Malassezia vespertilionis sp. nov.: a new cold-tolerant species of yeast isolated from bats.

Malassezia is a genus of medically-important, lipid-dependent yeasts that live on the skin of warm-blooded animals. The 17 described species have been documented primarily on humans and domestic animals, but few studies have examined Malassezia species associated with more diverse host groups such as wildlife. While investigating the skin mycobiota of healthy bats, we isolated a Malassezia sp. that exhibited only up to 92% identity with other known species in the genus for the portion of the DNA sequence of the internal transcribed spacer region that could be confidently aligned. The Malassezia sp. was cultured from the skin of nine species of bats in the subfamily Myotinae; isolates originated from bats sampled in both the eastern and western United States. Physiological features and molecular characterisation at seven additional loci (D1/D2 region of 26S rDNA, 18S rDNA, chitin synthase, second largest subunit of RNA polymerase II, ß-tubulin, translation elongation factor EF-1α, and minichromosome maintenance complex component 7) indicated that all of the bat Malassezia isolates likely represented a single species distinct from other named taxa. Of particular note was the ability of the Malassezia sp. to grow over a broad range of temperatures (7-40 °C), with optimal growth occurring at 24 °C. These thermal growth ranges, unique among the described Malassezia, may be an adaptation by the fungus to survive on bats during both the host's hibernation and active seasons. The combination of genetic and physiological differences provided compelling evidence that this lipid-dependent yeast represents a novel species described herein as Malassezia vespertilionis sp. nov. Whole genome sequencing placed the new species as a basal member of the clade containing the species M. furfur, M. japonica, M. obtusa, and M. yamatoensis. The genetic and physiological uniqueness of Malassezia vespertilionis among its closest relatives may make it important in future research to better understand the evolution, life history, and pathogenicity of the Malassezia yeasts.

Toward knowledge-based liver surgery: holistic information processing for surgical decision support.

PURPOSE: Malignant neoplasms of the liver are among the most frequent cancers worldwide. Given the diversity of options for liver cancer therapy, the choice of treatment depends on various parameters including patient condition, tumor size and location, liver function, and previous interventions. To address this issue, we present the first approach to treatment strategy planning based on holistic processing of patient-individual data, practical knowledge (i.e., case knowledge), and factual knowledge (e.g., clinical guidelines and studies). METHODS: The contributions of this paper are as follows: (1) a formalized dynamic patient model that incorporates all the heterogeneous data acquired for a specific patient in the whole course of disease treatment; (2) a concept for formalizing factual knowledge; and (3) a technical infrastructure that enables storing, accessing, and processing of heterogeneous data to support clinical decision making. RESULTS: Our patient model, which currently covers 602 patient-individual parameters, was successfully instantiated for 184 patients. It was sufficiently comprehensive to serve as the basis for the formalization of a total of 72 rules extracted from studies on patients with colorectal liver metastases or hepatocellular carcinoma. For a subset of 70 patients with these diagnoses, the system derived an average of [Formula: see text] assertions per patient. CONCLUSION: The proposed concept paves the way for holistic treatment strategy planning by enabling joint storing and processing of heterogeneous data from various information sources.

Polymer nanocomposites exhibiting magnetically tunable microwave properties.

Polymer nanocomposites (PNCs) have been synthesized using Rogers polymer and CoFe2O4 nanoparticles (CFO NPs). X-ray diffraction (XRD) confirms the inverse spinel crystal structure of CFO NPs and transmission electron microscopy (TEM) images show the uniform dispersion of nanoparticles (10 nm ± 1) into the polymer matrix. Magnetic measurements indicate superparamagnetic response near room temperature for all PNCs. A blocking temperature T(B)~298 K was observed and does not vary for different loading fractions of CFO NPs for the PNCs. The saturation magnetization (M(s)) was found to be 11 emu g⁻¹ for 30 wt% CFO, increasing to 32 emu g⁻¹ for the 80 wt% CFO loaded PNC. A large value of coercivity (H(c) = 19 kOe) is also observed at 10 K and is not affected by varying CFO loading. Microwave measurements show significant absorption in the 80 wt% CFO loading PNC and the quality factor shows a strong enhancement with applied magnetic field.

MRSA in children presenting to hospitals in Birmingham, UK.

Meticillin-resistant Staphylococcus aureus (MRSA) isolates from children presenting to Birmingham hospitals were characterized using molecular methods. The study was performed on MRSA isolates from children aged

An outbreak of Serratia marcescens on the neonatal unit: a tale of two clones.

