Characterization of a half-wave plate for cosmic microwave background circular polarization measurement with POLARBEAR.

A half-wave plate (HWP) is often used as a modulator to suppress systematic error in the measurements of cosmic microwave background (CMB) polarization. A HWP can also be used to measure circular polarization (CP) through its optical leakage from CP to linear polarization. The CP of the CMB is predicted from various sources, such as interactions in the Universe and extension of the standard model. Interaction with supernova remnants of population III stars is one of the brightest CP sources. Thus, the observation of the CP of CMB is a new tool for searching for population III stars. In this paper, we demonstrate the improved measurement of the leakage coefficient using the transmission measurement of an actual HWP in the laboratory. We measured the transmittance of linearly polarized light through the HWP used in Polarbear in the frequency range of 120-160 GHz. We evaluate the properties of the HWP by fitting the data with a physical model using the Markov Chain Monte Carlo method. We then estimate the band-averaged CP leakage coefficient using the physical model. We find that the leakage coefficient strongly depends on the spectra of CP sources. We thus calculate the maximum fractional leakage coefficient from CP to linear polarization as 0.133 ± 0.009 in the Rayleigh-Jeans spectrum. The nonzero value shows that Polarbear has a sensitivity to CP. Additionally, because we use the bandpass of detectors installed in the telescope to calculate the band-averaged values, we also consider systematic effects in the experiment.

Erratum to: Seasonal trend and clinical presentation of Bacillus cereus bloodstream infection: association with summer and indwelling catheter.

Bacillus cereus, an opportunistic pathogen, can cause fatal infection. However, B. cereus bloodstream infections (BSIs) have not been well characterised. From 2008 to 2013, B. cereus isolates from all of the specimens and patients with B. cereus BSIs were identified. Environmental samples were collected to detect B. cereus contamination. We also characterised the clinical presentation of B. cereus BSI through analyses of risk factors for BSI and mortality. A total of 143 clinical B. cereus isolates was detected. Fifty-one patients with nosocomial infections were diagnosed as B. cereus BSI, and 37 had contaminated blood cultures. The number of B. cereus isolates and BSI patients was significantly greater from June to September than from January to April (3.4 vs. 1.0 per month and 1.4 vs. 0.2, respectively). All BSIs were nosocomial and related to central or peripheral vascular catheter. Urinary catheter [odds ratio (OR) 6.93, 95 % confidence interval (CI) 2.40-20.0] was the independent risk factor associated with BSI patients when compared to patients regarded as contaminated. In-hospital mortality among BSI patients was 20 % and was associated with urinary catheter (OR 12.3, 95 % CI 0.67-225, p=0.045) and higher Charlson index (OR 1.99, 95 % CI 1.26-3.12). The number of B. cereus isolates and BSI increased during summer. Inpatients with indwelling vascular or urinary catheters should be carefully monitored for potential B. cereus BSIs.

Development and evaluation of MALDI-TOF MS-based serotyping for Streptococcus pneumoniae.

Surveillance of Streptococcus pneumoniae serotypes is important for the successful implementation of vaccination strategies to prevent the spread of invasive pneumococcal diseases. The standard method of serotyping of pneumococcal isolates is the phenotypic Neufeld test, which is cost- and labor-intensive. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been implemented as a rapid, simple and inexpensive method for identifying species. We evaluated the performance of MALDI-TOF MS for serotyping ten major serotypes of S. pneumoniae in Japan (serotypes 3, 6B, 15A, 15C, 19A, 19 F, 23A, 24 F, 35B and 38) using the Biotyper and ClinProTools. After optimizing the settings, we validated their serotyping performance for serotypes 3, 15A and 19A using a separate set of isolates that were not used in the creation of the classification algorithms. A total of 574 isolates of S. pneumoniae collected from Japanese nationwide surveillance studies were included. Of these, 407 isolates belonged to the ten major serotypes. Biotyper and ClinProTools correctly identified 77.9 % and 84.0 %, respectively, of the ten major serotype isolates. The validation analysis included a total of 113 isolates of the serotypes 3, 15A and 19A isolates. Biotyper and ClinProTools correctly identified 85.0 % and 69.9 % of the validation cohort isolates, respectively. MALDI-TOF MS has the potential to discriminate the ten major S. pneumoniae serotypes prevalent in Japan.

