Cytokine release syndrome-associated encephalopathy in patients with COVID-19.

BACKGROUND AND PURPOSE: Neurological manifestations in coronavirus disease (COVID)-2019 may adversely affect clinical outcomes. Severe COVID-19 and uremia are risk factors for neurological complications. However, the lack of insight into their pathogenesis, particularly with respect to the role of the cytokine release syndrome (CRS), is currently hampering effective therapeutic interventions. The aims of this study were to describe the neurological manifestations of patients with COVID-19 and to gain pathophysiological insights with respect to CRS. METHODS: In this longitudinal study, we performed extensive clinical, laboratory and imaging phenotyping in five patients admitted to our renal unit. RESULTS: Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Notably, neurological disturbances were accompanied by laboratory evidence of CRS. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was undetectable in the cerebrospinal fluid (CSF). Hyperalbuminorrachia and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain magnetic resonance imaging findings comprised evidence of acute leukoencephalitis (n = 3, one of whom had a hemorrhagic form), cytotoxic edema mimicking ischaemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted, resulting in rapid recovery from neurological disturbances in two cases. SARS-CoV2 was undetectable in 88 of the 90 patients with COVID-19 who underwent Reverse Transcription-PCR testing of CSF. CONCLUSIONS: Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory and imaging similarities with those of chimeric antigen receptor T-cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

Clinical, electrophysiological and genetic characteristics of childhood hereditary polyneuropathies.

BACKGROUND: Hereditary polyneuropathies are heterogeneous group of diseases of the peripheral nervous system. In this study, we investigated the demographic, clinical, electrophysiological, and genetic characteristics of hereditary polyneuropathy patients diagnosed and followed up in our tertiary center clinic in Izmir, Turkey. METHODS: Patients who were diagnosed with hereditary polyneuropathies during nerve conduction studies in our center were evaluated retrospectively. RESULTS: In a total of 1484 nerve conduction studies, 207 patients were diagnosed with polyneuropathy. Ninety-nine of those patients were determined to have hereditary polyneuropathy, 52 of which were male and 47 were female. Sixty-nine patients with hereditary polyneuropathy were compatible with axonal and 30 were compatible with demyelinating polyneuropathy. Genetic analysis was performed in 69 patients, and 49 of those patients were genetically diagnosed, leading to a diagnosis rate of 71%. CONCLUSIONS: Advances in genetics have led to an increase in the heterogeneity of hereditary polyneuropathies, causing difficulties in the use of existing classifications. Although typical mutations expected in childhood-onset polyneuropathies are seen less frequently, polyneuropathies are frequently encountered as findings of complex, multisystemic diseases.

FORTE - a multipurpose high-vacuum diffractometer for tender X-ray diffraction and spectroscopy at the SIRIUS beamline of Synchrotron SOLEIL.

A new high-vacuum multipurpose diffractometer (called FORTE from the French acronyms of the project) has recently been installed at the tender/hard X-ray SIRIUS beamline of Synchrotron SOLEIL, France. The geometry chosen allows one to work either in the classical Eulerian four-circle geometry for bulk X-ray diffraction (XRD) or in the z-axis geometry for surface XRD. The diffractometer nicely fits the characteristics of the SIRIUS beamline, optimized to work in the 1.1-4.5 keV range, and allows one to perform unprecedented diffraction anomalous fine structure (DAFS) experiments in the tender X-ray region, also around non-specular reflections, covering a large reciprocal-space volume. Installation of an X-ray fluorescence detector on a dedicated flange allows simultaneous DAFS and X-ray absorption (XAS) measurements. The access to the tender X-ray region paves the way to resonant investigations around the L-edges of second-row transition elements which are constituents of functional oxide materials. It also enables access to several edges of interest for semiconductors. Finally, the control architecture based on synchronized Delta Tau units opens up exciting perspectives for improvement of the mechanical sphere of confusion.

A cluster of invasive meningococcal disease revealed by the characterization of a novel serogroup B meningococcal clone.

The incidence of invasive infections due to Neisseria meningitidis in Israel is about 1/100 000 population annually. Three cases of meningococcal meningitis were reported in employees at a single plant; the first case appeared in March 2013 and the second and third cases appeared in December, almost 9 months later. N. meningitidis serogroup B was isolated from cerebrospinal fluid samples. Multilocus sequence typing assigned the three meningococcal isolates to ST10418, a new sequence type and a member of the ST32 clonal complex. The clonality was confirmed by performance of pulsed-field gel electrophoresis. Post-exposure antibiotic prophylaxis was administered to close contacts of the first case. Upon the diagnosis of the additional two cases, post-exposure prophylaxis was administered to all the plant employees. This report demonstrates the importance of combining public health measures and advanced laboratory studies to confirm clonality and to prevent further disease spread in a closed setting.

