Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K-1) in severe acute liver disease

Background/Aims: In patients with severe acute liver dysfunction, i.v. phylloquinone (vitamin K-1) may be given to exclude vitamin K deficiency, rather than impaired hepatic synthesis of coagulation factors alone, as the cause of the coagulopathy. However, there have been no studies of the pharmacokinetics or efficacy of i.v. or oral K-1 in such patients.Methods: 49 adults with severe acute liver disease were randomised double-blind to a single 10 mg dose of i.v. or oral mixed-micellar K-1, or placebo. Serum levels of phylloquinone and undercarboxylated prothrombin (PIVKA-II) were assessed before and after treatment.Results: At admission, 13 patients (27 %) had either low serum K-1 levels or elevated PIVKA-II concentrations, indicative of subclinical vitamin K deficiency. In the 16 patients who received i.v. K-1, there was one (6 %) treatment failure (K-1 rise < 10 ng/ml above baseline), compared with 12 of the 15 (80 %) who received oral K, (P < 0.0001). One patient in the placebo group developed overt vitamin K deficiency.Conclusions: A minority of patients with severe acute liver dysfunction have subclinical vitamin K deficiency at the time of presentation, which is corrected by a single dose of i.v. K-1. The intestinal absorption of mixed-micellar K, is unreliable in adults with severe acute liver dysfunction. (c) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection

We describe a method for the determination of the two major urinary metabolites of vitamin K as the methyl esters of their agyclone structures, 2-methyl-3-(3-3-carboxymethylpropyl)-1,4-naphthoquinone (5C-side-chain metabolite) and 2-methyl-3-(5-carboxy-3-methyl-2-pentenyl)-1,4-naphthoquinone (7C-side-chain metabolite), by HPLC with electrochemical detection (ECD) in the redox mode. Urinary salts were removed by reversed-phase (C18) solid phase extraction (SPE) and the predominately conjugated vitamin K metabolites hydrolysed with methanolic HCl. The resultant carboxylic acid aglycones were quantitatively methylated with diazomethane and fractionated by normal-phase (silica) SPE. Final analysis was by reversed-phase (C18) HPLC with a methanol-aqueous mobile phase. Metabolites were detected by amperometric, oxidative ECD of their quinol forms, which were generated by post-column coulometric reduction at an upstream electrode. The assay gave excellent linearity (r2 typically = 0.999) and high sensitivity with an on-column detection limit of <3.5 fmol (<1pg). The inter-assay precision was typically 10%. Metabolite recovery was compared to that of an internal standard (2-methyl-3-(7'-carboxy-heptyl)-1,4-naphthoquinone), added to urine samples just before analysis. Using this methodology we confirmed that the 5C- and 7C-metabolite were major catabolites of both phylloquinone (vitamin K1) and menaquinones (vitamin K2) in humans. We propose that the measurement of urinary vitamin K metabolite excretion is a candidate non-invasive marker of total vitamin K status

Carbon nanotubes in TiO2 nanofiber photoelectrodes for high-performance perovskite solar cells

1D semiconducting oxides are unique structures that have been widely used for photovoltaic (PV) devices due to their capability to provide a direct pathway for charge transport. In addition, carbon nanotubes (CNTs) have played multifunctional roles in a range of PV cells because of their fascinating properties. Herein, the influence of CNTs on the PV performance of 1D titanium dioxide nanofiber (TiO2 NF) photoelectrode perovskite solar cells (PSCs) is systematically explored. Among the different types of CNTs, single‐walled CNTs (SWCNTs) incorporated in the TiO2 NF photoelectrode PSCs show a significant enhancement (≈40%) in the power conversion efficiency (PCE) as compared to control cells. SWCNTs incorporated in TiO2 NFs provide a fast electron transfer within the photoelectrode, resulting in an increase in the short‐circuit current (J sc) value. On the basis of our theoretical calculations, the improved open‐circuit voltage (V oc) of the cells can be attributed to a shift in energy level of the photoelectrodes after the introduction of SWCNTs. Furthermore, it is found that the incorporation of SWCNTs into TiO2 NFs reduces the hysteresis effect and improves the stability of the PSC devices. In this study, the best performing PSC device constructed with SWCNT structures achieves a PCE of 14.03%

