Placebo Response of Non-Pharmacological and Pharmacological Trials in Major Depression: A Systematic Review and Meta-Analysis

Background: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device-rTMS) trials. Methodology/Principal Findings: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria-29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d-random-effects model-1.48; 95% C.I. 1.26 to 1.6) and rTMS studies (0.82; 95% C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. Conclusions/Significance: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself.

Identification of protein-coding and non-coding RNA expression profiles in CD34(+) and in stromal cells in refractory anemia with ringed sideroblasts

Background: Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by ineffective hematopoiesis with morphological evidence of marrow cell dysplasia resulting in peripheral blood cytopenia. Microarray technology has permitted a refined high-throughput mapping of the transcriptional activity in the human genome. Non-coding RNAs (ncRNAs) transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression, and in the regulation of exon-skipping and intron retention. Characterization of ncRNAs in progenitor cells and stromal cells of MDS patients could be strategic for understanding gene expression regulation in this disease. Methods: In this study, gene expression profiles of CD34(+) cells of 4 patients with MDS of refractory anemia with ringed sideroblasts (RARS) subgroup and stromal cells of 3 patients with MDS-RARS were compared with healthy individuals using 44 k combined intron-exon oligoarrays, which included probes for exons of protein-coding genes, and for non-coding RNAs transcribed from intronic regions in either the sense or antisense strands. Real-time RT-PCR was performed to confirm the expression levels of selected transcripts. Results: In CD34(+) cells of MDS-RARS patients, 216 genes were significantly differentially expressed (q-value <= 0.01) in comparison to healthy individuals, of which 65 (30%) were non-coding transcripts. In stromal cells of MDS-RARS, 12 genes were significantly differentially expressed (q-value <= 0.05) in comparison to healthy individuals, of which 3 (25%) were non-coding transcripts. Conclusions: These results demonstrated, for the first time, the differential ncRNA expression profile between MDS-RARS and healthy individuals, in CD34(+) cells and stromal cells, suggesting that ncRNAs may play an important role during the development of myelodysplastic syndromes.

Intermolecular vibrations and fast relaxations in supercooled ionic liquids

Short-time dynamics of ionic liquids has been investigated by low-frequency Raman spectroscopy (4 < omega < 100 cm(-1)) within the supercooled liquid range. Raman spectra are reported for ionic liquids with the same anion, bis(trifluoromethylsulfonyl)imide, and different cations: 1-butyl-3-methylimidazolium, 1-hexyl-3-methylimidazolium, 1-butyl-1-methylpiperidinium, trimethylbutylammonium, and tributylmethylammonium. It is shown that low-frequency Raman spectroscopy provides similar results as optical Kerr effect (OKE) spectroscopy, which has been used to study intermolecular vibrations in ionic liquids. The comparison of ionic liquids containing aromatic and non-aromatic cations identifies the characteristic feature in Raman spectra usually assigned to librational motion of the imidazolium ring. The strength of the fast relaxations (quasi-elastic scattering, QES) and the intermolecular vibrational contribution (boson peak) of ionic liquids with non-aromatic cations are significantly lower than imidazolium ionic liquids. A correlation length assigned to the boson peak vibrations was estimated from the frequency of the maximum of the boson peak and experimental data of sound velocity. The correlation length related to the boson peak (similar to 19 angstrom) does not change with the length of the alkyl chain in imidazolium cations, in contrast to the position of the first-sharp diffraction peak observed in neutron and X-ray scattering measurements of ionic liquids. The rate of change of the QES intensity in the supercooled liquid range is compared with data of excess entropy, free volume, and mean-squared displacement recently reported for ionic liquids. The temperature dependence of the QES intensity in ionic liquids illustrates relationships between short-time dynamics and long-time structural relaxation that have been proposed for glass-forming liquids. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3604533]

Involvement of Clostridium gasigenes and C. algidicarnis in `blown pack` spoilage of Brazilian vacuum-packed beef

