Sandersunesen7729

Given that the one-size-fits-all approach to mobile health interventions have limited effects, a personalized approach might be necessary to promote healthy behaviors and prevent chronic conditions. Our systematic review aims to evaluate the effectiveness of personalized mobile interventions on lifestyle behaviors (i.e., physical activity, diet, smoking and alcohol consumption), and identify the effective key features of such interventions. We included any experimental trials that tested a personalized mobile app or fitness tracker and reported any lifestyle behavior measures. We conducted a narrative synthesis for all studies, and a meta-analysis of randomized controlled trials. Thirty-nine articles describing 31 interventions were included (n = 77,243, 64% women). All interventions personalized content and rarely personalized other features. Source of data included system-captured (12 interventions), user-reported (11 interventions) or both (8 interventions). The meta-analysis showed a moderate positive effect on lifestyle behavior outcomes (standardized difference in means [SDM] 0.663, 95% CI 0.228 to 1.10). A meta-regression model including source of data found that interventions that used system-captured data for personalization were associated with higher effectiveness than those that used user-reported data (SDM 1.48, 95% CI 0.76 to 2.19). In summary, the field is in its infancy, with preliminary evidence of the potential efficacy of personalization in improving lifestyle behaviors. Source of data for personalization might be important in determining intervention effectiveness. To fully exploit the potential of personalization, future high-quality studies should investigate the integration of multiple data from different sources and include personalized features other than content.Cannabinoid (CB) receptor agonists show robust antinociceptive effects in various pain models. However, most of the clinically potent CB1 receptor-active drugs derived from cannabis are considered concerning due to psychotomimetic side effects. Selective CB receptor ligands that do not induce CNS side effects are of clinical interest. The venoms of marine snail Conus are a natural source of various potent analgesic peptides, some of which are already FDA approved. In this study we evaluated the ability of several Conus venom extracts to interact with CB1 receptor. HEK293 cells expressing CB1 receptors were treated with venom extracts and CB1 receptor internalization was analyzed by immunofluorescence. Results showed C. textile (C. Tex) and C. miles (C. Mil) samples as the most potent. These were serially subfractionated by HPLC for subsequent analysis by internalization assays and for analgesic potency evaluated in the formalin test and after peripheral nerve injury. Intrathecal injection of C. Tex and C. Mil subfractions reduced flinching/licking behavior during the second phase of formalin test and attenuated thermal and mechanical allodynia in nerve injury model. Treatment with proteolytic enzymes reduced CB1 internalization of subfractions, indicating the peptidergic nature of CB1 active component. Further HPLC purification revealed two potent antinociceptive subfractions within C. Tex with CB1 and possible CB2 activity, with mild to no side effects in the CB tetrad assessment. CB conopeptides can be isolated from these active Conus venom-derived samples and further developed as novel analgesic agents for the treatment of chronic pain using cell based or gene therapy approaches.The enzyme phosphodiesterase 1 (PDE1) is highly expressed in the striatum and cortex. However, its role in corticostriatal function has not been fully investigated. The present study was aimed at evaluating the therapeutic potential of PDE1 inhibitors in treating motivation deficits and 3,4-dihydroxy-L-phenylalanine (L-dopa)-induced dyskinesia, which are pathological conditions of the corticostriatal system. We used a novel PDE1 inhibitor 3-ethyl-2-[trans-4-(methoxymethyl)cyclohexyl]oxy-7-(tetrahydro-2H-pyran-4-yl)-imidazo[5,1-f][1,2,4]triazin-4(3H)-one (DSR-143136), which was identified in our drug discovery program. Maraviroc mw Motivation in monkeys was measured using a progressive ratio task. L-Dopa-induced dyskinesia and disability scores were measured in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. DSR-143136 had a high selectivity for PDE1 over other PDE families and 67 other biologic targets. A dopamine D1 receptor antagonist SCH-39166 at 0.01, 0.03 and 0.1 mg/kg potently decreased motivation in monkeys. However, DSR-143136 at 0.3 and 3 mg/kg did not affect motivation deficits induced by low-dose SCH-39166 (0.01 mg/kg). On the other hand, DSR-143136 at 3 mg/kg potently decreased L-dopa-induced dyskinesia in the Parkinsonian monkey model. Importantly, this antidyskinesic efficacy was NOT accompanied by detrimental effects on motor function. Further, this compound decreased on-time with marked or severe dyskinesia, without affecting on-time itself. These findings suggest that PDE1 inhibitor could be a therapeutic candidate for treating L-dopa-induced dyskinesia in Parkinson's disease, but not for motivation deficits.

Obesity is highly prevalent in patients with obstructive hypertrophic cardiomyopathy (HCM). In this study, we investigated the impact of body mass index (BMI) in patients undergoing septal myectomy (SM) for obstructive HCM.

We reviewed 2,746 patients who underwent transaortic SM for obstructive HCM from February 1993 through September 2018. Patients were stratified into 3 groups based on BMI (normal weight < 25 kg/m

, overweight 25 to < 30 kg/m

, and obese ≥ 30 kg/m

).

Preoperatively, median left ventricular outflow tract (LVOT) gradient was 58 mmHg, and there was no difference in gradients across BMI strata (P=0.35). Obese patients had lower percentage with moderate or greater mitral valve regurgitation (45.8%) compared to normal (52.9%) and overweight (55.4%) patients (P<0.001). However, patients with higher BMI were more likely to have New York Heart Association class III/IV limitation at presentation (P<0.001). After myectomy, both anteroseptal thickness (P=0.115) and LVOT gradient (P=0.