Seasonal trend and clinical presentation of Bacillus cereus bloodstream infection: association with summer and indwelling catheter.

Bacillus cereus, an opportunistic pathogen, can cause fatal infection. However, B. cereus bloodstream infections (BSIs) have not been well characterised. From 2008 to 2013, B. cereus isolates from all of the specimens and patients with B. cereus BSIs were identified. Environmental samples were collected to detect B. cereus contamination. We also characterised the clinical presentation of B. cereus BSI through analyses of risk factors for BSI and mortality. A total of 217 clinical B. cereus isolates was detected. Fifty-one patients with nosocomial infections were diagnosed as B. cereus BSI, and 37 had contaminated blood cultures. The number of B. cereus isolates and BSI patients was significantly greater from June to September than from January to April (4.9 vs. 1.5 per month and 1.2 vs. 0.2, respectively). All BSIs were nosocomial and related to central or peripheral vascular catheter. Urinary catheter [odds ratio (OR) 6.93, 95% confidence interval (CI) 2.40-20.0] was the independent risk factor associated with BSI patients when compared to patients regarded as contaminated. In-hospital mortality among BSI patients was 20% and was associated with urinary catheter (OR 34.7, 95 % CI 1.89-63.6) and higher Charlson index (OR 1.99, 95 % CI 1.26-3.12). The number of B. cereus isolates and BSI increased during summer. Inpatients with indwelling vascular or urinary catheters should be carefully monitored for potential B. cereus BSIs.

Itraconazole prophylaxis for invasive Aspergillus infection in lung transplantation.

Invasive Aspergillus infection (IA) is a significant cause of morbidity in lung transplantation (LT). However, its optimal prophylaxis is unclear. We routinely administer itraconazole (ITCZ) prophylaxis to all patients undergoing LT. In this study, we retrospectively evaluated the duration of prophylaxis and risk factors of IA. Among 30 adult patients who underwent LT, 5 patients developed IA. All patients with IA stopped ITCZ treatment within 1 year. At least 1 year of ITCZ prophylaxis is essential for the prevention of IA. Cytomegalovirus infection, renal replacement therapy, and tracheotomy were risk factors for IA.

Quality-of-life outcomes from a randomized phase III trial of dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin as a first-line treatment for stage II-IV ovarian cancer: Japanese Gynecologic Oncology Group Trial (JGOG3016).

BACKGROUND: Dose-dense weekly paclitaxel (Taxol) and carboplatin (dd-TC) improved survival compared with conventional tri-weekly paclitaxel and carboplatin (c-TC) as a first-line chemotherapy for newly diagnosed stage II-IV ovarian cancer in the Japanese Gynecologic Oncology Group 3016 trial. We report the quality-of-life (QoL) results from this trial. PATIENTS AND METHODS: A total of 637 patients were randomly assigned to receive c-TC or dd-TC (c-TC, n = 319; dd-TC, n = 312) and were asked to complete a QoL assessment at baseline, just after the third and sixth chemotherapy cycles, and at 12 months after randomization. QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-general (FACT-G), FACT-taxane subscale (FACT-T), and FACT-ovary subscale (FACT-Ov). The overall QoL and that according to each subscale were analyzed using mixed-effects models adjusted for treatment and time. RESULTS: Baseline QoL assessment was completed by 204 out of 319 (63.9%) and 200 out of 312 (64.1%) patients in the c-TC and dd-TC groups, respectively. In these groups, the compliance rates with regard to QoL assessment were 74.5% and 73.0%, respectively, after three chemotherapy cycles; 86.8% and 86.9%, respectively, after six chemotherapy cycles; and 74.2% and 71.6%, respectively, at 12 months after randomization. The overall QoL did not differ significantly between the two treatment groups up to 12 months after randomization (P = 0.46). However, QoL according to the FACT-T subscale was significantly lower in the dd-TC group than in the c-TC group (P = 0.02). CONCLUSION: dd-TC does not decrease overall QoL compared with c-TC.

