Double-blind Placebo-controlled Crossover Study Research Articles

The response of the central and peripheral tremor component to octanoic acid in patients with essential tremor

ObjectiveTo investigate the effect of octanoic acid (OA) on the peripheral component of tremor, as well as OA’s differential effects on the central and peripheral tremor component in essential tremor (ET) patients. MethodsWe analyzed postural tremor accelerometry data from a double-blind placebo-controlled cross-over study evaluating the effect of 4 mg/kg OA in ET. The weighted condition was used to identify tremor power for both the central and peripheral tremor components. Exploratory non-parametric statistical analyses were used to describe the relation between the central and peripheral component of tremor power. ResultsA peripheral tremor component was identified in 4 out of 18 subjects. Tremor power was reduced after OA administration in both the central and the peripheral tremor component. There was a positive correlation of tremor power between the central and peripheral component, both after placebo and OA. ConclusionsWhen present, the peripheral component was closely related to the central tremor component. We hypothesize that the magnitude of the peripheral mechanical component of tremor is determined by that of the central component. SignificanceBoth central and peripheral component of tremor are reduced after OA, with the central component providing the energy driving the peripheral component.

O3.7. EFFECT OF N-ACETYLCYSTEINE ON BRAIN GLUTAMATE LEVELS AND RESTING PERFUSION IN SCHIZOPHRENIA

BackgroundSchizophrenia may be associated with elevations in glutamate levels in the anterior cingulate cortex (ACC), and this may be particularly apparent in patients who have not responded well to conventional antipsychotic treatment (Egerton et al., 2012; Mouchliantis et al., 2016). This suggests that compounds that can decrease ACC glutamate levels may have therapeutic potential for this group. N-acetylcysteine (NAC) is one such compound, currently under investigation as an adjunctive therapy for schizophrenia. The effects of NAC on brain glutamate levels and physiology in schizophrenia have not been previously evaluated. The primary aim of this study was to examine whether a single oral dose of NAC can alter brain glutamate levels in schizophrenia. The secondary aim was to characterise the effects of NAC on regional brain perfusion.MethodsIn a double-blind placebo-controlled crossover study, twenty patients with a diagnosis of schizophrenia underwent two 3 Tesla MRI scans, performed one week apart, and following administration of a single oral dose of 2400mg NAC or matching placebo. Proton magnetic resonance spectroscopy (1H-MRS) was used to investigate the effect of NAC on glutamate and Glx (glutamate plus glutamine) levels scaled to creatine (Cr) in the anterior cingulate cortex (ACC) and in the right caudate nucleus. Pulsed continuous arterial spin labelling (pCASL) was used to measure the effects of NAC on resting cerebral blood flow (CBF) in the same regions. 1H-MRS spectra were analysed using LCModel version 6.3-0I using a standard basis set. Individual CBF maps were pre-processed in the Automatic Software for ASL Processing (ASAP) toolbox running in SPM-8 in Matlab 6.5. The effects of NAC on 1H-MRS metabolite levels were determined using paired samples t-tests. Changes in rCBF were determined using within-subjects, second-level analysis implemented in SPM-8.ResultsIn the ACC, Glx/Cr was significantly reduced in the NAC compared to placebo condition (t(17) = 2.40; P = .03, d = 0.64). There was no significant effect of condition on Glu/Cr in the ACC, or on Glx/Cr or Glu/Cr in the right caudate nucleus, or on any of the other metabolites quantifiable from the 1H-MRS spectra. There were no significant differences in CBF in the ACC (mean (SD) placebo = 47.22 (8.81); NAC = 46.83 (7.29); t(18) = .349, P = .73) or in the right caudate nucleus (mean (SD) placebo = 37.51 (7.48); NAC = 37.77 (6.71); t(18) -.310, P = .76) in the NAC compared to placebo condition. There was also no significant difference in global CBF between conditions (mean (SD) placebo = 39.64 (10.02); NAC = 40.03 (9.13); t(18) = -.398, P = .70).DiscussionThese results provide preliminary evidence that NAC may reduce ACC glutamate metabolites in schizophrenia. Future studies will need to determine the extent to which reductions in glutamate metabolites following a single dose of a glutamatergic compound are indicative of longer-term efficacy in improving symptoms.

