Altered Visual and Feet Proprioceptive Feedbacks during Quiet Standing Increase Postural Sway in Patients with Severe Knee Osteoarthritis

Objective

The objective was to investigate how postural control in knee osteoarthritis (KOA) patients, with different structural severities and pain levels, is reorganized under different sensory conditions.

Methods

Forty-two obese patients (BMI range from 30.1 to 48.7 kg*m⁻², age range from 50 to 74 years) with KOA were evaluated. One minute of quiet standing was assessed on a force platform during 4 different sensory conditions, applied 3 times at random: Eyes open (EO) and eyes closed (EC) standing on firm and soft (foam) surfaces (EO-soft and EC-soft). Centre of pressure (Cop) standard deviation, speed, range and Cop mean position in both directions (anterior-posterior and medial-lateral) were extracted from the force platform data. Structural disease severity was assessed from semiflexed standing radiographs and graded by the Kellgren and Lawrence (KL) score. Pain intensity immediately before the measurements was assessed by numeric rating scale (range: 0–10).

Results

The patients were divided into “less severe” (KL 1 and 2, n = 24) and “severe” (KL>2, n = 18) group. The CoP range in the medial-lateral direction was larger in the severe group when compared with the less severe group during EC-soft condition (P<0.01). Positive correlation between pain intensity and postural sway (range in medial-lateral direction) was found during EC condition, indicating that the higher the pain intensity, the less effective is the postural control applied to restore an equilibrium position while standing without visual information.

Conclusion

The results support that: (i) the postural reorganization under manipulation of the different sensory information is worse in obese KOA patients with severe degeneration and/or high pain intensity when compared with less impaired patients, and (ii) higher pain intensity is related to worse body balance in obese KOA patients.     

Hawthorne Effect with Transient Behavioral and Biochemical Changes in a Randomized Controlled Sleep Extension Trial of Chronically Short-Sleeping Obese Adults: Implications for the Design and Interpretation of Clinical Studies

Objective

To evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit.

Design

Subjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later.

Setting

Outpatient.

Patients

Obese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6±19.7 kg, <6.5 h sleep/night.

Intervention

Non-pharmacological sleep extension.

Measurements

Sleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids.

Results

Prior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 ±51.2 vs. 388.1±48.6 min/night; mean±SD; P<0.001 screening vs. randomization; actigraphy: 344.3 ±41.9 vs. 358.6±48.2 min/night; P<0.001) sleep quality improved (9.1±3.2 vs. 8.2±3.0 PSQI score; P<0.001), sleepiness tended to improve (8.9±4.6 vs. 8.3±4.5 ESS score; P = 0.06), insulin resistance decreased (0.327±0.038 vs. 0.351±0.045; Quicki index; P<0.001), and lipids improved, except for HDL-C. Abnormal fasting glucose (25% vs. 11%; P = 0.007), and metabolic syndrome (42% vs. 29%; P = 0.007) both decreased. In absence of intervention, the earlier metabolic improvements disappeared at the run-in visit.

Limitations

Relatively small sample size.

Conclusions

Improvements in biochemical and behavioral parameters between screening and randomization changed the “true” study baseline, thereby potentially affecting outcome. While regression to the mean and placebo effect were considered, these findings are most consistent with the “Hawthorne effect”, according to which behavior measured in the setting of an experimental study changes in response to the attention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898.     

Characterization of Cytomegalovirus Disease in Solid Organ Transplant Recipients by Markers of Inflammation in Plasma

Background

While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.

Patients and Methods

Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00431353","term_id":"NCT00431353"}}NCT00431353). Plasma markers of inflammation and endothelial cell activation were assessed at baseline by enzyme immunoassays.

Results

The major findings were: (i) Plasma levels of the CXC-chemokine interferon-inducible protein-10 (P<0.001) and C-reactive protein (P = 0.046) were independently associated with the presence of cytomegalovirus DNAemia above lower level of quantification. (ii) High levels of CC-chemokine ligand 21 (P = 0.027) and pentraxin 3 (P = 0.033) were independently associated with tissue invasive cytomegalovirus disease as opposed to cytomegalovirus syndrome.

