Cystitis: symptomatology in women with suspected uncomplicated urinary tract infection

Background: Although cystitis in women is very common in general practice, its evolution in symptoms has not been clearly studied. Qualitative research has pointed to other than the classic symptomatology. Methods: This was a prospective observational study of the symptomatology at presentation and the evolution of the symptoms in treated women with suspected uncomplicated urinary tract infection (UTI). Women consulting their general practitioner (GP) for dysuria, urgency, or frequency produced a urine sample (for bacteriologic processing) and kept a diary until the end of the symptoms. Exclusion criteria included complaints >1 week, fever, vaginal discharge, and known pathology. Results: Of the 300 asked to participate, 148 (49%) returned the diary. Although none of the patients developed acute pyelonephritis, a substantial number of the women had such complaints as feeling feverish (33% in culture-positive group, 38% in culture-negative group), back pains (44% vs. 56%), and feeling weak and tired (71% vs. 65%). Differences between the culture-positive and culture-negative groups were not statistically significant except for the duration of symptoms, which was shorter in the culture-positive group (4 vs. 6 days). More severe symptoms at inclusion were correlated with a longer duration of these symptoms. Conclusions: The spectrum of complaints in women with suspected uncomplicated UTI is broad and comprises a number of symptoms usually associated with an upper UTI. The occurrence of these symptoms should not automatically prompt GPs to prescribe broad-spectrum antibiotics. Moreover, the duration of symptoms exceeding the recommended duration of antibiotic therapy does not indicate therapy failure and, thus, the need for changing antibiotic therapy

Periplasmic Phosphorylation of Lipid a Is Linked to the Synthesis of Undecaprenyl Phosphate

One-third of the lipid A found in the Escherichia coli outer membrane contains an unsubstituted diphosphate unit at position 1 (lipid A 1-diphosphate). We now report an inner membrane enzyme, LpxT (YeiU), which specifically transfers a phosphate group to lipid A, forming the 1-diphosphate species. 32P-labelled lipid A obtained from lpxT mutants do not produce lipid A 1-diphosphate. In vitro assays with Kdo2-[4′- 32P]lipid A as the acceptor shows that LpxT uses undecaprenyl pyrophosphate as the substrate donor. Inhibition of lipid A 1-diphosphate formation in wild-type bacteria was demonstrated by sequestering undecaprenyl pyrophosphate with the cyclic polypeptide antibiotic bacitracin, providing evidence that undecaprenyl pyrophosphate serves as the donor substrate within whole bacteria. LpxT-catalysed phosphorylation is dependent upon transport of lipid A across the inner membrane by MsbA, a lipid A flippase, indicating a periplasmic active site. In conclusion, we demonstrate a novel pathway in the periplasmic modification of lipid A that is directly linked to the synthesis of undecaprenyl phosphate, an essential carrier lipid required for the synthesis of various bacterial polymers, such as peptidoglycan

Construction of matryoshka nested indecomposable N-replications of Kac-modules of quasi-reductive Lie superalgebras, including the sl(m/n) and osp(2/2n) series

We construct a new class of finite dimensional indecomposable representations of simple superalgebras which may explain, in a natural way, the existence of the heavier elementary particles. In type I Lie superalgebras sl(m/n) and osp(2/2n), one of the Dynkin weights labeling the finite dimensional irreducible representations is continuous. Taking the derivative, we show how to construct indecomposable representations recursively embedding N copies of the original irreducible representation, coupled by generalized Cabibbo angles, as observed among the three generations of leptons and quarks of the standard model. The construction is then generalized in the appendix to quasi-reductive Lie superalgebras.Comment: Revised version 2 with minor modifications. On the suggestion of the referee, we show that the construction does not apply to the psl(n/n) superalgebras. 15 pages, 32 references Revised version 3 no modification except reformatting the bibliography and adding do

Identification of cultured isolates of clinically important yeast species using fluorescent fragment length analysis of the amplified internally transcribed rRNA spacer 2 region