The Effect of a Short Period of Supplementation with Glutamine Dipeptide on the Cognitive Responses after a Resistance Training Session of Women with HIV/AIDS: A Randomized Double-Blind Placebo-Controlled Crossover Study.

The aim of the present study was to investigate the effect of a short period of supplementation with glutamine dipeptide (GDP) on the acute responses to resistance training on the executive functions of people with HIV/AIDS. The sample consisted of 10 HIV+ women (45.00 ± 12.77 years old; 65.71 ± 12.04 kg; 1.54 ± 0.05 m) who were submitted to a randomized double-blind crossover procedure according to two experimental conditions: orally supplemented with 20 g/day of GDP or with maltodextrin for seven days. On the seventh day of supplementation all participants did cognitive function tests before and immediately after a resistance training session. Seven days of washout were adopted between conditions. Stroop and N-back tests were used to evaluate the executive functions. The training reduced the response time of each card in isolation and the latency time among them. GDP supplementation increased the magnitude of this effect, thus, reducing the latency time from the first to the last card in the Stroop test by almost 50% (P < 0.01). Considering the N-back test, there were no significant differences. It is suggested that GDP supplementation may increase the magnitude of the effect of an acute resistance training session in cognitive functions, particularly in the inhibitory control of people with HIV/AIDS. This trial is registered with NCT03236532.

Deep Ocean Mineral Supplementation Enhances the Cerebral Hemodynamic Response during Exercise and Decreases Inflammation Postexercise in Men at Two Age Levels.

Background: Previous studies have consistently shown that oral supplementation of deep ocean minerals (DOM) improves vascular function in animals and enhances muscle power output in exercising humans.Purpose: To examine the effects of DOM supplementation on the cerebral hemodynamic response during physical exertion in young and middle-aged men.Design: Double-blind placebo-controlled crossover studies were conducted in young (N = 12, aged 21.2 ± 0.4 years) and middle-aged men (N = 9, aged 46.8 ± 1.4 years). The counter-balanced trials of DOM and Placebo were separated by a 2-week washout period. DOM and Placebo were orally supplemented in drinks before, during, and after cycling exercise. DOM comprises desalinated minerals and trace elements from seawater collected ~618 m below the earth's surface.Methods: Cerebral hemodynamic response (tissue hemoglobin) was measured during cycling at 75% VO2max using near infrared spectroscopy (NIRS).Results: Cycling time to exhaustion at 75% VO2max and the associated plasma lactate response were similar between the Placebo and DOM trials for both age groups. In contrast, DOM significantly elevated cerebral hemoglobin levels in young men and, to a greater extent, in middle-aged men compared with Placebo. An increased neutrophil to lymphocyte ratio (NLR) was observed in middle-aged men, 2 h after exhaustive cycling, but was attenuated by DOM.Conclusion: Our data suggest that minerals and trace elements from deep oceans possess great promise in developing supplements to increase the cerebral hemodynamic response against a physical challenge and during post-exercise recovery for middle-aged men.

26. A randomized controlled cross-over double blind study protocol on THC/CBD oromucosal spray as an add-on therapy for post-stroke spasticity

Understand if cannabinoids (THC:CBD) are useful in reducing post-stroke spasticity using a neurophysiological quantitative measure as primary endpoint. We will recruit 50 patients with spasticity following stroke to take THC:CBD in a double blind placebo-controlled crossover study. Spasticity will be assessed with a numeric rating scale for spasticity, the modified Ashworth scale and with the electromyographic recording of the stretch reflex. The cardiovascular risk will be assessed prior to inclusion. Blood pressure, heart rate, number of daily spasms, bladder function, sleep disruption and adverse events will be monitored throughout the study. A mixed-model ANOVA will be used to compare the stretch reflex amplitude between the time points; semi-quantitative measures will be compared using the Mann-Whitney test (THC:CBD vs placebo) and Wilcoxon test (baseline vs treatment). The study was registered on the EudraCT database with number 2016-001034-10 and approved by both the Italian Medicines Agency (AIFA) and local Ethics Committee. Data will be made anonymous and uploaded to an open access repository. Results will be disseminated by presentations at national and international conferences and by publication in journals of clinical neuroscience and neurology.

