Job stress and burnout among Finnish municipal employees without depression or anxiety.

BACKGROUND: Job burnout is associated with job stress but also with mental health symptoms, depression and anxiety. AIMS: This study aims to evaluate the effect of job stress on burnout without the effect of depression and anxiety. METHODS: A cross-sectional study was conducted in 2015 among 673 employees (88% female) from four public service sectors in Pori, Finland. Job burnout was assessed with the Bergen Burnout Indicator (BBI-15). Job stress was assessed by combining psychological risk factors (demand control, effort rewards and mental workload). Respondents who reported symptoms of depression and anxiety were excluded from the analyses. RESULTS: Of the eligible study subjects (n = 617), 10% reported symptoms of at least mild burnout but only 1% severe burnout. The burnout symptoms varied from 6% to 21% by sector of public service. Job burnout was cumulatively associated with job stress factors. One job stress factor increased the risk of burnout 2-fold (relative risk [RR] 2.13; confidence interval [CI] 0.97-4.68), two factors 6-fold (RR 6.56; 2.92-14.8Or), and three factors even more (RR 23.5; CI 8.67-63.8). Similar trends were observed in the analysis of job burnout components (exhaustion, cynicism and professional inadequacy). CONCLUSIONS: Our results indicate that job burnout is also strongly associated with job stress in employees who do not have depressive or anxiety symptoms. As job burnout may precede clinical depression or reduce productivity and well-being at work, it is essential to perform surveys to monitor burnout symptoms among the workforce, and design interventions to prevent remarkable job strain.

Altered PKR Signalling and C / EBPß Expression is Associated with HLA-B27 Expression in Monocytic Cells.

Infection caused by certain gram-negative bacteria, e.g. Salmonella, can trigger inflammatory joint disease reactive arthritis (ReA). It is suggested that the disease-triggering bacteria or bacterial components persist in patients for an abnormally long time. Development of ReA is strongly associated with tissue antigen HLA-B27. Previously, we reported an enhanced replication of Salmonella enteritidis and altered p38 MAP kinase signalling in HLA-B27-expressing monocytic cells. Here we aimed to investigate the role of HLA-B27 in regulation of double-stranded RNA-activated kinase (PKR)-related signalling in Salmonella-infected or Salmonella lipopolysaccharide (LPS)-stimulated human U937 monocytic cells, as PKR has been reported to modify p38 signalling in Salmonella-infected cells. In cells expressing HLA-B27, PKR is overexpressed and hypophosphorylated, and the expression of transcription factor CCAAT enhancer binding protein beta (C/EBPß) is increased upon Salmonella infection and LPS stimulation. The expression of C/EBPß is PKR-dependent in LPS-stimulated mock cells, whereas in LPS-stimulated B27 cells the majority of C/EBPß is expressed in a PKR-independent manner. Our results show that the expression of HLA-B27 disturbs the PKR-mediated signalling pathway. Moreover, altered signalling is related to misfolding-linked Glu45 in the B pocket of the HLA-B27 heavy chain. We suggest that the expression of HLA-B27 HCs modulates the intracellular environment of monocyte/macrophages and the mechanisms that are important in eliminating intracellular S. enteritidis by altering the intracellular signalling. This phenomenon is at least partly dependent on the misfolding feature of the B27 molecule. These observations offer a novel mechanism by which HLA-B27 may modulate inflammatory response induced by ReA-triggering bacteria.

Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly known. We studied 15 Fabry patients (mean age 35 years and mean BMI 24.8 kg/m2) and 30 age- and BMI-matched healthy controls to examine whether myocardial perfusion reserve and peripheral artery endothelial function are altered. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and H2(15)O. Myocardial blood flow reserve was calculated as the ratio between the dipyridamole-induced maximal blood flow and resting blood flow. Peripheral artery endothelial function was assessed by measuring the brachial artery flow-mediated dilatation using ultrasound at rest and during reactive hyperaemia. The myocardial perfusion reserve was significantly lower in Fabry patients than in controls (3.3+/-1.2 vs 4.4+/-1.6, p=0.02), while the brachial artery flow-mediated dilatation was similar (5.9%+/-3.9% vs 4.5%+/-3.6%, p=0.27). Thus, inFabry disease, myocardial perfusion reserve is reduced while the peripheral artery endothelial function is preserved.

Enrichment of the R77C alpha-sarcoglycan gene mutation in Finnish LGMD2D patients.

Limb-girdle muscular dystrophy 2D (LGMD2D) is caused by mutations in the alpha-sarcoglycan gene (SGCA). The most frequently reported mutation, 229CGC>TGC (R77C) in exon 3 of SGCA, results in the substitution of arginine by cysteine. We present here the clinical, immunohistochemical, and genetic data of 11 Finnish patients with LGMD2D caused by mutations in SGCA. Mutational analysis showed 10 patients homozygous and 1 compound heterozygous for R77C. A wide spectrum of SGCA mutations has been reported previously. Our results show an enrichment of R77C in Finland, further underlined by the observed carrier frequency of 1 per 150. According to the annual birth rate of approximately 60,000 in Finland, one LGMD2D patient with a homozygous mutation is expected to be born every 1 or 2 years on average. The presence of an ancient founder mutation is indicated by the fact that all patients shared a short common haplotype extending > or = 790 kilobases. Our results emphasize the need to include the SGCA gene R77C mutation test in routine DNA analyses of severe dystrophinopathy-like muscular dystrophies in Finland, and suggest that the applicability of this test in other populations should be studied as well.

