Urine culture doubtful in determining etiology of diffuse symptoms among elderly individuals: a cross-sectional study of 32 nursing homes

Background: The high prevalence of bacteriuria in elderly individuals makes it difficult to know if a new symptom is related to bacteria in the urine. There are different views concerning this relationship and bacteriuria often leads to antibiotic treatments. The aim of this study was to investigate the relationship between bacteria in the urine and new or increased restlessness, fatigue, confusion, aggressiveness, not being herself/himself, dysuria, urgency and fever in individuals at nursing homes for elderly when statistically considering the high prevalence of asymptomatic bacteriuria in this population.\ud \ud Methods: In this cross-sectional study symptoms were registered and voided urine specimens were collected for urinary cultures from 651 elderly individuals. Logistic regressions were performed to evaluate the statistical correlation between bacteriuria and presence of a symptom at group level. To estimate the clinical relevance of statistical correlations at group level positive and negative etiological predictive values (EPV) were calculated.\ud \ud Results: Logistic regression indicated some correlations at group level. Aside from Escherichia coli in the urine and not being herself/himself existing at least one month, but less than three months, EPV indicated no clinically useful correlation between any symptoms in this study and findings of bacteriuria.\ud \ud Conclusions: Urinary cultures provide little or no useful information when evaluating diffuse symptoms among elderly residents of nursing homes. Either common urinary tract pathogens are irrelevant, or urine culture is an inappropriate test

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms

10.1371/journal.pone.0066663PLoS ONE86-POLN

UniCarb-DB: a database resource for glycomic discovery

Summary: Glycosylation is one of the most important post-translational modifications of proteins, known to be involved in pathogen recognition, innate immune response and protection of epithelial membranes. However, when compared to the tools and databases available for the processing of high-throughput proteomic data, the glycomic domain is severely lacking. While tools to assist the analysis of mass spectrometry (MS) and HPLC are continuously improving, there are few resources available to support liquid chromatography (LC)-MS/MS techniques for glycan structure profiling. Here, we present a platform for presenting oligosaccharide structures and fragment data characterized by LC-MS/MS strategies. The database is annotated with high-quality datasets and is designed to extend and reinforce those standards and ontologies developed by existing glycomics databases. Availability: http://www.unicarb-db.org Contact: [email protected]

Evaluation of dipstick analysis among elderly residents to detect bacteriuria: a cross-sectional study in 32 nursing homes

Background: Up to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. Thus, it is difficult to know if new symptoms in residents with bacteriuria are caused by urinary tract infection (UTI), or if bacteriuria only represents an ABU. This is especially difficult in the presence of non-urinary tract specific symptoms. The diagnostic uncertainty is likely to generate significant overtreatment with UTI antibiotics. Aim: The general aim was to clarify the association between symptoms, bacteriuria, dipstick urinalysis and urine Interleukin-6 (IL-6) among nursing home residents to improve the diagnostic procedure of a suspected lower UTI. Methods: In 2003 a study protocol including newly onset symptoms was completed, and single voided urine specimens collected for dipstick urinalysis and cultures from 651 residents of 32 participating Swedish nursing homes for the elderly. This data was used for a study of dipstick urinalysis (Paper I) and for a study of nonspecific symptoms and bacteriuria (Paper II). In 2012, similar data was collected for 421 elderly residents of 22 nursing homes, which also included an analysis of IL-6 in urine and urine specimens from another 59 residents with urinary catheters. The association between bacteriuria, IL-6 in urine, dipstick urinalysis and newly onset symptoms was analysed (Paper III). Antimicrobial resistance rates were described among residents of nursing homes in 2012 and compared with those from 2003 (Paper IV). Results: Paper I: The negative predictive value for predicting absence of bacteriuria was 88 (84-92)% when dipstick urinalysis for nitrite and leukocyte esterase were simultaneously negative. A positive dipstick or any combination thereof could not sufficiently predict bacteriuria. Papers II-III: New or increased nonspecific symptoms were common among elderly residents of nursing homes. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Paper III: Residents with positive urine cultures had higher concentrations of IL-6 in the urine. However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms. Paper IV: The average rates of antimicrobial resistance were low and did not increase between 2003 and 2012 in Escherichia coli (E. coli) urinary isolates among Swedish nursing home residents. Any antibiotic treatment during the last month and hospitalization during the last six months predicted higher resistance rates among E. coli. Conclusions: Nonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. Therefore, dipstick urinalysis, IL-6 in the urine and urine cultures are of little or no value in clarifying the aetiology of nonspecific symptoms. If there is a reason for testing for bacteriuria, dipstick urinalysis for nitrite and leukocyte esterase can rule out but cannot reliably rule in bacteriuria. Antimicrobial resistance in urinary pathogens among Swedish nursing home residents remained low. It is important to use antibiotics rationally to preserve the effectiveness of antibiotics

