Epidemiological, clinical and laboratory characteristics of acute Q fever in an endemic area in Israel, 2006-2016.

Our purpose was to describe the clinical, epidemiological and laboratory characteristics of patients hospitalised with acute Q fever in an endemic area of Israel. We conducted a historical cohort study of all patients hospitalised with a definite diagnosis of acute Q fever, and compared them to patients suspected to have acute Q fever, but diagnosis was ruled out. A total of 38 patients had a definitive diagnosis, 47% occurred during the autumn and winter seasons, only 18% lived in rural regions. Leucopaenia and thrombocytopaenia were uncommon (16% and 18%, respectively), but mild hepatitis was common (mean aspartate aminotransferase 76 U/l, mean alanine aminotransferase 81 U/l). We compared them with 74 patients in which acute Q fever was ruled out, and found that these parameters were not significantly different. Patients with acute Q fever had a shorter hospitalisation and they were treated more often with doxycycline than those without acute Q fever (6.4 vs. 14 days, P = 0.007, 71% vs. 38%, P = 0.001, respectively). In conclusion, acute Q fever can manifest as an unspecified febrile illness, with no seasonality. We suggest that in endemic areas, Q fever should be considered in the differential diagnosis in any febrile patient with risk factors for a persistent infection.

Evaluating the appropriateness of antimicrobial treatment in hospitalized patients: a comparison of three methods.

BACKGROUND: Approximately 20-50% of antimicrobial therapy in hospitalized patients is considered inappropriate, which may be associated with increased morbidity and mortality. The best method for evaluation of appropriateness is not well defined. AIM: To evaluate the rate of appropriate antimicrobial therapy in a secondary hospital using three different methods, and determine the rate of agreement between the different methods. METHODS: A point prevalence study included all adult hospitalized patients receiving systemic antimicrobial therapy during 2016, screened on a single day. Clinical, laboratory and therapeutic data were collected from patient files, and appropriateness was rated with a qualitative evaluation by expert opinion. In addition, a quantitative evaluation was performed according to 11 quality indicators (QIs) rated for each patient. A strict definition of appropriateness was fulfilled if six essential QIs were met, and a lenient definition was fulfilled if at least five QIs were met. Agreement between methods was analysed using kappa statistic. FINDINGS: Among 106 patients included, rates of appropriateness of antimicrobial therapy ranged from 20% to 75%, depending on the method of evaluation. Very low agreement was found between the strict definition and expert opinion (kappa=0.068), and medium agreement was found between the lenient definition and expert opinion (kappa=0.45). CONCLUSIONS: Rates of appropriateness of antimicrobial therapy varied between evaluation methods, with low to moderate agreement between the different methods.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae carriage upon hospital admission: prevalence and risk factors.

The aim of this study was to assess the value of surveillance cultures in identifying extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL) carriers upon admission to hospital, and to identify risk factors for carriage. This prospective cross-sectional study included all hospital admissions over one week. Of 525 patients screened, 56 were positive for ESBLs. Half were only identified through screening. Four independent risk factors were identified: nursing home residency, hospitalization in the previous year, prior antibiotic treatment and prior ESBL carriage. Over 50% of the screened patients had at least one risk factor. By screening this targeted population, 87.5% of positive patients would have been identified.

The effect of empiric antibiotic therapy on mortality in debilitated patients with dementia.

The purpose of this investigation was to assess the effect of empirical antibiotic treatment on 30-day mortality among debilitated inpatients with dementia and Gram-negative bacteremia. A retrospective cohort study in the years 2005-2007 was undertaken. Data were collected through patient chart review. The association between individual variables and 30-day mortality was assessed through univariate analysis. Variables significantly associated with mortality (p < 0.05) were entered into a logistic regression analysis. Adjusted odds ratios (ORs) for mortality with 95% confidence intervals (CIs) are shown. Subgroup analysis of patients with and without decubitus ulcers was performed. In our cohort of 378 patients with dementia and Gram-negative bacteremia, the 30-day mortality was 39% overall and 61% in the subgroup of patients with decubitus ulcers. Inappropriate empirical therapy was associated with higher mortality, although this effect was not statistically significant (OR 1.41, 95% CI 0.86-2.29). Inappropriate empirical therapy did not affect mortality in the subgroup of patients with decubitus ulcers (OR 0.37, 95% CI 0.11-1.28). Other factors found to independently affect mortality included age, co-morbidities, source of infection, sepsis severity, and hospital-acquired infection. Appropriate empirical antibiotic therapy for patients with dementia and severe bacterial infection did not have a clear advantage, especially in the sickest group of patients with decubitus ulcers.