Insights into the Role of Infection in the Spondyloarthropathies.

Certain infections play an important role in the pathogenesis of the human leukocyte antigen (HLA)-B27-associated reactive arthritis. Whether infections play a role in other forms of spondyloarthropathies is not as clear. The role of HLA-B27 as an antigen-presenting molecule is important in the pathogenesis of these diseases. Recent evidence has been obtained indicating that this molecule may have other functions unrelated to antigen-presentation in the interaction of reactive arthritis-triggering microbes and host. This paper reviews the recent studies on the role of infection in the spondyloarthropathies.

The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal dysplasia.

Mutations in ectodysplasin, the protein product of the EDA or ED1 gene, cause X-linked anhidrotic ectodermal dysplasia. From sixteen families we have identified thirteen mutations, of which nine were novel: a deletion of the entire exon 1, altered splicing site in intron 7 (IVS-2A-->G) and in intron 9 (IVS9+8 C-->G), deletion of 8 bp (1967-1974 nt), four missense mutations (G255C, G255D, W274G, C332Y) and nonsense mutation W274X. Previously identified and the novel mutations form four clusters: 1) at the junction of the transmembrane and extracellular domains, 2) at a putative protease recognition site, possibly affecting cleavage of ectodysplasin, 3) at the trimerizing collagen-like domain, and 4) at regions of high homology to tumor necrosis factor domains. Truncating and splice site mutations occur within the proximal two-thirds of the protein. Our data suggest the functional importance of specific ectodysplasin domains. Hum Mutat 17:349, 2001.

Clinical and genetic findings in Finnish ataxia patients with the spinocerebellar ataxia 8 repeat expansion.

Spinocerebellar ataxia 8 (SCA8) is caused by a CTG repeat expansion in an untranslated region of a recently cloned gene on 13q21. The pathogenic role of this trinucleotide repeat was evaluated by examining 154 Finnish ataxia patients and 448 controls. Expansions ranging from 100 to 675 repeats were present in 9 (6%) unrelated patients and in 13 (3%) controls. There was a threefold excess of shorter expansions (<204 repeats) in the ataxia series, and the expansions tended to cluster in patients with a family history for the disease. Clinical and genetic data were subsequently collected from 15 patients. Common initial symptoms included gait instability, dysarthria, and tremor. A marked cerebellar atrophy in magnetic resonance imaging or computed tomography was found in all patients. Pyramidal affection was often seen, and various kinds of cognitive impairment were evident in 40% of patients. Disease progression was slow, and fluctuation of symptoms was commonly observed. A maternal penetrance bias was not seen, nor was there any clear-cut negative correlation between age of onset and repeat number. Meiotic but not mitotic instability of the repeat expansion was evident. Haplotype analysis suggests multiple origins for the Finnish spinocerebellar ataxia 8 repeat expansions.

Prenatal diagnosis of variant late infantile neuronal ceroid lipofuscinosis (vLINCL[Finnish]; CLN5).

The first prenatal diagnosis of variant late infantile neuronal ceroid lipofuscinosis (vLINCL[Finnish]; CLN5) is reported. The disease belongs to the group of progressive encephalopathies in children with psycho-motor deterioration, visual failure and premature death. Neurons and several extraneural cells harbour lysosomal inclusions showing accumulation of material with histochemical characteristics of ceroid and lipofuscin. A Finnish woman with a daughter with vLINCL came for genetic counselling for her current pregnancy. Electron microscopy of a chorionic villus sample (CVS) at the 11th week of gestation did not reveal inclusions characteristic for NCL. DNA analysis showed that the fetus had inherited the major mutation, a 2 bp deletion of the CLN5 gene from the mother, and the same paternal (and maternal) haplotypes for COLAC1 and AC224 as the affected daughter. The pregnancy was terminated. Electron microscopy of the CVS of the aborted fetus at the 14th week of pregnancy showed lysosomal electron dense inclusions with straight and curved lamellar profiles consistent with vLINCL. Prenatal diagnosis of NCL-disorders (CLN1, CLN2, CLN3) can be made from CVS by demonstrating the mutations of the affected genes or by haplotype analysis using the closely linked markers in most cases. In various clinical settings the DNA diagnostics may not be possible. Demonstration of the characteristic inclusions of the placenta and fetal tissues remains a helpful adjunct in such cases.

Magnetic resonance imaging and proton MR spectroscopy in Wilson's disease.