Conclusion

Our findings illustrate the complex interaction between cytomegalovirus and the immune system, involving a wide range of inflammatory mediators that could be associated to disease manifestations in cytomegalovirus related disease.     

Proprioceptive Changes Impair Balance Control in Individuals with Chronic Obstructive Pulmonary Disease

Introduction

Balance deficits are identified as important risk factors for falling in individuals with chronic obstructive pulmonary disease (COPD). However, the specific use of proprioception, which is of primary importance during balance control, has not been studied in individuals with COPD. The objective was to determine the specific proprioceptive control strategy during postural balance in individuals with COPD and healthy controls, and to assess whether this was related to inspiratory muscle weakness.

Methods

Center of pressure displacement was determined in 20 individuals with COPD and 20 age/gender-matched controls during upright stance on an unstable support surface without vision. Ankle and back muscle vibration were applied to evaluate the relative contribution of different proprioceptive signals used in postural control.

Results

Individuals with COPD showed an increased anterior-posterior body sway during upright stance (p = 0.037). Compared to controls, individuals with COPD showed an increased posterior body sway during ankle muscle vibration (p = 0.047), decreased anterior body sway during back muscle vibration (p = 0.025), and increased posterior body sway during simultaneous ankle-muscle vibration (p = 0.002). Individuals with COPD with the weakest inspiratory muscles showed the greatest reliance on ankle muscle input when compared to the stronger individuals with COPD (p = 0.037).

Conclusions

Individuals with COPD, especially those with inspiratory muscle weakness, increased their reliance on ankle muscle proprioceptive signals and decreased their reliance on back muscle proprioceptive signals during balance control, resulting in a decreased postural stability compared to healthy controls. These proprioceptive changes may be due to an impaired postural contribution of the inspiratory muscles to trunk stability. Further research is required to determine whether interventions such as proprioceptive training and inspiratory muscle training improve postural balance and reduce the fall risk in individuals with COPD.     

Levels of Cholesterol in Small LDL Particles Predict Atherosclerosis Progression and Incident CHD in the HDL-Atherosclerosis Treatment Study (HATS)

Objective

Test whether angiographically-documented changes in percent stenosis and clinical endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) in the HDL-Atherosclerosis Treatment Study (HATS) were attributable to specific LDL-subclasses.

Methods

Gradient gel electrophoresis of on-study LDL-subclass cholesterol concentrations were measured in 32 placebo, 33 simvastatin-niacin, 38 antioxidant, and 39 simvastatin-niacin & antioxidant treated participants. The prespecified primary end point was the mean change per patient from the initial arteriogram to the final arteriogram in the percent stenosis caused by the most severe lesion in each of the nine proximal coronary segments.

Results

The change in the percent stenosis of the most severe proximal lesions increased in association with higher concentrations of the small LDL subfractions LDL-IIIb (24.2–24.6 nm) and LDL-IVa (23.3–24.1 nm) before (both P = 0.002) and after (P = 0.01 and P = 0.03 respectively) adjustment for treatment group and on-study HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations. The associations appeared specific to lesions with <30% baseline stenosis. When adjusted for age, sex, baseline BMI and cigarette use, the odds for primary clinical endpoints (death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia) were significantly greater in subjects with higher on-study LDL-IIIb levels both before (P = 0.01) and after (P = 0.03) adjustment for treatment group and the standard lipid values.

Conclusions

Plasma LDL-IIIb cholesterol concentrations were related to changes in coronary artery stenosis and cardiovascular events in patients with coronary artery disease and low HDL-cholesterol.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00000553","term_id":"NCT00000553"}}NCT00000553     

Influence of GLP-1 on Myocardial Glucose Metabolism in Healthy Men during Normo- or Hypoglycemia

Background and Aims

Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia.

Materials and Methods

We included eighteen healthy men in two randomized, double-blinded, placebo-controlled cross-over studies. MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo- (plasma glucose (PG): 4.5 mM, n = 10) and hypoglycemic clamps (PG: 3.0 mM, n = 8) by positron emission tomography with ¹⁸fluoro-deoxy-glucose (¹⁸F-FDG) as tracer.

