Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus-United States, May 2013-August 2016.

November 11, 2016/65(44);1234-1237. What is already known about this topic? Candida auris is an emerging pathogenic fungus that has been reported from at least a dozen countries on four continents during 2009-2015. The organism is difficult to identify using traditional biochemical methods, some isolates have been found to be resistant to all three major classes of antifungal medications, and C. auris has caused health care-associated outbreaks. What is added by this report? This is the first description of C. auris cases in the United States. C. auris appears to have emerged in the United States only in the last few years, and U.S. isolates are related to isolates from South America and South Asia. Evidence from U.S. case investigations suggests likely transmission of the organism occurred in health care settings. What are the implications for public health practice? It is important that U.S. laboratories accurately identify C. auris and for health care facilities to implement recommended infection control practices to prevent the spread of C. auris. Local and state health departments and CDC should be notified of possible cases of C. auris and of isolates of C. haemulonii and Candida spp. that cannot be identified after routine testing.

Personality diatheses and Hurricane Sandy: effects on post-disaster depression.

BACKGROUND: According to diathesis-stress models, personality traits, such as negative emotionality (NE) and positive emotionality (PE), may moderate the effects of stressors on the development of depression. However, relatively little empirical research has directly examined whether NE and PE act as diatheses in the presence of stressful life events, and no research has examined whether they moderate the effect of disaster exposure on depressive symptoms. Hurricane Sandy, the second costliest hurricane in US history, offers a unique opportunity to address these gaps. METHOD: A total of 318 women completed measures of NE and PE 5 years prior to Hurricane Sandy. They were also assessed for lifetime depressive disorders on two occasions, the latter occurring an average of 1 year before the hurricane. Approximately 8 weeks after the disaster (mean = 8.40, s.d. = 1.48 weeks), participants completed a hurricane stress exposure questionnaire and a measure of current depressive symptoms. RESULTS: Adjusting for lifetime history of depressive disorders, higher levels of stress from Hurricane Sandy predicted elevated levels of depressive symptoms, but only in participants with high levels of NE or low levels of PE. CONCLUSIONS: These findings support the role of personality in the development of depression and suggest that personality traits can be useful in identifying those most vulnerable to major stressors, including natural disasters.

Multi-pathogen waterborne disease outbreak associated with a dinner cruise on Lake Michigan.

We report an outbreak associated with a dinner cruise on Lake Michigan. This took place on the same day as heavy rainfall, which resulted in 42·4 billion liters of rainwater and storm runoff containing highly diluted sewage being released into the lake. Of 72 cruise participants, 41 (57%) reported gastroenteritis. Stool specimens were positive for Shigella sonnei (n=3), Giardia (n=3), and Cryptosporidium (n=2). Ice consumption was associated with illness (risk ratio 2·2, P=0·011). S. sonnei was isolated from a swab obtained from the one of the boat's ice bins. Environmental inspection revealed conditions and equipment that could have contributed to lake water contaminating the hose used to load potable water onto the boat. Knowledge of water holding and distribution systems on boats, and of potential risks associated with flooding and the release of diluted sewage into large bodies of water, is crucial for public health guidance regarding recreational cruises.

Metabolism and disposition of [14C]dibromoacetonitrile in rats and mice following oral and intravenous administration.

1. Tissue distribution, metabolism, and disposition of oral (0.2-20 mg/kg) and intravenous (0.2 mg/kg) doses of [2-(14)C]dibromoacetonitrile (DBAN) were investigated in male rats and mice. 2. [(14)C]DBAN reacts rapidly with rat blood in vitro and binds covalently. Prior depletion of glutathione (GSH) markedly diminished loss of DBAN. Chemical reaction with GSH readily yielded glutathionylacetonitrile. 3. About 90% of the radioactivity from orally administered doses of [(14)C]DBAN was absorbed. After intravenous administration, 10% and 20% of the radioactivity was recovered in mouse and rat tissues, respectively, at 72 h. After oral dosing, three to four times less radioactivity was recovered, but radioactivity in stomach was mostly covalently bound. 4. Excretion of radioactivity into urine exceeded that in feces; 9-15% was exhaled as labeled carbon dioxide and 1-3% as volatiles in 72 h. 5. The major urinary metabolites were identified by liquid chromatography-mass spectrometry, and included acetonitrile mercaptoacetate (mouse), acetonitrile mercapturate, and cysteinylacetonitrile. 6.The primary mode of DBAN metabolism is via reaction with GSH, and covalent binding may be due to reaction with tissue sulphydryls.