MRI of the brain and liver using T2 relaxation time measurements and proton spectroscopy (1H-MRS) of the brain was performed in four siblings with Wilson's disease (one with clinical disease and three asymptomatic) as well as age- and sex-matched control subjects. The T2 values of the liver were correlated with liver biopsy results. 1H-MRS of the left and right globus pallidus was obtained. The patient with clinical disease was examined three times, and two of three asymptomatic siblings twice. MR images of the brain were abnormal in all four patients. High signal intensity areas in the posterior thalamus, general atrophy and pontine myelinolysis were present in the patient with clinical manifestations. The T2 measurements of these areas confirmed the results of image analysis. Apart from general brain atrophy, the changes in the patient with clinical disease were largely reversible. The T2 values were significantly different from those of the control subjects only in the globus pallidus. The NAA/Cho, NAA/Cr and Cho/Cr ratios from the 1H-MR spectra of globus pallidus showed no significant difference between patients and control subjects. The mean values of NAA/Cho and NAA/Cr were lower in patients with Wilson's disease than in the control subjects. One of the patients had hepatic steatosis, but the liver T2 values were no different to those of the control subjects. In conclusion, the MRI findings reflect the success of the specific therapy in patients. MRI thus seems to be useful in the follow-up of Wilson's disease.

Unusual pyramidal ice in the atmosphere as the origin of elliptical halos.

The formation mechanism of elliptical halos and Bottlinger's rings has long remained uncertain. The current model for elliptical halos requires multiple scattering from two different populations of ice crystals in a complex mode of motion. New evidence indicates that elliptical halos, and possibly Bottlinger's rings, are due to refraction through ice crystals shaped like obtuse pyramids. This unusual ice crystal may not have been documented previously.

Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay.

Mutation screening in neurofibromatosis type 1 (NF1) families has long been hampered by the complexity of the NF1 gene. By using a novel multi-track screening strategy, 67 NF1 families (54 two-generation, 13 three-generation) with a de novo mutation in the germline of the first generation were studied with two extragenic and 11 intragenic markers. The pathological lesion was identified in 31 cases. Loss of heterozygosity (LOH) in the affected individual revealed a gross gene deletion in 15 of the two-generation families; in 12 (80%) of them, the deletion was maternally derived. Eleven patients with a gross deletion exhibited developmental delay, ten had dysmorphic features and six manifested a learning disability. No gross deletion was apparent in any of the 13 three-generation families, suggesting that such lesions are subject to more intense selection. In these families, the new mutation was of paternal origin in 11 kindreds and the underlying mutational event could be characterised in three of them.

IgM, IgG and IgA class enterobacterial antibodies in serum and synovial fluid in patients with ankylosing spondylitis and rheumatoid arthritis.

IgM, IgG and IgA class antibodies against three Klebsiella pneumoniae capsular types, Escherichia coli and Proteus mirabilis, as well as total immunoglobulin concentrations, were measured by enzyme immunoassay and radial immunodiffusion technique, respectively, in paired serum and synovial fluid samples from eight patients with ankylosing spondylitis and 10 with rheumatoid arthritis. No clear evidence for intra-articular antibody production against any of the studied microbes was found.

Syndecan-1: a new prognostic marker in laryngeal cancer.

The cell adhesion molecule syndecan-1 expression is induced during keratinocyte differentiation and reduced during the formation of squamous cell carcinomas (SCCs). A significant correlation between decreased syndecan-1 expression in head and neck SCC measured from frozen sections with immuohistochemical methods and clinical outcome are reported. The clinical relevance of the cellular proliferation marker Ki-67 is controversial in SCC of the head and neck. The purpose of this study was to determine the expression of syndecan-1 and Ki-67 in SCC of the larynx and correlate the results with known prognostic factors and clinical outcome. Paraffin-embedded samples of 100 patients with laryngeal SCC (44 glottic, 36 supraglottic, 20 transglottic) treated at Turku University Central Hospital were re-examined and divided into four histological grades of differentiation, four grades of keratinisation, and four grades of 104-9 (syndecan-1) immunostaining. The mitotic index was analysed as the number of mitoses per volume corrected high power fields. The relative number of Ki-67 positive cells was evaluated. The patients mean age was 64 years and the 5-year survival was 69%. In univariate analysis, intermediate or strong staining for syndecan-1 was associated with higher overall survival than those tumours with no or little syndecan-1 expression (p = 0.048). Nodal status (p = 0.0001), tumour size (p = 0.0004) and localisation (p = 0.0008), general condition (p = 0.0001), histological grade (p = 0.02) and patient age (p = 0.03) correlated with overall survival whereas the Ki-67 index (p = 0.093), mitotic index (p = 0.23) and grade of keratinisation (p = 0.90) failed to do so. The results suggest that syndecan-1 could be a useful prognostic factor in SCC of the larynx.

New progeroid disorder.

We report on a 10-year-old Caucasian male with a prematurely aged appearance, delayed bone maturation and dental development, pronounced acro-osteolysis with brachydactyly, and distinctive cutaneous findings including hard, confluent skin lesions with some clinical and histologic resemblance to those of juvenile hyaline fibromatosis (JHF). He also had hyperopia, sensorineural hearing loss, and elevated TSH. Linear growth and intellectual functions were normal. We believe that this patient represents a new progeroid disorder.