Effectiveness of brief interventions in primary care for cannabis users aged from 12 to 25 years old: a systematic review.

INTRODUCTION: The aim of this systematic review was to assess the effectiveness of brief interventions realized in primary care in reducing cannabis use for adolescents and emerging adults. METHODS: PubMed, CINAHL, Embase, PsycInfo, and Central (Cochrane Library) were searched until December 2020. Randomized controlled trials conducted in primary care, concerning in-person brief interventions for non-medical cannabis users aged from 12 to 25 years old were eligible for inclusion. Brief interventions had to last 30 min or less. Patients with comorbid mental health disorder or very specific populations were not included. RESULTS: One thousand eighty hundred and fifty-five studies were identified through database searching; only 8 studies involving 2,199 patients were included for qualitative synthesis after double reading and data extraction. Randomized controlled trials selected were heterogeneous regarding screening tools, initial levels of cannabis use and cannabis outcomes measures. Brief interventions were all based on motivational interviewing techniques or personalized feedback. Seven studies consisted in a single session of brief intervention. Six studies involved also other substance users. No significant reduction of cannabis use after brief intervention was found for most studies, especially in the long term. A trend of decreased cannabis consequences, such as negative psychosocial repercussions, perception of cannabis use by peers, or driving under the influence of cannabis, was reported. CONCLUSION: The current state of knowledge does not allow us to say that the brief intervention is effective in reducing cannabis use among adolescents in primary care. We found a mild positive effect on cannabis consequences after brief intervention. Mixed qualitative and quantitative studies are need to better evaluate the impact of brief intervention and his faisability. PROSPERO (International Prospective Register of Systematic Reviews): n° CRD42016033080.

Patients' adherence to smartphone apps in the management of bipolar disorder: a systematic review.

BACKGROUND: Despite an increasing number of available mental health apps in the bipolar disorder field, these tools remain scarcely implemented in everyday practice and are quickly discontinued by patients after downloading. The aim of this study is to explore adherence characteristics of bipolar disorder patients to dedicated smartphone interventions in research studies. METHODS: A systematic review following PRISMA guidelines was conducted. Three databases (EMBASE, PsychInfo and MEDLINE) were searched using the following keywords: "bipolar disorder" or "mood disorder" or "bipolar" combined with "digital" or "mobile" or "phone" or "smartphone" or "mHealth" or "ehealth" or "mobile health" or "app" or "mobile-health". RESULTS: Thirteen articles remained in the review after exclusion criteria were applied. Of the 118 eligible studies, 39 did not provide adherence characteristics. Among the selected papers, study length, sample size and definition of measures of adherence were strongly heterogeneous. Activity rates ranged from 58 to 91.6%. CONCLUSION: The adherence of bipolar patients to apps is understudied. Standardised measures of adherence should be defined and systematically evaluated in future studies dedicated to these tools.

Sex Differences in Recovery-Related Outcomes and Needs for Psychiatric Rehabilitation in People With Schizophrenia Spectrum Disorder.

BACKGROUND: Female sex/gender has been associated with better longitudinal outcomes in schizophrenia spectrum disorders (SSDs). Few studies have investigated the relationships between female gender and recovery-related outcomes. Women's specific psychiatric rehabilitation needs remain largely unknown. OBJECTIVE: The objectives of the present study are to investigate sex differences in (1) objective and subjective aspects of recovery and (2) psychiatric rehabilitation needs in a multicenter non-selected psychiatric rehabilitation SSD sample. METHODS: 1,055 outpatients with SSD (DSM-5) were recruited from the French National Centers of Reference for Psychiatric Rehabilitation (REHABase) cohort between January 2016 and November 2019. Evaluation included standardized scales for quality of life, satisfaction with life, and well-being and a broad cognitive battery. Socially valued roles at enrollment were recorded. Functional recovery was measured using the Global Assessment of Functioning scale (GAF) and personal recovery with the Stages of Recovery Instrument (STORI). RESULTS: Female sex was the best predictor of having more than 2 socially valued roles in the multivariate analysis (P < .001; OR [95% CI] = 5.42 [2.34-13.06]). No sex differences were found for functional recovery or personal recovery. Female gender was positively associated with self-stigma (P = .036) and suicidal history (P < .001) and negatively correlated with quality of life (P = .004) and satisfaction with interpersonal relationships (P = .029), an area in which women reported more unmet needs (P = .004). CONCLUSIONS: The present study found that women had poorer subjective recovery-related outcomes and more unmet needs than men. It would therefore be beneficial to develop recovery-oriented interventions addressing women's specific needs and implement these in psychiatric rehabilitation services.