The objectives of this study were to isolate psychrotrophic clostridia from Brazilian vacuum-packed beef cuts (spoiled or not) and to identify the isolates by using 16S rRNA gene sequencing. Anaerobic psychrotrophic microorganisms were also enumerated and samples were collected to verify the incidence of psychrotrophic clostridia in the abattoir environment. Vacuum-packed beef cuts (n = 8 grossly distended and n = 5 non-spoiled) and environmental samples were obtained from a beef packing plant located in the state of Sao Paulo, Brazil. Each sample was divided in three subsamples (exudate, beef surface and beef core) that were analyzed for vegetative forms, total spore-forming, and sulfide reducing spore-forming, both activated by alcohol and heat. Biochemical profiles of the isolates were obtained using API20A, with further identification using 16S rRNA gene sequencing. The growth temperature and the pH range were also assessed. Populations of psychrotrophic anaerobic vegetative microorganisms of up to 10(10) CFU/(g, mL or 100 cm(2)) were found in `blown pack` samples, while in non-spoiled samples populations of 10(5) CFU/(g, CFU/mL or CFU/100cm(2)) was found. Overall, a higher population of total spores and sulfide reducing spores activated by heat in spoiled samples was found. Clostridium gasigenes (n = 10) and C. algidicarnis (n = 2) were identified using 16S rRNA gene sequencing. Among the ten C. gasigenes isolates, six were from spoiled samples (C1, C2 and C9), two were isolated from non-spoiled samples (C4 and C5) and two were isolated from the hide and the abattoir corridor/beef cut conveyor belt. C. algidicarnis was recovered from spoiled beef packs (C2). Although some samples (C3, C7, C10 and C14) presented signs of `blown pack` spoilage, Clostridium was not recovered. C. algidicarnis (n = 1) and C. gasigenes (n = 9) isolates have shown a psychrotrophic behavior, grew in the range 6.2-8.2. This is the first report on the isolation of psychrotrophic Clostridium (C. gasigenes and C. algidicarnis) in Brazil. This study shows that psychrotrophic Clostridium may pose a risk for the stability of vacuum-packed beef produced in tropical countries during shelf-life and highlights the need of adopting control measures to reduce their incidence in abattoir and the occurrence of `blown pack` spoilage. (C) 2011 Elsevier B.V. All rights reserved.

Effect of bench press exercise intensity on muscle soreness and inflammatory mediators

This study compared four different intensities of a bench press exercise for muscle soreness, creatine kinase activity, interleukin (IL)-1, IL-6, tumor necrosis factor- (TNF-), and prostaglandin E2 (PGE2) concentrations in the blood. Thirty-five male Brazilian Army soldiers were randomly assigned to one of five groups: 50% one-repetition maximum (1-RM), 75% 1-RM, 90% 1-RM, 110% 1-RM, and a control group that did not perform the exercise. The total volume (setsrepetitionsload) of the exercise was matched among the exercise groups. Muscle soreness and plasma creatine kinase activity increased markedly (P0.05) after exercise, with no significant differences among the groups. Serum PGE2 concentration also increased markedly (P0.05) after exercise, with a significantly (P0.05) greater increase in the 110% 1-RM group compared with the other groups. A weak but significant (P0.05) correlation was found between peak muscle soreness and peak PGE2 concentration, but no significant correlation was evident between peak muscle soreness and peak creatine kinase activity, or peak creatine kinase activity and peak PGE2 concentration. All groups showed no changes in IL-1, IL-6 or TNF-. Our results suggest that the intensity of bench press exercise does not affect the magnitude of muscle soreness and blood markers of muscle damage and inflammation.

Contuse lesion of the rat spinal cord of moderate intensity leads to a higher time-dependent secondary neurodegeneration than severe one - An open-window for experimental neuroprotective interventions

Secondary neurodegeneration takes place in the surrounding tissue of spinal cord trauma and modifies substantially the prognosis, considering the small diameter of its transversal axis. We analyzed neuronal and glial responses in rat spinal cord after different degree of contusion promoted by the NYU Impactor. Rats were submitted to vertebrae laminectomy and received moderate or severe contusions. Control animals were sham operated. After 7 and 30 days post surgery, stereological analysis of Nissl staining cellular profiles showed a time progression of the lesion volume after moderate injury, but not after severe injury. The number of neurons was not altered cranial to injury. However, same degree of diminution was seen in the caudal cord 30 days after both severe and moderate injuries. Microdensitometric image analysis demonstrated a microglial reaction in the white matter 30 days after a moderate contusion and showed a widespread astroglial reaction in the white and gray matters 7 days after both severities. Astroglial activation lasted close to lesion and in areas related to Wallerian degeneration. Data showed a more protracted secondary degeneration in rat spinal cord after mild contusion, which offered an opportunity for neuroprotective approaches. Temporal and regional glial responses corroborated to diverse glial cell function in lesioned spinal cord. (C) 2007 Elsevier Ltd. All rights reserved.