Results

In the normoglycemia study mean (± SD) age was 25±3 years, and BMI was 22.6±0.6 kg/m² and in the hypoglycemia study the mean age was 23±2 years with a mean body mass index of 23±2 kg/m². GLP-1 did not change MGU during normoglycemia (mean (+/− SD) 0.15+/−0.04 and 0.16+/−0.03 µmol/g/min, P = 0.46) or during hypoglycemia (0.16+/−0.03 and 0.13+/−0.04 µmol/g/min, P = 0.14). However, the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo- and hypoglycemia, (P = 0.006, r² = 0.64 and P = 0.018, r² = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r² = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study. No differences in other circulating hormones or metabolites were found.

Conclusions

While GLP-1 does not affect overall MGU, GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU. GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects.ClinicalTrials.gov registration numbers: {"type":"clinical-trial","attrs":{"text":"NCT00418288","term_id":"NCT00418288"}}NCT00418288: (hypoglycemia) and {"type":"clinical-trial","attrs":{"text":"NCT00256256","term_id":"NCT00256256"}}NCT00256256: (normoglycemia).     

Clinical and Biochemical Correlates of Serum L-Ergothioneine Concentrations in Community-Dwelling Middle-Aged and Older Adults

Background

Despite the increasing interest towards the biological role of L-ergothioneine, little is known about the serum concentrations of this unusual aminothiol in older adults. We addressed this issue in a representative sample of community-dwelling middle-aged and older adults.

Methods

Body mass index, estimated glomerular filtration rate, serum concentrations of L-ergothioneine, taurine, homocysteine, cysteine, glutathione, cysteinylglycine, and glutamylcysteine were evaluated in 439 subjects (age 55–85 years) randomly selected from the Hunter Community Study.

Results

Median L-ergothioneine concentration in the entire cohort was 1.01 IQR 0.78–1.33 µmol/L. Concentrations were not affected by gender (P = 0.41) or by presence of chronic medical conditions (P = 0.15). By considering only healthy subjects, we defined a reference interval for L-ergothioneine serum concentrations from 0.36 (90% CI 0.31–0.44) to 3.08 (90% CI 2.45–3.76) µmol/L. Using stepwise multiple linear regression analysis L-ergothioneine was negatively correlated with age (rpartial = −0.15; P = 0.0018) and with glutamylcysteine concentrations (rpartial = −0.13; P = 0.0063).

Conclusions

A thorough analysis of serum L-ergothioneine concentrations was performed in a large group of community-dwelling middle-aged and older adults. Reference intervals were established. Age and glutamylcysteine were independently negatively associated with L-ergothioneine serum concentration.     

Effects of High Doses of Cholecalciferol in Normal Subjects: A Randomized Double-Blinded,Placebo-Controlled Trial

Background

Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.

Methods

In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.

Results

Both 25(OH)vitamin D and 1,25(OH)₂vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus – 8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).

Conclusion

High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)₂vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00952562","term_id":"NCT00952562"}}NCT00952562.     

Aerobic and Combined Exercise Sessions Reduce Glucose Variability in Type 2 Diabetes: Crossover Randomized Trial

Purpose

To evaluate the effects of aerobic (AER) or aerobic plus resistance exercise (COMB) sessions on glucose levels and glucose variability in patients with type 2 diabetes. Additionally, we assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS).

Methods

Fourteen patients with type 2 diabetes (56±2 years) wore a CGMS during 3 days. Participants randomly performed AER and COMB sessions, both in the morning (24 h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods).

Results

Baseline fasting glycemia was 139±05 mg/dL and HbA1c 7.9±0.7%. Glucose levels decreased immediately after AER and COMB protocols by ∼16%, which was sustained for approximately 3 hours. Comparing the two exercise modalities, responses over a 24-h period after the sessions were similar for glucose levels, glucose variance and glucose coefficient of variation. In the symbolic analysis, increases in 0 V pattern (COMB, 67.0±7.1 vs. 76.0±6.3, P = 0.003) and decreases in 1 V pattern (COMB, 29.1±5.3 vs. 21.5±5.1, P = 0.004) were observed only after the COMB session.

Conclusions

Both AER and COMB exercise modalities reduce glucose levels similarly for a short period of time. The use of non-conventional analysis indicates reduction of glucose variability after a single session of combined exercises.

