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.

Intention to comply with post-exposure management among nurses exposed to blood and body fluids in Taiwan: application of the theory of planned behaviour.

Nurses are at significant risk from occupationally acquired bloodborne virus infections following a needlestick and sharps injury. This study aimed to apply the theory of planned behaviour (TPB) to predict nurses' intention to comply with occupational post-exposure management. A cross-sectional survey was applied to select registered nurses who worked in human immunodeficiency virus (HIV)-designated hospitals. An anonymous, self-administered questionnaire based on the TPB was distributed to 1630 nurses and 1134 (69.5%) questionnaires were returned. From these, a total of 802 nurses (71%) reported blood and body fluid exposure incidents during 2003-2005 and this group was used for analysis. Only 44.6% of the 121 exposed nurses who were prescribed post-exposure prophylaxis (PEP) by infectious disease doctors returned to the clinic for interim monitoring, and only 56.6% of exposed nurses confirmed their final serology status. Structural equation modelling was used to test the TPB indicating perceived behavioural control (the perception of the difficulty or ease of PEP management, ß=0.58), subjective norm (the perception of social pressure to adhere to PEP, ß=0.15), and attitudes (ß=0.12) were significant direct effects on nurses' intention to comply with post-exposure management. The hypothesised model test indicated that the model fitted with the expected relationships and directions of theoretical constructs [χ(2) (14, N=802)=23.14, P=0.057, GFI=0.987, RMSEA=0.039]. The TPB model constructs accounted for 54% of the variance in nurses' intention to comply with post-exposure management. The TPB is an appropriate model for predicting nurses' intention to comply with post-exposure management. Healthcare facilities should have policies to decrease the inconvenience of follow-up to encourage nurses to comply with post-exposure management.

Effects of caponization and different forms of exogenous androgen implantation on immunity in male chicks.

This study determined the caponization effects on the immune responses in male chicks. Different forms of exogenous androgen implantation on male chick immunity were compared. Healthy, uniform male Single Comb White Leghorn chicks were caponized at 3 wk of age. Birds were housed in individual cages (35 x 30 x 40 cm, length x width x height). Each of 27 sham-operated (sham) and caponized (capon) male chickens were used for trial 1. Trial 2 used 60 capons divided into 4 treatments with implants of either 1 mm i.d. x 3 mm o.d. 58 mg of cholesterol, testosterone (TES), 5alpha-dihydrotestosterone (5alpha-DHT), or 19-nortestosterone (19-NorT). The exogenous androgen was implanted immediately after caponization and resupplied every 4 wk for an entire 13-wk feeding trial. The results from trial 1 showed that the relative bursa weight increased compared with the sham treatment (P < 0.05). The 2 wk post-Newcastle disease virus titer and the delayed-type hypersensitivity (DTH) of 48 h post-phytohemagglutinin phosphate (PHA-P) injection were increased compared with the sham treatment (P < 0.05). In trial 2, implanted 5alpha-DHT and 19-NorT could decrease the relative bursa weight in capons (P < 0.05). The 2 wk post-Newcastle disease virus titer in the 5alpha-DHT group was higher than that in the cholesterol group (P < 0.05). The 19-NorT group had the highest (P < 0.05) PHA-P response. Peripheral blood lymphocyte subset population analysis revealed that the percentage of CD4 T cells in the TES group was lower (P < 0.05) compared with that of the 5alpha-DHT group. Differently, the percentage of CD8 T cells in the TES and 19-NorT groups was higher (P < 0.05) than that in the 5alpha-DHT group. Male chicks that were caponized had increased bursa weight and PHA-P response, whereas different forms of exogenous androgen implantation reverted the phenomena in an order of potency of 5alpha-DHT and 19-NorT > TES, and the PHA-P response was TES > 5alpha-DHT >19-NorT.

A modified mini nutritional assessment without BMI predicts nutritional status of community-living elderly in Taiwan.

