Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

Background: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. Methods: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. Results: The $AUC_{0-10 hr}$ and $C_{max}$ values increased nonlinearly between 100 mg and 1500 mg. The slope of the $AUC_{0-10 hr}$ vs dose, as well as the $C_{max}$ vs dose, plots are steepest at the lowest thiamine doses. Conclusion: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation

Development of a Quantitative Instrument to Measure Mobile Collaborative Learning (MCL) Using WhatsApp: The Conceptual Steps

It has been reported that WhatsApp, a social media application, had approximately 1.6 billion active users globally as of July 2019, almost one-fifth of the total world’s population. Thus, research about WhatsApp’s influence in general and especially its influence in education was relevant and significant. While there was much research involving WhatsApp and learning, it was not conclusive about the effects of WhatsApp on student learning. Specifically, research focusing on collaborative learning using WhatsApp was lacking, including research instruments for measuring collaboration on WhatsApp. Consequently, the paper’s research problem was the lack of research instruments for measuring collaboration on WhatsApp in relation to academic achievement. To address the research problem, the study followed the important initial and conceptual steps of the instrument development process to develop a research instrument to measure collaboration on WhatsApp in relation to academic achievement. The result of the paper was a developed instrument that provides researchers with a basis to measure the explanatory constructs involved in mobile collaborative learning (MCL) processes on WhatsApp and potentially other social media platforms. Therefore, the paper made an appropriately theoretical contribution, which was grounded in the scientific literature. The study facilitated positivistic research and epistemology for acquiring objective and precise scientific knowledge. Such deductive research promotes theory testing and development and presents educators and students with scientific evidence about learning with MCL applications such as WhatsApp from which both curriculum and learning design can be informed and benefited. In the age of connected mobility this is a necessity.School of Computin

Social media in undergraduate medical education: A systematic review.

INTRODUCTION: There are over 3.81 billion worldwide active social media (SoMe) users. SoMe are ubiquitous in medical education, with roles across undergraduate programmes, including professionalism, blended learning, well being and mentoring. Previous systematic reviews took place before recent explosions in SoMe popularity and revealed a paucity of high-quality empirical studies assessing its effectiveness in medical education. This review aimed to synthesise evidence regarding SoMe interventions in undergraduate medical education, to identify features associated with positive and negative outcomes. METHODS: Authors searched 31 key terms through seven databases, in addition to references, citation and hand searching, between 16 June and 16 July 2020. Studies describing SoMe interventions and research on exposure to existing SoMe were included. Title, abstract and full paper screening were undertaken independently by two reviewers. Included papers were assessed for methodological quality using the Medical Education Research Study Quality Instrument (MERSQI) and/or the Standards for Reporting Qualitative Research (SRQR) instrument. Extracted data were synthesised using narrative synthesis. RESULTS: 112 studies from 26 countries met inclusion criteria. Methodological quality of included studies had not significantly improved since 2013. Engagement and satisfaction with SoMe platforms in medical education are described. Students felt SoMe flattened hierarchies and improved communication with educators. SoMe use was associated with improvement in objective knowledge assessment scores and self-reported clinical and professional performance, however evidence for long term knowledge retention was limited. SoMe use was occasionally linked to adverse impacts upon mental and physical health. Professionalism was heavily investigated and considered important, though generally negative correlations between SoMe use and medical professionalism may exist. CONCLUSIONS: Social media is enjoyable for students who may improve short term knowledge retention and can aid communication between learners and educators. However, higher-quality study is required to identify longer-term impact upon knowledge and skills, provide clarification on professionalism standards and protect against harms

Methods in capillary electrophoresis coupled to mass spectrometry for the identification of clinical proteomic/peptidomic biomarkers in biofluids

Proteomic biomarkers hold the promise of enabling assessment of patients according to a pathological condition aiming at improvements in diagnosis, prognosis, in general clinical patient management. Capillary electrophoresis coupled to an electrospray ionization time-of-flight mass spectrometer (CE-MS) allows the detection of thousands of small proteins and peptides in various biofluids, in a single, reproducible and time-limited step, enabling the simultaneous comparison of multiple individual proteins and peptides in biomarker discovery, but also in clinical applications. The reliability of the CE-MS platform, together with the use of a validated approach for data processing and mining is, to date, the most advanced technique for biomarker discovery of clinical significance. In this chapter, we report on the materials, methods and protocols used for CE-MS-based clinical proteomics allowing the reproducible profiling of biofluids