[14C]bis(2-chloroethoxy)methane: comparative absorption, distribution, metabolism and excretion in rats and mice.

bis(2-Chloroethoxy)methane (BCM) is used primarily as a precursor in the synthesis of polysulfide elastomers. After administration of [(14)C]BCM, radioactivity is readily absorbed from the gastrointestinal tract and moderately absorbed through skin. Following absorption, BCM-derived radioactivity is rapidly distributed to all tissues, rapidly metabolized and excreted primarily in urine. Minimal effects of sex, species or dose in the range studied (0.1-10 mg kg(-1)) were observed on the fate of BCM in rats and mice after all routes of administration. The major metabolite (about 40% of the dose) of BCM in rat was isolated and identified as thiodiglycolic acid (TDGA) indicating that the ether linkage of BCM is cleaved to form 2-chloroethyl fragments that may be further metabolized to 2-chloracetaldehyde, conjugated with glutathione and the latter subsequently metabolized to TDGA. 2-chloroacetaldehyde has also been shown to be cardiotoxic, possibly accounting for BCM cardiotoxicity observed in repeated dose studies.

Metabolism and disposition of alpha-methylstyrene in rats.

alpha-Methylstyrene (AMS) is a volatile hydrocarbon used primarily in the production of specialty polymers and resins. In the present study, the tissue distribution, metabolism, and excretion of [(14)C]AMS was investigated in male rats after i.v. administration (11 mg/kg). Over 90% of AMS administered intravenously to rats was excreted in 72 h. Urinary excretion accounted for 86% of the administered dose, volatile breath and feces accounted for 2.2 and 1.9%, respectively, and elimination as carbon dioxide was negligible. Metabolites were isolated from rat urine following a high oral dose of AMS (1000 mg/kg) and characterized using gas chromatography/mass spectrometry and NMR spectrometry. The metabolites were 2-phenyl-1,2-propanediol (3% of urinary radioactivity) and its glucuronide (50%), atrolactic acid (27%), S-(2-hydroxy-2-phenylpropyl)-N-acetylcysteine (13%), and 2-phenylpropionic acid (1%); the glucuronides and mercapturates were each conjugated on the methylene carbon beta to the ring. The presence of both of the diastereomeric isomers of the mercapturates and of the glucuronides suggested that the initial epoxidation of AMS was not stereoselective and proceeded with addition of active oxygen to yield enantiomeric epoxides. Incubation of AMS with human liver slices produced the same metabolites as those excreted in rat urine, with 2-phenyl-1,2-propanediol present as the predominant metabolite after 5 h of incubation.

Semantic satiation and lexical ambiguity resolution.

This study examines the effects of semantic satiation on lexical ambiguity resolution. On a given trial, participants were presented with a word triad. The first word (e.g., HEART) was presented on average 2.5, 12.5, or 22.5 times, and then participants received 2 new words for relatedness judgments. The first of the two new words was always a homograph (e.g., "ORGAN") and the other word was a related or unrelated pairmate (e.g., "KIDNEY"). In Experiment 1, when blocks of trials were intermixed with concordant (e.g., "HEART-ORGAN-KIDNEY"), discordant (e.g., "PIANO-ORGAN-KIDNEY"), and neutral (e.g., "CEILING-ORGAN-KIDNEY") trials, participants did not produce evidence of semantic satiation. In a second experiment in which only concordant and neutral trials were presented, however, participants did produce evidence of semantic satiation in the concordant condition. Taken together, Experiments 1 and 2 indicate that semantic satiation of the context-appropriate meaning of a homograph may impede ambiguity resolution.

Metabolism and disposition of 4-t-butylcatechol in rats and mice.

4-t-Butylcatechol (TBC) is an antioxidant used primarily as a polymerization inhibitor for reactive monomers. Annual production and use of TBC in the United States is approximately 1.5 million pounds. The absorption, tissue distribution, metabolism, and excretion of [(14)C]TBC, labeled in the methine carbon, was investigated in male Fischer 344 rats and B6C3F(1) mice after i.v., oral, and dermal administration. Oral (2 and 200 mg/kg in rats; 3 and 300 mg/kg in mice) and dermal (0.6, 6, and 63 mg/kg in rats; 1.3 and 157 mg/kg in mice) doses of TBC were well absorbed, then rapidly metabolized and excreted primarily in urine. Dermal absorption of the highest dose in the rat (87% of the 63 mg/kg dose) was significantly higher than that of the two lower doses (0.6 and 6 mg/kg, 44 and 57%, respectively). Dermally administered TBC was also well absorbed in the mouse (72-86%). Polar metabolites of TBC comprise all of the radioactivity in the urine of both species after all routes of administration. These were shown to consist mostly of the sulfate conjugates (and lesser amounts of the glucuronides) of TBC and of a less polar metabolite. The deconjugated metabolite was isolated and determined by mass spectrometry and (1)H-NMR to be mono-O-methylated TBC.

The effect of repeat administration of GTS-21 on mixed-function oxidase activities in rat.

