COVID-19 Infection: Implications for Perioperative and Critical Care Physicians.

Healthcare systems worldwide are responding to Coronavirus Disease 2019 (COVID-19), an emerging infectious syndrome caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. Patients with COVID-19 can progress from asymptomatic or mild illness to hypoxemic respiratory failure or multisystem organ failure, necessitating intubation and intensive care management. Healthcare providers, and particularly anesthesiologists, are at the frontline of this epidemic, and they need to be aware of the best available evidence to guide therapeutic management of patients with COVID-19 and to keep themselves safe while doing so. Here, the authors review COVID-19 pathogenesis, presentation, diagnosis, and potential therapeutics, with a focus on management of COVID-19-associated respiratory failure. The authors draw on literature from other viral epidemics, treatment of acute respiratory distress syndrome, and recent publications on COVID-19, as well as guidelines from major health organizations. This review provides a comprehensive summary of the evidence currently available to guide management of critically ill patients with COVID-19

The role of surface energetics in the mixing of powders

The mixing of powders is governed by the presence of interparticulate forces, which are dependent on the surface nature of powders. Surface energy, which provides a measure of the hydrophilic and hydrophobic nature of surfaces, was found to play a significant role in the behaviour of powders in mixes. Preliminary work involved the use of surface energetics to predict the spreading behaviour in binary mixes of iron oxide with three excipients; microcrystalline cellulose, magnesium stearate and titanium dioxide. Subsequent work was carried out on binary and tertiary mixes of an active compound, zamifenacin, with starch and/or lactose. The surface nature of the powders was determined using the Wilhelmy plate (DCA) technique, sessile drop technique (DAT), inverse gas chromatography (IGC) and triboelectric charging. These techniques (except for triboelectric charging) involve the use of non-polar and polar liquids to probe the surfaces of powders. Spreading coefficients determined from the DCA data, correctly predicted the spreading behaviour of powders in binary and tertiary systems of iron oxide, as confirmed by visual inspection and scanning electron microscopy of the mixes. The suitability of each technique in characterising surfaces of pharmaceutical powders was assessed and IGC was found to be superior to the DCA and DAT techniques since IGC relied on the direct interaction between the vapour probes and the powder surface. The interaction parameter (I) derived from IGC and the electrostatic charges developed on charging with stainless steel predicted that the interaction between zamifenacin and starch would be more favourable than between zamifenacin and lactose. These predictions were confirmed by homogeneity studies on binary and tertiary mixes of zamifenacin using high-pressure liquid chromatography and near-infrared spectroscopy (NIRS). NIRS was found to be a good alternative analytical technique for monitoring the mixing of powders, in particular the order of addition of excipients to zamifenacin

Myeloid cells and beyond: previously unidentified roles of colony stimulated factor 1 in neuroinflammation and 5-lipoxygenase in myelination

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. Importantly, it is an illness with unmet medical need. Although current therapeutics mitigate relapses, there is no treatment that halts the progression of MS. In order to develop improved medicines, we must better understand the disease and factors that drive it. Hence, the mouse model of MS, experimental autoimmune encephalomyelitis (EAE) has been employed in the field of neuroimmunology. In my thesis, I elucidate the roles of two myeloid cell-associated proteins in affecting EAE pathogenesis.In chapter 1, I review the current understanding of the role of myeloid cells in MS. In the healthy CNS, dendritic cells, granulocytes, tissue resident macrophages are present in small quantities. Importantly, microglia reside in the healthy CNS and continuously monitor the milieu. During inflammatory conditions, microglia become activated, and a host of other myeloid cells and lymphocytes infiltrate into the CNS and cause demyelination. Although lymphocytes are important, myeloid cells are an underappreciated component of MS disease which initiate and perpetuate the disease. Additionally, I review a few of the current MS therapeutics on the market, their targets, and their impact on myeloid cells. One target that has been studied for its therapeutic potential in MS treatment is CSF1R. PLX5622, a CSF1R antagonist, is known to deplete microglia. Microglial depletion has been previously proposed to be the cause of reduced EAE clinical symptoms that are detected in CSF1R-antagonized mice. In chapter 2, I show that PLX5622 formulated into rodent chow (PLX5622 diet; PD), in addition to ameliorating EAE clinical score, also increases infiltration into the CNS of PD mice. I determined that this was not due to changes in peripheral priming. Furthermore, although spinal cords were largely devoid of infiltration, cerebella showed increased infiltration in PD compared to CD mice. I propose that decreased incidence of ascending paralysis, a symptom associated with spinal cord demyelinating damage, is due to immune cell relocation to the cerebellum. Lastly, I explore possible mechanisms causing the observed relocation. An area of unmet therapeutic need is in developmental and adult myelination. In chapter 3, I explore the function of 5 lipoxygenase (5LO) in the healthy central nervous system (CNS). First, I show that 5LO, 5LO pathway, and 5LO’s enzymatic products, leukotrienes (LTs), are detected in development and adulthood in the CNS; this suggests that the 5LO pathway is present and active in healthy conditions. Due to the detection of the highest levels of 5LO pathway components being detected during developmental myelination, we investigate the connection between 5LO and the most dynamic cell type in the CNS, oligodendrocyte lineage cells (OLCs). Addition of leukotrienes onto differentiating oligodendrocyte progenitor cells in vitro promotes oligodendrocyte differentiation in my experiments, providing initial evidence of the link between LTs and OLCs. Next, in vivo experiments involving fate mapping of cells in the corpus callosum of 5LO global knockout mice and their littermate controls confirms that 5LO and LTs promote OLC differentiation. Lastly, pharmacological and genetic methods reveal that microglia are the primary expressors of 5LO and ostensibly, LTs