Trial Registration

Aerobic training, aerobic-resistance training and glucose profile (CGMS) in type 2 diabetes (CGMS exercise). ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT00887094","term_id":"NCT00887094"}}NCT00887094.     

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

Background

Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.

Objective

To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.

Data Sources

MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.

Study Selection

Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.

Data Extraction and Synthesis

Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I²).

Results

Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.

Limitations

Majority of trials were of short duration and poor quality.

Conclusions

Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01630980","term_id":"NCT01630980"}}NCT01630980     

Calcium Supplementation Increases Blood Creatinine Concentration in a Randomized Controlled Trial

Background

Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.

Methods

We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004–2013 at 11 clinical centers in the United States. Healthy participants (N = 1,675) aged 45–75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D₃ (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations.

Results

After one year of treatment, blood creatinine was 0.013±0.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (P = 0.03). However, the effect of calcium treatment appeared to be larger among participants who consumed the most alcohol (2–6 drinks/day) or whose estimated glomerular filtration rate (eGFR) was less than 60 ml/min/1.73 m² at baseline. The effect of calcium treatment on creatinine was only partially mediated by a concomitant increase in blood total calcium concentration and was independent of randomized vitamin D treatment. There did not appear to be further increases in creatinine after the first year of calcium treatment.

Conclusions

Among healthy adults participating in a randomized clinical trial, daily supplementation with 1200 mg of elemental calcium caused a small increase in blood creatinine. If confirmed, this finding may have implications for clinical and public health recommendations for calcium supplementation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00153816","term_id":"NCT00153816"}}NCT00153816     

Omega-3 Fatty Acid Deficiency in Infants before Birth Identified Using a Randomized Trial of Maternal DHA Supplementation in Pregnancy

Background

DHA is accumulated in the central nervous system (CNS) before birth and is involved in early developmental processes, such as neurite outgrowth and gene expression.

Objective

To determine whether fetal DHA insufficiency occurs and constrains CNS development in term gestation infants.

Design

A risk reduction model using a randomized prospective study of term gestation single birth healthy infants born to women (n = 270) given a placebo or 400 mg/day DHA from 16 wk gestation to delivery. Fetal DHA deficiency sufficient to constrain CNS development was assessed based on increased risk that infants in the placebo group would not achieve neurodevelopment scores in the top quartile of all infants in the study.

Results

Infants in the placebo group were at increased risk of lower language development assessed as words understood (OR 3.22, CL 1.49–6.94, P = 0.002) and produced (OR 2.61, CL 1.22–5.58, P = 0.01) at 14 mo, and words understood (OR 2.77, CL 1.23–6.28, P = 0.03) and sentences produced (OR 2.60, CL 1.15–5.89, P = 0.02) at 18 mo using the McArthur Communicative Developmental Inventory; receptive (OR 2.23, CL 1.08–4.60, P = 0.02) and expressive language (OR 1.89, CL 0.94–3.83, P = 0.05) at 18 mo using the Bayley Scales of Infant Development III; and visual acuity (OR 2.69, CL 1.10–6.54, P = 0.03) at 2 mo.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00620672","term_id":"NCT00620672"}}NCT00620672     

Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury

Introduction

Regional citrate anticoagulation (RCA) is gaining popularity in continous renal replacement therapy (CRRT) for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH) with RCA.

Methods

Critically ill patients with AKI (n = 12) and healthy volunteers (n = 12) were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients’ CVVH sessions with citrate anticoagulation.

Results

Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624). Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively). The predicted citrate curve showed excellent fit to the measurements.

Conclusions

Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation.

Trial Registration

ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT00948558","term_id":"NCT00948558"}}NCT00948558     

Effect of Arginase Inhibition on Ischemia-Reperfusion Injury in Patients with Coronary Artery Disease with and without Diabetes Mellitus

Background

Arginase competes with nitric oxide synthase for their common substrate L-arginine. Up-regulation of arginase in coronary artery disease (CAD) and diabetes mellitus may reduce nitric oxide bioavailability contributing to endothelial dysfunction and ischemia-reperfusion injury. Arginase inhibition reduces infarct size in animal models. Therefore the aim of the current study was to investigate if arginase inhibition protects from endothelial dysfunction induced by ischemia-reperfusion in patients with CAD with or without type 2 diabetes (Clinical trial registration number: {"type":"clinical-trial","attrs":{"text":"NCT02009527","term_id":"NCT02009527"}}NCT02009527).