Tying up loose ends: a method for constructing and evaluating decision aids that meet blunt and sharp-end goals.

We present a methodological framework for constructing and evaluating decision aids--fast and frugal trees (FFTs)--ideally suited to the front line of an organisation. Their performance can be analysed in signal detection theory, allowing for transparent selection of FFTs given managerial-level trade-offs among type I and II errors. We extend FFTs from binary classification to selection from multiple actions (FFT multiple) as well as performance analysis to organisational goal states beyond type I and II error reduction. Concepts and framework are introduced and a tutorial-style example application (threat assessment at military checkpoints) is provided. Throughout, we discuss ways to deal with missing or incomplete data and show that the performance of decision aids may be overestimated if the effectiveness of actions is not heeded. The methodology can be used to construct and evaluate decision aids in any area characterised by dichotomised cues and a one-to-many mapping between categorisation outcomes and actions.

Direct evidence of Fe(2+)-Fe3+ charge ordering in the ferrimagnetic hematite-ilmenite Fe(1.35)Ti(0.65)O(3-δ) thin films.

In this Letter we highlight direct experimental evidence of Fe(2+)-Fe3+ charge ordering at room temperature in hematite-ilmenite Fe(1.35)Ti(0.65)O(3-δ) epitaxial thin films grown by pulsed laser deposition, using aberration-corrected scanning transmission electron microscopy coupled to high-resolution energy electron-loss spectroscopy. These advanced spectromicroscopy techniques demonstrate a strong modulation of the Fe2+ valence state along the c axis. Density functional theory calculations provide crucial information on the key role of oxygen vacancies in the observed charge distributions. Their presence at significant levels leads to the localization of extra electrons onto reduced Fe2+ sites, while Ti remains solely +4. The magnetic and transport properties of these films are reviewed in the light of the present results regarding their ferrimagnetic character correlated with the Fe2+ modulation and their semiconducting behavior interpreted by an Efros-Shklovskii variable-range hopping conduction regime via Fe2+ and Fe3+ centers. The experimental evidence of only one type of mixed valence state, i.e., Fe2+ and Fe3+, in the Fe(2-x)Ti(x)O(3-δ) system will thus help to interpret further the origin of its geomagnetic properties and to illuminate fundamental issues regarding its spintronic potential.

The impact of pseudomembrane formation on the outcome of Clostridium difficile-associated disease.

PURPOSE: Although pseudomembranes are the hallmark manifestation of Clostridium difficile-associated diarrhea (CDAD), there are scant data specifically addressing their impact on the clinical outcome. We investigated whether the formation of pseudomembranes predicts a worse CDAD outcome. METHODS: CDAD patients hospitalized during 2010 underwent sigmoidoscopy and were followed prospectively. In addition, all hospitalized CDAD patients in the period 01/2000-12/2009 who underwent lower endoscopy were retrospectively identified and their charts reviewed. Patients with detectable pseudomembranes on endoscopy were compared to those in whom pseudomembranes were absent. Thirty-day mortality and a composite outcome comprised of mortality within 30 days of diagnosis, admission to the intensive care unit (ICU), colectomy, peritonitis, hemodynamic instability, or respiratory insufficiency were addressed. Additional clinical outcomes used for comparison between the two groups were 60-day mortality, duration of hospitalization, and the failure of metronidazole and vancomycin. RESULTS: A total of 117 CDAD patients (mean age 62.9 ± 19 years) who underwent lower endoscopy were included; 46 with pseudomembranes and 71 without. Seven out of the 46 patients with pseudomembranes died within 30 days compared to 9/71 in the non-pseudomembrane group [odds ratio (OR) 1.2, 95% confidence interval (CI) 0.4-3.6, P = 0.8]. Similarly, there was no correlation between the occurrence of pseudomembranes and the rate of the composite adverse outcome (P = 0.6). In contrast, acute renal insufficiency (OR 15, 95% CI 3.2-72, P < 0.001) and hypoalbuminemia (OR 5.7, 95% CI 1.8-18, P = 0.002) were both independently predictive of a severe clinical outcome. CONCLUSIONS: Our findings suggest that the presence of pseudomembranes is not associated with an adverse outcome in CDAD patients.