OBJECTIVE: The study was to determine whether a modified MNA (Mini Nutritional Assessment) which adopted population-specific anthropometric cut-points but without BMI could maintain its predicting ability in community-living elderly in Taiwan. DESIGN: Purposive sampling. SETTING: Community-living elderly. PARTICIPANTS: Three hundred and one (138 male and 163 female) > 65-year-old outpatients seeking free annual health examination at an area hospital in central Taiwan. MEASUREMENTS: A structured questionnaire elicited personal data, lifestyle information and answers to the MNA. Laboratory results from health checkup provided the needed biochemical data. Each subject's nutritional status was assessed with the MNA in three versions: the original, the MNA-TI (with population-specific cut-points), and the MNA-TII (further eliminated the BMI question and redistributed its score to the MAC and CC questions). RESULTS: All three versions identified the same 0.7% elderly malnourished. The proportions predicted at risk of malnutrition were 16.6, 12.0 and 10% according to the original, MNA-TI and MNA-TII, respectively. Friedman Test and post hoc analysis indicated that the pattern predicted by the original MNA was different from that predicted by the two modified versions whereas the patterns predicted by the two modified versions were not different from each other. CONCLUSION: Adoption of population-specific anthropometric cut-points improves the predicting ability of the MNA in Taiwanese elderly, and the improved functionality is maintained in a version without BMI (but with adjusted MAC and CC scores). A MNA without BMI has greater applicability and can enhance professional efficiency of healthcare workers.

Effects of caponization and testosterone implantation on immunity in male chickens.

This study examined the effects of caponization using different doses of testosterone (TES) on sexuality, hematology, and immune responses in male chickens. Healthy male chickens were caponized at 12 wk of age and selected at 16 wk of age for a 10-wk experiment. Fifteen intact male and 15 caponized male chickens were assigned to trial 1. In trial 2, ten sham-operated male chickens (sham) and 40 capons (randomly divided into 4 treatments) were implanted with cholesterol (CHOL, 9.24+/-0.36 mg), low TES (5.88+/-0.23 mg), medium TES (9.81+/-0.17 mg), or high TES (16.7+/-0.24 mg) administered at 16, 20, and 24 wk of age. Results from trial 1 showed caponization decreased the comb length, height and weight, and hematocrit (P<0.05) and increased the hemagglutination inhibition (HI; 1 wk postchallenge) and hemagglutination titer after Newcastle disease virus (NDV) and SRBC injections (P<0.05). In trial 2, the medium TES increased the comb length and height as compared with the CHOL group. Only the high TES increased the comb weight (P<0.05). The HI titer (1 wk postchallenge) in the CHOL group was higher than the sham (P<0.05). The medium TES decreased the HI titer (P<0.05) to the level of the sham (P>0.05). The phytohemagglutinin response was higher in the high TES group 24 h postinjection (P<0.05) and in the medium TES 48 h postinjection (P<0.05) as compared with the CHOL group. High dose TES implantation decreased the white blood cell counts as compared with the CHOL and sham groups (P<0.05). It appears that caponization decreased the blood androgen concentration and enhanced the humoral (anti-NDV and anti-SRBC) immune response. Testosterone implantation up to a threshold concentration could inhibit the humoral (anti-NDV) immune response and increase the cell-mediated (phytohemagglutinin) immune response.

Clinicopathological significance of survivin expression in patients with hepatocellular carcinoma.

AIMS: Survivin, a newly discovered member of the inhibitor of apoptosis protein family, is suggested to be involved in liver carcinogenesis. The aim was to investigate the clinical significance of survivin expression in resected hepatocellular carcinoma (HCC) and paired adjacent non-tumour tissue. METHODS AND RESULTS: Immunohistochemistry, reverse transcriptase-polymerase chain reaction and Western blots were used to examine survivin mRNA and protein levels in 94 specimens of HCC tissues at different TNM stages and the data were correlated with the clinicopathological profiles. Patients were categorized into those with high tumour survivin protein levels (T-N >or= -1) and those with low levels (T-N < -1). Follow-up data were collected prospectively. mRNA levels of survivin and its splice variants in tumour tissue were significantly higher than in paired non-tumour tissue. However, survivin protein levels in paired non-tumour tissue were significantly higher than in tumour tissue from all three TNM stages. Additionally, high tumour survivin protein levels (T-N >or= -1) correlated with a better prognosis and low levels (T-N < -1) with a worse survival rate. CONCLUSIONS: High cytoplasmic survivin protein levels in HCC tissues seem to be an indicator of better prognosis in HCC patients after resection.

Effects of caponization and different exogenous androgen on the bone characteristics of male chickens.