Patient and physician perspectives of a smartphone application for depression: a qualitative study.

BACKGROUND: Despite an increasing number of smartphone apps, such therapeutic tools have not yet consistently demonstrated their efficacy and many suffer from low retention rates. To ensure the development of efficient apps associated with high adherence, we aimed to identify, through a user-centred design approach, patient and physician expectations of a hypothetical app dedicated to depression. METHODS: We conducted semi-structured interviews with physicians (psychiatrists and general practitioners) and patients who had experienced a major depressive episode during the last 12 months using the focus group method. The interviews were audio recorded, transcribed and analysed using qualitative content analysis to define codes, categories and emergent themes. RESULTS: A total of 26 physicians and 24 patients were included in the study. The focus groups showed balanced sex and age distributions. Most participants owned a smartphone (83.3% of patients, 96.1% of physicians) and were app users (79.2% of patients and 96.1% of physicians). The qualitative content analysis revealed 3 main themes: content, operating characteristics and barriers to the use of the app. Expected content included the data collected by the app, aiming to provide information about the patient, data provided by the app, gathering psychoeducation elements, therapeutic tools and functionalities to help with the management of daily life and features expected for this tool. The "operating characteristics" theme gathered aims considered for the app, its potential target users, considered modalities of use and considerations around its accessibility and security of use. Finally, barriers to the use of the app included concerns about potential app users, its accessibility, safety, side-effects, utility and functioning. All themes and categories were the same for patients and physicians. CONCLUSIONS: Physician and patient expectations of a hypothetical smartphone app dedicated to depression are high and confirmed the important role it could play in depression care. The key points expected by the users for such a tool are an easy and intuitive use and a personalised content. They are also waiting for an app that gives information about depression, offers a self-monitoring functionality and helps them in case of emergency.

Continuous reduction in cerebral oxygenation during endurance exercise in patients with pulmonary arterial hypertension.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) have lower cerebral blood flow (CBF) and oxygenation compared to healthy sedentary subjects, the latter negatively correlating with exercise capacity during incremental cycling exercise. We hypothesized that patients would also exhibit altered CBF and oxygenation during endurance exercise, which would correlate with endurance time. METHODS: Resting and exercise cardiorespiratory parameters, blood velocity in the middle cerebral artery (MCAv; transcranial doppler) and cerebral oxygenation (relative changes in cerebral tissue oxygenation index (ΔcTOI) and cerebral deoxyhemoglobin (ΔcHHb); near-infrared spectroscopy) were continuously monitored in nine PAH patients and 10 healthy-matched controls throughout endurance exercise. Cardiac output (CO), systemic blood pressure (BP) and oxygen saturation (SpO2 ), ventilatory metrics and end-tidal CO2 pressure (PET CO2 ) were also assessed noninvasively. RESULTS: Despite a lower workload and endurance oxygen consumption, similar CO and systemic BP, ΔcTOI was lower in PAH patients compared to controls (p < .01 for interaction). As expected during exercise, patients were characterized by an altered MCAv response to exercise, a lower PET CO2 and SpO2 , as wells as a higher minute-ventilation/CO2 production ratio ( V˙E/V˙CO2 ratio). An uncoupling between changes in MCAv and PET CO2 during the cycling endurance exercise was also progressively apparent in PAH patients, but absent in healthy controls. Both cHHb and ΔcTOI correlated with V˙E/V˙CO2 ratio (r = 0.50 and r = -0.52; both p < .05 respectively), but not with endurance time. CONCLUSION: PAH patients present an abnormal cerebrovascular profile during endurance exercise with a lower cerebral oxygenation that correlate with hyperventilation but not endurance exercise time. These findings complement the physiological characterization of the cerebral vascular responses to exercise in PAH patients.

