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

The World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the WHO Minimal Generic Set of Domains of Functioning and Health versus Conventional Instruments in subacute stroke

Objective: To compare short generic International Classification of Functioning, Disability and Health (ICF)-based measures of functioning with traditional measures of stroke severity and dependence in subacute stroke.Methods: In this cross-sectional study patients with stroke (n = 195) and their significant others completed the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0) at discharge from rehabilitation. A neurologist assessed functioning with the 7-item World Health Organization (WHO) Minimal Generic Set of domains of functioning and health. These scores were compared with assessments of severity of stroke (National Institutes of Health Stroke Scale; NIHSS) and dependence (modified Rankin Scale; mRS; and Functional Independence Measure; FIM).Results: From mild to severe stroke, increasing disability was found in single items and sum scores of WHODAS and the WHO Minimal Generic Set. Although proxies rated 6 out of the 12 separate WHODAS functions more impaired than did the patients, correlations between the different measures (proxy- and patient-WHODAS, the WHO Minimal Generic Set, mRS, NIHSS and FIM total and sub-scores) were strong to very strong, except for moderate correlations between patient-WHODAS, and NIHSS or FIM cognitive sub-score.Conclusion: Despite their brevity, both generic ICF-based tools were useful in finding disabilities for patient- and family-centred goal-setting and service-planning after subacute rehabilitation

Hospital admissions and surgical treatment of children with lower-limb deficiency in Finland

Background and Aims: There are no population-based studies about hospital admissions and need for surgical treatment of congenital lower-limb deficiencies. The aim is to assess the impact children with lower-limb deficiencies pose to national hospital level health-care system. Materials and Methods: A population-based study was conducted using the national Register of Congenital Malformations and Care Register for Health Care. All 185 live births with lower-limb deficiency (1993-2008) were included. Data on hospital care were collected until 31 December 2009 and compared to data on the whole pediatric population (0.9 million) live born in 1993-2008. Results: The whole pediatric population had annually on average 0.10 hospital admissions and the mean length of in-patient care of 0.3 days per child. The respective figures were 1.5 and 5.6 in terminal lower-limb amputations (n = 7), 1.1 and 3.9 in long-bone deficiencies (n = 53), 0.6 and 1.9 in foot deficiencies (n = 26) and 0.4 and 2.6 in toe deficiencies (n = 101). Orthopedic surgery was performed in 72% (5/7) of patients with terminal amputations, in 62% (33/53) of patients with long bone, in 58% (14/24) of patients with foot and in 25% (25/101) of patients in toe deficiencies. Half (54%) of all procedures were orthopedic operations. Conclusion: In congenital lower-limb deficiencies the need of hospital care and the number of orthopedic procedures is multiple-fold compared to whole pediatric population. The burden to the patient and to the families is markedly increased, especially in children with terminal amputations and long-bone deficiencies of lower limbs.Peer reviewe

Predictors for occupational injuries and diseases among commercial fishers in Finland 1996–2015

Fishing is a hazardous occupation worldwide. Commercial fishers in Finland are an aging and diminishing population with a high injury rate. Insurance claims data for self-employed Finnish commercial fishers during the years 1996 through 2015 (n = 1951) were analysed to assess predictors for occupational injuries and diseases. Out of the available variables, fishery location, career length, and participation in the voluntary occupational health service programme were not significant predictors. Male gender (OR 2.02; 95% CI 1.37–2.99), Finnish mother tongue vs. Swedish (OR 1.98, 95% CI 1.53–2.55), and higher income levels from fishing (four income categories, OR range: 1.71–3.53) were associated with higher odds for a compensated occupational injury or disease claim among commercial fishers in the final multivariate model. The identified risk groups could be targeted for interventions, and the content of the occupational health service programme should be developed to gain protective effect

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

Bankart versus Latarjet operation as a revision procedure after a failed arthroscopic Bankart repair

