Experimentally Determined Hansen Solubility Parameters of Biobased and Biodegradable Polyesters.

Hansen solubility parameters (HSP) of 15 commercially relevant biobased and biodegradable polyesters were experimentally determined by applying a novel approach to the classic solubility study method. In this approach, the extent of swelling in polymer films was determined using a simple equation based on the mass difference between swollen and nonswollen film samples to obtain normalized solvent uptake (). Using and HSPiP software, highly accurate HSP values were obtained for all 15 polyesters.

Consensus statement: An evidence-based review of exercise, rehabilitation, rest, and return to activity protocols for the treatment of concussion and mild traumatic brain injury.

Background: Early diagnosis and appropriate management of concussion/mild traumatic brain injury (mTBI) is critical for preventing poor outcomes and minimizing health care burden. Current clinical guidelines for concussion management focus mostly on diagnosis and return to cognitive and physical activity but provide limited guidance on the use of specific therapeutic interventions.

Objective: To systematically review the available evidence on therapeutic interventions for concussion/mTBI and develop an evidence-based consensus statement on the use of these interventions in clinical practice.

Novel Selection Approaches to Identify Antibodies Targeting Neoepitopes on the C5b6 Intermediate Complex to Inhibit Membrane Attack Complex Formation.

The terminal pathway of complement is implicated in the pathology of multiple diseases and its inhibition is, therefore, an attractive therapeutic proposition. The practicalities of inhibiting this pathway, however, are challenging, as highlighted by the very few molecules in the clinic. The proteins are highly abundant, and assembly is mediated by high-affinity protein-protein interactions.

Prediction and identification of synergistic compound combinations against pancreatic cancer cells.

Resistance to current therapies is common for pancreatic cancer and hence novel treatment options are urgently needed. In this work, we developed and validated a computational method to select synergistic compound combinations based on transcriptomic profiles from both the disease and compound side, combined with a pathway scoring system, which was then validated prospectively by testing 30 compounds (and their combinations) on PANC-1 cells. Some compounds selected as single agents showed lower GI50 values than the standard of care, gemcitabine.

Predicting V[Combining Dot Above]O2max From Treadmill Performance in American-Style Football Athletes.

Crouse, SF, Tolson, H, Lytle, J, Johnson, KA, Martin, SE, Green, JS, Oliver, J, Carbuhn, A, Lambert, B, and Bramhall, JP. Predicting V[Combining Dot Above]O2max from treadmill performance in American-style football athletes. J Strength Cond Res 33(4): 1028-1034, 2019-Prediction equations are often used to estimate V[Combining Dot Above]O2max in the general population but are lacking for American-style football (ASF) athletes.

Combenefit: an interactive platform for the analysis and visualization of drug combinations.

Motivation: Many drug combinations are routinely assessed to identify synergistic interactions in the attempt to develop novel treatment strategies. Appropriate software is required to analyze the results of these studies.

Results: We present Combenefit, new free software tool that enables the visualization, analysis and quantification of drug combination effects in terms of synergy and/or antagonism.

Echocardiographic and Blood Pressure Characteristics of First-Year Collegiate American-Style Football Players.

Echocardiographic (echo) and blood pressure (BP) reference values may help identify athletes at cardiovascular risk, yet benchmarks are inadequate for collegiate American-style football (ASF) players. Our purpose was to describe echo characteristics and BP values in collegiate ASF athletes compared with normal. First-year players (n = 80, age = 18 ± 1 years, height = 186 ± 7 cm, weight = 100.

An automated fitting procedure and software for dose-response curves with multiphasic features.

In cancer pharmacology (and many other areas), most dose-response curves are satisfactorily described by a classical Hill equation (i.e. 4 parameters logistical).

Comparison of Neurocognitive Testing and the Measurement of Marinobufagenin in Mild Traumatic Brain Injury: A Preliminary Report.

The evaluation of concussed athletes, including testing to determine if and when they may return to play, has become an important task of athletic trainers and team physicians. Currently, concussion protocols are in place, which depend largely upon assessments based upon neurocognitive testing (NCT). The authors have evaluated the use of a biomarker of brain trauma, marinobufagenin (MBG), and compared its application in concussed athletes with the performance of NTC.

The EGFR demonstrates linear signal transmission.

