Emergency Department Management of the Covid-19 Pandemic.

BACKGROUND: Emergency departments (EDs) need to be prepared to manage crises and disasters in both the short term and the long term. The coronavirus disease 2019 (COVID-19) pandemic has necessitated a rapid overhaul of several aspects of ED operations in preparation for a sustained response. OBJECTIVE: We present the management of the COVID-19 crisis in 3 EDs (1 large academic site and 2 community sites) within the same health care system. DISCUSSION: Aspects of ED throughput, including patient screening, patient room placement, and disposition are reviewed, along with departmental communication procedures and staffing models. Visitor policies are also discussed. Special considerations are given to airway management and the care of psychiatric patients. Brief guidance around the use of personal protective equipment is also included. CONCLUSIONS: A crisis like the COVID-19 pandemic requires careful planning to facilitate urgent restructuring of many aspects of an ED. By sharing our departments' responses to the COVID-19 pandemic, we hope other departments can better prepare for this crisis and the next.

Motivated forgetting mediated by implicit verbal chaining: a laboratory analog of repression.

After learning an A-B paired-associates list, college students read a list of D words, several of which were consistently accompanied by unavoidable electric shock. The D words were members of implicit B-C, C-D chains, inferred from published word-association norms. In a subsequent recall test of the original A-B list, the B words that were implicitly associated with the shocked D words were forgotten significantly more often than control words.

One world of veterinary medicine.

The veterinary profession finds itself in the midst of a new world order. Today veterinarians are part of a world that is exquisitely interconnected culturally, economically, socially, and professionally. As a consequence, societal needs and expectations of the profession are more demanding, critical and far-reaching. Veterinarians must play important roles in five intersecting domains of work: public health, bio-medical research, global food safety and security, ecosystem health and the more traditional role of caring for animals. To be successful in this broad and complex range of services and activities, veterinarians must possess an expanded knowledge base, acquire new skills, and develop a new mindset that will ensure their success and excellence in all these domains. The veterinary profession is becoming more fragmented and specialised, and it needs to be brought back together by a single sphere of knowledge or discipline that can serve as an intellectual foundation. The concept of One World of Veterinary Medicine can do just that. With this mindset veterinarians will become better connected to the world around and gain new public recognition and esteem. To achieve this, a special commitment by academic veterinary medicine is, of course, essential. Veterinary schools must lead an educational transformation that reaffirms the social contract of veterinarians and works to align diverse sectors, build a global community, find a common purpose and expand the 21st Century veterinary portfolio of services, activities, and new possibilities.

The depressine Syndrome: a follow-up study of 130 professionals working overseas.

A four-year follow-up of professional personnel who had been working overseas indicates that the depressive syndrome was the most common diagnosable psychiatric illness in this population. The study also shows that in this content the syndrome had a good prognosis. It therefore seems reasonable not to exclude persons with diagnosable depression from assignment abroad but, rather, to identify the syndrome and recommend necessary treatment.

Orally active central dopamine and serotonin receptor ligands: 5-, 6-, 7-, and 8-[[trifluoromethyl)sulfonyl]oxy]-2-(di-n-propylamino)tetralins and the formation of active metabolites in vivo.

The racemic triflate derivatives 5-8 of the 5-, 6-, 7-, and 8-hydroxylated 2-(di-n-propylamino)-teralins 1-4 were shown to possess similar pharmacological profiles to their phenolic counterparts in in vitro binding and in vivo biochemical and behavioral assays in rats. Consequently, subcutaneous administration of the 5-, 6-, and 7-triflates displayed essentially dopaminergic agonist properties, while the 8-triflate was shown to be a selective 5-HT1A receptor agonist. With respect to their agonist activities, the triflates were less potent than their phenolic analogs. The absolute oral bioavailability of compound 8 (8-triflate) was 4-5 times greater than the corresponding hydroxylated compound. Interestingly, in the in vivo biochemical assay compound 8 was found to be more potent after oral than after subcutaneous administration, indicating formation of one or more active metabolites. Following a study of the metabolism of compound 8 in rat hepatocytes, the monopropyl analog 9 was identified as the major metabolite and was surprisingly found to be more potent than compound 8. Oral administration of compound 5 (5-triflate) resulted in behavioral and biochemical effects indicative of mixed DA/5-HT1A agonist properties not seen after subcutaneous administration. These results may also be indicative of the formation of active metabolites.

Synthesis and evaluation of pharmacological and pharmacokinetic properties of monopropyl analogs of 5-, 7-, and 8-[[(trifluoromethyl)sulfonyl]oxy]-2-aminotetralins: central dopamine and serotonin receptor activity.

In order to explore further the structure-activity relationships of serotonergic and dopaminergic ligands, a series of enantiopure 5-, 7-, or 8-triflate (-OTf)-substituted 2-(monopropylamino)-tetralins have been synthesized and evaluated in in vitro binding and in vivo biochemical and behavioral assays in rats. Consequently, the 8-OTf-substituted compound R-(+)-6 was found to be a potent and selective 5-HT1A (5-hydroxytryptamine) receptor agonist inducing a full-blown 5-HT syndrome in normal rats, while the corresponding 5-OTf-substituted compound S-(-)-12 was found to be a preferential dopamine (DA) autoreceptor agonist. A partial 5-HT syndrome was also observed for S-(-)-12, while the corresponding R-(+)-12 was found to be inactive at the DA and 5-HT receptors both in vitro and in vivo. Compounds 6 and 12 were found to be major urinary metabolites following oral administration of their dipropyl analogs (2 and 13, respectively). Thus 6 was proposed to be the metabolite responsible for the full-blown 5-HT syndrome seen after oral (but not subcutaneous) administration of 2. Similarly, 12 was proposed to be the metabolite responsible for the partial 5-HT syndrome seen after oral (but not subcutaneous) administration of 13. The bioavailability of R-(+)-6 (7.6 +/- 1.1%) appeared to be slightly lower than that of 2 (11.2 +/- 5.2%), although the in vitro metabolism of R-(+)-6 appeared to be slower than that of 2. Therefore first-pass metabolism was not thought to be the reason for the lower bioavailability of R-(+)-6, as compared to 2.

The mechanism of the suicidal, reductive inactivation of microsomal cytochrome P-450 by carbon tetrachloride.

1. Stoichiometric losses of microsomal haem and cytochrome P-450 were observed when carbon tetrachloride (CCl4) was incubated anaerobically with rat liver microsomes using NADPH or sodium dithionite as a reducing agent. A rapid destruction of haem was also observed during the non-enzymatic reductive incubation of CCl4 with soluble haem preparations (methaemalbumin) in presence of sodium dithionite. The results indicate that haem is both the site and the target of the suicidal activation of CCl4 by cytochrome P-450. 2. When an additional, fluorimetric assay for haem determination was used, an equimolar loss of protoporphyrin IX fluorescence was also observed in both the enzymatic and non-enzymatic system, indicating that the haem moiety of cytochrome P-450 has undergone a structural change, involving either loss or labilization of the porphyrin tetrapyrrolic structure. In both systems the loss of porphyrin was prevented by carbon monoxide (CO). 3. A dichlorocarbene-cytochrome P-450 ligand complex is partially responsible for the difference spectrum obtained on addition of CCl4 to anaerobically reduced rat liver microsomes. A molar extinction coefficient for this complex has been calculated. The carbene trapping agent 2,3-dimethyl-2-butene (DMB) strongly inhibited (greater than 95%) the formation of this spectrum but did not modify the loss of haem in reduced CCl4-supplemented microsomal incubations. The results suggest that dichlorocarbene (:CCl2) is not significantly involved in CCl4-dependent haem destruction. 4. Pretreatment of rats with different microsomal enzyme inducers was responsible for similar but not identical patterns of :CCl2 and CO formation and haem loss during incubation of CCl4 with reduced microsomes. This indicates a critical role of CCl4 metabolism in the suicidal destruction of cytochrome P-450 haem and suggests that the apoprotein of cytochrome P-450 is capable of modulating not only the metabolism of CCl4 to :CCl2 but also the hydrolysis of :CCl2 to CO. 5. Inactivation of cytochrome P-450 by CCl4 with reduced microsomes from Aroclor-pretreated rats was saturable and followed pseudo first-order kinetics. This provides further evidence to conclude that CCl4 activation is a suicidal process where the reactive metabolite(s) formed bind to haem, we predict, in a one to one stoichiometry. 6. The partition ratio between loss of cytochrome P-450 haem and CCl4 metabolism by liver microsomes from Aroclor pretreated rats has been investigated using limiting concentrations of CCl4. It was calculated that approximately 26 molecules of CCl4 had to be metabolised to achieve the loss of one molecule of haem.

Solubilisation, purification and reconstitution of hepatic microsomal azoreductase activity.

Microsomal NADPH-cytochrome c (P-450) reductase and cytochrome P-450 were purified from the livers of phenobarbitone-treated rats. Purified NADPH-cytochrome c (P-450) reductase effected the NADPH-dependent reduction of FMN and FAD under anaerobic conditions in a non-enzymic manner, but was unable to reduce directly the azo dye, amaranth. In the presence of FMN, the purified reductase effected reduction of amaranth through the production of reduced FMN. Incorporation of NADPH-cytochrome c (P-450) reductase into the microsomal fraction increased the azoreductase activity of liver preparations from phenobarbitone-treated rats, but had no effect on azoreductase activity in preparations from control animals. Azoreductase activity was reconstituted into dilauroyl phosphatidylcholine vesicles containing purified cytochrome P-450 and purified NADPH-cytochrome c (P-450) reductase. In the absence of supplementary FMN, amaranth reduction was completely dependent upon all three components, but in the presence of FMN, the omission of any one component failed to abolish completely azoreductase activity.

Possible role of intracellular Ca2+ in the toxicity of phenformin.

Selective use of various mitochondrial Ca2+ transport inhibitors indicated that significant Ca2+ redistribution may occur during the isolation of mitochondria. Exposure of guinea-pig liver mitochondria to phenformin (beta-phenethylbiguanide) during the isolation procedure resulted in decreased mitochondrial Ca2+. Novel isolation conditions were developed to determine liver mitochondrial calcium content considered to reflect that in vivo. Administration of phenformin to rats and guinea-pigs resulted in decreased mitochondrial Ca2+. Decreased liver mitochondrial Ca2+ correlated inversely with raised blood lactate concentrations in the guinea-pig; 2-oxoglutarate, but not succinate oxidation, was inhibited in these mitochondrial preparations. A mechanism of action for phenformin-associated lactic-acidosis, attributable to impaired mitochondrial function arising from inactivation of Ca2+-sensitive, NAD+-dependent mitochondrial dehydrogenases (e.g. 2-oxoglutarate dehydrogenase) due to alteration in mitochondrial calcium content, is proposed.

The mechanism of reductive dehalogenation of halothane by liver cytochrome P450.

The reductive dehalogenation of halothane leading to 2-chloro-1,1,1-trifluoroethane (CTE) and 2-chloro-1,1-difluoroethylene (CDE) has been investigated in vitro using at liver microsomes under anaerobic conditions. The stimulation of NADPH oxidation by halothane as well as the formation of the products were dependent upon cytochrome P450 as indicated by their CO and metyrapone inhibition. After replacement of NADPH by sodium dithionite as a reducing agent CDE was the only product of the enzymatic reaction. The product pattern was influenced by pretreatment with 3-methylcholanthrene, benzo(a)pyrene, phenobarbitone and Arochlor 1254 and by addition of anti-cytochrome P450-PB immunoglobulin. The CTE:CDE ratio was shifted by addition or inhibition of cytochrome b5 and by pH variation indicating a crucial role of the second electron donation to cytochrome P450 in determining the product pattern. The intermediate complex of cytochrome P450 with a Soret band at 470 nm formed with halothane in reduced liver microsomes was shown to decompose spontaneously to give CDE. Therefore we propose the 470 nm peak to represent a cytochrome P450 Fe3+----CHCl-CF3 carbanion complex. From these results a reaction pathway could be derived which includes radical and carbanion intermediates as reactive precursors of CTE and CDE, respectively.

The mechanism of action of phenformin in starved rats.

The ability of phenformin to lower the blood glucose concentration after an intraperitoneal glucose load, with a concomitant increase in blood lactate concentration, indicated that the drug was increasing the rate of anaerobic glycolysis. The results of experiments in which glucose and gluconeogenic precursors were given to starved rats were explained by a hypothesis for the mechanism of action of phenformin involving inhibition of certain NAD+-dependent dehydrogenases. Substrates with NAD+-linked oxidations could be discriminated from those, like succinate, with FAD-linked oxidations, and succinate may be of use in the treatment of clinical lacticacidosis caused by biguanide drugs.

