Adjuvant radiation in akimbo-like position in a case of post-mastectomy breast cancer - A case report.

In this report, we describe the radiotherapy planning and treatment of a 72-year-old postmenopausal lady with multiple comorbidities, who was diagnosed with carcinoma of the right breast. She underwent a right modified radical mastectomy with axillary clearance and was found to have axillary nodes harboring malignant metastasis. She was planned with adjuvant radiation to the chest wall and supraclavicular region.

Streamlining Food Effect Assessment - Are Repeated Food Effect Studies Needed? An IQ Analysis.

Current regulatory guidelines on drug-food interactions recommend an early assessment of food effect to inform clinical dosing instructions, as well as a pivotal food effect study on the to-be-marketed formulation if different from that used in earlier trials. Study waivers are currently only granted for BCS class 1 drugs. Thus, repeated food effect studies are prevalent in clinical development, with the initial evaluation conducted as early as the first-in-human studies.

Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in -Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study.

Purpose: No approved targeted therapy for the treatment of patients with neuroblastoma RAS viral (v-ras) oncogene homolog ()-mutant melanoma is currently available.

Patients And Methods: In this phase Ib escalation/expansion study (ClinicalTrials.gov identifier: NCT02974725), the safety, tolerability, and preliminary antitumor activity of naporafenib (LXH254), a BRAF/CRAF protein kinases inhibitor, were explored in combination with trametinib in patients with advanced/metastatic or -mutant non-small-cell lung cancer (escalation arm) or -mutant melanoma (escalation and expansion arms).

A single- and multiple-dose study to characterize the pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in healthy Chinese participants.

Ceftolozane/tazobactam (C/T) is approved in several countries to treat complicated urinary tract infections, complicated intra-abdominal infections, and nosocomial pneumonia. There is a paucity of pharmacokinetics and safety data for C/T in Chinese participants. This study evaluated the pharmacokinetics, safety, and tolerability of C/T in 12 healthy Chinese participants after three single administrations of increasing doses (0.

A Comparison of Wearable Tonometry, Photoplethysmography, and Electrocardiography for Cuffless Measurement of Blood Pressure in an Ambulatory Setting.

Objective: While non-invasive, cuffless blood pressure (BP) measurement has demonstrated relevancy in controlled environments, ambulatory measurement is important for hypertension diagnosis and control. We present both in-lab and ambulatory BP estimation results from a diverse cohort of participants.

Methods: Participants (N=1125, aged 21-85, 49.

Calibrating surface hyperelastic constitutive models in soft solids.

Soft solids such as silicone gels, with bulk shear modulus ranging from ∼10 to 1000kPa, exhibit strongly strain-dependent surface stresses. Moreover, unlike conventional stiffer materials, the effects of surface stress in these materials manifest at length scales of tens of micrometers rather than nanometers. However, the calibration of constitutive parameters for surface hyperelasticity has proved to be challenging.

Physiologically-based pharmacokinetics modeling to investigate formulation factors influencing the generic substitution of dabigatran etexilate.

The exposure-response relationship of direct acting oral anti-coagulants (DOACs) for bleeding risk is steep relative to ischemic stroke reduction. As a result, small changes in exposure may lead to bleeding events. The overall goal of this project was to determine the effect of critical formulation parameters on the pharmacokinetics (PKs) and thus safety and efficacy of generic DOACs.

Understanding Mechanisms of Food Effect and Developing Reliable PBPK Models Using a Middle-out Approach.

Over the last 10 years, 40% of approved oral drugs exhibited a significant effect of food on their pharmacokinetics (PK) and currently the only method to characterize the effect of food on drug absorption, which is recognized by the authorities, is to conduct a clinical evaluation. Within the pharmaceutical industry, there is a significant effort to predict the mechanism and clinical relevance of a food effect. Physiologically based pharmacokinetic (PBPK) models combining both drug-specific and physiology-specific data have been used to predict the effect of food on absorption and to reveal the underlying mechanisms.

Correction to: Use of Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Drug-Food Interactions: an Industry Perspective.

An Erratum to this paper has been published: https://doi.org/10.1208/s12248-020-00535-z.

Use of Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Drug-Food Interactions: an Industry Perspective.

The effect of food on pharmacokinetic properties of drugs is a commonly observed occurrence affecting about 40% of orally administered drugs. Within the pharmaceutical industry, significant resources are invested to predict and characterize a clinically relevant food effect. Here, the predictive performance of physiologically based pharmacokinetic (PBPK) food effect models was assessed via de novo mechanistic absorption models for 30 compounds using controlled, pre-defined in vitro, and modeling methodology.

Physiologically Based Pharmacokinetic Modeling of Monoclonal Antibodies in Pediatric Populations Using PK-Sim.

Physiologically based pharmacokinetic (PBPK) models are increasingly used to support pediatric dose selection for small molecule drugs. In contrast, only a few pediatric PBPK models for therapeutic antibodies have been published recently, and the knowledge on the maturation of the processes relevant for antibody pharmacokinetics (PK) is limited compared to small molecules. The aim of this study was, thus, to evaluate predictions from antibody PBPK models for children which were scaled from PBPK models for adults in order to identify respective knowledge gaps.

Mechanics of reversible wrinkling in a soft dielectric elastomer.

A parallel array of wrinkles can be generated in a simple parallel plate capacitor arrangement with a soft dielectric elastomer plate constrained all around its periphery and coated with flexible electrodes. The direction of the wrinkles is predetermined and the phenomenon is reversible in a range of applied potentials. A model of the wrinkled plate as a prestretched neo-Hookean membrane with superposed small out-of-plane bending displacements yields good estimates of the potential range for wrinkling as well as the number of parallel wrinkles.