The effects of caponization and androgen implantation on the bone characteristics of male chickens were evaluated. Healthy Single Comb White Leghorn cockerels were caponized or sham operated (sham) at 12 wk old. Sixteen birds from each group were selected for a 14-wk experiment in trial 1. Sixteen birds from the sham group and 64 from the caponized group (randomly allocated into 4 treatments) were implanted with 10.4 +/- 0.4 mg (1.62-mm i.d., 3.6-mm o.d.) of cholesterol, testosterone (TES), 5alpha-dihydrotestosterone (5alpha-DHT), or 19-nortestosterone (19-NorT) and were assigned to trial 2 for a 14-wk experiment. The results from trial 1 showed that caponization increased BW (P < 0.05) and decreased tibia stress, ash content, and P content with higher blood P concentration (P < 0.05) as compared with the sham group. In trial 2, the cholesterol implantation group showed the lowest tibia breaking strength, bending moment, stress, and ash content (P < 0.05). The 19-NorT implantation group showed decreased (P < 0.05) blood Ca and P concentration but increased tibia ash and P content, reaching the same level as the sham group (P > 0.05). The adverse effects of caponization on bone characteristics could be improved using androgen implantation. Among the implantation groups, the 19-NorT implantation group showed the best improvement in tibia breaking strength and bending moment, followed by the TES and 5alpha-DHT groups. The TES group showed the best improvement in tibia stress, followed by the 19-NorT and 5alpha-DHT groups.

Recurrent hepatocellular carcinoma after hepatic resection: prognostic factors and long-term outcome.

AIM: The prognosis of patients with recurrent hepatocellular carcinoma (HCC) after hepatic resection varies widely. This study analyzed long-term survival and prognostic factors of patients with recurrent HCC after hepatectomy. METHODS: From July 1991 to December 2000, 623 patients underwent hepatic resection for HCC. Of those, 347 (56.5%) patients had tumour recurrence, and 286 patients with follow-up time more than 24 months after recurrence were enrolled. Twenty-seven clinicopathologic factors underwent both univariate and multivariate analysis. RESULTS: Of these 286 patients, survival times after tumour recurrence were mean 672+/-619 days; median 468 days; and, range 10-3753 days. The overall 1-, 3-, 5-, and 10-year post-recurrence survival rates were 61.5, 33.4, 18.2, and 9.0%, respectively. Seventy (24.5%) patients were alive at the time of study, and 10 of the 34 patients who underwent re-resection were disease-free. By Cox regression analysis, multiple initial tumours (relative risk (RR) 1.428), recurrent multiple (RR 1.372), extrahepatic recurrence (RR 2.434), recurrent tumour size >2 cm (RR 1.926), post-hepatectomy period until recurrence <1 year (RR 1.769), and non-resectional treatment of recurrent tumours (RR 3.527) were independent prognostic factors for post-recurrent survival rates. CONCLUSIONS: In patients with recurrent HCC after hepatectomy, both initial and recurrent tumour factors influenced their prognosis. Early detection of recurrent tumours is important. Re-resection correlated with better post-recurrent survival rates.

Reliability of contemporary radiology to measure tumour size of hepatocellular carcinoma in patients undergoing resection: limitations and clinical implications.

BACKGROUND: Preoperative radiology has been widely used to detect and measure hepatocellular carcinoma (HCC). However, its accuracy and reliability are unclear. This study aimed to assess the ability of current radiology to measure tumour size in patients undergoing resection. METHODS: We evaluated 212 HCC patients undergoing curative resection. Tumour size measured in the pathological examination was correlated with that obtained in preoperative ultrasound (US) and contrast-enhanced dynamic computed tomography (CT). Accuracy and association with tumour recurrence were investigated. RESULTS: The mean size of the tumour was 4.5 +/- 2.6 cm and was accurate in both US and CT in only 6 (3%) patients. Cirrhosis (P = 0.015), absence of tumour stain (P = 0.002) and small (< or = 4 cm) tumour (P < 0.001) were the significant factors associated with size deviation using both US and CT. Ninety-four (44%) patients developed tumour recurrence within 17 +/- 11 months of resection. Recurrence rate was 52%, 52% and 67% in patients with underestimation in US (relative risk [RR]: 2.0, 95% confidence interval [CI]: 1.2-3.4, P = 0.01), CT (RR: 2.1, 95% CI: 1.1-4, P = 0.022) and both modalities (RR: 2.5, 95% CI: 1.4-4.2, P = 0.001), respectively, compared to 30% recurrence in patients with accurate estimation of tumour size. CONCLUSION: The accuracy of radiology in measuring tumour size was poor, and may lead to inappropriate treatment. The finding that underestimation of tumour size was associated with a higher tumour recurrence rate is consistent with the hypothesis that HCC may recur from pre-existing tumour foci which could not be identified from the current imaging modalities.