Dynamics of childhood invasive meningococcal disease in Israel during a 22-year period (1989-2010).

AIM: To describe the dynamics in the incidence of childhood invasive meningococcal disease (IMD) in Israel during a 22-year period (1989-2010). METHODS: A longitudinal prospective surveillance in all 27 medical centers with pediatric services in Israel. All cases of children <15 years old with positive blood/cerebrospinal fluid (CSF) culture for Neisseria meningitidis were reported. Demographic, clinical, and bacteriological data were recorded. Meningococcal vaccine was not routinely given to Israeli children during the study period. RESULTS: The mean age ± standard deviation (SD) among the 743 cases was 40.7 ± 40.2 months. The mean yearly incidence/100,000 was 2.0 ± 0.8. Age-specific incidences were 8.7 ± 2.8, 2.9 ± 1.5, and 0.8 ± 0.5 for children <1, 1-4, and >4 years old, respectively. The overall incidence decreased significantly from 3.7 in 1989 to 1.5 in 2010. Meningitis constituted 69.2 % of all cases. The most common serogroups were: B (76.9 %), C (10.9 %), Y (8.0 %), and W(135) (2.9 %). 78.6 % of all serogroup B isolates were from children <5 years old (p < 0.01). Serogroup C was found mainly in children ≥5 years old (63.4 %). The case fatality rates (CFRs) for children <1, 1-4, >4 years old, and the total study population were 9.2, 12.3, 7.7, and 9.9 %, respectively. CFRs were higher for children without meningitis (14.9 %) compared to children with meningitis (7.9 %) (p < 0.01). CONCLUSIONS: Overall, and for serogroups B and W135, childhood IMD rates decreased significantly in Israel during the study period, without routine vaccine usage. The most common serogroup in all age groups was B, which was most prevalent in children <5 years old. No change in the trend of the overall CFR was noted during the study period.

Recent trends in the epidemiology of non-typhoidal Salmonella in Israel, 1999-2009.

The aim of the present study was to assess the recent trends in the epidemiology of non-typhoid Salmonella in Israel using a sentinel laboratory-based surveillance network. Between 1999 and 2009, 8758 Salmonella stool isolates were reported by five sentinel laboratories. There was a significant decrease in the incidence rate of Salmonella isolates from 70·5/100,000 in 1999 to 21·6/100,000 in 2005 followed by a slight increase to 30·3/100,000 in 2009. Of all Salmonella, 64·3% were isolated from children in the 0-4 years age group. Up to 2008, S. Enteritidis was the most prevalent serotype and in 2009 S. Infantis emerged as the most common Salmonella serotype. The decrease in the incidence of S. Enteritidis and S. Typhimurium and increase in S. Infantis among humans were associated with a similar trend among breeding flocks, which followed significant preventive interventions conducted against S. Enteritidis and S. Typhimurium infections in poultry. Tight surveillance and education of food handlers and consumers should be enhanced to reduce the foodborne transmission of Salmonella in Israel.

Transient chemotherapy-induced alopecia after successful reversal of 5-fluorouracil myelosuppression and neurotoxicosis in a 9-month-old dog.

BACKGROUND: 5-Fluorouracil (5-FU) cream is a common human topical chemotherapy agent with potentially fatal neurotoxic effects on dogs if accidentally ingested. There are seldom reports in veterinary literature describing the successful outcome of intervention after accidental ingestion of 5-FU cream. CASE SUMMARY: A 9-month-old spayed female labradoodle presented 14 h after ingesting an unknown amount of 40 g tube of Efudex cream (5% 5-FU). The dog presented in status epilepticus, which was managed with benzodiazepines and levetiracetam in conjunction with induced coma and mechanical ventilation. No further seizure activity occurred throughout the ensuing 5 days of hospitalisation; however, myelosuppression was featured. The dog was discharged home after 5 days of hospitalisation. Three days post discharge, the dog was noted to develop focal alopecia around the eyes and temporal region. 14 days after discharge, the alopecia progressed to a majority of the head and body. CONCLUSION: To the authors' knowledge, this is the first report that documents the enduring adverse effects of 5-FU cream after survival of the initial episode, including an earlier onset of myelosuppression and diffuse alopecia. Successful treatment of accidental 5-FU ingestion is possible several hours after the initial event with minimal long-term consequences.