Serratia spp. are an important cause of hospital-acquired infections and outbreaks in high-risk settings. Twenty-one patients were infected or colonized over a nine-month period during 2001-2002 on a neonatal unit. Twenty-two isolates collected were examined for antibiotic susceptibility, beta-lactamase production and genotype. Random-amplified polymorphic DNA polymerase chain reaction and pulsed-field gel electrophoresis revealed that two clones were present. The first clone caused invasive clinical infection in four babies, and was subsequently replaced by a non-invasive clone that affected 14 babies. Phenotypically, the two strains also differed in their prodigiosin production; the first strain was non-pigmented whereas the second strain displayed pink-red pigmentation. Clinical features suggested a difference in their pathogenicity. No environmental source was found. The outbreak terminated following enhanced compliance with infection control measures and a change of antibiotic policy. Although S. marcescens continued to be isolated occasionally for another five months of follow-up, these were sporadic isolates with distinct molecular typing patterns.

The expanding role of the antibiotic pharmacist.

Widespread inappropriate prescribing of antibiotics in UK hospitals has led to the introduction of specialist antibiotic pharmacists. Their role is to monitor antibiotic use, advise clinicians, educate all grades of healthcare workers and help to develop policy. Antibiotic pharmacists have been shown to be effective in many situations. As these practitioners become more accomplished it will be possible to expand their role to include direct intervention in patient treatment. Simple measures, such as modification of intravenous treatment to oral and automatic stop orders, could greatly enhance patient care.

Parkinson's disease risks associated with dietary iron, manganese, and other nutrient intakes.

BACKGROUND: Dietary influences on oxidative stress have been thought to play important role in the etiology of PD. OBJECTIVE: To examine associations of PD with dietary nutrients, including minerals, vitamins, and fats. METHODS: A population-based case-control study was conducted among newly diagnosed case (n = 250) and control subjects (n = 388) identified between 1992 and 2002 from enrollees of the Group Health Cooperative health maintenance organization in western Washington state. Controls were frequency matched to cases on sex and age. In-person interviews elicited data on food frequency habits during most of adult life. Nutrient intakes were calculated and analyzed by adjusting each person's nutrient intake by their total energy intake (the nutrient density technique). RESULTS: Subjects with an iron intake in the highest quartile compared with those in the lowest quartile had an increased risk of PD (odds ratio = 1.7, 95% CI: 1.0, 2.7, trend p = 0.016). There was an apparent joint effect of iron and manganese; dietary intake above median levels of both together conferred a nearly doubled risk compared with lower intakes of each nutrient (odds ratio = 1.9, 95% CI: 1.2, 2.9). No strong associations were found for either antioxidants or fats. CONCLUSION: A high intake of iron, especially in combination with high manganese intake, may be related to risk for PD.

Inhibitors of the Plasmodium falciparum parasite aspartic protease plasmepsin II as potential antimalarial agents.

Malaria is a very serious infectious disease against which the currently available drugs are loosing effectiveness. The main problem is the emergence and the spreading of resistant parasite strains. New treatments are needed in order to regain control over the disease. Drug discovery efforts towards this goal are likely to be more successful, if they focus towards novel mechanisms of action. Such efforts will result in drugs that are functionally and structurally different from the existing drugs and therefore will overcome existing resistances. Here we focus on the aspartic protease plasmepsin II, which is a promising new drug target. We review the drug discovery efforts that were published in the literature on this enzyme, and we present the compounds synthesized at Actelion Pharmaceuticals Ltd.

MR nerve imaging in a prospective cohort of patients with suspected carpal tunnel syndrome.

