Rats were trained to lever press for intravenous cocaine (1.0 mg/kg/injection) and then switched to bromocriptine (0.3, 1.0, or 3.0 mg/kg/injection) on a FR-1 reinforcement schedule. Bromocriptine sustained responding at all three doses; hourly drug intake increased linearly with log-dose. In a second experiment, animals were trained to respond for cocaine (1.0 mg/kg/injection) or heroin (0.1 mg/kg/injection) reinforcement; drug was available for the first 2 h of each daily session; saline was substituted for cocaine or heroin for 5 subsequent hours. One hour into each saline substitution session, an intravenous injection of saline or bromocriptine (0.0, 0.5, 1.0, or 2.0 mg/kg) was given. Bromocriptine reinstated both cocaine-trained and heroin-trained lever pressing; under these conditions, the drug was most effective in the heroin-trained animals. Reinforcing doses of clonidine (0.0625 and 0.125 mg/kg), methohexital, and nicotine (0.05 and 0.1 mg/kg), and a sub-intoxicating dose of ethanol (2 g/kg) failed to reinstate cocaine-trained responding. These data indicate that bromocriptine has cocaine-like and heroin-like stimulus and reinforcing effects.

The behavior-change intervention demonstrates promise for increasing walking activity for people with dysvascular transtibial amputation (TTA). The efficacy of implementing such intervention in the scope of conventional TTA rehabilitation should be further studied.

No abstract

10Objective. To assess the effect of an intervention designed to enhance physiotherapists' 11 communication skills on chronic low back pain patients' adherence to home-based rehabilitation 12 recommendations. 13Design. Cluster randomized controlled trial. 14 Setting. Publicly funded physiotherapy clinics in Dublin, Ireland 15 Participants. Physiotherapists (N = 53) and patients with chronic low back pain (N = 255, 54% 16 female, M age = 45.3 years). 17 Interventions. Patients received publicly funded individual physiotherapy care. In the control arm, 18 care was delivered by a physiotherapist who had completed a 1-hour workshop on evidence-based 19 chronic low back pain management. Patients in the experimental arm received care from 20 physiotherapists who had also completed 8 hours of communications skills training. 21 Main Outcome Measure. Patient-reported adherence to their physiotherapist's recommendations 22regarding home-based rehabilitation, measured at 1, 4, 12, and 24 weeks after initial treatment 23 session. Pain and pain-related function measured at baseline, 4, 12 and 24 weeks. 24Results. Linear mixed model analysis showed the experimental arm patients' ratings of adherence 25 were greater than controls (overall mean difference = .41 [95% CI = .10 to .72, d = .28, p = .01). 26Moderation analyses showed that men, regardless of intervention, showed improvements in pain-27 related function over time. Only women in the experimental condition showed functional 28 improvements; female controls saw little change in function over time. The CONNECT 29 intervention did not influence patients' pain, regardless of their sex. 30 Conclusions. Communication skills training for physiotherapists had short-term positive effects on 31 patient adherence. This training may provide a motivational basis for behavior change and could be 32 a useful component in complex interventions to promote adherence. Communication skills training 33 may also improve some clinical outcomes for women, but not men. Trial 34 registration: ISRCTN63723433. 35 3 Abbreviations. 37 CONNECT: Communication Style and Exercise Compliance in Physiotherapy 38 RCT: Randomized controlled trial 39 40 41 4Patient adherence to interventions based on self-management principles is often poor [1]. For 42 example, patients with chronic musculoskeletal conditions often do not complete their home-based 43 exercise programs as recommended by their healthcare practitioners [2, 3]. Poor adherence to 44 treatment recommendations is problematic for both clinicians and patients, as it can limit the 45 potential for positive treatment outcomes [4, 5]. Despite acknowledgement that interventions 46 targeting patient behavior should be grounded in relevant behavior change theory [6], there is 47 limited evidence regarding the effect of theory-based interventions to promote adherence in chronic 48 pain populations [7][8][9]. 49According to self-determination theory [10] people have psychological needs for autonomy 50 (feeling free to engage in an activity), competence (feel...

The identification and validation of a targeted therapy for patients with triple-negative breast cancer (TNBC) is currently one of the most urgent needs in breast cancer therapeutics. One of the key reasons for the failure to develop a new therapy for this subgroup of breast cancer patients has been the difficulty in identifying a highly prevalent, targetable molecular alteration in these tumors. Recently however, the p53 gene was found to be mutated in approximately 80% of basal/TNBC, raising the possibility that targeting the mutant p53 protein product might be a new approach for the treatment of this form of breast cancer. In this study, we investigated the anti-cancer activity of PRIMA-1 and PRIMA-1 MET (APR-246), two compounds which were previously reported to reactivate mutant p53 and convert it to a form with wild-type (WT) properties. Using a panel of 18 breast cancer cell lines and 2 immortalized breast cell lines, inhibition of proliferation by PRIMA-1 and PRIMA-1 MET was found to be cell-line dependent, but independent of cell line molecular subtype. Although response was independent of molecular subtype, p53 mutated cell lines were significantly more sensitive to PRIMA-1 MET than p53 WT cells (p 5 0.029). Furthermore, response (measured as IC 50 value) correlated significantly with p53 protein level as measured by ELISA (p 5 0.0089, r520.57, n 5 19). In addition to inhibiting cell proliferation, PRIMA-1 MET induced apoptosis and inhibited migration in a p53 mutant-dependent manner. Based on our data, we conclude that targeting mutant p53 with PRIMA-1 MET is a potential new approach for treating p53-mutated breast cancer, including the subgroup with triple-negative (TN) disease.

A significant proportion of ankylosing spondylitis patients have poorer balance than normal subjects.

No abstract

The present study examines whether breastfeeding is associated with neuro-developmental advantages at 9 months of age on a standardised measure of infant development in a large cohort study of Irish children. It is hypothesised that if breast-milk confers an independent benefit, infants who were never breastfed will have reached fewer developmental milestones than those who were partially or exclusively breastfed, after controlling for putative confounding variables. Families with infants aged 9-months were recruited as part of a nationally representative sample for the birth cohort of the Growing Up in Ireland study (n = 11,134). Information was collected from mothers on breastfeeding practices, socio-demographic characteristics and developmental progress during a household interview. Parent-report items on development covered communication, gross motor, fine motor, problem solving and personal-social skills. Analysis of pass/fail status in each developmental domain using binary logistic regression showed a positive effect of any breastfeeding on gross motor, fine motor, problem solving and personal-social skills (but not communication) and these remained after adjustment for a range of confounding variables. There was, however, little evidence of a dose-response effect or advantage of exclusive over partial breastfeeding. A clear advantage of breastfeeding on infant development was demonstrated. However, the lack of a dose-response association on pass rates suggests that the breastfeeding effect may be confounded by other unobserved factors or that there is a critical threshold during which time the effect of breast milk may be particularly salient for bolstering brain development.