Cannabis users: Screen systematically, treat individually. A descriptive study of participants in a randomized trial in primary care.

PURPOSE: The aim of the present study was to describe the profiles of a sample of young cannabis users not seeking care, for use in general practice in France. METHODS: In this cross-sectional study, baseline data were used from a previous clinical randomized trial, in which a brief intervention was tested. The participants were 262 cannabis users aged 15 to 25 years who smoked at least one joint per month. Assessment was undertaken both by the GP and via an anonymous self-reporting questionnaire. All statistical analyses were performed using Stata software and R. We used multiple correspondence analysis to determine the profiles of users. RESULTS: Among the 262 patients, 46.2% were daily users (more than 30 joints per month), 25.6% were regular users (from 10 to 29 joints per month), and 28.2% were recent users (fewer than 10 joints per month). The higher the frequency of use, the greater the incidence of unaccompanied use, daily use and week use (p from <0.001 to 0.01). The motivations of daily users were mostly self-treatment and habit (p <0.05). The cannabis abuse screening trial score revealed risky use for 87.5% of daily users and 34.4% for recent users. Factorial analysis identified 5 profiles according to age, risk, and motive for use. The reasons for consultation were equally distributed among users regardless of their level of use or their profile (p > 0.05). CONCLUSIONS: The results provide support for the practice of asking young patients systematically about their cannabis use, allowing GPs to identify users who require medical care. GPs should consider the differences between participants according to their profile in order to determine the appropriate type of care. TRIAL REGISTRATION: Clinicaltrials.gov NCT01433692.

Implications of habitual endurance and resistance exercise for dynamic cerebral autoregulation.

NEW FINDINGS: What is the central question of this study? Does habitual resistance and endurance exercise modify dynamic cerebral autoregulation? What is the main finding and its importance? To the authors' knowledge, this is the first study to directly assess dynamic cerebral autoregulation in resistance-trained individuals, and potential differences between exercise training modalities. Forced oscillations in blood pressure were induced by repeated squat-stands, from which dynamic cerebral autoregulation was assessed using transfer function analysis. These data indicate that dynamic cerebral autoregulatory function is largely unaffected by habitual exercise type, and further document the systemic circulatory effects of regular exercise. ABSTRACT: Regular endurance and resistance exercise produce differential but desirable physiological adaptations in both healthy and clinical populations. The chronic effect of these different exercise modalities on cerebral vessels' ability to respond to rapid changes in blood pressure (BP) had not been examined. We examined dynamic cerebral autoregulation (dCA) in 12 resistance-trained (mean ± SD, 25 ± 6 years), 12 endurance-trained (28 ± 9 years) and 12 sedentary (26 ± 6 years) volunteers. The dCA was assessed using transfer function analysis of forced oscillations in BP vs. middle cerebral artery blood velocity (MCAv), induced via repeated squat-stands at 0.05 and 0.10 Hz. Resting BP and MCAv were similar between groups (interaction: both P ≥ 0.544). The partial pressure of end-tidal carbon dioxide ( PETCO2 ) was unchanged (P = 0.561) across squat-stand manoeuvres (grouped mean for absolute change +0.6 ± 2.3 mmHg). Gain and normalized gain were similar between groups across all frequencies (both P ≥ 0.261). Phase showed a frequency-specific effect between groups (P = 0.043), tending to be lower in resistance-trained (0.63 ± 0.21 radians) than in endurance-trained (0.90 ± 0.41, P = 0.052) and -untrained (0.85 ± 0.38, P = 0.081) groups at slower frequency (0.05 Hz) oscillations. Squat-stands induced mean arterial pressure perturbations differed between groups (interaction: P = 0.031), with greater changes in the resistance (P < 0.001) and endurance (P = 0.001) groups compared with the sedentary group at 0.05 Hz (56 ± 13 and 49 ± 11 vs. 35 ± 11 mmHg, respectively). The differences persisted at 0.1 Hz between resistance and sedentary groups (49 ± 12 vs. 33 ± 7 mmHg, P < 0.001). These results indicate that dCA remains largely unaltered by habitual endurance and resistance exercise with a trend for phase to be lower in the resistance exercise group at lower fequencies.