Regional dissemination of Acinetobacter species harbouring metallo-ß-lactamase genes in Japan.

Metallo-ß-lactamase (MBL) producers have been reported among the various Acinetobacter species worldwide. In this study, the epidemiology and molecular characteristics of carbapenemase-encoding genes and mobile elements were studied to analyse the regional dissemination of MBL genes in Acinetobacter species. From January 2001 to December 2006, 48 Acinetobacter isolates harbouring MBL genes identified from five hospitals in Kyoto and Shiga Prefecture, Japan were collected and analysed. The partial rpoB gene or the 16S-23S ribosomal RNA intergenic spacer region was sequenced to obtain a species-level identification. Molecular typing using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) was performed. Twenty-five Acinetobacter pittii isolates were divided into eight PFGE types and five sequence types (STs) using MLST. Nine Acinetobacter bereziniae isolates belonged to five PFGE types. Five Acinetobacter nosocomialis isolates were divided into two PFGE types and two STs. Three unclassified Acinetobacter species isolates were divided into two PFGE types. Eighteen of the 25 A. pittii isolates belonged to ST119 and were identified from four hospitals. The bla(IMP-19) gene was detected in 41 of 48 isolates, including all of the A. pittii ST119 isolates. The bla(IMP-1) and bla(IMP-11) genes were detected in four and three isolates, respectively. The MBL genes were all embedded within a class 1 integron as a gene cassette array: bla(IMP-19) -aac(6')-31-bla(OXA-21) -aadA1, catB8-like/aacA4-bla(IMP-1) and bla(IMP-11). This study is the first report demonstrating the regional dissemination of MBL-producing Acinetobacter species. A. pittii ST119 harbouring blaIMP-19 was widely spread throughout the Kyoto-Shiga region.

Molecular and clinical characterization of plasmid-mediated AmpC ß-lactamase-producing Escherichia coli bacteraemia: a comparison with extended-spectrum ß-lactamase-producing and non-resistant E. coli bacteraemia.

Plasmid-mediated AmpC ß-lactamase-producing Escherichia coli (AmpC-E) bacteraemia was characterized by comparison with bacteraemia caused by extended-spectrum ß-lactamase (ESBL)-producing E. coli (ESBL-E) and non-resistant E. coli (NR-E) in the era of the worldwide spread of the CTX-M-15-producing O25b-ST131-B2 clone. Of 706 bloodstream E. coli isolates collected between 2005 and 2010 in three Japanese university hospitals, 111 ESBL screening-positive isolates were analysed for AmpC and ESBL genes by PCR. A case-control study was performed in which the cases consisted of all of the patients with AmpC-E bacteraemia. Phylogenetic groups, sequence types and O25b serotype were determined. Twenty-seven AmpC-E isolates (26 of which were of the CMY-2 type) were identified, and 54 ESBL-E and 54 NR-E isolates were selected for the controls. Nineteen AmpC-E isolates were also positive for ESBL. CTX-M-14 was the most prevalent ESBL type among both the AmpC-E and ESBL-E isolates. The O25b-ST131-B2 clone was the most prevalent among the ESBL-E isolates (26%) and the second most prevalent among the NR-E isolates (13%), but only one O25b-ST131-B2 clone was found among the AmpC-E isolates. Twenty-three different sequence types were identified among the AmpC-E isolates. When compared with bacteraemia with ESBL-E, previous isolation of multidrug-resistant bacteria and intravascular catheterization were independently associated with a lower risk for AmpC-E. When compared with NR-E bacteraemia, prior use of antibiotics was the only significant risk factor for AmpC-E. Unlike the spread of the O25b-ST131-B2 clone between ESBL-E and NR-E, the AmpC-E isolates were not dominated by any specific clone.

Cefotaxime for the detection of extended-spectrum ß-lactamase or plasmid-mediated AmpC ß-lactamase and clinical characteristics of cefotaxime-non-susceptible Escherichia coli and Klebsiella pneumoniae bacteraemia.