Cells sense information encoded in extracellular ligand concentrations and process it using intracellular signalling cascades. Using mathematical modelling and high-throughput imaging of individual cells, we studied how a transient extracellular growth factor signal is sensed by the epidermal growth factor receptor system, processed by downstream signalling, and transmitted to the nucleus. We found that transient epidermal growth factor signals are linearly translated into an activated epidermal growth factor receptor integrated over time.

Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo.

Background: The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRAS(G12D); p53(R172H); pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism.

Methods: LC-MS/MS and NMR were used to measure drug and physiological analytes.

Anti-tumour efficacy of capecitabine in a genetically engineered mouse model of pancreatic cancer.

Capecitabine (CAP) is a 5-FU pro-drug approved for the treatment of several cancers and it is used in combination with gemcitabine (GEM) in the treatment of patients with pancreatic adenocarcinoma (PDAC). However, limited pre-clinical data of the effects of CAP in PDAC are available to support the use of the GEMCAP combination in clinic. Therefore, we investigated the pharmacokinetics and the efficacy of CAP as a single agent first and then in combination with GEM to assess the utility of the GEMCAP therapy in clinic.

Paclitaxel and CYC3, an aurora kinase A inhibitor, synergise in pancreatic cancer cells but not bone marrow precursor cells.

Background: Amplification of aurora kinase A (AK-A) overrides the mitotic spindle assembly checkpoint, inducing resistance to taxanes. RNA interference targeting AK-A in human pancreatic cancer cell lines enhanced taxane chemosensitivity. In this study, a novel AK-A inhibitor, CYC3, was investigated in pancreatic cancer cell lines, in combination with paclitaxel.

Subarachnoid lumbar drains: a case series of fractured catheters and a near miss.

Purpose: Lumbar subarachnoid catheters for cerebrospinal fluid (CSF) drainage (lumbar drains) are indicated for several medical and surgical conditions. A number of complications can occur from the placement of this type of catheter, including catheter breakage from excessive traction or shearing over the Tuohy needle.

Clinical Features: Five cases of lumbar subarachnoid catheter breakage/shearing and catheter fragment retention, as well as one near miss, were identified over a one-year period at a single institution.

Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (TaqMan).

Drug-induced changes in expression of cytochrome P450 (P450) genes are a significant issue in the preclinical development of pharmaceuticals. For example, preclinically, P450 induction can affect safety studies by reducing the systemic exposure of a compound undergoing toxicological evaluation, thus limiting the exposure that can be safely investigated in patients. Therefore, the induction potential of candidate drugs has been studied as part of the drug development process, typically using protein and/or catalytic end points.

The role of nurses in preoperative assessment.

When patients elect to have surgery, it is vital that they are assessed systematically in the preoperative period. This article discusses the principles of preoperative assessment, the government perspective on assessment and the resources available to underpin patient empowerment, as well as the importance of early discharge planning.

Arthroscopic management of the throwing athlete's shoulder: indications, techniques, and results.

This article briefly describes the various pathologic lesions seen in the throwing athlete's shoulder. The pathologic conditions discussed include primary and secondary impingement, tensile lesions of the rotator cuff and biceps-labral complex, glenohumeral laxity, labral tears, and AC joint injuries. Mechanism of injury, indications, and arthroscopic management of these lesions are discussed.

Histamine blocks interleukin 2 (IL-2) gene expression and regulates IL-2 receptor expression.

Histamine inhibited the proliferative response of human peripheral blood mononuclear cells (PBMC) to the T cell mitogen Phytohemagglutinin-P (PHA-P) in a dose-dependent fashion. This inhibition was mediated via the H2 receptor since cimetidine, a known H2 antagonist, removed the inhibition, whereas the addition of the H1 antagonist Diphenhydramine did not. Inhibition occurred during the inductive phase of the cell cycle, since histamine added 24 hours after PHA-P stimulation had no effect on subsequent T cell proliferation, and was attributable to inhibition of interleukin-2 (IL-2) gene expression.

Internucleosomal DNA cleavage precedes diphtheria toxin-induced cytolysis. Evidence that cell lysis is not a simple consequence of translation inhibition.

Diphtheria toxin (DTx) is an extremely potent inhibitor of protein synthesis. Cell death has been generally accepted as a straightforward effect of translation inhibition. Using human U937 cells, we found that DTx intoxication leads to cytolysis; indeed, release of 51Cr- and 75Se-labeled proteins could be detected within 7 h.