Exercise intensity optimization for men with high cardiorespiratory fitness

Exercise intensity is a key parameter for exercise prescription but the optimal range for individuals with high cardiorespiratory fitness is unknown. The aims of this study were (1) to determine optimal heart rate ranges for men with high cardiorespiratory fitness based on percentages of maximal oxygen consumption (%VO(2max)) and reserve oxygen consumption (%VO(2reserve)) corresponding to the ventilatory threshold and respiratory compensation point, and ( 2) to verify the effect of advancing age on the exercise intensities. Maximal cardiorespiratory testing was performed on 210 trained men. Linear regression equations were calculated using paired data points between percentage of maximal heart rate (%HR(max)) and %VO(2max) and between percentage of heart rate reserve (%HRR) and %VO(2reserve) attained at each minute during the test. Values of %VO(2max) and %VO(2reserve) at the ventilatory threshold and respiratory compensation point were used to calculate the corresponding values of %HRmax and %HRR, respectively. The ranges of exercise intensity in relation to the ventilatory threshold and respiratory compensation point were achieved at 78-93% of HR(max) and 70-93% of HRR, respectively. Although absolute heart rate decreased with advancing age, there were no age-related differences in %HR(max) and %HRR at the ventilatory thresholds. Thus, in men with high cardiorespiratory fitness, the ranges of exercise intensity based on %HR(max) and %HRR regarding ventilatory threshold were 78-93% and 70-93% respectively, and were not influenced by advancing age.

Endurance in judogi grip strength tests: comparison between elite and non-elite judo players

Background and Study Aim: The ability to develop a strong grip and maintain it during a judo match has become an important element for judo athletes. Therefore, the purpose of this investigation was to examine differences between measurements of maximal isometric time on judogi pull-up, and number of repetitions during dynamic judogi pull-up. Material/Methods: The sample was composed by two groups: 16 high-level judo athletes from the male Brazilian National Team and 12 male state-level judo athletes, with at least one athlete per weight category. The tests were compared through analysis of co-variance (body mass as co-variable), followed by a post-hoc test (Scheffe). Significance level was set at 5%. Results: No difference was found in the isometric test: Brazilian Team: 35 +/- 18s; Regional: 39 +/- 14s. However, the Brazilian Team performed a high number of repetitions (12 +/- 5 rep) compared to regional group (9 +/- 4 rep) during the dynamic grip strength endurance test. Conclusions: Thus, dynamic grip strength endurance seems to be a discriminating variable between judo athletes, probably because judo combat involves many elbow extensions and flexions in order to avoid the opponent`s grip and to subdue them.

Acute high-intensity exercise with low energy expenditure reduced LDL-c and total cholesterol in men

A reduction in LDL cholesterol and an increase in HDL cholesterol levels are clinically relevant parameters for the treatment of dyslipidaemia, and exercise is often recommended as an intervention. This study aimed to examine the effects of acute, high-intensity exercise (similar to 90% VO(2max)) and varying carbohydrate levels (control, low and high) on the blood lipid profile. Six male subjects were distributed randomly into exercise groups, based on the carbohydrate diets (control, low and high) to which the subjects were restricted before each exercise session. The lipid profile (triglycerides, VLDL, HDL cholesterol, LDL cholesterol and total cholesterol) was determined at rest, and immediately and 1 h after exercise bouts. There were no changes in the time exhaustion (8.00 +/- A 1.83; 7.82 +/- A 2.66; and 9.09 +/- A 3.51 min) and energy expenditure (496.0 +/- A 224.8; 411.5 +/- A 223.1; and 592.1 +/- A 369.9 kJ) parameters with the three varying carbohydrate intake (control, low and high). Glucose and insulin levels did not show time-dependent changes under the different conditions (P > 0.05). Total cholesterol and LDL cholesterol were reduced after the exhaustion and 1 h recovery periods when compared with rest periods only in the control carbohydrate intake group (P < 0.05), although this relation failed when the diet was manipulated. These results indicate that acute, high-intensity exercise with low energy expenditure induces changes in the cholesterol profile, and that influences of carbohydrate level corresponding to these modifications fail when carbohydrate (low and high) intake is manipulated.

