End-Of-Life Care in the Potential Donor after Circulatory Death: A Systematic Review.

BACKGROUND: Donation after circulatory death (DCD) is becoming increasingly common, yet little is known about the way potential donors receive end-of-life care. PURPOSE: The aims of this systematic review are to describe the current practice in end-of-life care for potential donors and identify metrics that are being used to assess discomfort among these patients. RESEARCH DESIGN AND STUDY SAMPLE: This review encompasses published literature between June 1, 2000 and June 31, 2020 of end-of-life care received by potential DCD patients. The population of interest was defined as patients eligible for Maastracht classification III donation after circulatory death for a solid organ transplantation. Outcomes examined included: analgesic or palliative protocols, and surrogates of discomfort (eg dyspnea, agitation). RESULTS: Among 141 unique articles, 27 studies were included for full review. The primary reason for exclusion was lack of protocol description, or lack of reporting on analgesic medications. No primary research studies specifically examined distress in the DCD eligible population. Numerous professional guidelines were identified. Surveys of critical care practitioners identified concerns regarding the impact of symptom management on hastening the dying process in the DCD population as a potential barrier to end-of-life palliative treatment. CONCLUSIONS: There is a paucity of empirical evidence for end-of-life symptom assessment and management for DCD patients. Key evidence gaps identified for DCD include the need for: i) a multidisciplinary structure of treatment teams and preferred environment for DCD, ii) objective tools for monitoring of distress in this patient population, and iii) evidence guiding the administration of analgesic medications following withdrawal of life sustaining therapy

Hepatotoxicity of a Cannabidiol-rich cannabis extract in the mouse model

© 2019 Xide Ye et al. Gastrodia elata Blume belongs to the Orchidaceae family. G. elata is often processed when used in traditional Chinese medicine (TCM). In the current study, a traditional processing method, known as Jianchang Bang, was applied. Steamed and dried (S&D) G. elata was processed with ginger juice for up to 5 days (GEP5D). An UHPLC-MS/MS combined with a chemometric method was developed for the analysis of processed G. elata along with the raw material as well as steamed and dried G. elata. As a result, the primary marker compounds were identified with the aid of TOF-MS and MS/MS analyses. Compared with the raw material of G. elata with GEP5D, three new parishin-type compounds were identified according to their retention time, accurate mass, and fragmentation patterns. The chromatographic peak areas for marker compounds, including S-(gastrodin)-glutathione, S-(4-hydroxybenzylamine)-glutathione, and parishin-type compounds, changed significantly. This result indicated that by applying the Jianchang Bang method, changes in chemical composition in G. elata contents were observed. The study also demonstrated that chemometric analysis is helpful in understanding the processing mechanism and will provide scientific support for the clinical application of G. elata

Safety and molecular-toxicological implications of cannabidiol-rich cannabis extract and methylsulfonylmethane co-administration

© 2020 by the authors. Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we investigated the interaction potential between the cannabidiol-rich cannabis extract (CRCE) and methylsulfonylmethane (MSM), a popular dietary supplement, in the mouse model. For this purpose, 8-week-old male C57BL6/J mice received MSM-containing water (80 mg/100 mL) ad libitum for 17 days. During the last three days of treatment, mice received three doses of CRCE administered in sesame oil via oral gavage (123 mg/kg/day). Administration of MSM alone did not result in any evidence of liver toxicity and did not induce expression of mouse cytochrome P450 (CYP) enzymes. Administration of CRCE did produce significant (p \u3c 0.05) increases in Cyp1a2, Cyp2b10, Cyp2c29, Cyp3a4, Cyp3a11, Cyp2c65, and Cyp2c66 messenger RNA, however, this effect was not amplified by MSM/CRCE cotreatment. Similarly, no evidence of liver toxicity was observed in MSM/CRCE dosed mice. In conclusion, short-term MSM/CRCE co-administration did not demonstrate any evidence of hepatotoxicity in the mouse model

Geodesic Paths On 3D Surfaces: Survey and Open Problems

This survey gives a brief overview of theoretically and practically relevant algorithms to compute geodesic paths and distances on three-dimensional surfaces. The survey focuses on polyhedral three-dimensional surfaces

False claims about false memory research

Pezdek and Lam [Pezdek, K. & Lam, S. (2007). What research paradigms have cognitive psychologists used to study “False memory,” and what are the implications of these choices? Consciousness and Cognition] claim that the majority of research into false memories has been misguided. Specifically, they charge that false memory scientists have been (1) misusing the term “false memory,” (2) relying on the wrong methodologies to study false memories, and (3) misapplying false memory research to real world situations. We review each of these claims and highlight the problems with them. We conclude that several types of false memory research have advanced our knowledge of autobiographical and recovered memories, and that future research will continue to make significant contributions to how we understand memory and memory errors

Decaffeinated green tea extract does not elicit hepatotoxic effects and modulates the gut microbiome in lean B6C3F\u3csub\u3e1\u3c/sub\u3e mice

© 2019 The Author(s) The aim of this study is the development of validated HPTLC method for the quantification of vitexin from Passiflora foetida commercial herbal formulations. The developed method was validated, in accordance with ICH guidelines for precision, accuracy, specificity and robustness. The plate was developed using ethyl acetate:methanol:water:formic acid 30:4:2:1(%, v/v/v/v) on 20 × 10 cm glass coated silica gel 60 F254 plates and the developed plate was scanned and quantified densitometrically at λ = 340 nm. Linear regression analysis revealed a good linear relationship between peak area and amount of vitexin in the range of 100–700 ng/spot. The amount of vitexin in nine commercial herbal formulations was successfully quantified by the developed HPTLC method. The developed and validated high performance thin layer chromatographic method offers a new sensitive and reliable tool for quantification of vitexinin in various herbal formulations containing Passiflora foetida

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets

Universal influenza vaccines should protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines, as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell-inducing nucleoside-modified messenger RNA (mRNA) vaccine that encodes the conserved nucleoprotein, matrix protein 1, and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naïve ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly reactive T cells in the circulation, bone marrow, and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with a potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins represent a promising strategy to induce broadly protective T cell immunity against influenza viruses.</p

Paradoxical patterns of sinusoidal obstruction syndrome-like liver injury in aged female CD-1 mice triggered by cannabidiol-rich cannabis extract and acetaminophen co-administration

© 2019 The Authors. Environmental Toxicology published by Wiley Periodicals, Inc. Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5-weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6-weeks. At the end of 6-weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE-RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α-smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase-1 and -2 (SOD-1 and SOD-2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling