‘Islands of understanding’ : Environmental journalism in the South Pacific

"We're expected to know too much. Journalists who specialise in science and the environment have to grasp, communicate and synthesise scientific, political and economic issues. And we have to do it on deadline with accuracy, authority and readability. Sometimes it can be overwhelming...

FORMULATION AND EVALUATION OF MUCOADHESIVE BUCCAL TABLETS OF CARVEDILOL

Objective: The aim of the study was to formulate and evaluate mucoadhesive buccal tablets of carvedilol to avoid the first-pass metabolism. Methods: Mucoadhesive Buccal tablets of carvedilol were prepared by direct compression techniques using a combination of bioadhesive polymers such as hydroxypropyl cellulose (HPC) and polyethlyelne oxide WSR-1105 (PEO WSR-1105). In order to improve solubility of carvedilol, solid dispersion was prepared using poloxamer 188. A 32 Full factorial design was applied to investigate the combined effect of the two independent variables i.e. concentration of HPC (X1) and concentration of PEO WSR-1105(X2) on the dependent variables, % in vitro drug release at 1 h (Y1), % in vitro drug release at 4 h (Y2), mucoadhesive strength (Y3) and mucoadhesion time (Y4). Results: Optimized mucoadhesive buccal tablets shows in vitro drug release of 96.23±2.45 in 8 h, mucoadhesive strength of 18.20±1.44 g, mucoadhesion time 420±2.6 min and surface pH 6.75±0.015. Drug excipients compatibility study by FTIR showed no interaction between drug and excipients. Conclusion: From all parameters and experimental design evaluation, it was concluded that the drug release rate decreased with an increase the concentration of HPC and PEO WSR-1105 and mucoadhesion property increased with increase the concentration of PEO WSR-1105. The in vitro release kinetics revealed the Korsmeyer-Peppas model is followed and drug release is by anomalous diffusion

Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury

We recently reported that the neuropathic pain medication, gabapentin (GBP; Neurontin), significantly attenuated both noxious colorectal distension (CRD)-induced autonomic dysreflexia (AD) and tail pinch-induced spasticity compared to saline-treated cohorts 2–3 weeks after complete high thoracic (T4) spinal cord injury (SCI). Here we employed long-term blood pressure telemetry to test, firstly, the efficacy of daily versus acute GBP treatment in modulating AD and tail spasticity in response to noxious stimuli at 2 and 3 weeks post-injury. Secondly, we determined whether daily GBP alters baseline cardiovascular parameters, as well as spontaneous AD events detected using a novel algorithm based on blood pressure telemetry data. At both 14 and 21 days after SCI, irrespective of daily treatment, acute GBP given 1 h prior to stimulus significantly attenuated CRD-induced AD and pinch-evoked tail spasticity; conversely, acute saline had no such effects. Moreover, daily GBP did not alter 24 h mean arterial pressure (MAP) or heart rate (HR) values compared to saline treatment, nor did it reduce the incidence of spontaneous AD events compared to saline over the three week assessment period. Power spectral density (PSD) analysis of the MAP signals demonstrated relative power losses in mid frequency ranges (0.2–0.8 Hz) for all injured animals relative to low frequency MAP power (0.02–0.08 Hz). However, there was no significant difference between groups over time post-injury; hence, GBP had no effect on the persistent loss of MAP fluctuations in the mid frequency range after injury. In summary, the mechanism(s) by which acute GBP treatment mitigate aberrant somatosensory and cardiophysiological responses to noxious stimuli after SCI remain unclear. Nevertheless, with further refinements in defining the dynamics associated with AD events, such as eliminating requisite concomitant bradycardia, the objective repeatability of automatic detection of hypertensive crises provides a potentially useful tool for assessing autonomic function pre- and post-SCI, in conjunction with experimental pharmacotherapeutics for neuropathic pain, such as GBP

Rate of Force Development Is Related to Maximal Force and Sit-to-Stand Performance in Men With Stages 3b and 4 Chronic Kidney Disease