OBJECTIVES: To evaluate the reliability and diagnostic accuracy of high-resolution MRI of the median nerve in a prospectively assembled cohort of subjects with clinically suspected carpal tunnel syndrome (CTS). METHODS: The authors prospectively identified 120 subjects with clinically suspected CTS from five Seattle-area clinics. All subjects completed a hand-pain diagram and underwent a standardized nerve conduction study (NCS). The reference standard for determining CTS status was a classic or probable hand pain diagram and NCS with a difference >0.3 ms between the 8-cm median and ulnar peak latencies. Readers graded multiple imaging parameters of the MRI on four-point scales. The authors also performed quantitative measurements of both the median nerve and carpal tunnel cross-sectional areas. NCS and MRI were interpreted without knowledge of the other study or the hand pain diagram. RESULTS: Intrareader reliability was substantial to near perfect (kappa = 0.76 to 0.88). Interreader agreement was lower but still substantial (kappa = 0.60 to 0.67). Sensitivity of MRI was greatest for the overall impression of the images (96%) followed by increased median nerve signal (91%); however, specificities were low (33 to 38%). The length of abnormal signal on T2-weighted images was significantly correlated with nerve conduction latency, and median nerve area was larger at the distal radioulnar joint (15.8 vs 11.8 mm(2)) in patients with CTS. A logistic regression model combining these two MR variables had a receiver operating characteristic area under the curve of 0.85. CONCLUSIONS: The reliability of MRI is high but the diagnostic accuracy is only moderate compared with a research-definition reference standard.

The successful introduction of a programme to reduce the use of i.v. ciprofloxacin in hospital.

The effectiveness of a programme to reduce the use of i.v. ciprofloxacin was assessed. i.v. ciprofloxacin was removed from ward stock and discussion occurred regarding appropriate use of the drug. Six months later, a factsheet containing recommendations was distributed to all medical staff and a requirement for justification before prescription was introduced. The programme reduced expenditure on i.v. ciprofloxacin to 34% of original levels. Savings of > 36,000 pounds sterling were made for two consecutive years. A sustained reduction in the use of i.v. ciprofloxacin was obtained by a combination of education and restriction.

Endothelin receptor antagonists: structures, synthesis, selectivity and therapeutic applications.

Endothelin (ET) was discovered in 1988 and is the most potent vasoconstrictive peptide known to date. It exists in three isoforms (ET-1 to ET-3) and acts on two endothelin receptor subtypes, the endothelin-A (ET(A))-receptor and the endothelin-B (ET(B))-receptor. Endothelin receptor antagonists are novel therapeutics in clinical development for different cardiovascular, cerebrovascular, and renal diseases. Several different structural classes of endothelin receptor antagonists have been discovered within the last decade, starting from peptidic- and peptidomimetic structures to small organic molecules suitable as therapeutics for oral administration. Focussing on the small organic molecules, the different structural classes of ET-receptor antagonists are described with respect to synthesis, structure-activity-relationships, receptor-subtype-selectivity profile, and where possible, intended therapeutic indications.

The in vitro activity of BMS-284756, a new des-fluorinated quinolone.

The in vitro activity of BMS-284756 (previously T-3811ME), a des-fluoro(6) quinolone, was investigated and compared with those of six other antimicrobial agents. Susceptibility tests were performed on 919 Gram-positive, Gram-negative (including nine quinolone-resistant Escherichia coli) and anaerobic bacteria, three Chlamydia isolates and four Mycobacteria spp. BMS-284756 was marginally less active against the Enterobacteriaceae, but was the most active quinolone against staphylococci, enterococci and peptostreptococci. Against Streptococcus pneumoniae, BMS-284756 and gemifloxacin were more active than other quinolones. The MIC(90) of BMS-284756 was > or = 2 mg/L for the following bacteria: E. coli (MIC(90) 16 mg/L), Acinetobacter spp. (8 mg/L), Pseudomonas aeruginosa (64 mg/L) and Enterococcus faecium (4 mg/L). The MIC of BMS-284756 for Mycobacterium spp. was within one dilution of the MIC of ciprofloxacin. BMS-284756 was markedly more active than ciprofloxacin against the Chlamydia isolates tested.

Genetic polymorphisms of microsomal and soluble epoxide hydrolase and the risk of Parkinson's disease.

Oxidative stress is hypothesized to play a major role in the destruction of dopaminergic neurons, which is associated with Parkinson's disease. Epoxides are potentially reactive intermediates formed through the oxidative metabolism of both exogenous and endogenous substances that contribute to cytotoxic damage mediated by oxidative stress. The microsomal (EPHX1) and soluble (EPHX2) epoxide hydrolases function to regulate the oxidation status of a wide range of xenobiotic- and lipid-derived substrates; therefore, interindividual variation in these pathways may mitigate epoxide-related cellular injury. In this investigation, we examined the potential association between the risk of Parkinson's disease and genetic variation within the EPHX1 and EPHX2 genes. Fluorescent 5' nuclease-based assays were developed to identify the allelic status of individuals with respect to specific single nucleotide polymorphisms in exons 3 and 4 of the EPHX1 gene and exons 8 and 13 of the EPHX2 gene. EPHX1 and EPHX2 genotype data were obtained from 133 idiopathic Parkinson's disease patients and 212 control subjects matched on age, gender and ethnicity. No statistically significant differences were found in the distribution of the reference and variant alleles between Parkinson's disease and control subjects, or when results were stratified by gender. Therefore, common polymorphisms within EPHX1 and EPHX2 do not appear to be important risk factors for Parkinson's disease.

