Few and often contradictory reports exist on the long-term neurobiological consequences of cannabinoid consumption in adolescents. The endocannabinoid system plays an important role during the different stages of brain development as cannabinoids influence the release and action of different neurotransmitters and promote neurogenesis. This study tested whether long-lasting interference by cannabinoids with the developing endogenous cannabinoid system during adolescence caused persistent behavioral alterations in adult rats. Adolescent female and male rats were treated with increasing doses of D 9 -tetrahydrocannabinol (THC) for 11 days (postnatal day (PND) 35-45) and left undisturbed until adulthood (PND 75) when behavioral and biochemical assays were carried out. CB1 receptor level and CB1/G-protein coupling were significantly reduced by THC exposure in the amygdala (Amyg), ventral tegmental area (VTA) and nucleus accumbens (NAc) of female rats, whereas male rats had significant alterations only in the amygdala and hippocampal formation. Neither female nor male rats showed any changes in anxiety responses (elevated plus maze and open-field tests) but female rats presented significant 'behavioral despair' (forced swim test) paralleled by anhedonia (sucrose preference). In contrast, male rats showed no behavioral despair but did present anhedonia. This different behavioral picture was supported by biochemical parameters of depression, namely CREB alteration. Only female rats had low CREB activity in the hippocampal formation and prefrontal cortex and high activity in the NAc paralleled by increases in dynorphin expression. These results suggest that heavy cannabis consumption in adolescence may induce subtle alterations in the emotional circuit in female rats, ending in depressive-like behavior, whereas male rats show altered sensitivity to rewarding stimuli.

BackgroundIndividuals with COPD may present reduced peripheral muscle strength, leading to impaired mobility. Comprehensive pulmonary rehabilitation (PR) should include strength training, in particular to lower limbs. Furthermore, simple tools for the assessment of peripheral muscle performance are required.ObjectivesTo assess the peripheral muscle performance of COPD patients by the sit-to-stand test (STST), as compared to the one-repetition maximum (1-RM), considered as the gold standard for assessing muscle strength in non-laboratory situations, and to evaluate the responsiveness of STST to a PR program.MethodsSixty moderate-to-severe COPD inpatients were randomly included into either the specific strength training group or into the usual PR program group. Patients were assessed on a 30-second STST and 1-minute STST, 1-RM, and 6-minute walking test (6MWT), before and after PR. Bland–Altman plots were used to evaluate the agreement between 1-RM and STST.ResultsThe two groups were not different at baseline. In all patients, 1-RM was significantly related to the 30-second STST (r=0.48, P<0.001) and to 1-minute STST (r=0.36, P=0.005). The 30-second STST was better tolerated in terms of the perceived fatigue (P=0.002) and less time consuming (P<0.001) test. In the specific strength training group significant improvements were observed in the 30-second STST (P<0.001), 1-minute STST (P=0.005), 1-RM (P<0.001), and in the 6MWT (P=0.001). In the usual PR program group, significant improvement was observed in the 30-second STST (P=0.042) and in the 6MWT (P=0.001).ConclusionOur study shows that in stable moderate-to-severe inpatients with COPD, STST is a valid and reliable tool to assess peripheral muscle performance of lower limbs, and is sensitive to a specific PR program.

BACKGROUND:The effect of pulmonary rehabilitation (PR) on the EuroQol Group's 5-dimension questionnaire (EQ-5D) in COPD has been poorly investigated. In addition, conflicting results were reported about the visual analog scale component of EQ-5D (EQ-VAS). The purpose of this study was to evaluate the responsiveness of EQ-VAS to PR and its relationship with clinical and functional parameters in subjects with COPD, as well as to define the minimal clinically important difference (MCID) estimate for the EQ-VAS after PR. METHODS: A total of 468 in-patients with stable moderate-to-severe COPD, allocated to a 3-wk PR program, were retrospectively evaluated. EQ-VAS was assessed before and after PR, and its relationship with baseline pulmonary function, changes in 6-min walk test, and baseline, and transitional dyspnea index (BDI/TDI) after PR were evaluated. Using an anchor-based approach and receiver operating characteristic curves, the EQ-VAS change cutoff that identified subjects achieving the known MCID for TDI after PR was identified. RESULTS: Four hundred and thirty-nine subjects (94%, mean FEV 1 55.3% predicted) completed pre-and post-PR EQ-VAS scores. After PR, EQ-VAS increased from 58 ؎ 17 to 72 ؎ 15 (⌬EQ-VAS 14 ؎ 12, P < .001). ⌬EQ-VAS was negatively related to baseline FEV 1 (r ‫؍‬ ؊0.32, P < .001) and positively to TDI (r ‫؍‬ 0.50, P < .001) and 6-min walk distance (r ‫؍‬ 0.46, P < .001) changes. Receiver operating characteristic curves identified an EQ-VAS change cutoff of 8 as the best discriminating value to identify the MCID for TDI (0.78 sensitivity and 0.81 specificity; area under curve: 0.845, P < .001). CONCLUSIONS: Our study shows that, in in-patients with stable moderate-to-severe COPD, EQ-VAS is a valid and reliable tool to assess the responsiveness to PR, with an estimated MCID of 8 points. The EQ-VAS can be a practical alternative to more timeconsuming measures of health-related quality of life.

