Determination of Impurities in Pharmaceuticals: Why and How?

The presence of impurities, particularly the API-related impurities, i.e., degradation-related impurities (DRIs) and interaction-related impurities (IRIs), may affect the quality, safety, and efficacy of drug products. Since the regulatory requirements and management strategies are required to be established and complied, sources of impurities shall be carefully classified prior to take subsequent steps such as development of analytical methods and acceptance criteria. Current international regulatory requirements for the management of impurities in pharmaceuticals were reviewed. Procedures for the identification of DPIs in pharmaceuticals, i.e., ethyl cysteinate dimer, (R)-N-methyl-3-(2-bromophenoxy)-3-phenylpropanamine, sestamibi, etc., using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were studied. Scheme for the establishment of analytical methods and acceptance criteria of process-related impurities (PRIs) and DRIs in accordance with the requirements of International Council for Harmonization (ICH) and algorithm to perform the identification of DPIs by using LC-MS/MS has been proposed. Practice of kinetic study to distinguish PRIs and DRIs, determination of the potential core fragments coupled with a predicted list of relevant transformations for conducting MS/MS scans, applications of stable isotope distribution patterns or natural abundances, practice of mass balance, etc., have been well demonstrated to justify the reliabilities of identification results

Improvement on thermal performance of a disk-shaped miniature heat pipe with nanofluid

The present study aims to investigate the effect of suspended nanoparticles in base fluids, namely nanofluids, on the thermal resistance of a disk-shaped miniature heat pipe [DMHP]. In this study, two types of nanoparticles, gold and carbon, in aqueous solution are used respectively. An experimental system was set up to measure the thermal resistance of the DMHP with both nanofluids and deionized [DI] water as the working medium. The measured results show that the thermal resistance of DMHP varies with the charge volume and the type of working medium. At the same charge volume, a significant reduction in thermal resistance of DMHP can be found if nanofluid is used instead of DI water

DEVELOPING SUPPLY CHAIN DYNAMIC CAPABILITY TO REALIZE THE VALUE OF INTER-ORGANIZATIONAL SYSTEMS

In face of increasingly complex supply chain, firms are taking steps to develop different kinds of inter-organizational systems (IOS) to facilitate information sharing and sustain competitive competency. These systems are expected to provide great business value, however many of them do not fulfill the expected promise as these systems are relatively more complicated and the usage is across supply chains. Built upon process theory and the view of dynamic capability, this study has defined two supply chain dynamic capabilities (SDC) -- supply chain integration capability and supply chain cooperation capability and proposed that they might significantly moderate IOS performance. A general survey is conducted in Taiwan PC industry to validate the research model. A linear regression is used to testify the hypotheses. The results show that improving SDC can create greater IOS performance. Furthermore, supply chain integration capability has stronger moderating effect of IOS performance than supply chain cooperation capability. These findings contribute to the literature by confirming the influence of SDC on IOS performance and also by showing which SDC is of primary importance to firms

Association of Alzhemier\u27s Disease With Hepatitis C Among Patients With Bipolar Disorder

Associations of hepatitis C virus infection with Alzheimer’s disease have not been studied among higher risk, bipolar disorder patients. This population-based case-control study investigated the risks of hepatitis C virus infection among Alzheimer’s disease patients with bipolar disorder in the years preceding their Alzheimer’s disease diagnosis. We used 2000–2013 data from the Longitudinal Health Insurance Database in Taiwan. Among patients with bipolar disorder, 73 were diagnosed with Alzheimer’s disease (cases), who were compared with 365 individuals with bipolar disorder but without Alzheimer’s disease (randomly selected controls matched on sex, age, and index year with cases). Prior claims (before the diagnosis year/index year for controls) were screened for a diagnosis of hepatitis C virus infection. Conditional logistic regression models were used for analysis. We found that 23 (31.51%) and 60 (16.44%) patients with bipolar disease were identified with a hepatitis C diagnosis among those with and without Alzheimer’s disease, respectively. Compared to controls, patients with Alzheimer’s disease showed 2.31-fold (95% confidence interval = 1.28–4.16) increased risk of hepatitis C infections adjusted for demographics and socio-economic status. Findings suggest an association of Alzheimer’s disease with a preceding diagnosis of hepatitis C infection among patients with bipolar disorder. Findings may suggest a need for increased awareness of and appropriate surveillance for Alzheimer’s disease in patients with bipolar disorder diagnosed with hepatitis C infection