Long-term evaluation of recombinant interferon alpha2b in the treatment of patients with hepatitis B e antigen-negative chronic hepatitis B in Taiwan.

The effect of interferon (IFN) on hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) has not been fully investigated in Chinese patients. We enrolled 58 HBeAg-negative CHB Chinese patients with hepatitis B viremia in Taiwan to evaluate the response to IFN. 30 patients received recombinant IFN 5 million units 3 times weekly for 6-10 months, and 28 patients who refused IFN treatment served as controls. Rates of virological response and biochemical response were higher in the treated group at the end of treatment (57% vs 18%, P = 0.006, and 73% vs 29%, P = 0.002, respectively). Both effects were superior in the treated group at 6 months after IFN withdrawal (virological: 30% vs 7%, P = 0.06; biochemical: 47% vs 7%, P = 0.002). Improvement of liver histological activities with persistently biochemical response was found in 65% of the treated patients. After a mean of 32 months' follow-up, virological response was rarely maintained (17% vs 4%, P = 0.228) but biochemical response was better in the treated group (27% vs 4%, P = 0.039). None of the treated patients but five controls developed severe complications of CHB during the follow-up period. A larger total IFN dosage or a younger age (< or = 40 years) were associated with 'sustained' virological response. Younger age and higher baseline alanine transaminase values (> or = 120 Ul(-1)) were related to 'sustained' biochemical response.

Interaction between 3-(p-tolylamino)-1,5-azulenequinone and the deoxyguanosine residue in various oligonucleotides upon photolysis.

Eight single-stranded oligodeoxyribonucleotides 32P-labeled at the 5'-end were synthesized; they were annealed with the complementary oligodeoxyribonucleotides to form the corresponding double-stranded helices. These duplexes possessed standard Watson-Crick base pairs, locally perturbed sites of a base mismatch, or a bulge. Further, 5'-32P-labeled oligodeoxyribonucleotides with a hairpin loop were also synthesized. Cleavage of these single- and double-stranded oligodexyribonucleotides selectively at the deoxyguanosine residue was accomplished by use of 3-(p-tolylamino)-1,5-azulenequinone 1 upon irradiation with 350 nm UV light. The single strands were cleaved more efficiently than the double-helices. For the helices containing a deoxyguanosine residue at a bulge, at a hairpin loop or toward the end, the cleaving efficiency was increased. Computation results indicate that two possibilities exist for agent 1 to form two "Watson-Crick type" hydrogen bonds with guanine in single-stranded oligodeoxyribonucleotides; yet, only one possibility exists in duplexes.

Clinicopathologic and prognostic differences between patients with hepatitis B- and C-related resectable hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Hepatitis B and C viral infections are important factors in the development of hepatocellular carcinoma (HCC). This study examined the clinicopathologic and prognostic differences in patients with hepatitis B- and C-related resectable HCC. METHODS: A total of 270 HCC patients who underwent hepatic resection were enrolled. Among these patients, 211 were positive for hepatitis B surface antigen (HBsAg) and 59 were positive for anti-hepatitis C virus antibody (anti-HCV). The clinical manifestations, pathologic features, and treatment outcomes were compared between the HBsAg-positive and anti-HCV-positive groups. RESULTS: Compared to anti-HCV-positive patients, HBsAg-positive patients were significantly younger, had a higher familial incidence of HCC, larger tumor size, and a higher incidence of multiple tumors. HCC patients who were anti-HCV positive had worse liver function and a higher incidence of history of blood transfusion. DNA flow cytometric analysis revealed significantly more proliferative activity in the non-tumor part of the liver in HBsAg-positive HCC patients. The 1-, 3-, and 5-year overall survival rates of HBsAg-positive patients were 79%, 57%, and 48%, respectively, and for anti-HCV-positive patients were 91%, 75%, and 62%, respectively. HBsAg-positive patients had a significantly lower overall survival rate than anti-HCV-positive patients (p = 0.018). CONCLUSIONS: HBsAg-positive patients with resectable HCC had a less favorable survival rate after tumor resection than anti-HCV-positive HCC patients. This survival difference might have been related to the relatively advanced stage of disease and the higher proliferative activity of the non-tumor part of the liver in HBsAg-positive HCC patients.

