 1.2-2.8) were associated with an awareness of CFG. CONCLUSIONS: Sex, ethnicity and income were associated with general awareness of CFG. Future studies could explore the relationship between awareness and other health-related behaviours.

Spinal and supraspinal motor control predictors of rate of torque development.

During explosive movements and potentially injurious situations, the ability to rapidly generate torque is critical. Previous research has suggested that different phases of rate of torque development (RTD) are differentiately controlled. However, the extent to which supraspinal and spinal mechanisms predict RTD at different time intervals is unknown. RTD of the plantarflexors across various phases of contraction (i.e., 0-25, 0-50, 0-100, 0-150, 0-200, and 0-250 ms) was measured in 37 participants. The following predictor variables were also measured: (a) gain of the resting soleus H-reflex recruitment curve; (b) gain of the resting homonymous post-activation depression recruitment curve; (c) gain of the GABAergic presynaptic inhibition recruitment curve; (d) the level of postsynaptic recurrent inhibition at rest; (e) level of supraspinal drive assessed by measuring V waves; and (f) the gain of the resting soleus M wave. Stepwise regression analyses were used to determine which variables significantly predicted allometrically scaled RTD. The analyses indicated that supraspinal drive was the dominant predictor of RTD across all phases. Additionally, recurrent inhibition predicted RTD in all of the time intervals except 0-150 ms. These results demonstrate the importance of supraspinal drive and recurrent inhibition to RTD.

How much will we pay to increase steps per day? Examining the cost-effectiveness of a pedometer-based lifestyle program in primary care.

We previously demonstrated the Healthy Eating and Active Living for Diabetes (HEALD) intervention was effective for increasing daily steps. Here, we consider the cost-effectiveness of the HEALD intervention implemented in primary care. HEALD was a pedometer-based program for adults with type-2 diabetes in Alberta, Canada completed between January 2010 and September 2012. The main outcome was the change in pedometer-determined steps/day compared to usual care. We estimated total costs per participant for HEALD, and total costs of health care utilization through linkage with administrative health databases. An incremental cost-effectiveness ratio (ICER) was estimated with regression models for differences in costs and effects between study groups. The HEALD intervention cost $340 per participant over the 6-month follow-up. The difference in total costs (intervention plus health care utilization) was $102 greater per HEALD participant compared to usual care. The intervention group increased their physical activity by 918 steps/day [95% CI 116, 1666] compared to usual care. The resulting ICER was $111 per 1000 steps/day, less than an estimated cost-effectiveness threshold. Increasing daily steps through an Exercise Specialist-led group program in primary care may be a cost-effective approach towards improving daily physical activity among adults with type-2 diabetes. Alternative delivery strategies may be considered to improve the affordability of this model for primary care.

JMH blood group system: a review.

The JMH blood group system consists of six high-prevalence antigens. These antigens are located on the Sema7A protein. The molecular basis of the JMH1- phenotype is not known; however, single nucleotide changes in the SEMA7A gene on chromosome 15 account for the other JMH antigens. JMH1, commonly known as JMH, is most notable because transient depression of the antigen occurs and anti-JMH may develop. These antibodies are most commonly observed and are not significant in transfusion. Antibodies developed in the rare JMH variant types may cause reduced red cell survival. This review provides a general overview of the JMH blood group system, including the serologic and molecular characteristics as well as proposed functions of the Sema7A protein.

The Alberta Diabetes and Physical Activity Trial (ADAPT): a randomized trial evaluating theory-based interventions to increase physical activity in adults with type 2 diabetes.

BACKGROUND: Physical activity (PA) is associated with reduced morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM); however, most T2DM adults are insufficiently active. PURPOSE: To explore the effectiveness of two innovative/theoretically based behavioral-change strategies to increase PA and reduce hemoglobin A1c (A1c) in T2DM adults. METHODS: Participants (n = 287) were randomly assigned to a control group or an intervention group (i.e., print-based materials/pedometer group or print-based materials/pedometer plus telephone-counseling group). Changes in PA and A1c and other clinical measures were examined by Linear Mixed Model analyses over 18 months, along with moderating effects for gender and age. RESULTS: PA and A1c levels did not significantly change in intervention groups. Step counts significantly increased in the print-based materials and pedometer plus telephone counseling group, for women. CONCLUSIONS: No significant effects were found for PA or A1c levels for T2DM adults. The multi-component strategy including telephone counseling may have potential for women. The trial was registered on ClinicalTrials.gov identifier: NCT00221234.