Euglena gracilis growth and cell composition under different temperature, light and trophic conditions

BackgroundEuglena gracilis, a photosynthetic protist, produces protein, unsaturated fatty acids, wax esters, and a unique β-1,3-glucan called paramylon, along with other valuable compounds. The cell composition of E. gracilis was investigated in this study to understand how light and organic carbon (photo-, mixo- and heterotrophic conditions) affected growth and cell composition (especially lipids). Comparisons were primarily carried out in cultures grown at 23 °C, but the effect of growth at higher temperatures (27 or 30 °C) was also considered.Cell growthSpecific growth rates were slightly lower when E. gracilis was grown on glucose in either heterotrophic or mixotrophic conditions than when grown photoautotrophically, although the duration of exponential growth was longer. Temperature determined the rate of exponential growth in all cultures, but not the linear growth rate during light-limited growth in phototrophic conditions. Temperature had less effect on cell composition.Cell compositionAlthough E. gracilis was not expected to store large amounts of paramylon when grown phototrophically, we observed that phototrophic cells could contain up to 50% paramylon. These cells contained up to 33% protein and less than 20% lipophilic compounds, as expected. The biomass contained about 8% fatty acids (measured as fatty acid methyl esters), most of which were unsaturated. The fatty acid content of cells grown in mixotrophic conditions was similar to that observed in phototrophic cells, but was lower in cells grown heterotrophically. Heterotrophic cells contained less unsaturated fatty acids than phototrophic or mixotrophic cells. α-Linolenic acid was present at 5 to 18 mg g-1 dry biomass in cells grown in the presence of light, but at [less than] 0.5 mg g-1 biomass in cells grown in the dark. Eicosapentaenoic and docosahexaenoic acids were detected at 1 to 5 mg g-1 biomass. Light was also important for the production of vitamin E and phytol

1,10-Phenanthrolin-1-ium hydrogen (S,S)-tartrate trihydrate and a correction

The title structure, C12H9N2 +·C4H5O6 −·3H2O, shows that one of the protons of d-tartaric acid has been transferred to 1,10-phenanthroline. The d-hydrogen tartrate anions are joined together in a head-to-tail fashion via a short hydrogen bond with donor–acceptor distance of 2.4554 (12) Å, unsymmetrical O—H distances of 1.01 (4) Å and 1.45 (4) Å, and a 174 (4)° O—H—O bond angle. The phenanthrolinium rings are π-stacked with an average separation of 3.58 (11) Å. The structural report corrects a previous report in the literature [Wang et al. (2006 ▶). Acta Cryst. E62, o2508–o2509] of the isostructural l-hydrogen tartrate enanti­omer in which the proton transfer and short hydrogen bond were missed

Alcohol Use, Abuse, and Dependency in Shanghai

The use of alcohol for social and ceremonial occasions was recorded in Chinese history as early as 1760 B.C. during the Yin Dynasty (Ci-Hai Encyclopedia, 1979:936). The cultural tradition of ancient China placed alcoholic beverages at the center of social occasions, which presumably was the origin of the adage: Without wine, there is no li (or etiquette). Thus, the use of alcoholic beverages has always been accompanied by the concept of propriety and the discharging of one\u27s role obligations m social functions, rather than that of personal indulgence