Background: Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. Methods: This question was explored in a pre-specified analysis of a 52week, open-label, randomized, parallel-group trial in patients with mild asthma receiving only reliever inhalers, comparing salbutamol 200µg asneeded, maintenance budesonide 200µg twice-daily with salbutamol as needed, and budesonide/formoterol 200/6µg as-needed. Outcomes were compared between patients with blood eosinophils of <0.15, 0.15-<0.3 and ≥0.3x109/L; FeNO of <20, 20-50 and >50ppb; and a composite score based on both. Results: The proportion of patients randomised to as-needed salbutamol having a severe exacerbation increased progressively with increasing blood eosinophil sub-group (4.1%, 6.5% and 19.5%; p=0.014). There were no significant interactions between either biomarker and the effect of as-needed budesonide/formoterol compared with as-needed salbutamol for either exacerbations or severe exacerbations. However, there were significant interactions between blood eosinophil sub-groups and the effect of maintenance budesonide compared with as needed salbutamol for exacerbations (p<0.001) and severe exacerbations (p<0.001). Maintenance budesonide was more effective than as-needed salbutamol in patients with eosinophils ≥0.3x109/L for exacerbations (odds ratio 0.13; 95% CI 0.05-0.33) and severe exacerbations (0.11; 0.03-0.45). This was not the case for eosinophils <0.15x109/L (odds ratio for exacerbations 1.15; 0.51-1.28 and severe exacerbations 5.72; 0.97-33.6). There was no consistent interaction between treatment response and FeNO or the composite score. Conclusions: In patients with mild asthma the effects of as-needed budesonide/formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts.

sures after PR was assessed. Both univariate and multiple logistic analyses were performed to evaluate the presence of independent predictors of the efficacy of PR. Results: One hundred and eight patients [49 males, mean age 71 years, mean forced expiratory volume in 1 s (FEV 1 ) 76% predicted] were included. After PR, there was a significant improvement in 6MWD, TDI, and EQ-VAS score (p < 0.001). Changes in 6MWD and EQ-VAS score correlated with baseline FEV 1 , FEV 1 /vital capacity (VC), residual volume, transfer factor of the lung for carbon monoxide, and the number of exacerbations in the previous year. Both univariate and multivariate logistic regression analyses showed that male gender, baseline FEV 1 /VC <70%, and >2 exacerbations in the previous year were independent predictors of PR efficacy in terms of an improvement in 6MWD. Conclusions: Our study supports the inclusion of patients with bronchiectasis in PR programs. Clinical and functional baseline findings partially predict the response to PR in terms of exercise tolerance. Further prospective, randomized, controlled trials are needed. © 2015 S. Karger AG, Basel Key Words Bronchiectasis · Pulmonary rehabilitation · Predictors of efficacy Abstract Background:International guidelines recommend the inclusion of patients with bronchiectasis in pulmonary rehabilitation (PR) to improve exercise capacity and health-related quality of life (HRQoL). At present, the effect of PR in these patients has been poorly investigated. Objective: The aim of our retrospective analysis was to evaluate the effects and predictors of success for a PR program in patients with bronchiectasis not related to cystic fibrosis (non-CF bronchiectasis). Methods: One hundred and thirty-five non-CF bronchiectasis inpatients, allocated to a 3-week PR program, were retrospectively evaluated. Exercise capacity (6-min walk distance, 6MWD), dyspnea (Baseline/Transition Dyspnea Index, BDI/TDI), and HRQoL [EuroQol visual analogue scale (EQ-VAS)] were assessed before and after PR. The relationship between baseline parameters and changes in outcome mea-