Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform: relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus.

AIMS: To investigate whether the N-terminal truncated glutamic acid decarboxylase 65 (GAD65) isoform is as well recognized by people with stiff person syndrome as it is by people with Type 1 diabetes, and whether conformational GAD65 antibody epitopes are displayed properly by the isoform. METHODS: GAD65 antibody-positive healthy individuals (n=13), people with stiff-person syndrome (n=15) and children with new-onset Type 1 diabetes (n=654) were analysed to determine binding to full-length GAD65 and the N-terminal truncated GAD65 isoform in each of these settings. GAD65 autoantibody epitope specificity was correlated with binding ratios of full-length GAD65/N-terminal truncated GAD65. RESULTS: The N-terminal truncated GAD65 isoform was significantly less recognized in GAD65Ab-positive people with stiff-person syndrome (P=0.002) and in healthy individuals (P=0.0001) than in people with Type 1 diabetes. Moreover, at least two specific conformational GAD65Ab epitopes were not, or were only partially, presented by the N-terminal truncated GAD65 isoform compared to full-length GAD65. Finally, an N-terminal conformational GAD65Ab epitope was significantly less recognized in DQ8/8 positive individuals with Type 1 diabetes (P=0.02). CONCLUSIONS: In people with stiff person syndrome preferred binding to the full-length GAD65 isoform over the N-terminal truncated molecule was observed. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N-terminal truncated molecule. These findings support the notion of disease-specific GAD65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.

Author Correction: Rapid susceptibility profiling of carbapenem-resistant Klebsiella pneumoniae.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Rapid susceptibility profiling of carbapenem-resistant Klebsiella pneumoniae.

The expanding global distribution of multi-resistant Klebsiella pneumoniae demands faster antimicrobial susceptibility testing (AST) to guide antibiotic treatment. Current ASTs rely on time-consuming differentiation of resistance and susceptibility after initial isolation of bacteria from a clinical specimen. Here we describe a flow cytometry workflow to determine carbapenem susceptibility from bacterial cell characteristics in an international K. pneumoniae isolate collection (n = 48), with a range of carbapenemases. Our flow cytometry-assisted susceptibility test (FAST) method combines rapid qualitative susceptible/non-susceptible classification and quantitative MIC measurement in a single process completed shortly after receipt of a primary isolate (54 and 158 minutes respectively). The qualitative FAST results and FAST-derived MIC (MICFAST) correspond closely with broth microdilution MIC (MICBMD, Matthew's correlation coefficient 0.887), align with the international AST standard (ISO 200776-1; 2006) and could be used for rapid determination of antimicrobial susceptibility in a wider range of Gram negative and Gram positive bacteria.

Norwegian patients and retail chicken meat share cephalosporin-resistant Escherichia coli and IncK/blaCMY-2 resistance plasmids.

OBJECTIVES: In 2012 and 2014 the Norwegian monitoring programme for antimicrobial resistance in the veterinary and food production sectors (NORM-VET) showed that 124 of a total of 406 samples (31%) of Norwegian retail chicken meat were contaminated with extended-spectrum cephalosporin-resistant Escherichia coli. The aim of this study was to compare selected cephalosporin-resistant E. coli from humans and poultry to determine their genetic relatedness based on whole genome sequencing (WGS). METHODS: Escherichia coli representing three prevalent cephalosporin-resistant multi-locus sequence types (STs) isolated from poultry (n=17) were selected from the NORM-VET strain collections. All strains carried an IncK plasmid with a blaCMY-2 gene. Clinical E. coli isolates (n=284) with AmpC-mediated resistance were collected at Norwegian microbiology laboratories from 2010 to 2014. PCR screening showed that 29 of the clinical isolates harboured both IncK and blaCMY-2. All IncK/blaCMY-2-positive isolates were analysed with WGS-based bioinformatics tools. RESULTS: Analysis of single nucleotide polymorphisms (SNP) in 2.5 Mbp of shared genome sequences showed close relationship, with fewer than 15 SNP differences between five clinical isolates from urinary tract infections (UTIs) and the ST38 isolates from poultry. Furthermore, all of the 29 clinical isolates harboured IncK/blaCMY-2 plasmid variants highly similar to the IncK/blaCMY-2 plasmid present in the poultry isolates. CONCLUSIONS: Our results provide support for the hypothesis that clonal transfer of cephalosporin-resistant E. coli from chicken meat to humans may occur, and may cause difficult-to-treat infections. Furthermore, these E. coli can be a source of AmpC-resistance plasmids for opportunistic pathogens in the human microbiota.