Taekwondo: physiological responses and match analysis

Matsushigue, KA, Hartmann, K, and Franchini, E. Taekwondo: Physiological responses and match analysis. J Strength Cond Res 23(4): 1112-1117, 2009-The aim of the present study was to determine the time structure and physiological responses during Songahm Taekwondo (TKD) competition and to compare these variables between winner and non-winner athletes. Fourteen men subjects were analyzed. Blood lactate concentration (LA) and heart rate (HR) were determined before and after the match. The match was filmed for the determination of the number of techniques used, the duration of effort and rest periods (RPs), and the interval between high-intensity movements (HM). Post-match LA was 7.5 +/- 3.8 mmol.L(-1), HR was 183 +/- 9 b.min(-1), and HM was 31 +/- 16 seconds. The mean effort time (862 seconds) did not differ from mean interval time (8 +/- 3 seconds). Winners used a smaller total number of techniques, but post-match LA or HR did not differ from that of non-winners. In conclusion, the glycolytic metabolism was not the predominant energy source and the physiological responses did not differ between winners and non-winners. Coaches and sports scientists should prepare a technical or physical training session considering the low glycolytic contribution in this sport, hence the training protocol should involve high-intensity movements interspersed with longer RPs to provide the creatine phosphate recovery, with special attention given to the technical quality of TKD skills and not to higher technique volume during a simulation of matches.

Low carbohydrate diet affects the oxygen uptake on-kinetics and rating of perceived exertion in high intensity exercise

The aim of this study was to determine if the carbohydrate (CHO) availability alters the rate of increase in the rating of perceived exertion (RPE) during high intensity exercise and whether this would be associated with physiological changes. Six males performed high intensity exercise after 48 h of controlled, high CHO (80%) and low CHO (10%) diets. Time to exhaustion was lower in the low compared to high CHO diet. The rate of increase in RPE was greater and the VO(2) slow component was lower in the low CHO diet than in the control. There was no significant condition effect for cortisol, insulin, pH, plasma glucose, potassium, or lactate concentrations. Multiple linear regression indicated that the total amplitude of VO(2) and perceived muscle strain accounted for the greatest variance in the rate of increase in RPE. These results suggest that cardiorespiratory variables and muscle strain are important afferent signals from the periphery for the RPE calculations.

Effect of performance level on pacing strategy during a 10-km running race

The aim of this study was to examine the influence of the performance level of athletes on pacing strategy during a simulated 10-km running race, and the relationship between physiological variables and pacing strategy. Twenty-four male runners performed an incremental exercise test on a treadmill, three 6-min bouts of running at 9, 12 and 15 km h(-1), and a self-paced, 10-km running performance trial; at least 48 h separated each test. Based on 10-km running performance, subjects were divided into terziles, with the lower terzile designated the low-performing (LP) and the upper terzile designated the high-performing (HP) group. For the HP group, the velocity peaked at 18.8 +/- A 1.4 km h(-1) in the first 400 m and was higher than the average race velocity (P < 0.05). The velocity then decreased gradually until 2,000 m (P < 0.05), remaining constant until 9,600 m, when it increased again (P < 0.05). The LP group ran the first 400 m at a significantly lower velocity than the HP group (15.6 +/- A 1.6 km h(-1); P > 0.05) and this initial velocity was not different from LP average racing velocity (14.5 +/- A 0.7 km h(-1)). The velocity then decreased non-significantly until 9,600 m (P > 0.05), followed by an increase at the end (P < 0.05). The peak treadmill running velocity (PV), running economy (RE), lactate threshold (LT) and net blood lactate accumulation at 15 km h(-1) were significantly correlated with the start, middle, last and average velocities during the 10-km race. These results demonstrate that high and low performance runners adopt different pacing strategies during a 10-km race. Furthermore, it appears that important determinants of the chosen pacing strategy include PV, LT and RE.