Methods

Male patients with CAD (n = 12) or CAD + type 2 diabetes (n = 12), were included in this cross-over study with blinded evaluation. Endothelium-dependent vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial artery before and after 20 min ischemia-reperfusion during intra-arterial infusion of the arginase inhibitor (N^ω-hydroxy-nor-L-arginine, 0.1 mg/min) or saline.

Results

The forearm ischemia-reperfusion was well tolerated. Endothelium-independent vasodilatation was assessed by sublingual nitroglycerin. Ischemia-reperfusion decreased FMD in patients with CAD from 12.7±5.2% to 7.9±4.0% during saline administration (P<0.05). N^ω-hydroxy-nor-L-arginine administration prevented the decrease in FMD in the CAD group (10.3±4.3% at baseline vs. 11.5±3.6% at reperfusion). Ischemia-reperfusion did not significantly reduce FMD in patients with CAD + type 2 diabetes. However, FMD at reperfusion was higher following nor-NOHA than following saline administration in both groups (P<0.01). Endothelium-independent vasodilatation did not differ between the occasions.

Conclusions

Inhibition of arginase protects against endothelial dysfunction caused by ischemia-reperfusion in patients with CAD. Arginase inhibition may thereby be a promising therapeutic strategy in the treatment of ischemia-reperfusion injury.     

Vagus Nerve Stimulation Increases Energy Expenditure: Relation to Brown Adipose Tissue Activity

Background

Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT.

Methods and Findings

Fifteen patients with stable VNS therapy (age: 45±10yrs; body mass index; 25.2±3.5 kg/m²) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUV^Mean; 0.55±0.25 versus 0.67±0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001).

Conclusions

VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy.

Trial Registration

The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT01491282","term_id":"NCT01491282"}}NCT01491282.     

Anemia and Risk Factors in HAART Na?ve and HAART Experienced HIV Positive Persons in South West Ethiopia: A Comparative Study

Background

Human immunodeficiency virus (HIV) infection and its treatment cause a range of hematological abnormalities. Anemia is one of the commonly observed hematologic manifestations in HIV positive persons and it has multifactorial origin.

Objective

We aimed to determine the prevalence and risk factors of anemia in highly active antiretroviral therapy (HAART) naïve and HAART experienced HIV positive persons.

Methods

A facility-based comparative cross sectional study was conducted in Jimma University Specialized Hospital from February 1 to March 30, 2012. A total of 234 HIV positive persons, 117 HAART naïve and 117 HAART experienced, were enrolled in this study. Blood and stool specimens were collected from each participant. Blood specimens were examined for complete blood count, CD4 count and blood film for malaria hemoparasite; whereas stool specimens were checked for ova of intestinal parasites. Socio-demographic characteristics and clinical data of the participants were collected using pre-tested questionnaire. Statistical analysis of the data (Chi-square, student’s t-test, logistic regression) was done using SPSS V-16.

Results

The overall prevalence of anemia was 23.1%. The prevalence of anemia in HAART naïve and HAART experienced persons was 29.9% and 16.2%, respectively (P = 0.014). Presence of opportunistic infections (P = 0.004, 95% CI = 1.69–15.46), CD4 count <200 cells/µl (P = 0.001, 95% CI = 2.57–36.89) and rural residence (P = 0.03, 95% CI = 1.12–10.39) were found to be predictors of anemia for HAART naïve participants. On the other hand, HAART regimen (ZDV/3TC/NVP) (P = 0.019, 95% CI = 0.01–1.24) and the duration of HAART (P = 0.007, 95% CI = 0.003–0.40.24) were found to be predictors of anemia for HAART experienced groups.

Conclusion

The prevalence of anemia in HAART naïve persons was higher than HAART experienced persons. Risk factors for anemia in HAART naïve and HAART experienced HIV positive persons were different. Hence, there is a need for longitudinal study to further explore the causes of HIV associated anemia and the pattern of hemoglobin changes with initiation of HAART.     

