Ionic Hydrogel for Accelerated Dopamine Delivery via Retrodialysis.

Local drug delivery directly to the source of a given pathology using retrodialysis is a promising approach to treating otherwise untreatable diseases. As the primary material component in retrodialysis, the semipermeable membrane represents a critical point for innovation. This work presents a new ionic hydrogel based on polyethylene glycol and acrylate with dopamine counterions. The ionic hydrogel membrane is shown to be a promising material for controlled diffusive delivery of dopamine. The ionic nature of the membrane accelerates uptake of cationic species compared to a nonionic membrane of otherwise similar composition. It is demonstrated that the increased uptake of cations can be exploited to confer an accelerated transport of cationic species between reservoirs as is desired in retrodialysis applications. This effect is shown to enable nearly 10-fold increases in drug delivery rates from low concentration solutions. The processability of the membrane is found to allow for integration with microfabricated devices which will in turn accelerate adaptation into both existing and emerging device modalities. It is anticipated that a similar materials design approach may be broadly applied to a variety of cationic and anionic compounds for drug delivery applications ranging from neurological disorders to cancer

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Chemiluminescence studies on comparison of antioxidant effectiveness on multiextruded polyethylenes

Several polyethylene resins; high density polyethylene (Ph-HDPE, Phillips metal oxide catalyst) and linear low density polyethytlenes (LLDPE, formed using Ziegler–Natta catalyst and metallocene catalyst technology, m-LLDPE) were used in order to acquire an insight in to the effect of different polymerization catalyst systems on the melt stabilization performance of single AO. Chemiluminescence (CL) and melt flow rate (MFR) were used to analyze the degradation as a function of the number of passes through a twin-screw extruder. A good correlation was obtained, and the additives resulting with the best melt flow stability in the polymer were the same as those that promote the best CL results

Total Shoulder Arthroplasty

Shoulder arthroplasty has been the subject of marked advances over the last few years. Modern implants provide a wide range of options, including resurfacing of the humeral head, anatomic hemiarthroplasty, total shoulder arthroplasty, reverse shoulder arthroplasty and trauma-specific implants for fractures and nonunions. Most humeral components achieve successful long-term fixation without bone cement. Cemented all-polyethylene glenoid components remain the standard for anatomic total shoulder arthroplasty. The results of shoulder arthroplasty vary depending on the underlying diagnosis, the condition of the soft-tissues, and the type of reconstruction. Total shoulder arthroplasty seems to provide the best outcome for patients with osteoarthritis and inflammatory arthropathy. The outcome of hemiarthroplasty for proximal humerus fractures is somewhat unpredictable, though it seems to have improved with the use of fracture-specific designs, more attention to tuberosity repair, and the selective use of reverse arthroplasty, as well as a shift in indications towards internal fixation. Reverse shoulder arthroplasty has become extremely popular for patients with cuff-tear arthropathy, and its indications have been expanded to the field of revision surgery. Overall, shoulder arthroplasty is a very successful procedure with predictable pain relief and substantial improvements in motion and function

The Role of Percentage of Prostate-specific Antigen Reduction After Focal Therapy Using High-intensity Focused Ultrasound for Primary Localised Prostate Cancer. Results from a Large Multi-institutional Series

Focal therapy (FT) for prostate cancer (PCa) is emerging as a novel therapeutic approach for patients with low- to intermediate-risk disease, in order to provide acceptable oncological control, whilst avoiding the side effects of radical treatment. Evidence regarding the ideal follow-up strategy and the significance of prostate-specific antigen (PSA) kinetics after treatment is needed. In this study, we aimed to assess the value of the percentage of PSA reduction (%PSA reduction) after FT in predicting the likelihood of any additional treatment or any radical treatment. We retrospectively analysed a multicentre cohort of 703 men receiving FT for low- and intermediate-risk PCa. Overall, the rates of any additional treatment and any radical treatment were 30% and 13%, respectively. The median follow-up period was 41 mo. The median %PSA reduction after FT was 73%. At Cox multivariable analysis, %PSA reduction was an independent predictor of any additional treatment (hazard ratio [HR]: 0.96; p 90%, the probability of any additional treatment within 5 yr was 20%. Conversely, for %PSA reduction of <10%, the probability of receiving any additional treatment within 5 yr was roughly 70%. This study is the first to assess the role of %PSA reduction in the largest multicentre cohort of men receiving FT for PCa. Given the lack of standardised follow-up strategies in the FT field, the use of the %PSA reduction should be considered

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, &lt;72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Digestibility in selected rainbow trout families and modelling of growth from the specific intake of digestible protein

The experiments aimed to clarify variations in digestibility of dietary nutrients in rainbow trout. Furthermore, the objective was to study how differences in digestibility might be related to growth and feed utilisation at various growth rates. When comparing the results from the experiments it appeared that particularly protein digestibility was closely related to specific growth rate and feed conversion ratio at high growth rates. As a tool to visualise the relationship between protein digestibility and growth of rainbow trout a growth model was developed based on the specific intake of digestible protein, and general assumptions on protein content and protein retention efficiency in rainbow trout. The model indicated that increased protein digestibility only partly explained growth increase and that additional factors were important for growth increment

Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts

In spite of aggressive surgery, irradiation and/or chemotherapy, treatment of malignant gliomas remains a major challenge in adults and children due to high treatment failure. We have demonstrated significant cell lysis and antitumour activity of the E1B-55 kDa-gene-deleted adenovirus ONYX-015 (dl1520, CI-1042; ONYX Pharmaceuticals) in subcutaneous human malignant glioma xenografts deriving from primary tumours. Here, we show the combined efficacy of this oncolytic therapy with radiation therapy. Total body irradiation (5 Gy) of athymic nude mice prior to intratumoral injections of ONYX-015 1 x 10(8) PFU daily for 5 consecutive days yielded additive tumour growth delays in the p53 mutant xenograft IGRG88. Radiation therapy was potentiated in the p53 functional tumour IGRG121 with a 'subtherapeutic' dose of 1 x 10(7) PFU daily for 5 consecutive days, inducing significant tumour growth delay, 90% tumour regression and 50% tumour-free survivors 4 months after treatment. These potentiating effects were not due to increased adenoviral infectivity or replication. Furthermore, cell lysis and induction of apoptosis, the major mechanisms for adenoviral antitumour activity, did not play a major role in the combined treatment strategy. Interestingly, the oncolytic adenovirus seemed to accelerate radiation-induced tumour fibrosis. Potentiating antitumour activity suggests the development of this combined treatment for these highly malignant tumours

Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex: Post hoc analysis of randomized controlled phase 3 trial GWPCARE6.

OBJECTIVE: To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo-controlled, phase 3 trial in patients with drug-resistant epilepsy associated with tuberous sclerosis complex (TSC). METHODS: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks (4-week titration, 12-week maintenance). Treatment started at 5 mg/kg/day for all groups and reached 25 mg/kg/day on Day 9 and 50 mg/kg/day on Day 29. Percentage change from baseline in TSC-associated seizure (countable focal or generalized) count was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. RESULTS: Of 224 patients, 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo. Median (range) age was 11.3 (1.1-56.8) years. Patients had discontinued a median (range) of 4 (0-15) antiseizure medications and were currently taking 3 (0-5). Difference in seizure reduction between CBD and placebo emerged on Day 6 (titrated dose, 15 mg/kg/day) and became nominally significant (p < .049) by Day 10. Separation between placebo and CBD in ≥50% responder rate also emerged by Day 10. Onset of AEs occurred during the first 2 weeks of the titration period in 61% of patients (CBD25, 61%; CBD50, 67%; placebo, 54%). In patients with an AE, resolution occurred within 4 weeks of onset in 42% of placebo and 27% of CBD patients and by end of trial in 78% of placebo and 51% of CBD patients. SIGNIFICANCE: Onset of treatment effect occurred within 6-10 days. AEs lasted longer for CBD than placebo, but the most common (diarrhea, decreased appetite, and somnolence) resolved during the 16-week trial in most patients

Physical fitness profile in elite beach handball players of different age categories

This is an accepted manuscript of an article published by Edizioni Minerva Medica in Journal of Sports Medicine and Physical Fitness, available online: https://www.minervamedica.it/en/journals/sports-med-physical-fitness/article.php?cod=R40Y2020N12A1536# The accepted version of the publication may differ from the final published version.BACKGROUND: The aims of this study were to compare anthropometric and fitness variables of high-level beach handball players across under-19 (u-19), under-21 (u-21) and senior male categories, and between male and female senior players; and to test the correlations among those measures. MeThodS: a total of 70 high-level players (53 male of different ages) were evaluated for 5-m acceleration, 15-m sprint, horizontal jump, handgrip strength, specific beach handball throwing velocities, and anthropometric variables. Differences between age groups were tested using anoVa. independent t-test was used to compare fitness variables between male and female elite athletes, and Pearson partial correlation coefficients were calculated between each of the fitness variables using BMI and age as covariates. SPSS Software was used, and the level of significance was set at 95%. reSulTS: The u-21 athletes better performed on horizontal jump and 6-m throw than the u-19 athletes. Senior athletes showed better performance on horizontal jump than U-19 athletes (P≤0.05). Positive correlation was seen for handgrip on dominant and non-dominant hands and 6-m throwing speed, and for handgrip on dominant hand and inflight velocity (P≤0.05). Negative correlations were observed between horizontal jump and 5-m acceleration, and 15-m sprint (P≤0.01 and P≤0.05, respectively). CONCLUSIONS: Male athletes better performed than women in all the fitness tests. The study, for the first time, showed physical fitness comparisons between beach handball elite male athletes of different ages and between genders. These are key steps for coaches and athletes and may support future beach handball studies and practice.Published versio