Clinical characteristics of Stenotrophomonas maltophilia infection in hematopoietic stem cell transplantation recipients: a single center experience.

BACKGROUND: Recipients of hematopoietic stem-cell transplantation (HSCT) are at high risk for infections caused by Stenotrophomonas maltophilia. METHODS: We conducted a retrospective analysis of all infections caused by S. maltophilia in HSCT recipients in a single center in Israel during a 4 year period. RESULTS: Of 570 patients undergoing HSCT, 19 patients with an invasive S. maltophilia infection were identified. Sixteen had allogeneic HSCT and 3 had autologous HSCT. Seventeen patients (90%) had an indwelling central venous catheter (CVC) at the time of infection. S. maltophilia infections were detected in three clinical settings: as a complication of prolonged neutropenia (n = 9), as a CVC-related non-neutropenic infection occurring after CVC manipulation (n = 8) and as a respiratory tract infection (n = 2). Eleven patients (58%) had a polymicrobial infection. Ten patients (52.6%) received carbapenems during the previous month. The treatment for all patients included broad spectrum antibiotics, which were switched according to susceptibilities upon identification of the isolates. All isolates were susceptible in vitro to TMP-SMX. CVCs were removed in 12 patients (70%). Six patients, all after allogeneic HSCT, died. The CVC was removed in only two of the five patients with CVCs who died. CONCLUSIONS: Stenotrophomonas maltophilia is an emerging nosocomial pathogen in HSCT recipients, both in the early neutropenic phase and in the non-neutropenic phase. It is commonly associated with the presence and manipulation of an indwelling CVC. Removal of the CVC in addition to appropriate antibiotic therapy (TMP-SMX) is crucial for infection control.

An outbreak of Burkholderia cenocepacia bacteremia in immunocompromised oncology patients.

BACKGROUND: Burkholderia cepacia is a common environmental bacterium that is resistant to disinfectants, and therefore is often encountered as a hospital-acquired pathogen. We describe an outbreak of B. cenocepacia bacteremia among hospitalized oncology patients. METHODS: A matched case-control study and an extensive environmental investigation were conducted. Species were identified by RFLP of the amplified recA gene. DNA was fingerprinted by pulsed-field gel electrophoresis (PFGE). RESULTS: Between November 2005 and September 2006, B. cenocepacia bacteremia developed in 17 patients with underlying malignancy of whom 14 had tunneled central venous catheters. All patients had fever and chills which subsided following removal of the central catheter and administration of ceftazidime. Extensive epidemiological investigation could not find a common source for the outbreak. Patients were hospitalized in three different buildings with different health care personnel. Medications were prepared in different sites by different personnel. A multivariate analysis demonstrated that the independent risk factors for developing nosocomial B. cenocepacia bacteremia were hospitalization at the center for long-term support (OR 28.8; 95% CI 1.83-453.4) and reduced use of antibiotics during the last month (OR 0.07; 95% CI 0.01-0.40). All isolates had identical antimicrobial susceptibility; PFGE indicated that a complex of closely related strains was involved in the outbreak. All isolates were identified as B. cenocepacia, known to infect cystic fibrosis patients. Strict infection control measures terminated the outbreak. CONCLUSIONS: B. cenocepacia is an emerging nosocomial pathogen among oncology patients.

Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates.

The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of great economic importance to humans. Despite the focus on A. nidulans, very little is known about the natural diversity in secondary metabolism within this species. We determined the BGC content and looked for evolutionary patterns in BGCs from whole-genome sequences of two clinical isolates and the A4 reference genome of A. nidulans Differences in BGC content were used to explain SM profiles determined using liquid chromatography-high-resolution mass spectrometry. We found that in addition to genetic variation of BGCs contained by all isolates, nine BGCs varied by presence/absence. We discovered the viridicatumtoxin BGC in A. nidulans and suggest that this BGC has undergone a horizontal gene transfer from the Aspergillus section Nigri lineage into Penicillium sometime after the sections Nigri and Nidulantes diverged. We identified the production of viridicatumtoxin and several other compounds previously not known to be produced by A. nidulans One isolate showed a lack of sterigmatocystin production even though it contained an apparently intact sterigmatocystin BGC, raising questions about other genes and processes known to regulate this BGC. Altogether, our work uncovers a large degree of intraspecies diversity in BGC and SM production in this genetic model species and offers new avenues to understand the evolution and regulation of secondary metabolism.IMPORTANCE Much of what we know about the genetics underlying secondary metabolite (SM) production and the function of SMs in the model fungus Aspergillus nidulans comes from a single reference genome. A growing body of research indicates the importance of biosynthetic gene cluster (BGC) and SM diversity within a species. However, there is no information about the natural diversity of secondary metabolism in A. nidulans We discovered six novel clusters that contribute to the considerable variation in both BGC content and SM production within A. nidulans We characterize a diverse set of mutations and emphasize how findings of single nucleotide polymorphisms (SNPs), deletions, and differences in evolutionary history encompass much of the variation observed in nonmodel systems. Our results emphasize that A. nidulans may also be a strong model to use within-species diversity to elucidate regulatory cross talk, fungal ecology, and drug discovery systems.