Cell to cell contacts control the transcription activity of the glucocorticoid receptor.

Contact interactions between glia and neurons are required for hormonal induction of glutamine synthetase in Müller glial cells. Glucocorticoids induce a pronounced increase in glutamine synthetase gene transcription in the intact retinal tissue but not in separated retinal cells. However, if the separated cells are reaggregated and glial cells reestablish contacts with neurons, glutamine synthetase inducibility is restored. This study examines the possible involvement of the glucocorticoid receptor (GR) in cell contact control of glutamine synthetase induction. Using the glucocorticoid-inducible reporter construct, p delta G46TCO, and control constructs that are not inducible by glucocorticoids, we demonstrated that the trans-activating capability of GR markedly declines upon cell separation. Analysis of GR protein revealed that cell separation results in a pronounced decrease in GR expression. This decrease temporally correlated with the decline in glutamine synthetase gene transcription. Cell separation also results in a marked increase in c-Jun expression. This increase might be related to the decline in GR activity since elevation of c-Jun expression in the intact tissue inhibits the transcription activity of GR. Over-expression of GR by transfection of a GR expression vector or activation of endogenous GR molecules by 8-bromo-cAMP enhanced the responsiveness of separated retinal cells to glucocorticoids. These results demonstrate that transcription activity of the receptor protein depends on contact interactions between retinal cells and suggest that GR is involved in cell contact control of glutamine synthetase induction.

Molecular basis for differential expression of glutamine synthetase in retina glia and neurons.

Glutamine synthetase (GS) is a differentiation marker of retina glial cell. It is expressed in the chicken neural retina at a particularly high level, is inducible by glucocorticoids and is always confined to Müller glia. This study investigated the molecular basis for tissue and cell-type specific expression of the GS gene. A high level of GS expression in the retina was found to coincide with the accumulation of a relatively high level of GS mRNA in this tissue. The gliatoxic agent alpha-aminoadipic acid, which can selectively destroy glia cells, was used to demonstrate that restriction of GS induction to Müller glia is controlled at a transcriptional level. Cortisol could induce accumulation of GS mRNA and transcription of the GS gene in Müller glia but not in retina neurons. Glia and neurons were also found to differ in their ability to express the glucocorticoid inducible CAT construct, p delta G46TCO, which is controlled by a 'simple GRE' promoter. When introduced into cells of retina tissue, this construct was cortisol-inducible in glia whereas in neurons it was only slightly inducible or not at all. Introduction of a glucocorticoid receptor expression vector into the cells facilitated induction of the CAT construct in neurons. Analysis by immunoblotting revealed that expression of the glucocorticoid receptor protein is predominantly restricted to Müller glia. These results suggest that differential levels of glucocorticoid receptor expression in glia and neurons might be the basis for cell-type specific induction of GS.

An Okazaki piece of simian virus 40 may be synthesized by ligation of shorter precursor chains.

It is generally accepted that an aphidicolin-sensitive DNA polymerase elongates the eucaryotic RNA primer (iRNA) into a mature Okazaki piece reaching ca. 200 nucleotides. Yet, as shown here, nascent DNA chains below 40 nucleotides accumulated in simian virus 40 (SV40) DNA replicating in isolated nuclei in the presence of aphidicolin. These products resembled precursors of longer Okazaki pieces synthesized in the absence of aphidicolin (termed here DNA primers) in size distribution, lagging-replication-fork polarity, and content of iRNA. Within the isolated SV40 replicative intermediate, DNA primers could be extended in a reaction catalyzed by the Escherichia coli DNA polymerase I large fragment. This increased their length by an average of 21 deoxyribonucleotide residues, indicating that single-stranded gaps of corresponding length existed 3' to the DNA primers. Incubation with T4 DNA ligase converted most of the extended DNA primers into products resembling long Okazaki pieces. These data led us to propose that the synthesis of an SV40 Okazaki piece could be itself discontinuous and could comprise the following steps: (i) iRNA synthesis by DNA primase, (ii) iRNA extension into a DNA primer by an aphidicolin-resistant activity associated with DNA primase-DNA polymerase alpha, (iii) removal of iRNA moieties between adjacent DNA primers, (iv) "gap filling" between DNA primers by the aphidicolin-sensitive DNA polymerase alpha, and (v) ligation of DNA primer units onto a growing Okazaki piece. Eventually, a mature Okazaki piece is ligated onto a longer nascent DNA chain.