Fibrocytes in Human Pulmonary Fibrosis: Double-Blind Placebo-Controlled Crossover Pilot Study of Sirolimus in Idiopathic Pulmonary Fibrosis

SESSION TITLE: Diffuse Lung Disease I SESSION TYPE: Original Investigation Slide PRESENTED ON: Sunday, October 29, 2017 at 03:15 PM - 04:15 PM PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with poor prognosis. Fibrocytes are a novel population of bone marrow-derived circulating cells that traffic to the lungs and contribute to fibrosis in animal models of pulmonary fibrosis via the interaction of the chemokine CXCL12, made in the lung, and the chemokine receptor CXCR4, expressed on fibrocytes. In human interstitial lung disease, the concentration of CXCR4+ circulating fibrocytes correlates with survival. The expression of fibrocyte CXCR4 is dependent on the mTOR pathway, and is reduced by in vitro treatment with the mTOR inhibitor, sirolimus. In animal models of lung fibrosis, sirolimus therapy reduces both the trafficking of fibrocytes to the lungs and the extent of lung fibrosis. The effect of sirolimus in human IPF has not been examined. We hypothesized that therapy with the mTOR inhibitor sirolimus reduces the number of circulating fibrocytes in patients with idiopathic pulmonary fibrosis and is associated with an acceptable side-effect profile. METHODS: We performed a short-term randomized double-blinded placebo-controlled crossover study of 30 subjects diagnosed with IPF by consensus definition. Subjects were randomized to placebo or sirolimus for a 1-3 week run-in period with dose adjustment to achieve therapeutic drug levels, followed by 4 weeks of dose maintenance, and then a 4 week washout period. Subjects were then crossed over to the alternate treatment (placebo or sirolimus) for same length run-in, maintenance and washout periods. The concentration of circulating fibrocytes plasma chemokine ligands, pulmonary function tests, and adverse events were measured at specific time points. Adverse events were classified as serious per the NCI CTCAE criteria and were adjudicated as unrelated or possibly related to the study drug by an independent DSMB. RESULTS: We enrolled 30 subjects between 2011 and 2015; 2 withdrew prior to randomization. The remaining 28 had a median age of 69 (IQR 65-73), 22 were men and 8 were on concurrent therapy with pirfenidone or nintedanib. Sirolimus therapy resulted in a statistically significant reduction in the concentration of circulating fibrocytes (median change -62%, IQR -40% to -29%) whereas placebo did not (median change -32%; IQR -47% to +6%). A total of 49 adverse events occurred during treatment with sirolimus and 29 with placebo, of which 35 (2 serious: elevated liver enzymes and angioedema) were adjudicated as possibly related to therapy during sirolimus and 15 (1 serious: worsened dyspnoea) during placebo treatments. The incidence of total adverse events, serious adverse events, and total and serious adverse events that were potentially related to therapy did not differ significantly during therapy with drug and placebo. CONCLUSIONS: As compared with placebo, short-term treatment with sirolimus resulted in reduction of circulating fibrocyte concentrations in subjects with IPF and was associated with an acceptable safety profile. CLINICAL IMPLICATIONS: Given the benefit of sirolimus in animal models of pulmonary fibrosis and evidence of similar mechanism of action in human IPF in this study, future studies should assess the effect of long-term sirolimus treatment on the natural history of IPF. DISCLOSURE: The following authors have nothing to disclose: Dierdre Axell-House, Victor Yu, Zhimin Zhang, Marie Burdick, Robert Strieter, Borna Mehrad No Product/Research Disclosure Information

A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity

IntroductionStroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis....

The Effect of Buffering High Acid Load Meal with Sodium Bicarbonate on Postprandial Glucose Metabolism in Humans-A Randomized Placebo-Controlled Study.