Role for serial prenatal anti-Vel quantitative serologic monitoring with 2-ME serum treatment during pregnancy: case report.

Anti-Vel is an uncommon antibody to a high-prevalence antigen. Its clinical significance and management in the prenatal setting are not well characterized. We present a case that demonstrates the utility of serial prenatal anti-Vel quantitative serologic monitoring with 2-ME serum treatment during pregnancy. The patient is a 23-year-old Hispanic woman with history of prior pregnancy and prior transfusion who was discovered to have an antibody to the high-prevalence Vel antigen in the first trimester (week 7) of her second pregnancy. Interval measurements of the serologic antibody titers were performed during the next 26 weeks. The untreated serum (IgM and IgG) titer increased from a baseline of 4 to 16 during that interval, while the 2-ME (presumed IgG component) titer remained stable at 4. Responding to ultrasound findings suspicious for fetal anemia, the child was delivered without complications at 34 weeks' gestation. At birth, the DAT was negative and there was no evidence of HDN. Placed in the context of other similar reports, this case demonstrates the importance of separately reporting the IgG fraction (after either DTT treatment or 2-ME treatment) from the untreated (IgM and IgG) fraction and the importance of correlating the treated serum titer with potential clinical significance.

Child Health Ecological Surveillance System (CHESS) for childhood obesity: a feasibility study.

OBJECTIVE: To assess the feasibility of employing an ecologically guided childhood obesity relevant surveillance system. METHODS: Cross-sectional qualitative and quantitative data were collected from 31 organizational representatives across 28 unique organizations and/or departments from three purposively sampled communities in the Capital Health Region in Alberta, Canada. RESULTS: All the organizational representatives surveyed reported awareness of childhood obesity and 36% reported participation in child obesity initiatives. Data to support a surveillance system are available but not in a suitable format, and privacy legislation present significant barriers. Interest in developing and sustaining an ecologically based surveillance system was low (18%). CONCLUSION: Due to the heterogeneity of available data and limited vision for the development and implementation of a surveillance system, the application of an ecologically based surveillance system relevant to childhood obesity may be constrained. Broad-based awareness of childhood obesity by a wide range of organizations could assist in establishing an effective coalition to address this issue over the long term by supporting the establishment of a surveillance system.

Improved cardiovascular health following a progressive walking and dietary intervention for type 2 diabetes.

AIM: To examine the impact of two different lifestyle programmes on cardiovascular health and glycaemic control among people with type 2 diabetes. METHODS: A two-phase 24-week randomized trial. During the first phase, participants were to increase daily steps using a pedometer. At week 12, participants were randomly allocated to either an enhanced lifestyle programme (ELP) targeting walking speed or a basic lifestyle programme (BLP) targeting total daily steps. Both programmes focused on increasing the intake of low glycaemic index foods but utilized different goal setting strategies. Clinical measurements were completed at baseline, week 12 and week 24. Principal outcomes were change in resting pulse rate (PR) and glycated haemoglobin A1c (A1c) between week 12 and week 24 compared between groups using analysis of covariance. RESULTS: Forty-one participants [mean +/- s.d. : age = 56.5 +/- 7.2 years, body mass index (BMI) = 32.7 +/- 6.1 kg/m(2)] were randomized. After 12 weeks, we observed an increase in average total daily steps of 1688 (95% confidence interval: 330-3040, [corrected] p = 0.02). Weight, BMI and systolic and diastolic blood pressure improved (p < 0.01 for all). No changes were observed for energy intake. At week 24, those in the ELP had a lower resting PR (71 +/- 12 b.p.m.) compared with those in the BLP (78 +/- 12 b.p.m.) (adjusted p = 0.03), while no group differences for total daily steps or glycaemic control were observed. CONCLUSIONS: Improvements in cardiovascular health can be expected following a pedometer-based lifestyle modification programme that progresses from walking more to walking faster.