Loss of the N-myc oncogene in a patient with a small interstitial deletion of the short arm of chromosome 2.

To our knowledge, only four previous cases of distal chromosome 2p deletions exist in the literature. We present a patient with minor facial anomalies who had a distal interstitial deletion of the short arm of chromosome 2, del(2)(p24.2p25.1). This patient had many features seen in other patients with distal 2p deletion including short stature, "rectangular" facies, microcephaly, hypotonia, and mental retardation. This patient also has sensorineural hearing loss which has been described in one other patient with a similar deletion. The N-myc oncogene has been mapped to 2p24. By fluorescence in situ hybridization using a cDNA probe for the N-myc oncogene, this patient was found to have a deletion of the N-myc oncogene. This confirms the previous map location for N-myc.

Biotransformation of genistein in the rat: elucidation of metabolite structure by product ion mass fragmentology.

Biotransformation of the phytoestrogen [14C]genistein was investigated in male and female rats by application of narrow-bore radio-HPLC-MSn (LCQ, Finnigan) to determine intermediates in metabolism. Urine contained five metabolites, Gm1-Gm5, 24 h after dosing by gavage with [14C]genistein (4 mg kg(-1)). Structural analysis following ESI revealed molecular ions [M+H]+ of m/z 447, 449, 273, and 271 for metabolites Gm2, Gm3, Gm5 and genistein, respectively and an [M-H]- of m/z 349 for Gm4. Metabolite structure was deduced by evaluation of product ion spectra derived from unlabelled and [14C]-labelled ions and sensitivity to treatment with beta-glucuronidase. These studies indicated identity of metabolites with genistein glucuronide (Gm2), dihydrogenistein glucuronide (Gm3), genistein sulphate (Gm4) and dihydrogenistein (Gm5). Detection of the beta-glucuronidase resistant major metabolite Gm1 by ESI was poor and so was analysed by negative ion APCI; this revealed a deprotonated molecular ion of m/z 165 which had chromatographic and mass spectral properties consistent with authentic 4-hydroxyphenyl-2-propionic acid, a novel metabolite of genistein. In vitro metabolism studies with anaerobic caecal cultures derived from male and female rats revealed metabolism of genistein to Gm1 via Gm5 and an additional metabolite (Gm6) which was identified from product ion spectra as 6'-hydroxy-O-desmethylangolensin. Biotransformation of genistein by both isolated hepatocytes and precision-cut liver slices was limited to glucuronidation of parent compound. Commonality of genistein metabolites found in rats with those reported in man suggest similar pathways of biotransformation, primarily involving gut micro-flora.

Appropriateness of drugs prescribed by primary care physicians for depressed outpatients.

In a sample of middle class individuals seeking martial and sexual counseling, 30% had diagnosable psychiatric illness, including 14% who had depressions at the time of interview. Those with psychiatric syndromes were significantly more likely to have prescribed psychoactive than those without these syndromes. Those with depression were more likely to have received diazepam and similar drugs than antidepressants. The same was true for those with other syndromes but in many of these cases, diazepam or other antianxiety agents seemed more appropriate. Thus, affective disorder might well be the psychiatric syndrome for which these drugs are most often inappropriately prescribed. Inappropriate treatment is a matter of concern in an illness which is potentially fatal.

The effect of sodium aurothiomalate (myochrysin) on the distribution of calcium, magnesium, copper, zinc and iron in the rat.

Sodium aurothiomalate was given to male Wistar rats (initial body weights: 150 g) by subcutaneous (s.c.) injection at doses of up to 7.5 mg/kg (corresponding to 4.27 mg gold/kg), twice a week, for 4-5 weeks. The concentrations of Ca, Mg, Fe, Cu and Zn were measured in serum, urine, faeces and in the liver, kidney, spleen, heart, lung, testis, bone and muscle. Kidney cytosol was separated by gel chromatography and the fractions analysed for protein, copper, zinc, iron and gold concentrations. The concentration of copper was increased 5-fold in kidney while smaller increases of zinc in kidney, copper in muscle, iron in muscle and testis and calcium in spleen were found. There was a significant reduction in the concentration of copper in serum. Kidney cytosol from gold-treated but not from control animals contained a low molecular weight protein which was associated with copper, zinc and gold. The rats developed proteinuria and microscopic changes to renal tubular cell structure were also observed. It is suggested that the gold-induced accumulation of copper may follow from an increased rate of synthesis of metallothionein and could be responsible for the renal dysfunction which develops in a proportion of rheumatoid arthritis patients who are treated with gold.