Background: High dietary acid load relates to increased risk of type 2 diabetes in epidemiological studies. We aimed to investigate whether buffering a high acid load meal with an alkalizing treatment changes glucose metabolism post meal. Methods: Non-diabetic participants (n = 32) were randomized to receive either 1680 mg NaHCO3 or placebo, followed by a high acid load meal in a double-blind placebo-controlled crossover (1–4 weeks apart) study. Thirty (20 men) participants completed the study. Venous blood pH, serum bicarbonate, blood glucose, serum insulin, C-peptide, non-esterified fatty acid (NEFA), and plasma glucagon-like peptide-1 (GLP-1) concentrations were measured at baseline (fasting) and at 15–30 min intervals for 3 h post meal. Results: The treatment was well tolerated. Venous blood pH declined in the first 15 min post meal with the placebo (p = 0.001), but not with NaHCO3 (p = 0.86) and remained decreased with the placebo for 3 h (pinteraction = 0.04). On average over the 3 h blood pH iAUC was greater with NaHCO3 compared with placebo (p = 0.02). However, postprandial glucose, insulin, C-peptide, NEFA and GLP-1 were not different between treatments (pinteraction ≥ 0.07). Conclusions: An alkalizing medication administered pre-meal has no acute effect on glycaemia and insulin response in healthy individuals. Long-term interventions in at-risk populations are necessary to investigate the effect of sustained alkalization on glucose metabolism.

Effects of progressive resistance or high-intensity strength training on muscle function and Achilles tendon mechanical properties in children with cerebral palsy

In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by α2-adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was coadministered orally with the α2-adrenoceptor antagonist yohimbine in 16 healthy women in a double-blind placebo-controlled crossover study. In each session, mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, pain ratings to electrical stimulation of HFS-treated or control sites in the forearm were assessed during and after painful stimulation of each temple. Unlike yohimbine alone, the naltrexone with yohimbine combination blocked analgesia evoked by HFS in the ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory effect of pain in the temple on electrically-evoked pain at the HFS-treated site in the forearm. These findings imply involvement of opioid peptides in an ipsilateral analgesic response that complements the more generalized form of conditioned pain modulation. Opioid mediation of this ipsilateral analgesic response appears to override opposing α2-adrenoceptor effects.HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral antinociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study

BackgroundIt has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs.MethodsWe performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales.ResultsD-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower.ConclusionIt was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity.Trial registrationUMIN Clinical Trials Registry (number UMIN000000468). Registered 18 August 2006

Dietary nitrate supplementation increases acute mountain sickness severity and sense of effort during hypoxic exercise.

Dietary nitrate supplementation enhances sea level performance and may ameliorate hypoxemia at high altitude. However, nitrate may exacerbate acute mountain sickness (AMS), specifically headache. This study investigated the effect of nitrate supplementation on AMS symptoms and exercise responses with 6-h hypoxia. Twenty recreationally active men [age, 22 ± 4 yr, maximal oxygen consumption (V̇o2max), 51 ± 6 ml·min-1·kg-1, means ± SD] completed this randomized double-blinded placebo-controlled crossover study. Twelve participants were classified as AMS- on the basis of Environmental Symptoms Questionnaire [Acute Cerebral Mountain Sickness score (AMS-C)] <0.7 in both trials, and five participants were classified as AMS+ on the basis of AMS-C ≥0.7 on placebo. Five days of nitrate supplementation (70-ml beetroot juice containing ~6.4 mmol nitrate daily) increased plasma NO metabolites by 182 µM compared with placebo but did not reduce AMS or improve exercise performance. After 4-h hypoxia [inspired O2 fraction ([Formula: see text]) = 0.124], nitrate increased AMS-C and headache severity (visual analog scale; whole sample ∆10 [1, 20] mm, mean difference [95% confidence interval]; P = 0.03) compared with placebo. In addition, after 5-h hypoxia, nitrate increased sense of effort during submaximal exercise (∆7 [-1, 14]; P = 0.07). In AMS-, nitrate did not alter headache or sense of effort. In contrast, in AMS+, nitrate increased headache severity (∆26 [-3, 56] mm; P = 0.07), sense of effort (∆14 [1, 28]; P = 0.04), oxygen consumption, ventilation, and mean arterial pressure during submaximal exercise. On the next day, in a separate acute hypoxic exercise test ([Formula: see text] = 0.141), nitrate did not improve time to exhaustion at 80% hypoxic V̇o2max In conclusion, dietary nitrate increases AMS and sense of effort during exercise, particularly in those who experience AMS. Dietary nitrate is therefore not recommended as an AMS prophylactic or ergogenic aid in nonacclimatized individuals at altitude.NEW & NOTEWORTHY This is the first study to identify that the popular dietary nitrate supplement (beetroot) does not reduce acute mountain sickness (AMS) or improve exercise performance during 6-h hypoxia. The consumption of nitrate in those susceptible to AMS exacerbates AMS symptoms (headache) and sense of effort and raises oxygen cost, ventilation, and blood pressure during walking exercise in 6-h hypoxia. These data question the suitability of nitrate supplementation during altitude travel in nonacclimatized people.

Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men.

Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid nongenomic and slow genomic mechanisms. Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD but impairs these abilities in healthy individuals. We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men. In a double-blind placebo-controlled crossover study, we examined the time-dependent effects of a single low dose of hydrocortisone [10 mg; low-dose hydrocortisone (LDH)] on cognition in 45 HIV-infected men. Participants were randomized to receive either LDH or placebo and one month later, were given the opposite treatment. At each intervention session, cognition was assessed 30 minutes (assessing nongenomic effects) and 4 hours (assessing genomic effects) after pill administration. Self-reported stress/anxiety and cortisol/cytokines in saliva were measured throughout each session. Compared with placebo, LDH doubled salivary cortisol levels. Cortisol returned to baseline 4 hours postadministration. At the 30-minute assessment, LDH enhanced verbal learning compared with placebo. Greater increases in cortisol were associated with greater enhancements in verbal learning. LDH did not affect subjective stress/anxiety or any other cognitive outcomes at the 30-minute or 4-hour time point. The rapid effects of LDH on verbal learning suggests a nongenomic mechanism by which glucocorticoids can enhance cognition in HIV-infected men. The nonenduring nature of this enhancement may limit its clinical utility but provides insight into mechanisms underlying the effects of acute glucocorticoids on learning.

Methylphenidate-Related Improvements in Math Performance Cannot Be Explained by Better Cognitive Functioning or Higher Academic Motivation: Evidence From a Randomized Controlled Trial

Objective: This study investigated whether improvements in working memory, reaction time, lapses of attention, interference control, academic motivation, and perceived competence mediated effects of methylphenidate on math performance. Method: Sixty-three children (ADHD diagnosis; methylphenidate treatment; age 8-13; IQ > 70) were randomly allocated to a 7-day methylphenidate or placebo treatment in this double-blind placebo-controlled crossover study and compared with 67 controls. Data were collected at schools and analyzed using mixed-model analysis. Methylphenidate was hypothesized to improve all measures; all measures were evaluated as potential mediators of methylphenidate-related math improvements. Results: Controls mostly outperformed the ADHD group. Methylphenidate did not affect measures of cognitive functioning (p = .082-.641) or academic motivation (p = .199-.865). Methylphenidate improved parent ratings of their child’s self-perceived competence (p < .01), which mediated methylphenidate efficacy on math productivity. Conclusion: These results question the necessity of improvements in specific cognitive and motivational deficits associated with ADHD for medication-related academic improvement. They also stimulate further study of perceived competence as a mediator.

Statin Therapy Does Not Significantly Alter Microvascular Function in Uncomplicated Hypertension

Objective Young patients with uncomplicated hypertension are frequently exempt from statin therapy as they generally fall below current treatment thresholds. This study examined whether there may be evidence of improved microvascular function in young patients with grade 1 hypertension after 12 weeks of statin therapy. Methods This was a randomized double-blind placebo-controlled crossover study in which 42 statin-naïve participants with grade 1 hypertension (mean systolic/diastolic blood pressure 142/92 mmHg) were randomized to receive either simvastatin 40 mg or a placebo for 12 weeks, followed by a 4-week washout period, after which the arms crossed for a further 12 weeks. Measures of vascular function were recorded at the beginning and end of each study period equating to four measures in total. The brachial artery was studied by flow-mediated dilatation (FMD) together with the resistive and pulsatility indices and mean velocity of flow. Results Statin therapy did not significantly alter the change in FMD seen in the brachial artery [standardized differential mean = 0.02 (0.23), confidence interval (CI) = −0.45 to 0.48, p = 0.932]. No significant changes were seen in the brachial artery mean velocity (CI = −9.68 to 11.51, p = 0.861), resistive index (CI = −0.11 to 0.12, p = 0.903), or pulsatility index (CI = −5.82 to 4.91, p = 0.864). Conclusion This study did not demonstrate any significant changes in established measures of microvascular function after treatment with a statin in a young hypertensive population with no antecedent cardiovascular disease. This may indicate that either the intervention was insufficiently vasoactive to produce a clinically detectable improvement in vascular function, or that the means used to assess the microvasculature were insufficiently sensitive to detect what may have been quite minor changes.

Intake of a Ketone Ester Drink during Recovery from Exercise Promotes mTORC1 Signaling but Not Glycogen Resynthesis in Human Muscle.

Purpose: Ketone bodies are energy substrates produced by the liver during prolonged fasting or low-carbohydrate diet. The ingestion of a ketone ester (KE) rapidly increases blood ketone levels independent of nutritional status. KE has recently been shown to improve exercise performance, but whether it can also promote post-exercise muscle protein or glycogen synthesis is unknown.Methods: Eight healthy trained males participated in a randomized double-blind placebo-controlled crossover study. In each session, subjects undertook a bout of intense one-leg glycogen-depleting exercise followed by a 5-h recovery period during which they ingested a protein/carbohydrate mixture. Additionally, subjects ingested a ketone ester (KE) or an isocaloric placebo (PL).Results: KE intake did not affect muscle glycogen resynthesis, but more rapidly lowered post-exercise AMPK phosphorylation and resulted in higher mTORC1 activation, as evidenced by the higher phosphorylation of its main downstream targets S6K1 and 4E-BP1. As enhanced mTORC1 activation following KE suggests higher protein synthesis rates, we used myogenic C2C12 cells to further confirm that ketone bodies increase both leucine-mediated mTORC1 activation and protein synthesis in muscle cells.Conclusion: Our results indicate that adding KE to a standard post-exercise recovery beverage enhances the post-exercise activation of mTORC1 but does not affect muscle glycogen resynthesis in young healthy volunteers. In vitro, we confirmed that ketone bodies potentiate the increase in mTORC1 activation and protein synthesis in leucine-stimulated myotubes. Whether, chronic oral KE intake during recovery from exercise can facilitate training-induced muscular adaptation and remodeling need to be further investigated.

Empagliflozin increases urinary volume output in healthy volunteers with artificial SIADH - a placebo-controlled double blind crossover study

Empagliflozin increases urinary volume output in healthy volunteers with artificial SIADH - a placebo-controlled double blind crossover study

Short-Term Effects of Methylphenidate on Math Productivity in Children With Attention-Deficit/Hyperactivity Disorder are Mediated by Symptom Improvements: Evidence From a Placebo-Controlled Trial.

Although numerous studies report positive effects of methylphenidate on academic performance, the mechanism behind these improvements remains unclear. This study investigates the effects of methylphenidate on academic performance in children with attention-deficit/hyperactivity disorder (ADHD) and the mediating and moderating influence of ADHD severity, academic performance, and ADHD symptom improvement. Sixty-three children with ADHD participated in a double-blind placebo-controlled crossover study comparing the effects of long-acting methylphenidate and placebo. Dependent variables were math, reading, and spelling performance. The ADHD group performance was compared with a group of 67 typically developing children. Methylphenidate improved math productivity and accuracy in children with ADHD. The effect of methylphenidate on math productivity was partly explained by parent-rated symptom improvement, with greater efficacy for children showing more symptom improvement. Further, children showing below-average math performance while on placebo profited more from methylphenidate than children showing above-average math performance. The results from this study indicate positive effects of methylphenidate on academic performance, although these were limited to math abilities. In light of these results, expectations of parents, teachers, and treating physicians about the immediate effects of methylphenidate on academic improvement should be tempered. Moreover, our results implicate that positive effects of methylphenidate on math performance are in part due directly to effects on math ability and in part due to reductions in ADHD symptoms.

Endurance, aerobic high-intensity, and repeated sprint cycling performance is unaffected by normobaric "Live High-Train Low": a double-blind placebo-controlled cross-over study.