Genetic polymorphisms of superoxide dismutase in Parkinson's disease.

Oxidative stress reactions may contribute to the pathogenesis of Parkinson's disease (PD). The superoxide dismutases potentially play significant roles in PD by detoxifying superoxide radical. We developed genomic DNA and cDNA-based sequencing assays to identify genetic variants in the copper/zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) genes. No genetic variants were detected in the gene encoding SOD1 in DNA from 45 idiopathic PD cases and 49 controls from a population-based case-control study. However, we identified a previously described polymorphism of the mitochondrial targeting sequence consisting of a C47T in exon 2 of SOD2, which results in an alanine to valine substitution. We analyzed this SOD2 variant in DNA from 155 cases and 231 controls from the same study, using an allele-specific fluorogenic 5' nuclease assay, and found no differences in the distributions of allelic frequencies. These results indicate that SOD gene variants do not contribute to PD pathogenesis.

The in vitro activity of ABT773, a new ketolide antimicrobial agent.

The in vitro activity of ABT773, a ketolide antimicrobial agent, was investigated and compared with those of seven other antibiotics. Type strains and 733 Gram-positive, Gram-negative and anaerobic isolates of clinical origin and four CHLAMYDIA: isolates were used. The activity of ABT773 was very similar to that of telithromycin, the other ketolide tested. The MIC(90) was < or = 0.5 mg/L for all bacteria examined except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae and BACTEROIDES: spp. The antichlamydial activity of ABT773 was greater than that of telithromycin, erythromycin and ciprofloxacin. Neither an increase in the size of the inoculm nor the addition of human serum had any marked affect on the in vitro activity of ABT773.

Mitochondrial ND1 sequence analysis and association of the T4216C mutation with Parkinson's disease.

Mitochondrial dysfunction originating from mutations in Complex I genes may play a role in the pathogenesis of Parkinson's disease (PD). In this study, the entire ND1 coding sequence was sequenced in 84 newly diagnosed PD cases and 127 age/gender-matched controls. Numerous missense mutations were found at low frequency (<5%), whereas a thymidine to cytosine missense mutation at position 4216 that results in the replacement of tyrosine with histidine was found in 25% of the PD case samples and in 18% of the controls. When calculated according to gender, the 4216 mutation was observed in 26% of the male cases versus 16% of male controls (Odds Ratio [OR] = 1.85; 95% CI = 0.79-4.34). In contrast, females exhibited approximately equal frequencies among cases (22.5%) and controls (21%), yielding an OR of 1.08 (95% C.I. = 0.36-3.22). The findings indicate only a weak association of this genetic variant with PD.

Genetic polymorphism of dopamine D2 receptors in Parkinson's disease and interactions with cigarette smoking and MAO-B intron 13 polymorphism.

Genetic polymorphisms of dopamine D2 receptors (DRD2) may be susceptibility factors for Parkinson's disease due to their influence on dopamine response and association with cigarette smoking, which is inversely related to risk of Parkinson's disease. Relations of TaqIA and TaqIB DRD2 genotypes with Parkinson's disease were investigated and tested for interactive effects with smoking and the monoamine oxidase B (MAO-B) intron 13 polymorphism previously found to be related to smoking. Study subjects were 152 cases of idiopathic Parkinson's disease and 231 controls. The smoking history of all genotyped subjects was known. Subjects of genotype B12 were more frequent among cases than controls (27% and 23.8%, respectively), and were more frequent among "ever smokers" than "never smokers", among controls (27.8% and 17.2%, respectively), although these associations were not statistically significant. Neither TaqIA or TaqIB genotypes modified the inverse relation of smoking and Parkinson's disease. When genotypes for DRD2 were considered in combination with genotypes for intron 13 of MAO-B, genotype combinations with high risk of Parkinson's disease were found; although the MAO-B/DRD2 interaction did not reach statistical significance after Bonferroni correction for multiple comparisons, these results are suggestive of a possible synergism between MAOB and DRD2 genes with respect to Parkinson's disease.