Impact of Positive Emotion Regulation Training on Negative Symptoms and Social Functioning in Schizophrenia: A Field Test.

Background: The poor efficacy of drug or psychological treatments on the primary negative symptoms of schizophrenia has led to the development of new interventions. The Positive Emotions Program for Schizophrenia (PEPS) is an emotion regulation strategy training that aims to intensify positive emotions and develop positive performance beliefs. A randomized controlled trial showed that PEPS is effective in reducing the composite score of the reduction of experience syndrome (anhedonia and apathy). The present study is designed to evaluate its feasibility in natural conditions to measure external validity of PEPS. Materials and Methods: Twenty-one participants recruited through the French national network of expert centers followed eight sessions of PEPS and were assessed pre- and posttest with the Scale for Assessment of Negative Symptoms (SANS) and the Personal and Social Performance (PSP). The scales of the SANS were divided into a composite score of the reduction of the ability to experience and a composite score of the reduction of expression. Results: All participants followed the 8 sessions of PEPS, and both composite scores were significantly and clinically improved at posttest. Social functioning assessed with the PSP was also improved. Conclusions: This field test shows that participation in PEPS is accompanied by a reduction of negative symptoms and an improvement of social functioning. Both negative syndromes, reduction of expression and reduction of experience, are improved. Participants are younger than those in previous studies, which may explain this unexpected result. However, this calls for a controlled study with younger participants.

Six weeks of high-intensity interval training to exhaustion attenuates dynamic cerebral autoregulation without influencing resting cerebral blood velocity in young fit men.

Elevated cardiorespiratory fitness (CRF) is associated with reduced dynamic cerebral autoregulation (dCA), but the impact of exercise training per se on dCA remains equivocal. In addition, resting cerebral blood flow (CBF) and dCA after high-intensity interval training (HIIT) in individuals with already high CRF remains unknown. We examined to what extent 6 weeks of HIIT affect resting CBF and dCA in cardiorespiratory fit men and explored if potential changes are intensity-dependent. Endurance-trained men were assigned to group HIIT85 (85% of maximal aerobic power, 1-7 min effort bouts, n = 8) and HIIT115 (115% of maximal aerobic power, 30 sec to 1 min effort bouts, n = 9). Training sessions were completed until exhaustion 3 times/week over 6 weeks. Mean arterial pressure (MAP) and middle cerebral artery mean blood velocity (MCAvmean ) were measured continuously at rest and during repeated squat-stands (0.05 and 0.10 Hz). Transfer function analysis (TFA) was used to characterize dCA on driven blood pressure oscillations during repeated squat-stands. Neither training nor intensity had an effect on resting MAP and MCAvmean (both P > 0.05). TFA phase during 0.10 Hz squat-stands decreased after HIIT irrespective of intensity (HIIT85 : 0.77 ± 0.22 vs. 0.67 ± 0.18 radians; HIIT115 : pre: 0.62 ± 0.19 vs. post: 0.59 ± 0.13 radians, time effect P = 0.048). These results suggest that HIIT over 6 weeks have no apparent benefits on resting CBF, but a subtle attenuation in dCA is seen posttraining irrespective of intensity training in endurance-trained men.

Cardiac remodeling after six weeks of high-intensity interval training to exhaustion in endurance-trained men.

High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate, and cardiac cavities' size and function in endurance-trained adults. Seventeen endurance-trained men underwent 24-h ambulatory blood pressure monitoring and Doppler echocardiography at baseline and after 6 wk of HIIT. Participants were divided into 2 groups [85% maximal aerobic power (HIIT85), n = 8 and 115% maximal aerobic power (HIIT115), n = 9] to compare the impact of different HIIT intensities. Ambulatory blood pressure monitoring and cardiac chambers' size and function were similar between groups at baseline. HIIT reduced heart rate (55 ± 8 vs. 51 ± 7 beats/min; P = 0.003), systolic blood pressure (121 ± 11 vs. 118 ± 9 mmHg; P = 0.01), mean arterial pressure (90 ± 8 vs. 89 ± 6 mmHg; P = 0.03), and pulse pressure (52 ± 6 vs. 49 ± 5 mmHg; P = 0.01) irrespective of training intensity. Left atrium volumes increased after HIIT (maximal: 50 ± 14 vs. 54 ± 14 mL; P = 0.02; minimal: 15 ± 5 vs. 20 ± 8 mL; P = 0.01) in both groups. Right ventricle global longitudinal strain lowered after training in the HIIT85 group only (20 ± 4 vs. 17 ± 3%, P = 0.04). In endurance-trained men, 6 wk of HIIT reduced systolic blood pressure and mean arterial pressure and increased left atrium volumes irrespective of training intensity, whereas submaximal HIIT deteriorated right ventricle systolic function.NEW & NOTEWORTHY The novel findings of this study are that 6 wk of high-intensity interval training increases left atrial volumes irrespective of training intensity (85 or 115% maximal aerobic power), whereas the submaximal training decreases right ventricular systolic function in endurance-trained men. These results may help identify the exercise threshold for potential toxicity of intense exercise training for at-risk individuals and ideal exercise training regimens conferring optimal cardiovascular protection and adapted endurance training for athletes.

Dynamic cerebral autoregulation is attenuated in young fit women.

Young women exhibit higher prevalence of orthostatic hypotension with presyncopal symptoms compared to men. These symptoms could be influenced by an attenuated ability of the cerebrovasculature to respond to rapid blood pressure (BP) changes [dynamic cerebral autoregulation (dCA)]. The influence of sex on dCA remains unclear. dCA in 11 fit women (25 ± 2 years) and 11 age-matched men (24 ± 1 years) was compared using a multimodal approach including a sit-to-stand (STS) and forced BP oscillations (repeated squat-stand performed at 0.05 and 0.10 Hz). Prevalence of initial orthostatic hypotension (IOH; decrease in systolic ≥ 40 mmHg and/or diastolic BP ≥ 20 mmHg) during the first 15 sec of STS was determined as a functional outcome. In women, the decrease in mean middle cerebral artery blood velocity (MCAvmean ) following the STS was greater (-20 ± 8 vs. -11 ± 7 cm sec-1 ; P = 0.018) and the onset of the regulatory change (time lapse between the beginning of the STS and the increase in the conductance index (MCAvmean /mean arterial pressure) was delayed (P = 0.007). Transfer function analysis gain during 0.05 Hz squat-stand was ~48% higher in women (6.4 ± 1.3 vs. 3.8 ± 2.3 cm sec-1 mmHg-1 ; P = 0.017). Prevalence of IOH was comparable between groups (women: 4/9 vs. men: 5/9, P = 0.637). These results indicate the cerebrovasculature of fit women has an attenuated ability to react to rapid changes in BP in the face of preserved orthostasis, which could be related to higher resting cerebral blood flow allowing women to better face transient hypotension.

Probing Cell Mechanics with Bead-Free Optical Tweezers in the Drosophila Embryo.

Morphogenesis requires coordination between genetic patterning and mechanical forces to robustly shape the cells and tissues. Hence, a challenge to understand morphogenetic processes is to directly measure cellular forces and mechanical properties in vivo during embryogenesis. Here, we present a setup of optical tweezers coupled to a light sheet microscope, which allows to directly apply forces on cell-cell contacts of the early Drosophila embryo, while imaging at a speed of several frames per second. This technique has the advantage that it does not require the injection of beads into the embryo, usually used as intermediate probes on which optical forces are exerted. We detail step by step the implementation of the setup, and propose tools to extract mechanical information from the experiments. By monitoring the displacements of cell-cell contacts in real time, one can perform tension measurements and investigate cell contacts' rheology.

Diminished dynamic cerebral autoregulatory capacity with forced oscillations in mean arterial pressure with elevated cardiorespiratory fitness.

The effect that cardiorespiratory fitness has on the dynamic cerebral autoregulatory capacity during changes in mean arterial pressure (MAP) remains equivocal. Using a multiple-metrics approach, challenging MAP across the spectrum of physiological extremes (i.e., spontaneous through forced MAP oscillations), we characterized dynamic cerebral autoregulatory capacity in 19 male endurance athletes and eight controls via three methods: (1) onset of regulation (i.e., time delay before an increase in middle cerebral artery (MCA) conductance [MCA blood velocity (MCAv)/MAP] and rate of regulation, after transient hypotension induced by sit-to-stand, and transfer function analysis (TFA) of MAP and MCAv responses during (2) spontaneous and (3) forced oscillations (5-min of squat-stand maneuvers performed at 0.05 and 0.10 Hz). Reductions in MAP and mean MCAv (MCAVmean) during initial orthostatic stress (0-30 sec after sit-to-stand) and the prevalence of orthostatic hypotension were also determined. Onset of regulation was delayed after sit-to-stand in athletes (3.1 ± 1.7 vs. 1.5 ± 1.0 sec; P = 0.03), but rate of regulation was not different between groups (0.24 ± 0.05 vs. 0.21 ± 0.09 sec-1; P = 0.82). While both groups had comparable TFA metrics during spontaneous oscillations, athletes had higher TFA gain during 0.10 Hz squat-stand versus recreational controls (P = 0.01). Reductions in MAP (P = 0.15) and MCAVmean (P = 0.11) during orthostatic stress and the prevalence of initial orthostatic hypotension (P = 0.65) were comparable between groups. These results indicate an intact ability of the cerebral vasculature to react to spontaneous oscillations but an attenuated capability to counter rapid and large changes in MAP in individuals with elevated cardiorespiratory fitness.

Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary Arterial Hypertension.

BACKGROUND: Functional cerebrovascular regulatory mechanisms are important for maintaining constant cerebral blood flow and oxygen supply in heathy individuals and are altered in heart failure. We aim to examine whether pulmonary arterial hypertension (PAH) is associated with abnormal cerebrovascular regulation and lower cerebral oxygenation and their physiological and clinical consequences. METHODS AND RESULTS: Resting mean flow velocity in the middle cerebral artery mean flow velocity in the middle cerebral artery (MCAvmean); transcranial Doppler), cerebral pressure-flow relationship (assessed at rest and during squat-stand maneuvers; analyzed using transfer function analysis), cerebrovascular reactivity to CO2, and central chemoreflex were assessed in 11 patients with PAH and 11 matched healthy controls. Both groups also completed an incremental ramp exercise protocol until exhaustion, during which MCAvmean, mean arterial pressure, cardiac output (photoplethysmography), end-tidal partial pressure of CO2, and cerebral oxygenation (near-infrared spectroscopy) were measured. Patients were characterized by a significant decrease in resting MCAvmean (P<0.01) and higher transfer function gain at rest and during squat-stand maneuvers (both P<0.05). Cerebrovascular reactivity to CO2 was reduced (P=0.03), whereas central chemoreceptor sensitivity was increased in PAH (P<0.01), the latter correlating with increased resting ventilation (R2=0.47; P<0.05) and the exercise ventilation/CO2 production slope (V˙E/V˙CO2 slope; R2=0.62; P<0.05) during exercise for patients. Exercise-induced increases in MCAvmean were limited in PAH (P<0.05). Reduced MCAvmean contributed to impaired cerebral oxygen delivery and oxygenation (both P<0.05), the latter correlating with exercise capacity in patients with PAH (R2=0.52; P=0.01). CONCLUSIONS: These findings provide comprehensive evidence for physiologically and clinically relevant impairments in cerebral hemodynamic regulation and oxygenation in PAH.