The effect of chronic parenteral administration of cadmium on isoenzyme levels of alkaline phosphate in intestinal mucosa.

Chronic administration of cadmium chloride to rats (13.3 mumol/kg body wt per dose subcutaneously) produced a decrease in the activity of alkaline phosphatase in the intestinal mucosa to less than half that in control rats by the time cumulative doses of between 30 and 48 mumol had been administered. The reduced level of activity remained approximately steady following further dosing. Three isoenzymes of intestinal alkaline phosphatase were separated electrophoretically. Chronic cadmium treatment markedly decreased the proportion of the 2 isoenzymes with lower electrophoretic mobility. Some analogies are drawn between the effect of cadmium administration, and magnesium deficiency on changes in intestinal alkaline phosphatase.

Spontaneous development of fatty liver in ferrets in a toxicology study.

Ferrets were maintained for 12 months on different diets (A, meat and biscuit; B, all meat; C, meat and fish; D, high fibre) to ascertain the cause of spontaneous development of fatty liver. High hepatic triglyceride contents resulted on diets B = C > D; whereas ferrets on diet A (control) showed no accumulation of lipid in liver. Serum triglyceride and total cholesterol were unchanged by diet. These ferrets (F0 generation) were mated with ferrets on the same diet and the offspring (F1 generation), maintained on the same diets as the parents, were killed at 12 months and the livers studied similarly. Histology showed that hepatic lipid accumulation in the F1 generation was identical with that in the same dietary groups of the F0 generation; liver glutathione (GSH) reductase and thiobarbituric acid-reacting substances (an index of lipid peroxidation) were increased in ferrets maintained on diets B, C and D, liver GSH concentration and GSH peroxidase activities were unchanged. Other ferrets fed a high-fat diet (diet A plus 20% w/w beef suet) for 18 days exhibited hepatic lipid accumulation and decreased hepatic cyanide-insensitive palmitoyl CoA oxidation (-30%), but hepatic lauric acid hydroxylation and carnitine acyl transferase activities were unchanged. These data indicate that ferrets on high-fat diets show no increased rates of liver fatty acid oxidation, as seen in rats, but instead accumulate triglyceride in the liver with some degree of lipid peroxidation.

The influence of high dietary zinc on tissue disposition and urinary excretion of cadmium, zinc, copper and iron after repeated parenteral administration of cadmium to rats.

The administration of a high dietary supplement of zinc sulphate (2000 ppm) to rats for 28 days produced no effect upon growth rate of the animals but caused in increased food intake. The supplement had no effect upon the reduction of growth rate caused by the daily injection of cadmium chloride (1.5 mg/kg). Zinc-supplemented animals showed an increased accumulation of zinc in the liver and kidney, plasma zinc levels were significantly increased and there was an elevated excretion of zinc in the urine compared to control animals. Cadmium-treated, zinc-supplemented animals had a higher concentration of cadmium in the liver compared to animals treated only with cadmium. The high dietary zinc did not interfere with tissue or plasma concentration of copper and iron, nor did it influence the cadmium-induced changes in these metals. There was some indication however of a decreased urinary excretion of copper.

Effects of acute and sub-chronic administration of iron nitrilotriacetate in the rat.

Parenteral administration of iron nitrilotriacetate (FeNTA) to rats resulted in marked loss in body weight, and increases in liver/and kidney/body weight ratios. Fatalities, due to renal failure, depended on dosage and age of the animals, and were greater (70%) after a single large dose (12 mg iron) than after repeated smaller doses (30%). FeNTA administered subchronically gave rise to an increase in ethane exhalation, and to decreased liver glutathione peroxidase activity, and decreased cytochrome P-450 concentration and benzphetamine N-demethylase activity. It also resulted in severe renal tubular necrosis, with deposition of iron in the tubular cells and loss of brush border alkaline phosphatase activity, resulting in a dose-dependent diuresis, with increased urinary excretion of glucose, iron and lipid peroxidation products, and decreased urine creatinine concentration. NTA alone had none of these effects but slightly decreased the hepatic concentration of iron.