Cloning, sequencing, heterologous expression, purification, and characterization of adenosylcobalamin-dependent D-ornithine aminomutase from Clostridium sticklandii.

D-Ornithine aminomutase from Clostridium sticklandii catalyzes the reversible rearrangement of d-ornithine to (2R,4S)-2,4-diaminopentanoic acid. The two genes encoding d-ornithine aminomutase have been cloned, sequenced, and expressed in Escherichia coli. The oraS gene, which encodes a protein of 121 amino acid residues with M(r) 12,800, is situated upstream of the oraE gene, which encodes a protein of 753 amino acid residues with M(r) 82,900. The holoenzyme appears to comprise a alpha(2)beta(2)-heterotetramer. OraS shows no significant homology to other proteins in the Swiss-Prot data base. The deduced amino acid sequence of OraE includes a conserved base-off/histidine-on cobalamin-binding motif, DXHXXG. OraE was expressed in E. coli as inclusion bodies. Refolding experiments on OraE indicate that the interactions between OraS and OraE and the binding of either pyridoxal phosphate or adenosylcobalamin play important roles in refolding process. The K(m) values for d-ornithine, 5'-deoxyadenosylcobalamin (AdoCbl), and pyridoxal 5'-phosphate (PLP) are 44.5 +/- 2.8, 0.43 +/- 0.04, and 1.5 +/- 0.1 microm, respectively; the k(cat) is 6.3 +/- 0.1 s(-1). The reaction was absolutely dependent upon OraE, OraS, AdoCbl, PLP, and D-ornithine being present in the assay; no other cofactors were required. A red-shift in UV-visible absorption spectrum is observed when free adenosylcobinamide is bound by recombinant D-ornithine aminomutase and no significant change in spectrum when free adenosylcobinamide is bound by mutant OraE-H618G, demonstrating that the enzyme binds adenosylcobalamin in base-off/histidine-on mode.

Malignant melanoma of the eustachian tube.

The case report describes the diagnosis and the management of malignant melanoma of the eustachian tube. This is an exceedingly rare condition that was treated with endoscopic surgery and post-operative radiotherapy. During a 15-month follow-up, there was no evidence of recurrence.

An unusual cutaneous metastasis from hepatocellular carcinoma.

Cutaneous metastases from hepatocellular carcinoma are rare. In this report we detail a case of hepatocellular carcinoma with the unusual manifestations of multiple skin metastases. A 49-year-old male, who had received surgical resection of hepatocellular carcinoma one year prior, presented with multiple reddish-blue, firm, painless and nonulcerative cutaneous papules and nodules over the fingers, palms, toes, soles and back. Pathology of the cutaneous nodules showed characteristic hepatocellular carcinoma with trabecular gland formation. These lesions grew very rapidly and developed to cauliflower appearances which had not been described previously in the literature. The patient died of respiratory failure secondary to lung metastasis two months after the first appearance of the skin lesions.

Clinical, virological, and pathological significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C.

PURPOSE: Hepatic bile duct injuries are characteristic histological findings in patients with chronic hepatitis C virus (HCV) infection. However, the pathogenesis and clinical significance of this phenomenon remain unclear. The aims of this study were to evaluate the prevalence and clinical significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C. METHODS: One hundred and seventeen Chinese patients with chronic hepatitis C were enrolled. Clinical, biochemical, immunological (serum autoantibodies and cryoglobulinemia), histological, and virological data (serum HCV RNA titer and HCV genotype) were compared between patients with and without hepatic bile duct injuries. RESULTS: Eighty-three (71%) of the 117 patients with chronic hepatitis C had hepatic bile duct injuries. Patients with hepatic bile duct injuries had a significantly higher frequency of HCV genotype 1b; a higher mean serum globulin level; significantly higher mean scores for histological periportal necro-inflammation, portal inflammation, and fibrosis; and more severe portal lymphoid aggregation/follicles when compared with patients without hepatic bile duct injuries (P < 0.05, all). No significant differences in the presence of serum autoantibodies, cryoglobulinemia, mean serum HCV RNA titer, or response to interferon treatment were noted between the two groups. Multivariate logistic regression analysis showed that HCV genotype 1b infection, portal inflammation, and lymphoid aggregation/follicles were significant independent predictors associated with hepatic bile duct injuries. CONCLUSIONS: The presence of hepatic bile duct injuries in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection, and the patients with these injuries had more severe portal inflammation and formation of lymphoid aggregates/follicles.