Aspergillus mycoviruses are targets and suppressors of RNA silencing.

RNA silencing can function as a virus defense mechanism in a diverse range of eukaryotes, and many viruses are capable of suppressing the silencing machinery targeting them. However, the extent to which this occurs between fungal RNA silencing and mycoviruses is unclear. Here, three Aspergillus dsRNA mycoviruses were partially characterized, and their relationship to RNA silencing was investigated. Aspergillus virus 1816 is related to Agaricus bisporus white button mushroom virus 1 and suppresses RNA silencing through a mechanism that alters the level of small interfering RNA. Aspergillus virus 178 is related to RNA virus L1 of Gremmeniella abietina and does not appear to affect RNA silencing. The third virus investigated, Aspergillus virus 341, is distantly related to Sphaeropsis sapinea RNA virus 2. Detection of mycovirus-derived siRNA from this mycovirus demonstrates that it is targeted for degradation by the Aspergillus RNA silencing machinery. Thus, our results indicate that Aspergillus mycoviruses are both targets and suppressors of RNA silencing. In addition, they suggest that the morphological and physiological changes associated with some mycoviruses could be a result of their antagonistic relationship with RNA silencing.

RNA silencing gene truncation in the filamentous fungus Aspergillus nidulans.

The genus Aspergillus is ideally suited for the investigation of RNA silencing evolution because it includes species that have experienced a variety of RNA silencing gene changes. Our work on this subject begins here with the model species Aspergillus nidulans. Filamentous ascomycete fungi generally each encode two of the core RNA silencing proteins, Dicer and Argonaute, but A. nidulans appears to have lost one of each to gene truncation events. Although a role in growth, development, or RNA silencing was not detected for the truncated genes, they do produce spliced and poly(A)-tailed transcripts, suggesting that they may have an undetermined biological function. Population analysis demonstrates that the truncated genes are fixed at the species level and that their full-length orthologs in a closely related species are also unstable. With these gene truncation events, A. nidulans encodes only a single intact Dicer and Argonaute. Their deletion results in morphologically and reproductively normal strains that are incapable of experimental RNA silencing. Thus, our results suggest that the remaining A. nidulans RNA silencing genes have a "nonhousekeeping" function, such as defense against viruses and transposons.

Predicting extinction phenotype to optimize fear reduction.

Fear conditioning is widely employed to study dysregulations of the fear system. The repeated presentation of a conditioned stimulus in the absence of a reinforcer leads to a decrease in fear responding-a phenomenon known as extinction. From a translational perspective, identifying whether an individual might respond well to extinction prior to intervention could prove important to treatment outcomes. Here, we test the hypothesis that CO2 reactivity predicts extinction phenotype in rats, and that variability in CO2 reactivity as well as extinction long-term memory (LTM) significantly predicts orexin activity in the lateral hypothalamus (LH). Our results validate a rat model of CO2 reactivity and show that subcomponents of behavioral reactivity following acute CO2 exposure explain a significant portion of the variance in extinction LTM. Furthermore, we show evidence that variability in CO2 reactivity is also significantly predictive of orexin activity in the LH, and that orexin activity, in turn, significantly accounts for LTM variance. Our findings open the possibility that we may be able to use CO2 reactivity as a screening tool to determine if individuals are good candidates for an extinction/exposure-based approach.

Human polyspecific immunoglobulin attenuates group A streptococcal virulence factor activity and reduces disease severity in a murine necrotizing fasciitis model.

