Cerebrospinal fluid cytokines in Lyme neuroborreliosis

Background: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods. A few other cytokines have also been analyzed as possible diagnostic markers. However, multiplex analyses simultaneously evaluating the concentrations of a large number of different cytokines in the CSF of LNB patients have been lacking thus far. Extensive cytokine profiling CSF samples of LNB patients would also help in understanding the complex immunopathogenesis of LNB.Methods: CSF samples were analyzed from 43 LNB patients, 19 controls, 18 tick-borne encephalitis patients, and 31 multiple sclerosis patients. In addition, CSF samples from 23 LNB patients obtained after the antibiotic treatment were examined. Altogether, the concentrations of 49 different cytokines were determined from all of the samples. The concentrations of 48 different cytokines were analyzed by magnetic bead suspension array using the Bio-Plex Pro Human Cytokine 21- and 27-plex panels, and the concentration of CXCL13 was analyzed by an ELISA based method.Results: Distinct cytokine profiles which were able to distinguish LNB patients from controls, tick-borne encephalitis patients, multiple sclerosis patients, and LNB patients treated with antibiotics were identified. LNB patients had elevated concentrations of all major T helper cell type cytokines (Th1, Th2, Th9, Th17, and Treg) in their CSF.Conclusions: Despite the great differences in the CSF cytokine profiles of different patient groups, CXCL13 still remained as the best marker for LNB. However, IL-1ra might also be helpful as a marker for the antibiotic treatment response. Concerning the immunopathogenesis, this is the first report suggesting the involvement of Th9 cells in the immune response of LNB

Circulating cell-free DNA level predicts all-cause mortality independent of other predictors in the Health 2000 survey

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Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease

Introduction: The biallelic repeat expansion (AAGGG)(exp) in RFC1 causes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Recently, cognitive impairment has been reported in patients with CANVAS and a broader neurodegenerative process associated with RFC1 has been suggested. Furthermore, rare cases of multiple system atrophy, Parkinson's disease, amyotrophic lateral sclerosis or CANVAS with features of dementia with Lewy bodies have been found. Objective: We hypothesized that the biallelic (AAGGG)(exp) is associated with neurodegeneration manifested as cognitive symptoms and that atypical RFC1 disease may be found among patients with cognitive disorder. Methods: Clinical data on nine patients with biallelic (AAGGG()exp) were reviewed and 564 patients with Alz-heimer's disease or frontotemporal dementia (FTD) were investigated for biallelic RFC1 (AAGGG)(exp). Results: Five patients with biallelic (AAGGG)(exp) were found with a cognitive impairment and in four of them the phenotype resembled FTD. However, biallelic (AAGGG)(exp) was not detected among patients with Alzheimer's disease or FTD. Conclusion: Cognitive impairment is a feature in patients with the biallelic (AAGGG)(exp), but the pathogenic expansion seems to be rare in patients with dementia. Studies on patients with diverse phenotypes would be useful to further explore the involvement of RFC1 in neuronal degeneration and to identify atypical phenotypes, which should be taken into account in clinical practice.Peer reviewe

Reading comprehension in digital and printed texts

Recent studies have yielded contradictory results regarding how reading from print or from the screen influences reading comprehension. This study examined 12-year-old students’ (N = 142) reading comprehension using printed text and digital text. The results indicated that performance was similar for printed text and digital text, even when gender, decoding skills, preference for school tasks on paper, screen, or both, and self-concept as a reader and computer user were controlled for. Regardless of the reading medium, students with better decoding skills and a higher self-concept as a reader performed better, boys outperformed girls, and students equally willing to study with books and computers outperformed students who preferred computers. The results of this study highlight the benefits of flexible use of both printed texts and digital texts for reading comprehension. As students are getting as used to studying via computers as they are to studying from books, the emphasis on the medium of studying seems to become less important. The topic of this study is of great relevance in a modern school context where ICT use has become a part of daily schoolwork worldwide.</p

Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes

Objective: Interleukin (IL)-1 impairs insulin secretion and induces beta-cell apoptosis. Pancreatic beta-cell IL-1 expression is increased and interleukin-1-receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes mellitus. Treatment with recombinant IL-1Ra improves glycemia and beta-cell function and reduces inflammatory markers in patients with type 2 diabetes mellitus. Here we investigated the durability of these responses. Research Design and Methods: Among 70 ambulatory patients with type 2 diabetes and A1C and body mass index higher than 7.5% and 27, respectively, randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blinded 39 week follow-up study. Primary outcome was change in betacell function following anakinra withdrawal. Analysis was done by intention-to-treat. Results: Thirty-nine weeks following anakinra withdrawal the proinsulin to insulin (PI/I) ratio but not stimulated C-peptide remained improved by -0.07 (95% CI -0.14 to -0.02, P=0.011) compared to placebo treated patients. Interestingly, a subgroup characterized by genetically determined low baseline IL-1Ra serum levels, maintained the improved stimulated C-peptide obtained by 13 weeks of IL-1Ra treatment. Reductions of C-reactive protein (-3.2 mg/l [95% CI -6.2 to -1.1, P=0.014]) and of IL-6 (-1.4 ng/l [95% CI -2.6 to -0.3, P=0.036]) were maintained until end of study. Conclusions: IL-1 blockade with anakinra induces improvement of the PI/I ratio and in markers of systemic inflammation lasting 39 weeks following treatment withdrawal

Validation of indirect calorimetry for measurement of energy expenditure in healthy volunteers undergoing pressure controlled non-invasive ventilation support

The aim of this validation study was to assess the reliability of gas exchange measurement with indirect calorimetry among subjects who undergo non-invasive ventilation (NIV). Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in twelve healthy volunteers. Respiratory quotient (RQ) and resting energy expenditure (REE) were then calculated from the measured VO2 and VCO2 values. During the measurement period the subjects were breathing spontaneously and ventilated using NIV. Two different sampling air flow values 40 and 80 l/min were used. The gas leakage from the measurement setup was assessed with a separate capnograph. The mean weight of the subjects was 93 kg. Their mean body mass index was 29 (range 22-40) kg/m(2). There was no statistically significant difference in the measured values for VO2, VCO2, RQ and REE during NIV-supported breathing and spontaneous breathing. The change of sampling air flow had no statistically significant effect on any of the above parameters. We found that REE can be accurately measured with an indirect calorimeter also during NIV-supported breathing and the change of sampling air flow does not distort the gas exchange measurement. A higher sampling air flow in indirect calorimetry decreases the possibility for air leakages in the measurement system and increases the reliability of REE measurement

On-farm deaths of dairy cows are associated with features of freestall barns

ABSTRACT On-farm death (OFD) of a dairy cow is always a financial loss for a farmer, and potentially a welfare issue that has to be addressed within the dairy industry. The aim of this study was to explore the associations between OFD of dairy cows, housing, and herd management in freestall barns. To achieve the goal, we followed 10,837 cows calving in 2011 in 82 herds. Data were gathered with observations and a structured interview during farm visits and from a national dairy herd improvement database. The hazard of OFD was modeled with a shared frailty survival model, with SAS 9.3 PHREG procedure (SAS Institute Inc., Cary, NC). The study population was 58% Ayrshire and 42% Holstein cows. The median herd size and mean milk yield in the study herds were 116 cows and 9,151 kg of milk per cow per year. The overall probability of OFD was 6.0%; 1.8% of the cows died unassisted and 4.2% were euthanized. Variation in OFD percentage between individual herds was large, from 0 to 16%, accounting for 0 to 58% of all removals in the herds. Keeping close-up dry cows in an own group was associated with higher hazard of OFD [hazard ratio (HR) = 1.37] compared with keeping them in the same pen with far-off dry cows. Higher hazard on OFD was observed when barns had only one kind of calving pens; single (HR = 2.09) or group pens (HR = 1.72), compared with having both of those types. The hazard of OFD was lower if the whole herd was housed in barns or pens that had only 1 type of feed barrier at the feed bunk, namely post-and-rail (HR = 0.51) or a type with barriers between the cow's heads (HR = 0.49), compared with having 2 types. Lower OFD hazard was observed with wider than 340 cm of walking alley next to the feeding table (HR = 0.75), and with housing a whole herd in pens with only 1 type of walking alley surface, specifically slatted (HR = 0.53) or solid (HR = 0.48), compared with having both types. The hazard of OFD was higher with stalls wider than 120 cm (HR = 1.38) compared with narrower stalls. The hazard of OFD was also associated with breed, parity, and calving season. This study identified many factors that contribute to the incidence of OFD of dairy cows. The solutions for reducing on-farm mortality include housing, management, and breeding choices that are most probably herd specific.Peer reviewe