Cannabis and Young Users-A Brief Intervention to Reduce Their Consumption (CANABIC): A Cluster Randomized Controlled Trial in Primary Care.

PURPOSE: Brief intervention to reduce cannabis is a promising technique that could be adapted for use in primary care, but it has not been well studied in this setting. We tested the efficacy of a brief intervention conducted by general practitioners among cannabis users aged 15 to 25 years. METHODS: We performed a cluster randomized controlled trial with 77 general practitioners in France. The intervention consisted of an interview designed according to the FRAMES (feedback, responsibility, advice, menu, empathy, self-efficacy) model, while the control condition consisted of routine care. RESULTS: The general practitioners screened and followed up 261 young cannabis users. After 1 year, there was no significant difference between the intervention and control groups in the median number of joints smoked per month among all users (17.5 vs 17.5; P = .13), but there was a difference in favor of the intervention among nondaily users (3 vs 10; P = .01). After 6 months, the intervention was associated with a more favorable change from baseline in the number of joints smoked (-33.3% vs 0%, P = .01) and, among users younger than age of 18, smoking of fewer joints per month (12.5 vs 20, P = .04). CONCLUSIONS: Our findings suggest that a brief intervention conducted by general practitioners with French young cannabis users does not affect use overall. They do, however, strongly support use of brief intervention for younger users and for moderate users.

Evidence for hysteresis in the cerebral pressure-flow relationship in healthy men.

The cerebrovasculature is more efficient at compensating for pharmacologically induced transient hypertension versus transient hypotension. Whether this phenomenon exists during nonpharmacologically induced hypertension and hypotension is currently unknown. We compared the percent change in mean velocity in the middle cerebral artery (MCAvmean) per percent change in mean arterial pressure (MAP) (%ΔMCAVmean/%ΔMAP) during transient hypertension and hypotension induced during squat-stand maneuvers performed at 0.05 Hz (20-s cycles) and 0.10 Hz (10-s cycles) in 58 male volunteers. %ΔMCAvmean/%ΔMAP was attenuated by 25% (P = 0.03, 0.05 Hz) and 47% (P < 0.0001, 0.10 Hz) during transient hypertension versus hypotension. Thus, these findings indicate that the brain in healthy men is better adapted to compensate for physiologically relevant transient hypertension than hypotension.NEW & NOTEWORTHY The novel finding of this study is that the change in middle cerebral artery mean flow velocity is attenuated during hypertension compared with hypotension physiologically induced by oscillations in blood pressure in men. These results support that the human brain is more effective at compensating for transient hypertension than hypotension.

Attitudes toward antipsychotic medications as a useful feature in exploring medication non-adherence in schizophrenia.

OBJECTIVE: To investigate the interest in the attitudes toward antipsychotic medication in exploring medication non-adherence. METHODS: Schizophrenic patients (N=120) completed the Beliefs about Medicines Questionnaire and measures of medication adherence, and clinical outcomes. Comparison between four attitudinal groups and logistic regressions were performed. RESULTS: High level of adherence varied significantly between attitudinal groups (Accepting, 70%; Indifferent, 63%; Ambivalent, 50%; Sceptical, 14%; p<0.001). Poor insight and psychic side effects were the most significant predictors of negative beliefs. CONCLUSION: The attitudinal groups approach could facilitate the identification of patients with non-adherence and determine individual targets of interventions to improve negative beliefs.

Direct laser manipulation reveals the mechanics of cell contacts in vivo.