OBJECTIVES: Streptococcus pyogenes causes life-threatening invasive infections including necrotizing fasciitis (NF). Current treatment guidelines recommend the use of a cell-wall-active antibiotic combined with a protein synthesis inhibitor and surgical debridement in NF patients. Adjunctive therapy with intravenous immunoglobulin (IVIG) has been proposed for superantigen-associated streptococcal toxic shock syndrome. So far, benefits of IVIG treatment remain unclear and prospective clinical studies are scarce. Thus, we aimed to assess the effects of IVIG on virulence factor activity in vitro, ex vivo in patients and in vivo in a NF mouse model. METHODS: We investigated the effect of IVIG on the activity of the virulence factors streptolysin O (SLO), streptodornase 1 (Sda1), S. pyogenes cell envelope protease and streptococcal pyrogenic exotoxin B in vitro and ex vivo in patient sera. Additionally, we assessed the influence of IVIG on the clinical outcome in a murine NF model. RESULTS: In vitro, IVIG inhibited various streptococcal virulence factors. Further, IVIG treatment of group A Streptococcus-infected mice led to a reduced skin lesion size (median (interquartile range) day 3 intraperitoneal administration: 12 mm2 (9-14.5) vs. 4 mm2 (0.8-10.5), subcutaneous: 10.3 mm2 (6.9-18.6) vs. 0.5 mm2 (0.1-6.8)) and lower SLO activity. After treatment with IVIG, patient sera showed an elevated titre of specific SLO (7/9) and Sda1 (5/9) antibodies, reducing SLO and Sda1 activity. CONCLUSIONS: The clear reduction in disease severity in IVIG-treated mice and inhibition of virulence factor activity in mouse and human sera suggest that IVIG may be beneficial in invasive group A Streptococcus infections such as NF in addition to streptococcal toxic shock syndrome.

Universal screening for Clostridioides difficile in a tertiary hospital: risk factors for carriage and clinical disease.

OBJECTIVES: The role of asymptomatic carriers in Clostridioides difficile infection (CDI) epidemiology is not fully understood. Our aim was to evaluate CD carriage prevalence on admission, associated risk factors, and the risk of developing CDI. METHODS: A 10-week surveillance program for CD carriage of all medical patients admitted to the Sheba Medical Centre was implemented, utilizing an admission rectal swab PCR. Healthcare facility-onset CDI (HO-CDI) was recorded and divided into HO-CDI diagnosed in CD carriers and non-carriers. RESULTS: A total of 4601 admissions were recorded in 3803 patients; 2368 patients had technically analysable rectal swabs, of whom 81 (3.4%) were CD carriers. A multivariate logistic regression model showed that previous hospitalization, old age (>85 years) and low Norton scores were significant independent predictors of CD carriage. Carriers were more likely to receive antimicrobial therapy during hospitalization than non-carriers were. The incidence of HO-CDI in non-carriers was 4.6 cases per 10 000 patient-days; the incidence of HO-CDI in carriers was 76.7 cases per 10 000 patient-days (RR 16.6, 95% CI 4.0-69.1, p .002). CONCLUSIONS: In a prospective study, the rate of CD carriage on admission in medical patients was 3.4%. CD carriers were older, frailer, and more likely to have been hospitalized recently. HO-CDI incidence was significantly higher among CD carriers than among non-carriers, with at least a third of CDI in screened patients developing in carriers. Targeted screening of high-risk groups for CD carriage should be further considered.

Morphological transitions governed by density dependence and lipoxygenase activity in Aspergillus flavus.

Aspergillus flavus differentiates to produce asexual dispersing spores (conidia) or overwintering survival structures called sclerotia. Results described here show that these two processes are oppositely regulated by density-dependent mechanisms and that increasing the cell density (from 10(1) to 10(7) cells/plate) results in the lowest numbers of sclerotial and the highest numbers of conidial. Extract from spent medium of low-cell-density cultures induced a high-sclerotium-number phenotype, whereas high-cell-density extract increased conidiation. Density-dependent development is also modified by changes in lipid availability. Exogenous linoleic acid increased sclerotial production at intermediate cell densities (10(4) and 10(5) cells/plate), whereas oleic and linolenic acids inhibited sclerotium formation. Deletion of Aflox encoding a lipoxygenase (LOX) greatly diminished density-dependent development of both sclerotia and conidia, resulting in an overall increase in the number of sclerotia and a decrease in the number of conidia at high cell densities (>10(5) cells/plate). Aflox mutants showed decreased linoleic acid LOX activity. Taken together, these results suggest that there is a quorum-sensing mechanism in which a factor(s) produced in dense cultures, perhaps a LOX-derived metabolite, activates conidium formation, while a factor(s) produced in low-density cultures stimulates sclerotium formation.