The aim was to investigate whether 6weeks of normobaric "Live High-Train Low" (LHTL) using altitude tents affect highly trained athletes incremental peak power, 26-km time-trial cycling performance, 3-min all-out performance, and 30-s repeated sprint ability. In a double-blinded, placebo-controlled cross-over design, seven highly trained triathletes were exposed to 6weeks of normobaric hypoxia (LHTL) and normoxia (placebo) for 8h/day. LHTL exposure consisted of 2 weeks at 2500m, 2weeks at 3000m, and 2weeks at 3500m. Power output during an incremental test, ~26-km time trial, 3-min all-out exercise, and 8 × 30s of all-out sprint was evaluated before and after the intervention. Following at least 8weeks of wash-out, the subjects crossed over and repeated the procedure. Incremental peak power output was similar after both interventions [LHTL: 375 ± 74 vs. 369 ± 70W (pre-vs-post), placebo: 385 ± 60 vs. 364 ± 79W (pre-vs-post)]. Likewise, mean power output was similar between treatments as well as before and after each intervention for time trial [LHTL: 257 ± 49 vs. 254 ± 54W (pre-vs-post), placebo: 267 ± 57 vs. 267 ± 52W (pre-vs-post)], and 3-min all-out [LHTL: 366 ± 68 vs. 369 ± 72W (pre-vs-post), placebo: 365 ± 66 vs. 355 ± 71W (pre-vs-post)]. Furthermore, peak- and mean power output during repeated sprint exercise was similar between groups at all time points (n = 5). In conclusion, 6weeks of normobaric LHTL using altitude tents simulating altitudes of 2500-3500m conducted in a double-blinded, placebo-controlled cross-over design do not affect power output during an incremental test, a ~26-km time-trial test, or 3-min all-out exercise in highly trained triathletes. Furthermore, 30s of repeated sprint ability was unaltered.

A Randomized, Double-Blinded Placebo Controlled Crossover Study Evaluating 0.03% Tacrolimus Ointment Monotherapy in the Treatment of Discoid Lupus Erythematosus in Dogs

A Randomized, Double-Blinded Placebo Controlled Crossover Study Evaluating 0.03% Tacrolimus Ointment Monotherapy in the Treatment of Discoid Lupus Erythematosus in Dogs

Triterpenoids and polysaccharide peptides-enriched Ganoderma lucidum: a randomized, double-blind placebo-controlled crossover study of its antioxidation and hepatoprotective efficacy in healthy volunteers

Context: Ganoderma lucidum (Leyss: Fr) Karst. (Polyporaceae) is an oriental medicinal fungus, commonly used in traditional Chinese medicine (TCM) for treating various condition or diseases such as hypertension, hyperglycaemia, hepatitis and cancer. Objective : The current study examines whether triterpenoids and polysaccharide-enriched G. lucidum (GL) influence antioxidation and hepatoprotective efficacy by suppressing oxidative stress. Materials and methods: Forty-two healthy subjects (22 male and 20 female) were recruited and segregated into two groups as experimental or placebo and requested to intake GL (n = 21) or placebo (n = 21) capsule (225 mg; after lunch or dinner) for six consecutive months and vice versa with one month washout period in between. The anthropometric analysis and biochemical assays, as well as abdominal ultrasonic examination were performed. Results: Consumption of GL substantially improved (p < 0.05) the total antioxidant capacity (TEAC; 79.33–84.04), total thiols and glutathione content (6–8.05) in plasma as well as significant (p < 0.05) enhanced the activities of antioxidant enzymes. Whereas, the levels of thiobarbituric acid reactive substances (TBARS; 3.37–2.47), 8-hydroxy-deoxy-guanosine (8-OH-dG; 15.99–11.98) and hepatic marker enzymes (glutamic-oxaloacetic transaminase; GOT and glutamic-pyruvic transaminase; GPT) were concomitantly reduced (42 and 27%) on treatment with GL. Furthermore, the abdominal ultrasonic examination in GL subjects displayed a notable alteration on hepatic condition by reversing from mild fatty liver condition (initial) to normal condition. Discussion and Conclusion: The outcome of the present intervention demonstrated the antioxidation, anti-aging and hepatoprotective nature of GL by effectively curbing oxidative stress.