Molecular Differentiation of Shigella Spp. from Enteroinvasive E. Coli.

A real-time polymerase chain reaction (PCR) assay, amplifying the genes encoding lactose permease (lacY) and invasion plasmid antigen H (ipaH), was run on 121 isolates phenotypically classified as Shigella spp., enteroinvasive Escherichia coli (EIEC), or EIEC O nontypable (ONT). The results were compared with data from a generic E. coli multiple-locus variable-number of tandem repeat analysis (MLVA) and a Shigella MLVA. The real-time PCR verified all Shigella spp. (n = 53) as Shigella (lacY negative) and all EIEC O121 (n = 15) and EIEC O124 (n = 2) as EIEC (lacY positive). However, the real-time PCR typed EIEC O164 as either EIEC (n = 2) or Shigella (n = 2) and, thus, was not suited for classifying this group of isolates. Interestingly, the majority (42/47, 89.4%) of the EIEC ONT were classified as Shigella (lacY negative) by the real-time PCR, and in nearly all cases, (92.9%, 39/42) data from both MLVA assays supported these findings. Overall, in 94.7% (114/121) of the isolates, the results from the real-time PCR were substantiated by the results from the MLVA assays. In conclusion, the real-time PCR assay was fast and accurate in differentiating Shigella spp. from EIEC, with the exception of the EIEC O164 group. This molecular assay was particularly pragmatic for the challenging EIEC ONT group.

[Alcohol-related cognitive impairment and the DSM-5]. / Alcoholgerelateerde cognitieve stoornissen in de DSM-5.

BACKGROUND: It is evident from the dsm-iv-tr that alcohol-related impairment is extremely difficult to classify accurately. As a result, cognitive deficits can easily be overlooked. The dsm-5, however, incorporates a new category, namely 'neurocognitive disorders', which may lead to significant improvements in clinical practice. AIM: To compare the classification of alcohol-related cognitive dysfunction in dsm-iv-tr and dsm-5 and to discuss the clinical relevance of the revised classification in the dsm-5. METHOD: We compare the chapters of the dsm-iv-tr and the dsm-5 concerning alcohol-related cognitive impairment and describe the changes that have been made. RESULTS: The dsm-5 puts greater emphasis on alcohol-related neurocognitive impairment. Not only does dsm-5 distinguish between the degree of severity (major or minor neurocognitive disorder), it also distinguishes between the type of impairment (non-amnestic-type versus confabulating-amnestic type). It also makes a distinction between the durations of impairment (behavioural and/or persistent disorders). CONCLUSION: The dsm-5 gives a clearer description of alcohol-related neurocognitive dysfunction than does dsm-iv-tr and it stresses the essential role of neuropsychological assessment in the classification, diagnosis, and treatment of neurocognitive disorders.

Are ready-to-eat salads ready to eat? An outbreak of Salmonella Coeln linked to imported, mixed, pre-washed and bagged salad, Norway, November 2013.

We investigated a nationwide outbreak of Salmonella Coeln in Norway, including 26 cases identified between 20 October 2013 and 4 January 2014. We performed a matched case-control study, environmental investigation and detailed traceback of food purchases to identify the source of the outbreak. In the case-control study, cases were found to be more likely than controls to have consumed a ready-to-eat salad mix (matched odds ratio 20, 95% confidence interval 2·7-∞). By traceback of purchases one brand of ready-to-eat salad was indicated, but all environmental samples were negative for Salmonella. This outbreak underlines that pre-washed and bagged salads carry a risk of infection despite thorough cleaning procedures by the importer. To further reduce the risk of infection by consumption of ready-to-eat salads product quality should be ensured by importers. Outbreaks linked to salads reinforce the importance of implementation of appropriate food safety management systems, including good practices in lettuce production.

An outbreak of enterotoxigenic Escherichia coli (ETEC) infection in Norway, 2012: a reminder to consider uncommon pathogens in outbreaks involving imported products.

