High-fat overfeeding does not exacerbate rapid changes in forearm glucose and fatty acid balance during immobilization

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordCONTEXT: Physical inactivity and high-fat overfeeding have been shown to independently induce insulin resistance. OBJECTIVE: Establish the contribution of muscle disuse and lipid availability to the development of inactivity-induced insulin resistance. Design, setting, participants, and interventions: Twenty healthy males underwent seven days of forearm cast immobilization combined with a fully-controlled eucaloric (CON, n=10, age 23±2 yr, BMI 23.8±1.0 kg·m-2) or high-fat diet providing 50% excess energy from fat (HFD, n=10, age 23±2 yr, BMI 22.4±0.8 kg·m-2). MAIN OUTCOME MEASURES: Prior to casting, and following 2 and 7 days of immobilization, forearm glucose uptake (FGU) and non-esterified fatty acid (NEFA) balance were assessed using the arterialized venous-deep venous (AV-V) forearm balance method following ingestion of a mixed macronutrient drink. RESULTS: Seven days of HFD increased body weight by 0.9±0.2 kg (P=0.002), but did not alter fasting, arterialized whole-blood glucose and serum insulin concentrations or the associated HOMA-IR or Matsuda indices. Two and seven days of forearm immobilization led to a 40±7% and 52±7% decrease in FGU, respectively (P<0.001), with no difference between day 2 and 7 and no effect of HFD. Forearm NEFA balance tended to increase following two and seven days of immobilization (P=0.095). CONCLUSIONS: forearm immobilization leads to a rapid and substantial decrease in FGU, which is accompanied by an increase in forearm NEFA balance but is not exacerbated by excess dietary fat intake. Altogether, our data suggest that disuse-induced insulin resistance of glucose metabolism is occurs as a physiological adaptation in response to the removal of muscle contraction.Physiological Societ

The impact of disuse and high-fat overfeeding on forearm muscle amino acid metabolism in humans

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordCONTEXT: Anabolic resistance is mechanistically implicated in muscle disuse atrophy. OBJECTIVE: Assess whether anabolic resistance is associated with reduced postprandial amino acid uptake or exacerbated by excess lipid availability. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Twenty men underwent 7 days of forearm immobilization while consuming a eucaloric (CON; n=11) or high-fat overfeeding (HFD; n=9; 50% excess energy as fat) diet (parallel design) within our Nutritional Physiology Research Unit. MAIN OUTCOME MEASURES: Pre- and post- immobilization we measured forearm muscle cross sectional area (aCSA), and postabsorptive and postprandial (3 h post ingestion of a liquid, protein rich, mixed meal) forearm amino acid metabolism using the arterialised venous-deep venous balance method and infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine. RESULTS: Immobilization did not affect forearm muscle aCSA in either group, but tended to reduce postabsorptive phenylalanine (P=0.07) and leucine (P=0.05) net balances equivalently in CON and HFD. Mixed meal ingestion switched phenylalanine and leucine net balances from negative to positive (P0.05). CONCLUSIONS: Disuse impairs the ability of a protein-rich meal to promote positive muscle amino acid balance, which is aggravated by dietary lipid oversupply. Moreover, disuse reduced postprandial forearm amino acid uptake; however, this is not worsened under high-fat conditions.Physiological Societ

EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines.</p> <p>In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet.</p> <p>Methods/Design</p> <p>This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge.</p> <p>Discussion</p> <p>Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage.</p> <p>Trial registration</p> <p>www.clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01258257">NCT01258257</a></p

The cost-effectiveness of the WINGS intervention: a program to prevent HIV and sexually transmitted diseases among high-risk urban women