We investigated the performance of cefotaxime for the detection of extended-spectrum ß-lactamase (ESBL) or plasmid-mediated AmpC ß-lactamase (pAmpC) and the clinical characteristics of cefotaxime-non-susceptible Escherichia coli or Klebsiella pneumoniae (CTXNS-EK) bacteraemia. All of the consecutive bloodstream isolates between 2005 and 2010 in a Japanese university hospital were characterised using polymerase chain reaction (PCR). Risk factors and outcomes of CTXNS-EK were analysed by multivariate logistic regression analysis. We identified 58 CTXNS-EK (15.6%) from 249 E. coli and 122 K. pneumoniae. Cefotaxime with a minimum inhibitory concentration (MIC) of >1 µg/mL had a sensitivity of 98.3% and a specificity of 99.7% for the detection of ESBL or pAmpC. CTXNS-EK had increased from 4.5% in 2005 to 23% in 2009. Risk factors for CTXNS-EK were previous isolation of multidrug-resistant bacteria, use of oxyimino-cephalosporins or fluoroquinolones, and high Sequential Organ Failure Assessment (SOFA) score. Patients with CTXNS-EK bacteraemia less frequently received appropriate empirical therapy than patients with cefotaxime-susceptible EK bacteraemia (81% vs. 97%, p<0.001) and died within 30 days (21% vs. 5%, p=0.001). Using the current breakpoints of the Clinical and Laboratory Standards Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST), cefotaxime alone can identify ESBL or pAmpC producers. CTXNS-EK is an important and increasingly prevalent bacteraemia pathogen.

The outcome of Japanese anorexia nervosa patients treated with an inpatient therapy in an internal medicine unit.

OBJECTIVE: To investigate the outcome of Japanese anorexia nervosa (AN) patients who were treated with the standard Japanese inpatient therapy. METHOD: Of the 88 female AN patients treated with our inpatient therapy between January 1997 and December 2002, 67 (76.1%) who agreed to cooperate in this study were assessed by the Global Clinical Score (GCS) at admission and follow-up, 6.3±1.8 years after discharge. Their clinical characteristics at admission and discharge were also examined. RESULTS: Four (6.0%) patients had died before follow-up. BMI was significantly increased during inpatient therapy. At follow-up, excellent, much improved, symptomatic, and poor outcomes on GCS were 57.1%, 14.3%, 14.3% and 14.3%, respectively. Younger age at admission and larger BMI at discharge were significantly associated with a better outcome. DISCUSSION: This study shows the potential for the use of this method for the treatment of AN patients in countries without specialized eating disorder units.

Quantitative real-time PCR and the (1→3)-ß-D-glucan assay for differentiation between Pneumocystis jirovecii pneumonia and colonization.

We evaluated whether quantitative PCR (qPCR) and (1 → 3)-ß-d-glucan assays could be used to differentiate Pneumocystis pneumonia (PCP) from Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. A total of 40 bronchoalveolar lavage samples and 107 induced sputum samples from 147 patients who were suspected of having PCP were obtained for PCR detection of P. jirovecii. Diagnoses of definite PCP, probable PCP, pneumonia with P. jirovecii colonization (colonization) and pneumonia without colonization (non-colonization) were made in 11, 42, 15 and 60 patients, respectively. A PCP diagnosis was undetermined in 19 patients. The copy numbers, determined using qPCR, were significantly higher in definite PCP and probable PCP patients than in colonized patients. The area under the receiver-operating characteristic curve (AUC), sensitivity and specificity for discriminating definite PCP from colonization were 0.96, 100.0% and 80.0%, respectively, at a cut-off value of 1300 copies/mL. The values for discriminating probable PCP from colonization were 0.71, 66.7% and 73.3%, respectively, at a cut-off value of 340 copies/mL. ß-d-glucan levels were significantly higher in patients with both definite PCP and probable PCP than in colonized patients. The AUC, sensitivity and specificity for discriminating definite PCP were 0.91, 100.0% and 80.0%, respectively, at a cut-off value of 15.6 pg/mL. The values for discriminating probable PCP were 0.78, 76.2% and 73.3%, respectively, at a cut-off value of 6.0 pg/mL. Both qPCR and the ß-d-glucan assay displayed high accuracy for discriminating colonization from definite PCP and displayed moderate accuracy for discriminating colonization from probable PCP.