Acute effect of metformin on exercise capacity in active males.

AIM: Physical activity and metformin are often used concomitantly in the treatment of diabetes, even though little is known about possible interactions between these treatment modalities. This study was designed to examine the acute effect of metformin on oxygen consumption and lactate concentration during exercise. METHODS: Eleven healthy, active men [mean +/- s.d.: age = 29.9 +/- 3.7 years; body mass index = 25.2 +/- 2.8 kg/m2; maximal oxygen consumption (VO2max) = 53.5 +/- 8.9 ml/kg/min] completed a randomized, double-blind, placebo-controlled, crossover study. The testing protocol consisted of a standardized breakfast with metformin (1000 mg) or placebo. Three hours after breakfast, participants underwent a graded maximal exercise test on a cycle ergometer. Approximately 30 min after this exercise test, participants cycled continuously at an intensity below their ventilatory threshold for 45 min (mean exercise intensity = 69 +/- 5.5% of VO2max). RESULTS: During the graded exercise test, average oxygen consumption was higher for the metformin condition (2.9 vs. 2.8 l/min, p = 0.04); however, there was no treatment effect on VO2max or ventilatory threshold. During continuous exercise, lactate was lower for the metformin condition (4.7 vs. 5.4 mmol/l, p = 0.05). Following a standardized lunch, glucose concentrations were lower in the metformin compared with the placebo condition (5.8 vs. 6.4 mmol/l, p = 0.04). CONCLUSION: A single dose of metformin does not acutely influence maximal oxygen consumption or ventilatory threshold in healthy active males. The lower lactate concentration observed during continuous exercise with metformin was an unexpected finding considering that, in the resting state, metformin has been previously associated with a modest increase in lactate concentrations.

Promotion of physical activity by Canadian Registered Dietitians in daily practice.

BACKGROUND: Dietitians are in an opportunistic position to promote healthy eating and active living. The purpose of this study was to determine counselling strategies of dietitians 1 year after attending a workshop designed to strengthen dietitians' self-efficacy for promoting physical activity (PA) as an adjunct to regular nutrition practice. METHODS: A convenience sample of Registered Dietitians (RDs) in Alberta, Canada (n=103) responded to an invitation via an electronic newsletter to complete a web-based survey that asked about counselling practices related to PA. RESULTS: Thirty-seven workshop attendees (n=37) were compared with a group of dietitians (n=66) who completed the survey but who did not attend the workshop. Nearly all (91%) respondents reported promoting PA in daily practice. Those who attended the workshop were more likely to refer clients to PA professionals (chi2=12.68, P<0.05) than those who were not workshop attendees. CONCLUSIONS: Despite a relatively modest response rate, there were clear suggestions that RDs in Alberta, Canada promote PA in daily practice and attending a workshop designed to facilitate the use of specific tools and strategies for promoting PA in daily practice resulted in increased referral of their clients to exercise specialists.

Incidence of weak D in blood donors typed as D positive by the Olympus PK 7200.

The incidence of weak D has been reported to be between 0.23 and 0.5 percent in Europe and 3.0 percent in the United States. All studies were performed before the introduction of monoclonal anti-D reagents. Using current commercial reagents, this study evaluated D+ samples for the presence of weak D. D+ donors, typed by the Olympus PK 7200, using diluted monoclonal blend anti-D and diluted polyclonal anti-D, were selected by sampling batches of 100 to 200 samples from the previous day's collection. Anti-D reagents used on the Olympus PK 7200 are required to detect RBCs with the weak D phenotype which do not agglutinate at immediate spin (IS) when tested with polyclonal anti-D by manual tube methods. More than 95 percent of donors tested were Caucasian. Using tube tests with two different monoclonal blend anti-D reagents and one polyclonal anti-D typing reagent, the presence or absence of the D antigen was evaluated after the IS reading. Donors found negative or weakly positive (< 2+) at IS were further typed for weak D by the IAT. The weak D samples were RHD genotyped by allele-specific PCR. Of 1,005 donors tested, 4 (0.4%) were classified as weak D by one or more anti-D reagents. Polyclonal anti-D reagent demonstrated weaker reactions when compared with the monoclonal blends. All weak D samples were found positive for exon 4, intron 4, and exon 10, a finding consistent with most D+ samples. The incidence of weak D found in this study is not significantly different from that found in earlier studies using polyclonal anti-D reagents.

Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti-inflammatory drug.

BACKGROUND: Immune hemolytic anemia can be caused by sensitivity to many different drugs. In some instances, the sensitizing compound can be identified by in vitro testing, but results are often negative. One reason for this is that a drug metabolite formed in vivo can be the sensitizing agent, but the responsible metabolites have rarely been identified at a chemical level. This report describes a patient who developed severe, Coombs-positive hemolytic anemia on two occasions after taking the nonsteroidal anti-inflammatory drug etodolac. Studies were performed to characterize etodolac metabolites to which this patient was sensitive. CASE REPORT: Serum was tested for antibody in the presence and absence of drug using conventional methods and urine from individuals taking etodolac as a source of drug metabolites. Urinary metabolites of etodolac were identified by high-pressure liquid chromatography analysis. Glucuronide conjugates of etodolac and the 6-OH metabolite of etodolac were synthesized in a rat liver microsomal system to obtain reference standards. RESULTS: The patient's serum gave only trace (+/-) reactions with normal RBCs in the presence of etodolac but reacted strongly (4+) in the presence of urine from an individual taking this drug. The active urinary metabolites were identified as etodolac glucuronide and 6-OH etodolac glucuronide. CONCLUSION: This patient appears to have experienced acute, severe immune hemolytic anemia on two occasions because of sensitivity to the glucuronides of etodolac and 6-OH etodolac. In patients suspected of having drug-induced immune hemolytic anemia, RBC-reactive antibodies can sometimes be detected by using urine from an individual taking the implicated medication as the source of drug metabolites in in vitro reactions. For patients who present with acute immune hemolysis, a careful history of drug exposure should be taken, and, where indicated, confirmatory testing should be performed to identify the sensitizing drug and prevent inadvertent reinduction of hemolysis at a later time.

Immunoglobulin isotype identification in red cell antibodies using flow cytometry.

BACKGROUND: Identifying the isotype of an immunoglobulin (IgM vs. IgG) detected in a patient sample is especially important in anticipating the risk of hemolytic disease of the newborn. Currently, 2-mercaptoethanol (2-ME) treatment of a sample is used in the authors' laboratory to degrade IgM, and this is followed by retesting. This method has multiple drawbacks. The purpose of this study was to develop a flow cytometry (FC) assay that would replace the 2-ME treatment protocol (2-ME treatment). STUDY DESIGN AND METHODS: A preliminary FC assay was developed, modified, and refined through the use of stock antibodies. Then, 10 samples containing antibodies were tested in parallel by the FC assay and 2-ME treatment. RESULTS: When a 10-unit mean channel fluorescence change was used as an index of a positive result, the FC assay detected all isotypes identified by 2-ME treatment. The FC assay was also able to identify mixtures of isotypes. One antibody that had not reacted in conventional agglutination testing was detected by the FC assay. The amount of fluorescence and the agglutinating strength of the antibody did not parallel each other. In one case, this discrepancy may have reflected an antibody that was primarily IgA. CONCLUSIONS: The FC assay appears to be as accurate as 2-ME treatment in differentiating IgG from IgM. The FC assay produces a positive endpoint for both isotypes, will identify IgA, requires less sample, and has no odor.

Prenatal genotyping of the Duffy blood group system by allele-specific polymerase chain reaction.

Maternal allo-immunization to antigens of the Duffy blood group system can result in haemolytic disease of the newborn (HDN), therefore, the application of allele-specific polymerase chain reaction (ASPCR) for prenatal genotyping of the Duffy antigen system to identify pregnancies at risk for HDN was evaluated. Oligonucleotide primers were designed for ASPCR of FYA, FYB and nullFY alleles. A validation study was performed using DNA isolated from 94 serotyped whole blood samples and 8 amniocentesis samples. A concordance rate of 100 per cent was observed between serotyping and ASPCR detection of the FYA, FYB and nullFY alleles. This assay is particularly useful for rapid genotyping of fetal amniotic cells to identify pregnancies at risk for HDN due to maternal fetal incompatibilities within the Duffy blood group system.