GlycoDigest: a tool for the targeted use of exoglycosidase digestions in glycan structure determination

Summary: Sequencing oligosaccharides by exoglycosidases, either sequentially or in an array format, is a powerful tool to unambiguously determine the structure of complex N- and O-link glycans. Here, we introduce GlycoDigest, a tool that simulates exoglycosidase digestion, based on controlled rules acquired from expert knowledge and experimental evidence available in GlycoBase. The tool allows the targeted design of glycosidase enzyme mixtures by allowing researchers to model the action of exoglycosidases, thereby validating and improving the efficiency and accuracy of glycan analysis. Availability and implementation: http://www.glycodigest.org. Contact: [email protected] or [email protected]

UniCarbKB: building a knowledge platform for glycoproteomics

The UniCarb KnowledgeBase (UniCarbKB; http://unicarbkb.org) offers public access to a growing, curated database of information on the glycan structures of glycoproteins. UniCarbKB is an international effort that aims to further our understanding of structures, pathways and networks involved in glycosylation and glyco-mediated processes by integrating structural, experimental and functional glycoscience information. This initiative builds upon the success of the glycan structure database GlycoSuiteDB, together with the informatic standards introduced by EUROCarbDB, to provide a high-quality and updated resource to support glycomics and glycoproteomics research. UniCarbKB provides comprehensive information concerning glycan structures, and published glycoprotein information including global and site-specific attachment information. For the first release over 890 references, 3740 glycan structure entries and 400 glycoproteins have been curated. Further, 598 protein glycosylation sites have been annotated with experimentally confirmed glycan structures from the literature. Among these are 35 glycoproteins, 502 structures and 60 publications previously not included in GlycoSuiteDB. This article provides an update on the transformation of GlycoSuiteDB (featured in previous NAR Database issues and hosted by ExPASy since 2009) to UniCarbKB and its integration with UniProtKB and GlycoMod. Here, we introduce a refactored database, supported by substantial new curated data collections and intuitive user-interfaces that improve database searchin

Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARKAGE Study

Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players. In fact, TETs catalyze the stepwise oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), driving the DNA demethylation process based on thymine DNA glycosylase (TDG)-mediated DNA repair pathway. The present paper reports the expression of DNA hydroxymethylation components, the levels of 5hmC and of its derivatives in peripheral blood mononuclear cells of age-stratified donors recruited in several European countries in the context of the EU Project ‘MARK-AGE’. The results provide evidence for an age-related decline of TET1, TET3 and TDG gene expression along with a decrease of 5hmC and an accumulation of 5caC. These associations were independent of confounding variables, including recruitment center, gender and leukocyte composition. The observed impairment of 5hmC-mediated DNA demethylation pathway in blood cells may lead to aberrant transcriptional programs in the elderly

Climate variability in the subarctic area for the last 2 millennia

To put recent climate change in perspective, it is necessary to extend the instrumental climate records with proxy data from paleoclimate archives. Arctic climate variability for the last 2 millennia has been investigated using statistical and signal analyses from three regionally averaged records from the North Atlantic, Siberia and Alaska based on many types of proxy data archived in the Arctic 2k database v1.1.1. In the North Atlantic and Alaska, the major climatic trend is characterized by long-term cooling interrupted by recent warming that started at the beginning of the 19th century. This cooling is visible in the Siberian region at two sites, warming at the others. The cooling of the Little Ice Age (LIA) was identified from the individual series, but it is characterized by wide-range spatial and temporal expression of climate variability, in contrary to the Medieval Climate Anomaly. The LIA started at the earliest by around AD 1200 and ended at the latest in the middle of the 20th century. The widespread temporal coverage of the LIA did not show regional consistency or particular spatial distribution and did not show a relationship with archive or proxy type either. A focus on the last 2 centuries shows a recent warming characterized by a well-marked warming trend parallel with increasing greenhouse gas emissions. It also shows a multidecadal variability likely due to natural processes acting on the internal climate system on a regional scale. A similar to 16-30-year cycle is found in Alaska and seems to be linked to the Pacific Decadal Oscillation, whereas similar to 20-30- and similar to 50-90-year periodicities characterize the North Atlantic climate variability, likely in relation with the Atlantic Multidecadal Oscillation. These regional features are probably linked to the sea ice cover fluctuations through ice-temperature positive feedback.Peer reviewe

Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study

Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases DNMT1 and DNMT3B with age has been analysed in the context of the MARK-AGE study, a large-scale cross-sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of DNMT1 and DNMT3B gene expression in more than two thousand age-stratified women and men (35-75 years) recruited across eight European countries. Significant age-related changes were detected for both transcripts. The level of DNMT1 gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of DNMT3B decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age-related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of DNMT1 and DNMT3B as an almost independent variable in respect of all other variables evaluated