Regional spread and control of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis in Kyoto, Japan.

The purpose of this investigation was to control the post-outbreak prevalence of vancomycin-resistant enterococci (VRE) in the affected Kyoto region. The study period was from 2005 to 2010. Faecal samples were subjected to VRE screening, and vancomycin resistance genes were detected by polymerase chain reaction (PCR). The genotype was determined by pulsed-field gel electrophoresis (PFGE) of genomic DNA digested with SmaI and by multilocus sequence typing (MLST). A VRE control programme was established in 2006, consisting of a laboratory-based faecal VRE screening system, annual surveillance of hospital inpatients and the promotion of adequate infection control measures. vanA-Enterococcus faecium, vanB-E. faecium and vanB-E. faecalis were detected at 35, 12 and 5 hospitals, respectively. Genotype analysis revealed that all of the vancomycin-resistant E. faecium isolates obtained since 2005 belonged to ST78, and that clonally related vanB-E. faecalis of ST64 had spread to three hospitals. The rate of faecal VRE carriage among the patients enrolled in the annual surveillance increased until 2007, when it reached 24 (1.2%) of the 2,035 enrolled patients. The rate began to decrease in 2008 and, by 2010, reached a low of 4 (0.17%) of the 2,408 enrolled patients. While VRE did spread within the Kyoto region, the VRE control programme succeeded in controlling the overall VRE spread.

Control of an outbreak of carbapenem-resistant Pseudomonas aeruginosa in a haemato-oncology unit.

An outbreak of a multidrug-resistant Pseudomonas aeruginosa producing metallo-ß-lactamase (MBLPA) in a haemato-oncology unit was controlled using multidisciplinary interventions. The present study assesses the effects of these interventions by active surveillance of the incidence of MBLPA infection at the 1,240-bed tertiary care Kyoto University Hospital in Kyoto, Japan. Infection control strategies in 2004 included strengthening contact precautions, analysis of risk factors for MBLPA infection and cessation of urine collection. However, new MBLPA infections were identified in 2006, which prompted enhanced environmental cleaning, routine active surveillance, and restricting carbapenem usage. Between 2004 and 2010, 17 patients in the unit became infected with indistinguishable MBLPA strains. The final five infected patients were found by routine active surveillance, but horizontal transmission was undetectable. The MBLPA outbreak in the haemato-oncology unit was finally contained in 2008.

Distribution and clonal relationship of cell surface virulence genes among Streptococcus pneumoniae isolates in Japan.

Streptococcus pneumoniae resides on mucosal surfaces in the nasopharynx, where selection for horizontal transfer of antimicrobial resistance genes and virulence factors may provide a survival advantage. We investigated the distribution of genes for pneumococcal cell surface proteins and their correlations with multilocus sequence typing (MLST), Pneumococcal Molecular Epidemiology Network (PMEN) clones and antimicrobial resistance, to identify pneumococcal virulence factors predicting prevalent clones from 156 pneumococcal isolates recovered from adult patients with community-acquired pneumonia in Japan. Pneumococcal eno, pavA, piuA, cbpA and cbpG were present in all isolates, and hyl and piaA were distributed among the clinical isolates. In contrast, pneumococcal rlrA, pclA, psrP, nanC and pspA family 1-type genes were variably distributed and significantly associated with MLST (Wallace coefficients (W) were over 84%). Serotype was a weaker predictor of sequence type (W, 0.75) than vice versa (W, 0.97). A multiple logistic regression analysis adjusted to the presence of virulence genes, pspA family 1 genes and carriage serotypes revealed that pclA and rlrA correlated with PMEN clones and antimicrobial resistance, and are likely to contribute to the selection of prevalent clones.