Efficient and Fast Synthesis of Few-Layer Black Phosphorus via Microwave-Assisted Liquid-Phase Exfoliation

High‐quality, few‐layer black‐phosphorus (BP) flakes are prepared in a common organic solvent with very short processing times using microwave‐assisted liquid‐phase exfoliation. A comprehensive range of analysis, combined with density‐functional theory calculations, confirms that the product prepared using the microwave technique is few‐layer BP with small‐ and large‐area flakes. The suspended exfoliated BP sheets show excellent stability, while samples dispersed onto silicon from the suspensions exhibit low oxidation levels after several days in ambient conditions. This straightforward synthesis method is facile, efficient, and extremely fast, and does not involve use of any surfactant or ultrasonication steps and will facilitate future development of phosphorene research

There Is an “Eye” in Team: Exploring the Interplay Between Emotion, Gaze Behavior, and Collective Efficacy in Team Sport Settings

Data Availability Statement: The datasets generated for this study are available on request to the corresponding author.Copyright © 2020 Shearer, Leeworthy, Jones, Rickards, Blake, Heirene, Gross and Bruton. . Little is understood about the attentional mechanisms that lead to perceptions of collective efficacy. This paper presents two studies that address this lack of understanding. Study one examined participant's (N = 59) attentional processes relating to positive, neutral, or negative emotional facial photographs, when instructed to select their “most confident” or “least confident” team. Eye gaze metrics of first fixation duration (FFD), fixation duration (FD), and fixation count (FC) were measured alongside individual perceptions of collective efficacy and emotional valence of the teams selected. Participants had shorter FFD, longer FD, and more FC on positive faces when instructed to select their most confident team (p < 0.05). Collective efficacy and emotional valence were significantly greater when participants selected their most confident team (p < 0.05). Study two explored the influence of video content familiarity of team-based observation interventions on attentional processes and collective efficacy in interdependent team-sport athletes (N = 34). When participants were exposed to familiar (own team/sport) and unfamiliar (unknown team/sport) team-based performance video, eye tracking data revealed similar gaze behaviors for the two conditions in terms of areas of interest. However, collective efficacy increased most for the familiar condition. Study one results indicate that the emotional expressions of team members influence both where and for how long we look at potential team members, and that conspecifics' emotional expression impacts on our perceptions of collective efficacy. For Study two, given the apparent greater increase in collective efficacy for the familiar condition, the similar attentional processes evident for familiar and unfamiliar team footage suggests that differences in meaning of the observed content dictates collective efficacy perceptions. Across both studies, the findings indicate the importance of positive emotional vicarious experiences when using team-based observation interventions to improve collective efficacy in teams.University of South Wales (Study 1); University of Roehampton (Study 2)

Clinical Rounds With Nutrition Support Services

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68406/2/10.1177_011542659400900273.pd

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Unhappy doctors? A longitudinal study of life and job satisfaction among Norwegian doctors 1994 – 2002

BACKGROUND: General opinion is that doctors are increasingly dissatisfied with their job, but few longitudinal studies exist. This study has been conducted to investigate a possible decline in professional and personal satisfaction among doctors by the turn of the century. METHODS: We have done a survey among a representative sample of 1 174 Norwegian doctors in 2002 (response rate 73 %) and compared the findings with answers to the same questions by (most of) the same doctors in 1994 and 2000. The main outcome measures were self reported levels of life satisfaction and job satisfaction according to the Job Satisfaction Scale (JSS). RESULTS: Most Norwegian doctors are happy. They reported an average life satisfaction of 5.21 in 1994 and 5.32 in 2002 on a scale from 1 (extremely dissatisfied) to 7 (extremely satisfied). Half of the respondents reported a very high level of general life satisfaction (a score of 6 or 7) while only one third said they would have reported this high level of satisfaction five years ago. The doctors thought that they had a higher level of job satisfaction than other comparable professional groups. The job satisfaction scale among the same doctors showed a significant increase from 1994 to 2002. Anaesthesiologists and internists reported a lower and psychiatrists and primary care doctors reported a higher level of job satisfaction than the average. CONCLUSION: Norwegian doctors seem to have enjoyed an increasing level of life and job satisfaction rather than a decline over the last decade. This challenges the general impression of unhappy doctors as a general and worldwide phenomenon