The effect of repeat administration of GTS-21 on hepatic microsomal enzymes was determined in rats administered the drug at levels of 3, 60 and 300 mg/kg/day for 7 days. Liver weight and cytochrome P450 (CYP) contents were not changed. Cytochrome b5 contents were increased at the mid and high doses of GTS-21, as the contents increased with increasing dose, but were unchanged at the low dose. Five selective activities of CYP isoforms, acetanilide hydroxylase (CYP1A2), tolbutamide hydroxylase (CYP2C6), dextromethorphan O-demethylase (CYP2D1), p-nitrophenol hydroxylase (CYP2E1) and erythromycin N-demethylase (CYP3A) were examined. Enzyme activities were changed only at the highest dose; the activity of CYP1A2 was increased by 71% and the activities of CYP2C6 and CYP2D1 were decreased by 37 and 19%, respectively. At low and mid doses of GTS-21, all activities were unchanged. These data indicate that GTS-21 is not a strong modulator of the mixed-function oxidase system.

Metabolism and disposition of GTS-21, a novel drug for Alzheimer's disease.

1. GTS-21, a novel drug for Alzheimer's disease, is currently under clinical development. In the current study, the metabolism and disposition of GTS-21 have been evaluated in rat and dog after single oral and intravenous administration. 2. Following oral administration of [14C]GTS-21 to rat, radioactivity was primarily excreted in the faeces (67%) via the bile with possible enterohepatic circulation. Urinary excretion of radioactivity in rat and dog was 20 and 19% respectively. 3. GTS-21 was rapidly and extensively absorbed after oral administration and rapidly cleared from plasma. The maximum concentration ratio of GTS-21 to total radioactivity in plasma was low, indicating first-pass or pre-systemic biotransformation. 4. In rat, GTS-21 showed linear pharmacokinetics over doses ranging from 1 to 10 mg/kg with an absolute bioavailability of 23%. In dog, the absolute bioavailability was 27% at an oral dose of 3 mg/kg. 5. GTS-21 was O-demethylated to yield compounds that were then subject to glucuronidation. Three of the metabolites in rat urine were isolated and characterized as 4-OH-GTS-21, 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. The major urinary metabolites were 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. 6. In vitro chemical inhibition of cytochrome P450 in human liver microsomes indicated that CYPIA2 and CYP2E1 were the isoforms primarily responsible for the O-demethylation of GTS-21, with some contribution from CYP3A.

Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration.

1. The disposition of 14C-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO2 (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.

Disposition of butanal oxime in rat following oral, intravenous and dermal administration.

1. The disposition of [1-14C]butanal oxime (BOX) was determined in the rat after oral, i.v. and dermal administration. 2. Oral doses of [14C]BOX (2 and 20 mg/kg) were predominantly excreted in the urine (> 42%) and converted to 14CO2 (> 30%) and about 10% of the dose remained in the tissues 72 h post-dosing. 3. Eight and 16% of a 2 and 20 mg/kg dermal dose of BOX, respectively, were absorbed, due in part to rapid volatilization from the surface of the skin. 4. Oral doses of BOX were transformed into several polar and/or anionic metabolites that include sulphate conjugates and a significant amount of thiocyanate. 5. The effect of inhibitors on the metabolism of BOX was investigated using 1-aminobenzotriazole (ABT; an inhibitor of diverse cytochrome P450s) and trans-1,2-dichloroethylene (DCE; an inhibitor of CYP2E1). No thiocyanate anion was detected in the urine of rat treated with DCE or ABT. ABT markedly increased the production of 14CO2 and excretion as volatile metabolites. DCE had no effect on 14CO2 excretion, but increased exhalation of radiolabel. ABT also effectively blocked the expression of toxic effects attributable to cyanide in rat given near-lethal doses of BOX. 6. The data are consistent with two distinct pathways of metabolism for BOX, (1) reduction to an imine, hydrolysis and subsequent conversion of butyraldehyde to 14CO2 and (2) CYP3A-catalysed dehydration of BOX to butyronitrile followed by CYP2E1-catalysed release of cyanide.

Selective inhibition of cytochrome P450 2E1 in vivo and in vitro with trans-1,2-dichloroethylene.