Introduction: The primary aims of the present study were to assess the relationships of early (0–50 ms) and late (100–200 ms) knee extensor rate of force development (RFD) with maximal voluntary force (MVF) and sit-to-stand (STS) performance in participants with chronic kidney disease (CKD) not requiring dialysis.Methods: Thirteen men with CKD (eGFR = 35.17 ±.5 ml/min per 1.73 m2, age = 70.56 ±.4 years) and 12 non-CKD men (REF) (eGFR = 80.31 ± 4.8 ml/min per 1.73 m2, age = 70.22 ±.9 years) performed maximal voluntary isometric contractions to determine MVF and RFD of the knee extensors. RFD was measured at time intervals 0–50 ms (RFD0−50) and 100–200 ms (RFD100−200). STS was measured as the time to complete five repetitions. Measures of rectus femoris grayscale (RF GSL) and muscle thickness (RF MT) were obtained via ultrasonography in the CKD group only. Standardized mean differences (SMD) were used to examine differences between groups. Bivariate relationships were assessed by Pearson's product moment correlation.Results: Knee extensor MVF adjusted for body weight (CKD=17.14 ±.1 N·kg0.67, REF=21.55 ±.3 N·kg0.67, SMD = 0.79) and STS time (CKD = 15.93 ±.4 s, REF = 12.23 ±.7 s, SMD = 1.03) were lower in the CKD group than the REF group. Absolute RFD100−200 was significantly directly related to adjusted MVF in CKD (r = 0.56, p = 0.049) and REF (r = 0.70, p = 0.012), respectively. STS time was significantly inversely related to absolute (r = −0.75, p = 0.008) and relative RFD0−50 (r = −0.65, p = 0.030) in CKD but not REF (r = 0.08, p = 0.797; r = 0.004, p = 0.991). Significant inverse relationships between RF GSL adjusted for adipose tissue thickness and absolute RFD100−200 (r =−0.59, p = 0.042) in CKD were observed.Conclusion: The results of the current study highlight the declines in strength and physical function that occur in older men with CKD stages 3b and 4 not requiring dialysis. Moreover, early RFD was associated with STS time in CKD while late RFD was associated MVF in both CKD and REF.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03160326 and NCT02277236

PTCOG Head and Neck Subcommittee Consensus Guidelines on Particle Therapy for the Management of Head and Neck Tumors

Purpose: Radiation therapy is a standard modality in the treatment for cancers of the head and neck, but is associated with significant short- and long-term side effects. Proton therapy, with its unique physical characteristics, can deliver less dose to normal tissues, resulting in fewer side effects. Proton therapy is currently being used for the treatment of head and neck cancer, with increasing clinical evidence supporting its use. However, barriers to wider adoption include access, cost, and the need for higher-level evidence.Methods: The clinical evidence for the use of proton therapy in the treatment of head and neck cancer are reviewed here, including indications, advantages, and challenges.Results: The Particle Therapy Cooperative Group Head and Neck Subcommittee task group provides consensus guidelines for the use of proton therapy for head and neck cancer.Conclusion: This report can be used as a guide for clinical use, to understand clinical trials, and to inform future research efforts.</p

Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy

Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and Materials: A block aperture module was integrated into VPMC. VPMC was validated by an opensource code, MCsquare, in eight water phantom simulations with 3cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45mm water equivalent thickness. VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 cc). Finally, 3 patients were selected for robust optimization with aperture blocks using VPMC. Results: In the water phantoms, 3D gamma passing rate (2%/2mm/10%) between VPMC and MCsquare were 99.71$\pm$0.23%. In the patient geometries, 3D gamma passing rates (3%/2mm/10%) between VPMC/MCsquare and RayStation MC were 97.79$\pm$2.21%/97.78$\pm$1.97%, respectively. The calculation time was greatly decreased from 112.45$\pm$114.08 seconds (MCsquare) to 8.20$\pm$6.42 seconds (VPMC), both having statistical uncertainties of about 0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 seconds. Conclusion: VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.Comment: 3 tables, 3 figure