BACKGROUND: We evaluated the cost-effectiveness of the WINGS project, an intervention to prevent HIV and other sexually transmitted diseases among urban women at high risk for sexual acquisition of HIV. METHODS: We used standard methods of cost-effectiveness analysis. We conducted a retrospective analysis of the intervention's cost and we used a simplified model of HIV transmission to estimate the number of HIV infections averted by the intervention. We calculated cost-effectiveness ratios for the complete intervention and for the condom use skills component of the intervention. RESULTS: Under base case assumptions, the intervention prevented an estimated 0.2195 new cases of HIV at a cost of $215,690 per case of HIV averted. When indirect costs of HIV were excluded from the analysis, the intervention's cost-effectiveness ratios were$357,690 per case of HIV averted and $31,851 per quality-adjusted life year (QALY) saved. Under base case assumptions, the condom use skills component of the intervention prevented an estimated 0.1756 HIV infections and was cost-saving. When indirect HIV costs were excluded, the cost-effectiveness ratios for the condom use skills component of the intervention were$97,404 per case of HIV averted and $8,674 per QALY saved. CONCLUSIONS: The WINGS intervention, particularly the two sessions of the intervention which focussed on condom use skills, could be cost-effective in preventing HIV among women

Emotional, behavioural problems and cigarette smoking in adolescence: findings of a Greek cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although several studies have reported findings concerning the association between smoking and emotional/behavioural problems, little research has investigated this association after controlling for confounding factors which have been found to be significantly correlated with both cigarette smoking and emotional/behavioural problems and may have a strong effect on the relationship between adolescents' mental health and smoking. The present study attempted to assess the association between adolescents' smoking status and their emotional/behavioural problems after controlling for a number of possible confounders (i.e. age, gender, parental smoking status, exposure to family smoking, family socioeconomic status, adolescents' leisure time) in a Greek nation-wide school-based sample.</p> <p>Methods</p> <p>Participants completed a questionnaire which retrieved information about age, gender, family socioeconomic status, smoking status, parental smoking, adolescents' leisure time and emotional/behavioural problems. Data were modelled using multiple logistic regression analysis with adolescents' smoking status as the dependent variable.</p> <p>Results</p> <p>A total of 1194 (i.e. 63% response rate) of self-reported questionnaires (40.1% boys, 59.9% girls; 12-18 years old) were returned. Data from 1030 participants with full data were analyzed. Cigarette smoking was strongly associated with higher levels of emotional/behavioural problems (p < 0.001) and the association was not moderated (OR = 1.13, 95% CI: 1.08-1.18) after controlling for the effects of other covariates. Emotional symptoms, conduct problems and hyperactivity/inattention were all significantly associated with adolescents' current smoking.</p> <p>Conclusions</p> <p>This study supports the association between smoking and emotional/behavioural problems among adolescents. Addressing adolescents' needs regarding their emotional/behavioural health could be helpful in the development of effective anti-smoking strategies in school environment and elsewhere.</p

A simple method for defining malaria seasonality

BACKGROUND: There is currently no standard way of defining malaria seasonality, resulting in a wide range of definitions reported in the literature. Malaria cases show seasonal peaks in most endemic settings, and the choice and timing for optimal malaria control may vary by seasonality. A simple approach is presented to describe the seasonality of malaria, to aid localized policymaking and targeting of interventions. METHODS: A series of systematic literature reviews were undertaken to identify studies reporting on monthly data for full calendar years on clinical malaria, hospital admission with malaria and entomological inoculation rates (EIR). Sites were defined as having 'marked seasonality' if 75% or more of all episodes occurred in six or less months of the year. A 'concentrated period of malaria' was defined as the six consecutive months with the highest cumulative proportion of cases. A sensitivity analysis was performed based on a variety of cut-offs. RESULTS: Monthly data for full calendar years on clinical malaria, all hospital admissions with malaria, and entomological inoculation rates were available for 13, 18, and 11 sites respectively. Most sites showed year-round transmission with seasonal peaks for both clinical malaria and hospital admissions with malaria, with a few sites fitting the definition of 'marked seasonality'. For these sites, consistent results were observed when more than one outcome or more than one calendar year was available from the same site. The use of monthly EIR data was found to be of limited value when looking at seasonal variations of malaria transmission, particularly at low and medium intensity levels. CONCLUSION: The proposed definition discriminated well between studies with 'marked seasonality' and those with less seasonality. However, a poor fit was observed in sites with two seasonal peaks. Further work is needed to explore the applicability of this definition on a wide-scale, using routine health information system data where possible, to aid appropriate targeting of interventions