5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

Photodynamic therapy (PDT) has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) signaling cascades are activated following 5-aminolevulinic acid (ALA)-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy

Transformer-based Image Compression with Variable Image Quality Objectives

This paper presents a Transformer-based image compression system that allows for a variable image quality objective according to the user's preference. Optimizing a learned codec for different quality objectives leads to reconstructed images with varying visual characteristics. Our method provides the user with the flexibility to choose a trade-off between two image quality objectives using a single, shared model. Motivated by the success of prompt-tuning techniques, we introduce prompt tokens to condition our Transformer-based autoencoder. These prompt tokens are generated adaptively based on the user's preference and input image through learning a prompt generation network. Extensive experiments on commonly used quality metrics demonstrate the effectiveness of our method in adapting the encoding and/or decoding processes to a variable quality objective. While offering the additional flexibility, our proposed method performs comparably to the single-objective methods in terms of rate-distortion performance

Elderly Patients with Laryngeal and Hypopharyngeal Cancer Undergoing Total Pharyngolaryngectomy with a Radial Forearm, Free Flap-reconstructed Phonation Tube

SummaryBackgroundThe radial forearm, free-flap (RFFF)-reconstructed phonation tube was developed for functional restoration of voice after total pharyngolaryngectomy. We aimed to report the efficacy of RFFF phonation tube after pharyngolaryngectomy with radiotherapy (RT) or concurrent chemoradiation therapy (CCRT) with intensity-modulated radiotherapy (IMRT) for elderly.Materials and methodsTen patients with laryngeal and hypopharyngeal cancer underwent total pharyngolaryngectomy and one-stage reconstruction with an RFFF-accompanied phonation tube, followed by RT or CCRT. Voice restoration was achieved with the RFFF-reconstructed phonation tube. Functional outcomes of phonation and speech were evaluated and scored.ResultsPercentages of stage III and stage IV patients among all participants were 10% and 90%, respectively. The median follow-up time was 31 months (range, 4–67 months). Almost 9 out of 10 (90%) patients experienced phonation efficacy greater than 80%. The maximal phonation time per breath was 70% longer than 3 sec. The graded as mild of wet voice was 90%. Percentage of mild decreased loudness was 60% and that of low and high pitch was 80%. Of the 10 patients, 40% could count more than 10 and 70% could pronounce more than 1 to 5 words per breath. After RT or CCRT, of patients had moderately good to excellent speech intelligibility.ConclusionThe RFFF phonation tube that was used after pharyngolaryngectomy with RT or CCRT with IMRT provided acceptable complications and functional restoration of voice for elderly patients

Accelerated colorimetric immunosensingusing surface-modified porous monolithsand gold nanoparticles

A rapid and sensitive immunoassay platform integrating polymerized monoliths and gold nanoparticles (AuNPs) has been developed. The porous monoliths are photopolymerized in situ within a silica capillary and serve as solid support for high-mass transport and high-density capture antibody immobilization to create a shorter diffusion length for antibody–antigen interactions, resulting in a rapid assay and low reagent consumption. AuNPs are modified with detection antibodies and are utilized as signals for colorimetric immunoassays without the need for enzyme, substrate and sophisticated equipment for quantitative measurements. This platform has been verified by performing a human IgG sandwich immunoassay with a detection limit of 0.1 ng ml−1. In addition, a single assay can be completed in 1 h, which is more efficient than traditional immunoassays that require several hours to complete