Characterization of entanglements in glassy polymeric ensembles using the Gaussian linking number.

We propose a method for enumerating entanglements between long chained, linear polymers that is based on the Gaussian linking number. The linking number is calculated between closely approaching segments of the macromolecular chains. Topological features of an entanglement, i.

Von Recklinghausen's Disease Presenting as Otolaryngologic Emergency: A Rare Occurrence.

Type 1 Neurofibromatosis (NF1) is a rare autosomal dominant genetic disorder. There are seven clinical features of which two are necessary to diagnose it. Another important feature is plexiform neurofibroma which commonly presents as painful expansile lesion.

Xiao-Chai-Hu-Tang (XCHT) Intervening Irinotecan's Disposition: The Potential of XCHT in Alleviating Irinotecan-Induced Diarrhea.

Background: Diarrhea is a severe side effect of irinotecan, a pro-drug of SN-38 used for the treatment of many types of cancers. Pre-clinical and clinical studies showed that decreasing the colonic exposure of SN-38 can mitigate irinotecan-induced diarrhea.

Objective: The purpose of this study is to evaluate the anti-diarrhea potential of Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese herbal formula, against irinotecan-induced diarrhea by determining if and how XCHT alters the disposition of SN-38.

Physiologically Based Pharmacokinetic Modeling to Evaluate Formulation Factors Influencing Bioequivalence of Metoprolol Extended-Release Products.

The University of Florida Center for Pharmacometrics and Systems Pharmacology and the Food and Drug Administration Office of Generic Drugs have collaborated on a research project to develop a mechanism- and risk-based strategy that systematically investigates postmarketing reports of therapeutic inequivalence following the switch between brand and generic drug products. In this study we developed and qualified a physiologically based pharmacokinetic model to systematically investigate the influence of drug- and formulation-related properties on the oral absorption and bioequivalence of modified-release products using metoprolol as an example. Our findings show that the properties of the release-controlling polymer are the critical attributes for in vitro dissolution, in vivo absorption, and systemic exposure (ie, pharmacokinetics) and, thus, the bioequivalence of metoprolol extended-release products rather than the properties of the drug itself.

Correlations between axial stiffness and microstructure of a species of bamboo.

Bamboo is a ubiquitous monocotyledonous flowering plant and is a member of the true grass family . In many parts of the world, it is widely used as a structural material especially in scaffolding and buildings. In spite of its wide use, there is no accepted methodology for standardizing a species of bamboo for a particular structural purpose.

Glucuronidation: driving factors and their impact on glucuronide disposition.

Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances. Although it is usually the secondary metabolic pathway for a compound preceded by phase I hydroxylation, glucuronidation alone could serve as the dominant metabolic pathway for many compounds, including some with high aqueous solubility. Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases (UGTs) into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters.

Role of Toll-like receptor 4 in drug-drug interaction between paclitaxel and irinotecan in vitro.

The bacterial receptor, Toll-like receptor (TLR) 4 mediates inflammatory responses and has been linked to a broad array of diseases. TLR4 agonists are being explored as potential treatments for cancer and other diseases. We have previously shown that activation of TLR4 by lipopolysaccharide (LPS) leads to down-regulation of drug metabolizing enzymes/transporters (DMETs), and altered pharmacokinetics/pharmacodynamics (PK/PD) of drugs.

Multi-omics analyses reveal metabolic alterations regulated by hepatitis B virus core protein in hepatocellular carcinoma cells.

Chronic hepatitis B virus (HBV) infection is partly responsible for hepatitis, fatty liver disease and hepatocellular carcinoma (HCC). HBV core protein (HBc), encoded by the HBV genome, may play a significant role in HBV life cycle. However, the function of HBc in the occurrence and development of liver disease is still unclear.

Measurement of microfibril angles in bamboo using Mueller matrix imaging.

The microfibril angle (MFA) giving the orientation of cellulose chains in hard sclerenchymatous bamboo fibers is one of the most important parameters determining the overall strength of the bamboo culm. In this work, Mueller matrix imaging polarimetry is implemented for determining MFA measured over a transverse section of group of fibers and parenchyma cells in bamboo of Dendrocalamus strictus species. The method, based on the Stokes-Mueller formalism, decouples the birefringence exhibited by crystalline cellulose from the clumped polarization parameters using 16 images taken with different polarization states at subcellular resolution.

Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats.

The objective of this research is to develop and validate a sensitive and reproducible UPLC-MS/MS method to quantify irinotecan, its active metabolite SN-38 and SN-38 glucuronide (phase II metabolite of SN-38) simultaneously in different bio-matrices (plasma, urine, feces), tissues (liver and kidney) and to use the method to investigate its pharmacokinetic behavior in rats. Irinotecan, SN-38 and SN-38 glucuronide has been resolved and separated by C18 column using acetonitrile and 0.1% formic acid in water used as the mobile phases.

Disposition of flavonoids via recycling: Direct biliary excretion of enterically or extrahepatically derived flavonoid glucuronides.

Scope: Enterohepatic recycling is often thought to involve mostly phase II metabolites generated in the liver. This study aims to determine if direct biliary excretion of extrahepatically generated glucuronides would also enable recycling.

Methods And Results: Conventional and modified intestinal perfusion models along with intestinal and liver microsomes were used to determine the contribution of extrahepatically derived glucuronides.