Background: An arthroscopic Bankart operation is the most common operative procedure to treat shoulder instability. In case of recurrence, both Bankart and Latarjet procedures are used as revision procedures. The purpose of this study was to compare the re-recurrence rate of instability and clinical results after arthroscopic revision Bankart and open revision Latarjet procedures following failed primary arthroscopic Bankart operations.Methods: Consecutive patients operatively treated for shoulder instability at Turku University Hospital between 2002 and 2013 were analyzed. Patients who underwent a primary arthroscopic Bankart operation followed by a recurrence of instability and underwent a subsequent arthroscopic Bankart or open Latarjet revision operation with a minimum of 1 year of follow-up were called in for a follow-up evaluation. The re-recurrence of instability, Subjective Shoulder Value, and Western Ontario Shoulder Instability index were assessed.Results: Of 69 patients, 48 (dropout rate, 30%) were available for follow-up. Recurrent instability symptoms occurred in 13 patients (43%) after the revision Bankart procedure and none after the revision Latarjet procedure. A statistically and clinically significant difference in the Western Ontario Shoulder Instability index was found between the patients after the revision Bankart and revision Latarjet operations (68% and 88%, respectively; P = .0166).Conclusions: The redislocation rate after an arthroscopic revision Bankart operation is high. Furthermore, patient-reported outcomes remain poor after a revision Bankart procedure compared with a revision Latarjet operation. We propose that in cases of recurring instability after a failed primary Bankart operation, an open Latarjet revision should be considered.</p

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

Prospective multicentre cohort trial on acute appendicitis and microbiota, aetiology and effects of antimicrobial treatment: study protocol for the MAPPAC (Microbiology APPendicitis ACuta) trial

Introduction Based on the epidemiological and clinical data, acute appendicitis can present either as uncomplicated or complicated. The aetiology of these different appendicitis forms remains unknown. Antibiotic therapy has been shown to be safe, efficient and cost-effective for CT-confirmed uncomplicated acute appendicitis. Despite appendicitis being one of the most common surgical emergencies, there are very few reports on appendicitis aetiology and pathophysiology focusing on the differences between uncomplicated and complicated appendicitis. Microbiology APPendicitis ACuta (MAPPAC) trial aims to evaluate these microbiological and immunological aspects including immune response in the aetiology of these different forms also assessing both antibiotics non-responders and appendicitis recurrence. In addition, MAPPAC aims to determine antibiotic and placebo effects on gut microbiota composition and antimicrobial resistance.Methods and analysis MAPPAC is a prospective clinical trial with both single-centre and multicentre arm conducted in close synergy with concurrent trials APPendicitis ACuta II (APPAC II) (per oral (p.o.) vs intravenous+p.o. antibiotics, NCT03236961) and APPAC III (double-blind trial placebo vs antibiotics, NCT03234296) randomised clinical trials. Based on the enrolment for these trials, patients with CT-confirmed uncomplicated acute appendicitis are recruited also to the MAPPAC study. In addition to these conservatively treated randomised patients with uncomplicated acute appendicitis, MAPPAC will recruit patients with uncomplicated and complicated appendicitis undergoing appendectomy. Rectal and appendiceal swabs, appendicolith, faecal and serum samples, appendiceal biopsies and clinical data are collected during the hospital stay for microbiological and immunological analyses in both study arms with the longitudinal study arm collecting faecal samples also during follow-up up to 12 months after appendicitis treatment.</p

Borrelia burgdorferi Infection in Biglycan Knockout Mice

Background: Borrelia burgdorferi sensu lato spirochetes (Borrelia) causing Lyme borreliosis are able to disseminate from the initial entry site to distant organs in the host. Outer-surface adhesins are crucial in the bacterial dissemination and adhesion to various tissues. Two well-characterized Borrelia adhesins, decorin-binding proteins A and B, have been shown to bind to 2 host receptors, decorin and biglycan. However, the role of biglycan in Borrelia infection has not been characterized in vivo.Methods: We infected biglycan knockout (KO) and wild-type (WT) C3H mice with strains representing 3 Borrelia genospecies, Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. The infection was monitored by measuring joint swelling, Borrelia culture, polymerase chain reaction analysis, and serologic analysis. The host immune responses were analyzed by histological scoring of the inflammation in tissues and by cytokine profiling.Results: B. burgdorferi sensu stricto and B. garinii established long-term infection in mice of both genotypes, while B. afzelii failed to disseminate in KO mice. Further, the B. burgdorferi sensu stricto–infected KO mice had persistent inflammation in the joints.Conclusions: The dissemination and tissue colonization of Borrelia and the inflammatory response of the host differ in a mouse biglycan expression– and Borrelia genospecies–dependent manner.</p