Regional spread of vanA- or vanB-positive Enterococcus gallinarum in hospitals and long-term care facilities in Kyoto prefecture, Japan.

Following an outbreak of vanA-positive Enterococcus faecium in 2005 in Kyoto prefecture, regional surveillance of vancomycin-resistant enterococci (VRE) was initiated. This revealed vanA- or vanB-positive Enterococcus gallinarum in multiple facilities. Eighty-eight vanA-positive E. gallinarum faecal carriers from 12 facilities and ten vanB-positive E. gallinarum faecal carriers from eight facilities were found. Pulsed-field gel electrophoresis profiles of the first isolate from each facility showed that 11 of the 12 vanA isolates and three of the eight vanB-positive E. gallinarum isolates belonged to a single clone. This study confirms the clonal spread of vanA- or vanB-positive E. gallinarum in a region and underlines the importance of surveillance of VRE for the presence of vancomycin resistance determinants.

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation.

Although fluoroquinolones or other antibiotics are commonly used to prevent bacterial infections after hematopoietic cell transplantation (HCT), because of the growing presence of multidrug-resistant microorganisms, it is important to identify patients who are more likely to benefit from antibacterial prophylaxis. To evaluate risk factors for early bacterial infection after allogeneic HCT, we retrospectively analyzed clinical data for 112 consecutive adult patients with hematological malignancies who received transplants without any antibacterial prophylaxis. The cumulative incidence of bacterial infection at 30 days after transplantation was 16%. Among various pre-transplant factors, only high serum ferritin (>700 ng/mL, 47 patients) and high C-reactive protein (CRP) (>0.3 mg/dL, 28 patients) levels were significantly associated with the development of bacterial infection in a multivariate analysis (hazard ratio (95% confidence interval): ferritin, 4.00 (1.32-12.17); CRP, 3.64 (1.44-9.20)). In addition, septic shock and sepsis with organ failure were exclusively observed in patients who had high ferritin and/or high CRP levels. These results suggest that pretransplant serum ferritin and CRP levels can be useful markers for predicting the risk of early bacterial infection after allogeneic HCT. It may be prudent to limit antibacterial prophylaxis to patients with predefined risk factors to ensure the safety of HCT with the use of fewer antibiotics.

Close cooperation between infectious disease physicians and attending physicians can result in better management and outcome for patients with Staphylococcus aureus bacteraemia.

Staphylococcus aureus bacteraemia (SAB) is a serious infection that demands prompt clinical attention for good outcome. To assess the impact of intervention by infectious diseases physicians (IDPs) in cases with SAB, a retrospective cohort study of patients with SAB was performed in a 1240-bed, university hospital in Japan, with the aim of comparing the management and outcome of patients during the initial and the latter half of the intervention period,. Three hundred and forty-six patients with SAB during the 7-year period, from 2002 to 2008, were included, and 194 patients in the initial half of the period (from 2002 to 2005) were compared with 152 patients in the later period (from 2006 to 2008). There was no significant difference between the two groups with respect to patient's clinical background, although more patients in the later period were receiving immunosuppressive treatment. The proportion of methicillin resistant S. aureus was lower during the later period (56.2% vs. 43.3%; p 0.02). Echocardiography was used more frequently (37.1% vs. 64.5%; p < 0.001). Infective endocarditis and metastatic infections were diagnosed more frequently (10.8% vs. 20.4%; p 0.01). Follow-up blood cultures were obtained more regularly (52.1% vs. 73.7%; p <0.001) and therapy was more frequently administered for at least 14 days (47.4% vs. 82.2%; p <0.001). The 30-day mortality improved during the intervention period (25.8% vs. 16.4%; p 0.04). The total number of blood cultures received by the laboratory increased annually and the total number of consultations increased by approximately 1.6-fold compared to 2002. Proactive intervention by IDPs raised awareness of optimal management of bacteraemia and improved the adherence to the standards of care, which subsequently resulted in an improvement in the outcome.

Predictors of menstrual resumption by patients with anorexia nervosa.