The effect of trans-1,2-dichloroethylene (DCE), an inhibitor of cytochrome P450 (P450) 2E1, on the catalytic activities and total content of hepatic P450 was determined in vivo and in vitro. Hepatic microsomes were prepared from groups of rats prior to dosing and at 2, 5, 12, and 24 h postdosing, and total P450 content and the activities of P450 1A2, P450 2A1, P450 2B, P450 2C6, P450 2C11, P450 2D1, P450 2E1, and P450 3A were determined. The lowest dose of DCE that yielded maximal inactivation of P450 2E1 was found to be 100 mg/kg. Significant decreases in total content of P450 or the activities of P450 1A2, P450 2A1, P450 2B, P450 2C6, P450 2C11, P450 2D1, and P450 3A were not observed during the 24 h following administration of DCE (100 mg/kg ip), but P450 2E1 activity was diminished about 65% at 2 and 5 h after DCE treatment and returned to control levels at 24 h. Additionally, there was little or no significant effect on the activities of hepatic cytosolic alcohol dehydrogenase or mitochondrial or microsomal aldehyde dehydrogenases 5 h postdosing. DCE showed the same selectivity for P450 inactivation in vitro, and P450 2E1 activity was inhibited by >80% without affecting the other isozymes. However, DCE (5 mM) also proved to be a good competitive inhibitor of the probe activities of P450 1A2 and P450 2C6. The in vivo inhibition of P450 2E1 was accompanied by decreases in the levels of the immunoreactive protein, and an additional immunoreactive band appeared at ca. 30 kDa in the Western blot of microsomes from DCE-treated rats, possibly arising from proteolytic degradation of P450 2E1 protein after covalent modification by the inhibitor. DCE is an effective, relatively nontoxic inhibitor of P450 2E1 in vivo and in vitro that has greater selectivity than other agents currently used.

Knemidocoptes sp. on wild passerines at the Mai Po Nature Reserve, Hong Kong.

Free-ranging passerine birds banded at the Mai Po Nature Reserve, Hong Kong, were affected with a skin disease characterized by crusty, proliferative lesions on legs, feet and beaks. Based on retrospective examination of 1990 to 1992 banding records, 83 of 16,353 birds and 5 of 161 species banded at Mai Po were identified as having these lesions. Eurasian tree sparrows (Passer montanus) were most commonly affected (58 of 411 birds) although 19 of 428 black-faced buntings (Emberiza pusilla), 3 of 92 spotted doves (Streptopelia chinensis), and 2 of 616 eastern great reed warblers (Acrocephalus orientalis) also had clinical signs of infestation. Adult Eurasian tree sparrows were affected more often than juveniles and males were affected more often than females. Lesions on juveniles usually were on the feet while on adults lesions also were found on legs and beak. The effects of this parasitic infestation on body weight of wild Eurasian tree sparrows was not significant.

Automatic and attentional priming in young and older adults: reevaluation of the two-process model.

Three experiments addressed the distinction between automatic and attentional mechanisms underlying semantic priming effects by factorially crossing prime-target relatedness, expectancy, and SOA in a task (pronunciation) that minimized postlexical checking processes. Also, possible age-related (young vs. older adults) differences in the automatic and attentional mechanisms were addressed. Across all experiments there was evidence of a Relatedness x Expectancy x SOA interaction, which is inconsistent with the notion of independent automatic and attentional mechanisms in semantic priming and the notion of a self-encapsulated modular lexicon. The results also indicated age-related differences in the build-up of the expectancy effect across SOAs when the prime was visually available for only 200 ms, independently of the prime-target SOA (Experiments 1 and 3), but not when the prime was visually available throughout the SOA (Experiment 2).

An epizootic of Mycoplasma ovipneumoniae infection in captive Dall's sheep (Ovis dalli dalli).

In late spring of 1986, 10 of 23 Dall's sheep (Ovis dalli dalli) at the Metropolitan Toronto Zoo were moved to a new exhibit, where all developed severe respiratory signs refractory to anthelmintic and antibiotic therapy. In July, two animals died with chronic active bronch-pneumonia, and a third was euthanized because of pneumonia several months later. Bacteria were not isolated from the lungs of the first, steptococci and Pasteurella hemolytica were isolated from the other two, respectively; Mycoplasma ovipneumoniae was isolated from both. Pulmonary lesions in all three sheep were consistent with Mycoplasma sp. infection. Nasal swabs of the remaining animals yielded no consistent bacterial isolates; however, four of eight sheep were positive for M. ovipneumoniae. Viral cultures yielded an as yet unidentified herpesvirus. Sheep in the original and new herds had no serologic titers to parainfluenza-3, equine viral rhinopneumonitis, or infectious bovine rhinotracheitis, and had variable titers against bovine respiratory syncytial virus. No titers against M. ovipneumoniae were present in 13 sheep still in the original exhibit, but titers varied from 1:32 to 1:256 in eight pneumonic sheep. Sera taken from three sheep before or early in the outbreak were all negative for antibody to M. ovipneumoniae. Two of the affected Dall's sheep had been in contact with domestic sheep in the winter of 1985-1986, and M. ovipneumoniae was subsequently cultured from the domestic flock. Exposure to a new pathogen, and environmental and social stress in a new exhibit may have resulted in this severe disease in Dall's sheep.