BACKGROUND: The number of patients with yeast infection has increased during the last years. Also the variety of species of clinical importance has increased. Correct species identification is often important for efficient therapy, but is currently mostly based on phenotypic features and is sometimes time-consuming and depends largely on the expertise of technicians. Therefore, we evaluated the feasibility of PCR-based amplification of the internally transcribed spacer region 2 (ITS2), followed by fragment size analysis on the ABI Prism 310 for the identification of clinically important yeasts. RESULTS: A rapid DNA-extraction method, based on simple boiling-freezing was introduced. Of the 26 species tested, 22 could be identified unambiguously by scoring the length of the ITS2-region. No distinction could be made between the species Trichosporon asteroides and T. inkin or between T. mucoides and T. ovoides. The two varieties of Cryptococcus neoformans (var. neoformans and var. gattii) could be differentiated from each other due to a one bp length difference of the ITS2 fragment. The three Cryptococcus laurentii isolates were split into two groups according to their ITS2-fragment lengths, in correspondence with the phylogenetic groups described previously. Since the obtained fragment lengths compare well to those described previously and could be exchanged between two laboratories, an internationally usable library of ITS2 fragment lengths can be constructed. CONCLUSIONS: The existing ITS2 size based library enables identification of most of the clinically important yeast species within 6 hours starting from a single colony and can be easily updated when new species are described. Data can be exchanged between laboratories

Extended-Spectrum β-lactamase (ESBL) producing Enterobacter aerogenes phenotypically misidentified as Klebsiella pneumoniae or K. terrigena

BACKGROUND: Enterobacter aerogenes and Klebsiella pneumoniae are common isolates in clinical microbiology and important as producers of extended spectrum β-lactamases (ESBL). The discrimination between both species, which is routinely based on biochemical characteristics, is generally accepted to be straightforward. Here we report that genotypically unrelated strains of E. aerogenes can be misidentified as K. pneumoniae by routine laboratories using standard biochemical identification and using identification automates. RESULTS: Ten clinical isolates, identified as K. pneumoniae or K. terrigena with the routinely used biochemical tests and with API-20E, were identified as E. aerogenes by tDNA-PCR – an identification that was confirmed by 16S rRNA gene sequencing for five of these isolates. Misidentification also occurred when using the automated identification systems Vitek 2 and Phoenix, and was due to delayed positivity for ornithine decarboxylase and motility. Subculture and prolonged incubation resulted in positive results for ornithine decarboxylase and for motility. It could be shown by RAPD-analysis that the E. aerogenes strains belonged to different genotypes. CONCLUSIONS: Clinical E. aerogenes isolates can be easily misidentified as Klebsiella due to delayed positivity for ornithine decarboxylase and motility. The phenomenon may be widespread, since it was shown to occur among genotypically unrelated strains from different hospitals and different isolation dates. A useful clue for correct identification is the presence of an inducible β-lactamase, which is highly unusual for K. pneumoniae. In several instances, the use of genotypic techniques like tDNA-PCR may circumvent problems of phenotypic identification

Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia

Background : Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in people with dementia although there is uncertainty about the effectiveness of their long-term use for this indication and concern that they may cause harm, including higher mortality. When behavioural strategies have failed and treatment with antipsychotic drugs is instituted, regular attempts to withdraw them have been recommended in guidelines. Physicians, nurses and families of older people with dementia may be reluctant to stop antipsychotics, fearing deterioration of NPS. This is an update of a Cochrane Review published in 2013. Objectives : To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia and NPS in primary care or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older participants with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on participants' behaviour and assess safety. Search methods : We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources up to 11 January 2018. Selection criteria : We included all randomised, controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia who had been treated with an antipsychotic drug for at least three months. Data collection and analysis : We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence for each outcome using the GRADE approach. Main results : We included 10 studies involving 632 participants. One new trial (19 participants) was added for this update. One trial was conducted in a community setting, eight in nursing homes and one in both settings. Different types of antipsychotics at varying doses were discontinued in the studies. Both abrupt and gradual withdrawal schedules were used. Reported data were predominantly from studies at low or unclear risk of bias. We included nine trials with 575 randomised participants that used a proxy outcome for overall success of antipsychotic withdrawal. Pooling data was not possible due to heterogeneity of outcome measures used. Based on assessment of seven studies, discontinuation may make little or no difference to whether or not participants complete the study (low-quality evidence). Two trials included only participants with psychosis, agitation or aggression who had responded to antipsychotic treatment. In these two trials, stopping antipsychotics was associated with a higher risk of leaving the study early due to symptomatic relapse or a shorter time to symptomatic relapse. We found low-quality evidence that discontinuation may make little or no difference to overall NPS, measured using various scales (7 trials, 519 participants). There was some evidence from subgroup analyses in two trials that discontinuation may reduce agitation for participants with less severe NPS at baseline, but may be associated with a worsening of NPS in participants with more severe NPS at baseline. None of the studies assessed withdrawal symptoms. Adverse effects of antipsychotics (such as falls) were not systematically assessed. Low-quality evidence showed that discontinuation may have little or no effect on adverse events (5 trials, 381 participants), quality of life (2 trials, 119 participants), or cognitive function (5 trials, 365 participants). There were insufficient data to determine whether discontinuation of antipsychotics has any effect on mortality (very low-quality evidence). Authors' conclusions : There is low-quality evidence that antipsychotics may be successfully discontinued in older people with dementia and NPS who have been taking antipsychotics for at least three months, and that discontinuation may have little or no important effect on behavioural and psychological symptoms. This is consistent with the observation that most behavioural complications of dementia are intermittent and often do not persist for longer than three months. Discontinuation may have little or no effect on overall cognitive function. Discontinuation may make no difference to adverse events and quality of life. Based on the trials in this review, we are uncertain whether discontinuation of antipsychotics leads to a decrease in mortality. People with psychosis, aggression or agitation who responded well to long-term antipsychotic drug use, or those with more severe NPS at baseline, may benefit behaviourally from continuation of antipsychotics. Discontinuation may reduce agitation for people with mild NPS at baseline. However, these conclusions are based on few studies or small subgroups and further evidence of benefits and harms associated with withdrawal of antipsychotic is required in people with dementia and mild and severe NPS. The overall conclusions of the review have not changed since 2013 and the number of available trials remains low

Expanding distribution of lethal amphibian fungus Batrachochytrium salamandrivorans in Europe

Emerging fungal diseases can drive amphibian species to local extinction. During 2010-2016, we examined 1,921 urodeles in 3 European countries. Presence of the chytrid fungus Batrachochytrium salamandrivorans at new locations and in urodeles of different species expands the known geographic and host range of the fungus and underpins its imminent threat to biodiversity

MPV17 does not control cancer cell proliferation

MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene result in hepato-cerebral mitochondrial DNA depletion syndrome in humans. In this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 does not control cancer cell proliferation despite the fact that we initially observed a reduced proliferation rate in five MPV17-silenced cancer cell lines with two different shRNAs. However, shRNA-mediated MPV17 knockdown performed in this work provided misguiding results regarding the resulting proliferation phenotype and only a rescue experiment was able to shed definitive light on the implication of MPV17 in cancer cell proliferation. Our results therefore emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-based gene silencing and clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results

Landscape epidemiology of Batrachochytrium salamandrivorans : reconciling data limitations and conservation urgency

Starting in 2010, rapid-fire salamander (Salamandra salamandra) population declines in northwestern Europe heralded the emergence of Batrachochytrium salamandrivorans (Bsal), a salamander-pathogenic chytrid fungus. Bsal poses an imminent threat to global salamander diversity owing to its wide host range, high pathogenicity, and long-term persistence in ecosystems. While there is a pressing need to develop further research and conservation actions, data limitations inherent to recent pathogen emergence obscure necessary insights into Bsal disease ecology. Here, we use a hierarchical modeling framework to describe Bsal landscape epidemiology of outbreak sites in light of these methodological challenges. Using model selection and machine learning, we find that Bsal presence is associated with humid and relatively cool, stable climates. Outbreaks are generally located in areas characterized by low landscape heterogeneity and low steepness of slope. We further find an association between Bsal presence and high trail density, suggesting that human-mediated spread may increase risk for spillover between populations. We then use distribution modeling to show that favorable conditions occur in lowlands influenced by the North Sea, where increased survey effort is needed to determine how Bsal impacts local newt populations, but also in hill- and mountain ranges in northeastern France and the lower half of Germany. Finally, connectivity analyses suggest that these hill- and mountain ranges may act as stepping stones for further spread southward. Our results provide initial insight into regional environmental conditions underlying Bsal epizootics, present updated invasibility predictions for northwestern Europe, and lead us to discuss a wide variety of potential survey and research actions needed to advance future conservation and mitigation efforts