OBJECTIVE: To investigate which factors predict the resumption of menstruation by patients with anorexia nervosa (AN). METHODS: Participants were AN patients who, even after weight recovery by inpatient treatment, had prolonged amenorrhea (N=11), AN patients who resumed menstruation after weight recovery (N=9), and age-matched healthy controls (N=12). Anthropometric data and the serum levels of leptin, insulin-like growth factor I (IGF-1), cortisol, luteinizing hormone (LH), estradiol (E2), and other hormones were measured at the beginning of the inpatient treatment and after weight recovery. RESULTS: Of the baseline anthropometric and hormonal factors, logistic regression analysis extracted a high serum cortisol level as a predictor of the inhibition of the resumption of menstruation. After weight recovery, the E2 and leptin levels were significantly higher for eumenorrheic patients than for amenorrheic patients. CONCLUSION: The baseline serum cortisol level was a predictor of the prolonged inhibition of menstrual recovery.

High prevalence of mutators among Enterobacter cloacae nosocomial isolates and their association with antimicrobial resistance and repetitive detection.

We determined the mutation frequencies of 59 nosocomial isolates of Enterobacter cloacae, and investigated their association with antimicrobial susceptibility, genotype, and history of exposure to antimicrobials. The frequencies of mutations leading to rifampicin resistance ranged from 5.8 × 10(-9) to 8.0 × 10(-6) (median, 5.0 × 10(-8)). Seven of the 59 (12%) isolates were graded as strong mutators exhibiting a more than 50-fold increase in the mutation frequency relative to that of E. cloacae ATCC 13047, and 30 (52%) were graded as weak mutators exhibiting a more than five-fold and not more than 50-fold increase in the mutation frequency. The isolates with higher grade of mutation frequency were resistant to significantly more antimicrobials (medians of two, one and zero agents for strong mutators, weak mutators and non-mutators, respectively; p 0.0078). The 59 isolates were classified into 36 genotypes, and all of the seven strong mutators had distinct genotypes. Mutation frequencies varied more than 10(2)-fold within a clone. In patient-based, univariate analysis, intensive-care unit admission, dense antimicrobial exposure (glycopeptide or multiple classes) and repetitive detection of this species were significantly more common among all of the four patients from whom strong mutators were obtained. Strong mutators are highly prevalent in surgical isolates of E. cloacae. Higher mutation frequency was associated with antimicrobial resistance and repetitive detection, and may contribute to the adaptability of this species.

Correlations of HHV-6 viral load and plasma IL-6 concentration with HHV-6 encephalitis in allogeneic stem cell transplant recipients.

This study investigated factors associated with the development of human herpesvirus (HHV)-6 encephalitis. Among 111 enrolled subjects, 12 patients developed central nervous system (CNS) dysfunction. CNS dysfunction in four patients was found to have no association with HHV-6. The remaining eight patients displayed HHV-6 encephalitis (n=3), limbic encephalitis (HHV-6 DNA in cerebrospinal fluid was not examined; n=3) or CNS dysfunction because of an unidentified cause (n=2). Real-time PCR showed CNS dysfunction in the latter eight patients, which developed concomitant with the appearance of high plasma levels of HHV-6 DNA (> or =10(4) copies/ml). Overall, eight of the 24 patients with high-level HHV-6 DNA developed CNS dysfunction, whereas no patients developed CNS dysfunction potentially associated with HHV-6 infection if peak HHV-6 DNA was <10(4) copies/ml. We next analyzed plasma concentrations of IL-6, IL-10 and tumor necrosis factor-alpha among patients who displayed high-level plasma HHV-6 DNA and found elevated IL-6 concentrations preceding HHV-6 infection in patients who developed CNS dysfunction. (Mean+/-s.d.: 865.7+/-1036.3 pg/ml in patients with CNS dysfunction; 56.5+/-192.9 pg/ml in others; P=0.01). These results suggest that high-level HHV-6 load is necessary for the development of HHV-6 encephalitis, and systemic inflammatory conditions before HHV-6 infection form the preparatory conditions for progression to encephalopathy.