Cell-generated forces produce a variety of tissue movements and tissue shape changes. The cytoskeletal elements that underlie these dynamics act at cell-cell and cell-ECM contacts to apply local forces on adhesive structures. In epithelia, force imbalance at cell contacts induces cell shape changes, such as apical constriction or polarized junction remodeling, driving tissue morphogenesis. The dynamics of these processes are well-characterized; however, the mechanical basis of cell shape changes is largely unknown because of a lack of mechanical measurements in vivo. We have developed an approach combining optical tweezers with light-sheet microscopy to probe the mechanical properties of epithelial cell junctions in the early Drosophila embryo. We show that optical trapping can efficiently deform cell-cell interfaces and measure tension at cell junctions, which is on the order of 100 pN. We show that tension at cell junctions equilibrates over a few seconds, a short timescale compared with the contractile events that drive morphogenetic movements. We also show that tension increases along cell interfaces during early tissue morphogenesis and becomes anisotropic as cells intercalate during germ-band extension. By performing pull-and-release experiments, we identify time-dependent properties of junctional mechanics consistent with a simple viscoelastic model. Integrating this constitutive law into a tissue-scale model, we predict quantitatively how local deformations propagate throughout the tissue.

CANABIC: CANnabis and Adolescents: effect of a Brief Intervention on their Consumption--study protocol for a randomized controlled trial.

BACKGROUND: Cannabis is the most consumed illegal substance in France. General practitioners (GPs) are the health professionals who are most consulted by adolescents. Brief intervention (BI) is a promising care initiative for the consumption of cannabis, and could be a tool for GPs in caring for adolescents who consume cannabis. The aim of the CANABIC study is to measure the impact of a BI carried out by a GP on the consumption of cannabis by adolescents of 15 to 25 years of age. METHODS: A randomized clustered controlled trial, stratified over three areas (Auvergne, Languedoc-Roussillon, and Rhône - Alpes), comparing an intervention group, which carries out the BI in consultation, and a control group, which ensures routine medical care. The main assessment criterion is the consumption of cannabis by amount of joints per month, at 12 months. The amount necessary to highlight a significant difference between the two groups of 30% of consumption at 12 months is 250 patients (50 GPs, 5 patients per GP; risk α = 5%; power = 90%; intra-cluster correlation coefficient ρ = 0.2; Hawthorne effect = 15%; lost to follow-up rates for GPs = 10% and for patients = 20%). This plan is replicated for the three areas, and therefore a total of 750 patients are expected.The secondary criteria for judgment are the associated consumption of tobacco and alcohol, the perception of the consequences of consumption, and the driving of a vehicle following consumption. DISCUSSION: Research about BI for young cannabis users is underway. The aim of the CANABIC study is to validate a BI suited to adolescents who consume cannabis, which may be performed in the general practice. This would provide a tool for their treatment by a GP, which could be widely distributed during initial or further medical training. TRIAL REGISTRATION: CANABIC is a randomized clustered trial (NCT01433692, registered 2011 Sept 12), PHRC funded: Clinical Research Hospital Program (Governmental Fund, Health Ministry). Date first patient randomized: March 2012.

A composite scale applied to evaluate anxiety in schizophrenic patients (SAES).

Anxiety in schizophrenia possesses specific features and is difficult to assess because no specific evaluating tool is currently available. The aim of this study was to develop and validate a hetero-assessment-based scale to specifically measure anxiety in schizophrenia. A literature review and a survey among psychiatrists allowed the selection of 29 items from 4 previous scales evaluating anxiety. Factor analysis allowed building up a final 22-item composite scale of anxiety evaluation in schizophrenia (SAES), which was then validated in 147 schizophrenic patients. One hundred and forty-seven (147) schizophrenic patients (70.8 % male, mean age = 36.9 years) were included in the study. Principal component analysis of the SAES revealed three factors, namely "expressed and perceived anxiety," "somatic anxiety," and "anxiety and environment". All total and factor scores of the SAES were significantly correlated (p < .001) with total and factor scores of the original scales. Finally, the SAES showed good inter-rater reliability [intra-class correlation coefficient (ICC) = .82]. In conclusion, a specific tool for evaluating anxiety in schizophrenia (SAES) was developed and validated in a sample of schizophrenic patients. The SAES can be useful to investigate clinical, psychopathological, and therapeutic aspects of anxiety in schizophrenia.