We investigated an outbreak of gastroenteritis following a Christmas buffet served on 4-9 December 2012 to ~1300 hotel guests. More than 300 people were reported ill in initial interviews with hotel guests. To identify possible sources of infection we conducted a cohort investigation through which we identified 214 probable cases. Illness was associated with consumption of scrambled eggs (odds ratio 9·07, 95% confidence interval 5·20-15·84). Imported chives added fresh to the scrambled eggs were the suspected source of the outbreak but were unavailable for testing. Enterotoxigenic Escherichia coli (ETEC) infection was eventually confirmed in 40 hotel guests. This outbreak reinforces that ETEC should be considered in non-endemic countries when the clinical picture is consistent and common gastrointestinal pathogens are not found. Following this outbreak, the Norwegian Food Safety Authority recommended that imported fresh herbs should be heat-treated before use in commercial kitchens.

PCR-based detection and molecular characterization of shiga toxin-producing Escherichia coli strains in a routine microbiology laboratory over 16 years.

Shiga toxin-producing Escherichia coli (STEC) is a heterogeneous group of bacteria causing disease ranging from asymptomatic carriage and mild infection to hemolytic uremic syndrome (HUS). Here, we describe patients with STEC infection and characterize the STEC strains detected in our laboratory by use of PCR for stx1, stx2, and eae from 1996 through 2011. Patient information was collected from referral forms and from the Norwegian Surveillance System for Communicable Diseases. STEC isolates were characterized with respect to serogroup or serotype, selected potential virulence genes, and multilocus variable-number tandem-repeat analysis (MLVA) genotype. STEC strains were isolated from 138 (1.09%) of 12,651 patients tested. STEC strains of serogroups O26, O103, O121, O145, and O157 were the most frequent. These serogroups, except non-sorbitol-fermenting O157, were also the most frequent among the 11 patients (all ≤5 years old) who developed HUS. Twenty-four STEC strains were classified as being HUS associated based on an epidemiological link to a HUS case, including an MLVA genotype identical to that of the STEC strain. The age of the patient (≤5 years) and the genes eae and stx2a were significantly associated with HUS-associated STEC (P < 0.05 for each parameter), while stx1 was associated with non-HUS-associated STEC (P < 0.05). All of the potential virulence genes analyzed, except ehxA, were significantly more frequent among HUS-associated than non-HUS-associated strains (P < 0.05 for each gene). However, these genes were also present in some non-HUS-associated STEC strains and could therefore not reliably differentiate between HUS-associated and non-HUS-associated STEC strains.

A Shigella sonnei outbreak traced to imported basil--the importance of good typing tools and produce traceability systems, Norway, 2011.

On 9 October 2011, the University Hospital of North Norway alerted the Norwegian Institute of Public Health (NIPH) about an increase in Shigella sonnei infections in Tromsø. The isolates had an identical 'multilocus variable-number tandem repeat analysis' (MLVA) profile. Most cases had consumed food provided by delicatessen X. On 14 October, new S. sonnei cases with the same MLVA-profile were reported from Sarpsborg, south-eastern Norway. An outbreak investigation was started to identify the source and prevent further cases. All laboratory-confirmed cases from both clusters were attempted to be interviewed. In addition, a cohort study was performed among the attendees of a banquet in Tromsø where food from delicatessen X had been served and where some people had reported being ill. A trace-back investigation was initiated. In total, 46 cases were confirmed (Tromsø= 42; Sarpsborg= 4). Having eaten basil pesto sauce or fish soup at the banquet in Tromsø were independent risk factors for disease. Basil pesto was the only common food item that had been consumed by confirmed cases occurring in Tromsø and Sarpsborg. The basil had been imported and delivered to both municipalities by the same supplier. No basil from the specific batch was left on the Norwegian market when it was identified as the likely source. As a result of the multidisciplinary investigation, which helped to identify the source, the Norwegian Food Safety Authority, together with NIPH, planned to develop recommendations for food providers on how to handle fresh plant produce prior to consumption.

QT interval prolongation during ECG evolution in takotsubo cardiomyopathy poses a threat of torsade de pointes to predisposed patients. Case report of a female patient with congenital AV block.

