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This pharmacokinetic (PK) drug-interaction trial investigated the effects of repeated dosing of a plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the United States and Epidyolex in Europe; 100 mg/mL oral solution) on caffeine clearance via modulation of cytochrome P450 (CYP) 1A2 activity in healthy adults. In this phase 1 open-label, fixed-sequence trial, all subjects received a single 200 mg caffeine dose and placebo on day 1. VTP50469 mouse Subjects then titrated CBD from 250 mg once daily to 750 mg twice daily between days 3 and 11 and took 750 mg CBD twice daily between days 12 and 27. On day 26, subjects received a single 200-mg caffeine dose with their morning CBD dose. Plasma concentrations of caffeine and its CYP1A2-mediated metabolite, paraxanthine, were determined on days 1 and 26 and PK parameters derived using noncompartmental analysis. Safety was monitored throughout. Sixteen subjects enrolled, and 9 completed treatment. When caffeine was administered with steady-state CBD, caffeine exposure increased by 15% for Cmax and 95% for AUC0-∞ , tmax increased from 1.5 to 3.0 hours, and t1/2 increased from 5.4 to 10.9 hours compared with caffeine administered with placebo. Under the same conditions, paraxanthine exposure decreased by 22% for Cmax and increased by 18% for AUC0-∞ , tmax increased from 8.0 to 14.0 hours, and t1/2 increased from 7.2 to 13.7 hours. Overall, there were no unexpected adverse events; diarrhea was most common, and 6 subjects discontinued because of elevated liver transaminases. These data suggest that CBD is an inhibitor of CYP1A2.

The relationship between body weight and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) is unclear.

This study aimed to investigate the impact of obesity and morbid obesity on mortality and ERCP-related complications in patients who underwent ERCP.

We conducted a US population-based retrospective cohort study using the Nationwide Readmissions Databases (2013-2014). A total of 159,264 eligible patients who underwent ERCP were identified, of which 137,158 (86.12%) were normal weight, 12,522 (7.86%) were obese, and 9584 (6.02%) were morbidly obese. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay, total cost, and ERCP-related complications. Multivariate analysis and propensity score (PS) matching analysis were performed. The analysis was repeated in a restricted cohort to eliminate confounders.

Patients with morbid obesity, as compared to normal-weight patients, were associated with a significantly higher in-hospital mortality (hazard ratio [HR] 5.54; 95% confidence interval [CI] 1.23-25.04). Obese patients were not associated with significantly different mortality comparing to normal weight (HR 1.00; 95% CI 0.14-7.12). Patients with morbid obesity were also found to have an increased length of hospital stay and total cost. The rate of ERCP-related complications was comparable among the three groups except for a higher cholecystitis rate after ERCP in obese patients.

Morbid obesity but not obesity was associated with increased mortality, length of stay, and total cost in patients undergoing ERCP.

Morbid obesity but not obesity was associated with increased mortality, length of stay, and total cost in patients undergoing ERCP.

Attention deficit/hyperactivity disorder is a prevalent mental disorder among children worldwide. The parents of children with ADHD experience great burden. However, burden and coping styles of these parents are seldom explored. The present study aimed to illustrate the burden and coping strategies of parents of children with Attention deficit/hyperactivity disorder.

A descriptive qualitative study design was employed.

Samples were recruited from a general primary school in Hong Kong using convenience sampling. An information sheet was provided to participants, and written informed consent was obtained. Content analysis was conducted after the interviews were recorded and transcribed verbatim. COREQ reporting guidelines were used.

Individual, face-to-face interviews were conducted, using a semi-structured interview guide with 12 parents of children with attention deficit/hyperactivity disorder. Four themes (academic burden, children’s social dependence, uncertainty regarding parenting strategies befort for parents to shift their coping strategies. Timely interventions, such as early assessment and diagnosis, are recommended during or after medical diagnosis.Limbal stem cells are involved in replenishing and maintaining the epithelium of the cornea. Damage to the limbus due to chemical/physical injury, infections, or genetic disorders leads to limbal stem cell deficiency (LSCD) with partial or total vision loss. Presently, LSCD is treated by transplanting limbal stem cells from the healthy eye of the recipient, living-related, or cadaveric donors. This review discusses limbal-derived stem cells, the importance of extracellular matrix in stem cell niche maintenance, the historical perspective of treating LSCD, including related advantages and limitations, and our experience of limbal stem cell transplantation over the decades.

Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for treatment of cancer cachexia. Carnosol (CS) is a bioactive diterpene compound present in Lamiaceae spp., which has been demonstrated to have antioxidant, anti-inflammatory, and anticancer properties. But its effects on cancer cachexia and the possible mechanism remain a mystery.

The in vitro cell models of C2C12 myotube atrophy and 3T3-L1 mature adipocyte lipolysis were used to check the activities of CS and its synthesized analogues. C26 tumour-bearing BALB/c mice were applied as the animal model to examine their therapeutic effects on cancer cachexia in vivo. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms.

Carnosol and its analogues [dimethyl-carnosol (DCS) and dimethyl-carnosol-D6 (DCSD)] alleviated myotube atrophy of C2C12 myotubes and lipolysis of 3T3-L1 adipocytes in vitro.