Cross-Sectional and Longitudinal Associations of Different Sedentary Behaviors with Cognitive Performance in Older Adults

Background

The deleterious health effects of sedentary behaviors, independent of physical activity, are increasingly being recognized. However, associations with cognitive performance are not known.

Purpose

To estimate the associations between different sedentary behaviors and cognitive performance in healthy older adults.

Methods

Computer use, time spent watching television (TV), time spent reading and habitual physical activity levels were self-reported twice (in 2001 and 2007) by participants in the SUpplémentation en Vitamines et MinérauX (SU.VI.MAX and SU.VI.MAX2) study. Cognitive performance was assessed at follow-up (in 2007–2009) via a battery of 6 neuropsychological tests used to derive verbal memory and executive functioning scores. Analyses (ANCOVA) were performed among 1425 men and 1154 women aged 65.6±4.5 at the time of the neuropsychological evaluation. We estimated mean differences with 95% confidence intervals (95%CI) in cognitive performance across categories of each type of sedentary behavior.

Results

In multivariable cross-sectional models, compared to non-users, participants using the computer for >1 h/day displayed better verbal memory (mean difference = 1.86; 95%CI: 0.95, 2.77) and executive functioning (mean difference = 2.15; 95%CI: 1.22, 3.08). A negative association was also observed between TV viewing and executive functioning. Additionally, participants who increased their computer use by more than 30 min between 2001 and 2007 showed better performance on both verbal memory (mean difference = 1.41; 95%CI: 0.55, 2.27) and executive functioning (mean difference = 1.41; 95%CI: 0.53, 2.28) compared to those who decreased their computer use during that period.

Conclusion

Specific sedentary behaviors are differentially associated with cognitive performance. In contrast to TV viewing, regular computer use may help maintain cognitive function during the aging process.

Clinical Trial Registration

clinicaltrial.gov (number {"type":"clinical-trial","attrs":{"text":"NCT00272428","term_id":"NCT00272428"}}NCT00272428).     

Progesterone Therapy,Endothelial Function and Cardiovascular Risk Factors: A 3-Month Randomized,Placebo-Controlled Trial in Healthy Early Postmenopausal Women

Background

Progesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation.

Methods and Results

We conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily) among 133 healthy postmenopausal women in Vancouver, Canada from 2003–2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1–11 y since last menstruation, not using hormones (for >6 months), non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1) women (55±4 years, body mass index 25±3) initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline) was not changed with progesterone (487±189%, n = 18) compared with placebo (408±278%, n = 16) (95% CI diff [−74 to 232], P = 0.30). Progesterone (n = 65) and placebo (n = 47) groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (−0.14 mmol/L, P = 0.001) on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo.

Conclusions

Results indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change).

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00152438","term_id":"NCT00152438"}}NCT00152438     

Obesity impact on the attentional cost for controlling posture

Background

This study investigated the effects of obesity on attentional resources allocated to postural control in seating and unipedal standing.

Methods

Ten non obese adults (BMI = 22.4±1.3, age = 42.4±15.1) and 10 obese adult patients (BMI = 35.2±2.8, age = 46.2±19.6) maintained postural stability on a force platform in two postural tasks (seated and unipedal). The two postural tasks were performed (1) alone and (2) in a dual-task paradigm in combination with an auditory reaction time task (RT). Performing the RT task together with the postural one was supposed to require some attentional resources that allowed estimating the attentional cost of postural control. 4 trials were performed in each condition for a total of 16 trials.

Findings

(1) Whereas seated non obese and obese patients exhibited similar centre of foot pressure oscillations (CoP), in the unipedal stance only obese patients strongly increased their CoP sway in comparison to controls. (2) Whatever the postural task, the additional RT task did not affect postural stability. (3) Seated, RT did not differ between the two groups. (4) RT strongly increased between the two postural conditions in the obese patients only, suggesting that body schema and the use of internal models was altered with obesity.

Interpretation

Obese patients needed more attentional resources to control postural stability during unipedal stance than non obese participants. This was not the case in a more simple posture such as seating. To reduce the risk of fall as indicated by the critical values of CoP displacement, obese patients must dedicate a strong large part of their attentional resources to postural control, to the detriment of non-postural events. Obese patients were not able to easily perform multitasking as healthy adults do, reflecting weakened psycho-motor abilities.