We report the case of a female patient with congenital complete atrioventricular block who developed torsade de pointes (TdP) in the course of takotsubo cardiomyopathy. On the basis of this case, we show that the electrocardiographic evolutionary changes with QT interval prolongation (in the course of takotsubo cardiomyopathy) may be a TdP threatening period in patients with underlying predispositions. After reviewing the literature, we also present the electrocardiographic similarities between takotsubo cardiomyopathy and other acute heart diseases associated with a large amount of stunned myocardium, i.e., other stress-related cardiomyopathies (e.g., those associated with subarachnoid hemorrhage, pheochromocytoma, or severe illnesses) as well as a reperfused myocardial infarction. QT interval prolongation is a common feature in the subacute phase of these entities; however, excessive QT prolongation may be a sign of predisposition to TdP. In such instances, measures should be taken to monitor cardiac rhythm closely and to prevent or treat TdP appropriately. Taking into account the risk of TdP, it is reasonable to consider takotsubo cardiomyopathy as a potential cause of acquired long QT syndrome.

[The neuropsychology of cognitive functions in alcohol abstinence]. / Neuropsychologische diagnostiek en cognitieve functies bij alcoholabstinentie.

BACKGROUND: There is a vast amount of scientific evidence for the negative effects of alcohol on the functioning of the whole human body and particularly of the brain. The literature, however, is unclear about whether these functions can fully recover and about how long the abstinence period must be before patients with alcohol use disorder (AUD) can be reliably assessed for cognitive and emotional functioning. AIM: To review current findings on the length of the abstinence period required before a reliable neuropsychological assessment of the cognitive and emotional functioning of AUD patients can be carried out. METHOD: Using PubMed, PsycINFO and Medline, we consulted the literature for the period from 1975 to October 2011 relating to the effects of alcohol abstinence on the brain. RESULTS: The longer the period of abstinence, the greater the improvement in a patient's neuropsychological functioning. In the case of AUD patients, it takes at least six weeks for neuropsychological functioning to return to a fairly stable level. CONCLUSION: An abstinence period of at least six weeks is needed before a reliable neuropsychological assessment can be carried out. This time period minimises the disturbance caused by earlier alcohol abuse. A neuropsychological standard of this kind, involving a six week period of abstinence, is needed for AUD patients if they are to receive an appropriate and individualised neuropsychological assessment.

Outbreak of Shigella sonnei infection in Norway linked to consumption of fresh basil, October 2011.

We report a Shigella sonnei outbreak of 46 cases that occurred in Norway during October 2011. Two municipalities were involved. A large cluster (42 cases)was concentrated in north Norway, while a smallcluster (4 cases) occurred in the south-east region.Epidemiological evidence and trace back investigations have linked the outbreak to the consumption of imported fresh basil. The product has been withdrawn from the market. No further cases have been reported since 25 October.

Yersinia enterocolitica O:9 infections associated with bagged salad mix in Norway, February to April 2011.

In March 2011, the Norwegian Institute of Public Health identified a possible outbreak involving 21 cases of Yersinia enterocolitica O:9 infection with similar MLVA-profiles. Preliminary results of epidemiological and microbiological investigations indicate bagged salad mix containing radicchio rosso (also known as Italian chicory) as a possible source. As a result of the investigation, bagged salad mixes of a specific brand were voluntarily withdrawn from the market by the producer.

Event-related potentials and secondary task performance during simulated driving.

Inattention and distraction account for a substantial number of traffic accidents. Therefore, we examined the impact of secondary task performance (an auditory oddball task) on a primary driving task (lane keeping). Twenty healthy participants performed two 20-min tests in the Divided Attention Steering Simulator (DASS). The visual secondary task of the DASS was replaced by an auditory oddball task to allow recording of brain activity. The driving task and the secondary (distracting) oddball task were presented in isolation and simultaneously, to assess their mutual interference. In addition to performance measures (lane keeping in the primary driving task and reaction speed in the secondary oddball task), brain activity, i.e. event-related potentials (ERPs), was recorded. Performance parameters on the driving test and the secondary oddball task did not differ between performance in isolation and simultaneous performance. However, when both tasks were performed simultaneously, reaction time variability increased in the secondary oddball task. Analysis of brain activity indicated that ERP amplitude (P3a amplitude) related to the secondary task, was significantly reduced when the task was performed simultaneously with the driving test. This study shows that when performing a simple secondary task during driving, performance of the driving task and this secondary task are both unaffected. However, analysis of brain activity shows reduced cortical processing of irrelevant, potentially distracting stimuli from the secondary task during driving.