Non-exhaustive tests for critical power estimation

Objective. - The aim of this study was to propose a new method that allows for the estimation of critical power (CP) from non-exhaustive tests using ratings of perceived exertion (RPE). Methods. - Twenty-two subjects underwent two practice trials for ergometer and Borg 15-point scale familiarization, and adaptation to severe exhaustive exercise. After then, four exercise bouts were performed on different days for the estimation of CP and anaerobic work capacity (AWC) by linear work-time equation, and CP(15), CP(17), AWC(15) and AWC(17) were estimated using the work and time to attainment of RPE15 and RPE17 based on the Borg 15-point scale. Results. - The CP, CP(15) and CP(17) (170-177W) were not significantly different (P>0.05). However, AWC, AWC(15) and AWC(17) were all different from each other. The correlations between CP(15) and CP(17), with CP were strong (R=0.871 and 0.911, respectively), but the AWC(15) and AWC(17) were not significantly correlated with AWC. Conclusion. - Sub-maximal. RPE responses can be used for the estimation of CP from non-exhaustive exercise protocols. (C) 2009 Elsevier Masson SAS. All rights reserved.

Pain threshold is achieved at intensity above anaerobic threshold in patients with intermittent claudication

PURPOSE: Walking training is considered as the first treatment option for patients with peripheral arterial disease and intermittent claudication (IC). Walking exercise has been prescribed for these patients by relative intensity of peak oxygen uptake (VO(2)peak), ranging from 40% to 70% VO(2)peak, or pain threshold (PT). However, the relationship between these methods and anaerobic threshold (AT), which is considered one of the best metabolic markers for establishing training intensity, has not been analyzed. Thus, the aim of this study was to compare, in IC patients, the physiological responses at exercise intensities usually prescribed for training (% VO(2) peak or % PT) with the ones observed at AT. METHODS: Thirty-three IC patients performed maximal graded cardiopulmonary treadmill test to assess exercise tolerance. During the test, heart rate (HR), VO(2), and systolic blood pressure were measured and responses were analyzed at the following: 40% of VO(2)peak; 70% of VO(2)peak; AT; and PT. RESULTS: Heart rate and VO(2) at 40% and 70% of VO(2)peak were lower than those at AT (HR: -13 +/- 9% and -3 +/- 8%, P < .01, respectively; VO(2): -52 +/- 12% and -13 +/- 15%, P < .01, respectively). Conversely, HR and VO(2) at PT were slightly higher than those at AT (HR: +3 +/- 8%, P < .01; VO(2): + 6 +/- 15%, P = .04). None of the patients achieved the respiratory compensation point. CONCLUSION: Prescribing exercise for IC patients between 40% and 70% of VO(2)peak will induce a lower stimulus than that at AT, whereas prescribing exercise at PT will result in a stimulus above AT. Thus, prescribing exercise training for IC patients on the basis of PT will probably produce a greater metabolic stimulus, promoting better cardiovascular benefits.

Exercise Intensity, Inflammatory Signaling, and Insulin Resistance in Obese Rats

DA SILVA, A. S. R., J. R. PAULI, E. R. ROPELLE, A. G. OLIVEIRA, D. E. CINTRA, C. T. DE SOUZA, L. A. VELLOSO, J. B. C. CARVALHEIRA, and M. J. A. SAAD. Exercise Intensity, Inflammatory Signaling, and Insulin Resistance in Obese Rats. Med. Sci. Sports Exerc., Vol. 42, No. 12, pp. 2180-2188, 2010. Purpose: To evaluate the effects of intensity of exercise on insulin resistance and the expression of inflammatory proteins in the skeletal muscle of diet-induced obese (DIO) rats after a single bout of exercise. Methods: In the first exercise protocol, the rats swam for two 3-h bouts, separated by a 45-min rest period (with 6 h in duration-DIO + EXE), and in the second protocol, the rats were exercised with 45 min of swimming at 70% of the maximal lactate steady state-MLSS (DIO + MLSS). Results: Our data demonstrated that both protocols of exercise increased insulin sensitivity and increased insulin-stimulated tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 and serine phosphorylation of protein kinase B in the muscle of DIO rats by the same magnitude. In parallel, both exercise protocols also reduced protein tyrosine phosphatase 1B activity and insulin receptor substrate 1 serine phosphorylation, with concomitant reduction in c-jun N-terminal kinase and I kappa B kinase activities in the muscle of DIO rats in a similar fashion. Conclusions: Thus, our data demonstrate that either exercise protocols with low intensity and high volume or exercise with moderate intensity and low volume represents different strategies to restore insulin sensitivity with the same efficacy.