Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Labeling of Biotechnology Products

labeling of biotech products in foodSpeakers t this symposium presented issues surround the issue of labeling of biotech products and the right of the consumer to know about the ingredients of the food they eat

Disinfection of football protective equipment using chlorine dioxide produced by the ICA TriNova system

<p>Abstract</p> <p>Backround</p> <p>Community-associated methicillin-resistant <it>Staphylococcus aureus </it>outbreaks have occurred in individuals engaged in athletic activities such as wrestling and football. Potential disease reduction interventions include the reduction or elimination of bacteria on common use items such as equipment. Chlorine dioxide has a long history of use as a disinfectant. The purpose of this investigation was to evaluate the ability of novel portable chlorine dioxide generation devices to eliminate bacteria contamination of helmets and pads used by individuals engaged in football.</p> <p>Methods</p> <p>In field studies, the number of bacteria associated with heavily used football helmets and shoulder pads was determined before and after overnight treatment with chlorine dioxide gas. Bacteria were recovered using cotton swabs and plated onto trypticase soy agar plates. In laboratory studies, <it>Staphylococcus aureus </it>was applied directly to pads. The penetration of bacteria into the pads was determined by inoculating agar plates with portions of the pads taken from the different layers of padding. The ability to eliminate bacteria on the pad surface and underlying foam layers after treatment with chlorine dioxide was also determined.</p> <p>Results</p> <p>Rates of recovery of bacteria after treatment clearly demonstrated that chlorine dioxide significantly (p < 0.001) reduce and eliminated bacteria found on the surface of pads. For example, the soft surface of shoulder pads from a university averaged 2.7 × 10³recoverable bacteria colonies before chlorine dioxide treatment and 1.3 × 10²recoverable colonies after treatment. In addition, the gas was capable of penetrating the mesh surface layer and killing bacteria in the underlying foam pad layers. Here, 7 × 10³to 4.5 × 10³laboratory applied <it>S. aureus </it>colonies were recovered from underlying layers before treatment and 0 colonies were present after treatment. Both naturally occurring bacteria and <it>S. aureus </it>were susceptible to the treatment process.</p> <p>Conclusion</p> <p>Results of this study have shown that chlorine dioxide can easily and safely be used to eliminate bacteria contamination of protective pads used by football players. This could serve to reduce exposure to potential pathogens such as the methicillin-resistant <it>Staphylococcus aureus </it>among this group of individuals.</p

Redefining happiness: Is the happiness pie literature missing some slices?

This study examined the relationships among happiness-related factors, as well as the relation between the antecedents of happiness (e.g., an individual\u27s personality, situations, and voluntary behavior) and self-reported individual differences. Three hundred forty-seven undergraduates completed measures of happiness, positive affect, subjective well-being, contentment, self-compassion, depression, neuroticism, mindfulness, and openness to experience. Participants also indicated the percentage of their happiness due to personality, the situation, and voluntary behaviors. The results corroborate evidence for happiness being most indicative of a multidimensional construct, as contentment, subjective well-being, and happiness were highly related. Additionally, in spite of research showing that almost half of our happiness is determined by voluntary actions, participants, on average, divided the happiness pie into thirds, attributing their happiness to personality (30.36%), the situation (36.88%), and voluntary actions (32.7%)

On the construction and sustainability of happiness: Where does my happiness come from?

Problem. Happiness is attributed to three sources: genetics and personality (50%), the situation (10%), and voluntary behaviors (40%) (Lyubomirsky, 2008). Few studies exist on the subject of happiness factors, their duration, and how these factors may relate to Lyubomirsky\u27s (2008) three sources of happiness, the purpose of this study. Method. Three hundred and forty-seven undergraduates listed what they felt contributed to their overall happiness. Then they indicated the three items they considered the most significant contributors. Finally, participants reported the duration (e.g., minutes, hours, days, weeks, or years) of happiness caused by each of these items. Results and Discussion. The number of happiness items participants expressed ranged from 0 to 77 (M = 28.58; SD = 13.74). The item listed most often was family (20.27%) followed by friends (15.18%). Most people gave priority to items that made them happy for years. As priority of the items decreased so did duration suggesting that people place greater value on factors that lead to prolonged levels of happiness. These findings have implications for happiness construction and sustainability as increasing individuals\u27 happiness levels may involve seeking out more socially-beneficial--as well as longer-lasting--resources

Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis (NASH) in the United Kingdom (UK) in 2018

BACKGROUNDS AND AIMS: Non-alcoholic steatohepatitis (NASH) – a progressive subset of non-alcoholic fatty liver disease (NAFLD) – is a chronic liver disease that can progress to advanced fibrosis, cirrhosis, and end-stage liver disease (ESLD) if left untreated. Early-stage NASH is usually asymptomatic, meaning a large proportion of the prevalent population are undiagnosed. Receiving a NASH diagnosis increases the probability that a patient will receive interventions for the purpose of managing their condition. The purpose of this study was to estimate the disease burden and economic impact of diagnosed NASH in the United Kingdom (UK) adult population in 2018. METHODS: The socioeconomic burden of diagnosed NASH from a societal perspective was estimated using cost-of-illness methodology applying a prevalence approach. This involved estimating the number of adults with diagnosed NASH in the UK in a base period (2018) and the economic and wellbeing costs attributable to diagnosed NASH in that period. The analysis was based on a targeted review of the scientific literature, existing databases and consultation with clinical experts, health economists and patient groups. RESULTS: Of the prevalent NASH population in the UK in 2018, an estimated 79.8% were not diagnosed. In particular, of the prevalent population in disease stages F0 to F2, only 2.0% (F0), 2.0% (F1) and 16.5% (F2), respectively, were diagnosed. Total economic costs of diagnosed NASH in the UK ranged from £2.3 billion (lower prevalence scenario, base probability of diagnosis scenario) to £4.2 billion (higher prevalence scenario, base probability of diagnosis scenario). In 2018, people with NASH in the UK were estimated to experience 94,094 to 174,564 disability-adjusted life years (DALYs) overall. Total wellbeing costs associated with NASH in 2018 were estimated to range between £5.6 to £10.5 billion. CONCLUSIONS: The prevention and appropriate management of adult NASH patients could result in reduced economic costs and improvements in wellbeing

HACA3: A Unified Approach for Multi-site MR Image Harmonization

The lack of standardization is a prominent issue in magnetic resonance (MR) imaging. This often causes undesired contrast variations due to differences in hardware and acquisition parameters. In recent years, MR harmonization using image synthesis with disentanglement has been proposed to compensate for the undesired contrast variations. Despite the success of existing methods, we argue that three major improvements can be made. First, most existing methods are built upon the assumption that multi-contrast MR images of the same subject share the same anatomy. This assumption is questionable since different MR contrasts are specialized to highlight different anatomical features. Second, these methods often require a fixed set of MR contrasts for training (e.g., both Tw-weighted and T2-weighted images must be available), which limits their applicability. Third, existing methods generally are sensitive to imaging artifacts. In this paper, we present a novel approach, Harmonization with Attention-based Contrast, Anatomy, and Artifact Awareness (HACA3), to address these three issues. We first propose an anatomy fusion module that enables HACA3 to respect the anatomical differences between MR contrasts. HACA3 is also robust to imaging artifacts and can be trained and applied to any set of MR contrasts. Experiments show that HACA3 achieves state-of-the-art performance under multiple image quality metrics. We also demonstrate the applicability of HACA3 on downstream tasks with diverse MR datasets acquired from 21 sites with different field strengths, scanner platforms, and acquisition protocols

Dimensional stability and tensile strength of irradiated Nicalon-CG and Hi-Nicalon SiC fibers

Nicalon-CG and Hi-Nicalon fibers were characterized by measuring their length, density, and tensile strength in the unirradiated, thermal annealed, and irradiated conditions. The irradiation was conducted in the EBR-II to a dose of 43 dpa-SiC at a nominal irradiation temperature of 1,000 C. The annealed specimens were held at 1,010 C for 165 days to approximately duplicate the thermal exposure of the irradiated specimens. The results indicate the fibers that perform best in an irradiation environment are those that approach stoichiometric and crystalline SiC. Hi-Nicalon exhibited negligible densification, accompanied by an increase in tensile strength after irradiation. Nicalon-CG possessed a higher tensile strength than hi-Nicalon in the unirradiated condition, but was significantly weakened in the annealed and irradiated conditions. In addition, Nicalon-CG exhibited unacceptable irradiation-induced shrinkage. Loss o fiber tensile strength after irradiation is shown to reduce the flexural strength of irradiated composites and Nicalon-CG fiber shrinkage observed in irradiated composites