Secondary amyloidosis in inflammatory bowel disease: a study of 18 patients admitted to Rikshospitalet University Hospital, Oslo, from 1962 to 1998.

BACKGROUND: Amyloidosis (A) is a well-known but rare complication to inflammatory bowel disease (IBD). We describe 18 patients with IBD and A, with special emphasis on clinicopathologic features and site relationships, comparing our results with previously reported cases in the world literature. METHODS: Patient records were collected from the files of the medical department at Rikshospitalet. Clinical data were compiled from records. RESULTS: Fifteen of the 18 patients had Crohn's disease (CD), 1 had ulcerative colitis (UC), one had UC preceding CD, and 1 had indeterminate colitis. There was a male preponderance of 13:5 = 2.6. Five of the patients had A at the time of diagnosis of IBD. Median time from diagnosis of IBD to A was 4 years, and A was diagnosed within 5 years after onset of IBD in 11 patients. Thirteen of the patients had suppurative complications; 12 had extraintestinal manifestations. Sixteen of the patients had been treated by bowel resection, 14 due to refractory IBD. Ten patients had been treated by renal transplantation. After 15 years of follow-up, the survival rate was 60%. CONCLUSIONS: Our findings strengthen the previous impression of an approximately 3-fold increased preponderance in males, with at least 10-fold increased frequency in CD compared with UC, and with a possible relationship to suppurative complications and extraintestinal manifestations, as well as an increased risk of having a bowel resection. The increased survival seems to be due to the introduction of renal transplantation.

The effect duration of candesartan cilexetil once daily, in comparison with enalapril once daily, in patients with mild to moderate hypertension.

OBJECTIVE: To determine the antihypertensive efficacy, effect duration and safety of the angiotensin II type 1 receptor blocker candesartan cilexetil and the angiotensin converting enzyme inhibitor enalapril once daily in patients with mild to moderate hypertension. METHODS: A multicenter, randomised, double-blind parallel group study was performed in Finland, France, the Netherlands, Spain and Sweden. Three-hundred-and-ninety-five men and women in the age range 20-80 years with primary hypertension were randomised to an 8-week double-blind treatment period with either candesartan cilexetil 8-16 mg or enalapril 10-20 mg once daily, with forced dose titration after 4 weeks. Non-invasive ambulatory blood pressure was measured for 36 h at baseline and after 8 weeks. The primary efficacy variable was the change in mean diastolic and systolic ambulatory blood pressure 22-24 h post-dose. RESULTS: There was a significant difference in the adjusted mean difference for the change from baseline to week 8 between candesartan cilexetil and enalapril 22-24 h post-dose by -3.5 mmHg (95% confidence interval, CI: -6.8 to -0.3 mmHg; p < 0.032) in ambulatory systolic blood pressure and -3.0 mmHg (95% CI: -5.1 to -0.8 mmHg; p < 0.008) in ambulatory diastolic blood pressure. There was a significant difference in adjusted mean daytime ambulatory blood pressure 24-36 h post-dose by -4.2 mmHg (95% CI: -6.8 to -1.6 mmHg; p < 0.002)/-3.5 mmHg (95% CI: -5.1 to -1.8 mmHg; p < 0.001). Both drugs were generally well tolerated. CONCLUSION: The results of the present study suggest that advantages may be attributed to the use of candesartan cilexetil, as compared to enalapril in the treatment of patients with essential hypertension. In comparison with enalapril 20 mg, candesartan cilexetil 16 mg more effectively lowered blood pressure at trough and in particular on the day following the day after the last dose.

Verminderde vergrijzing en M. Korsakov; toeval of een voorbeeld van serendiptisme?

The clinical observation that patients with an alcohol amnestic disorder get grey hair at a higher age was investigated by comparing a group of Korsakov patients and patients with alcohol abuse with a reference sample from the literature. Korsakoff patients appeared to be significantly less grey than age-matched alcoholics and controls. Some putative etiological factors including the mechanism of apoptosis are discussed.