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.

Umbilically and Peripherally Inserted Thin Central Venous Catheters Have Similar Risks of Complications in Very Low-Birth-Weight Infants.

Catheter complications can be life-threatening in very low-birth-weight (VLBW) infants. We retrospectively evaluated non-elective removals of the first thin (1-2F) umbilical vein catheters (tUVCs (n = 92)) and peripherally inserted central venous catheters (PICCs (n = 103)) among 195 VLBW infants. Catheters were removed non-electively in 78 infants (40%), typically due to suspected infection (n = 42) or catheter dislocation (n = 30). Infants with complications had lower birth weights and gestational ages than others. The frequencies and causes of catheter removal were similar in the tUVC and PICC groups. Thirty-one infants had true catheter infections. The number of infections/1000 catheter days was higher in the tUVC group than in the PICC group. In a multivariable analysis, gestational age was associated with catheter infection, but catheter type was not. The odds of catheter complications decreased with increasing gestational age, but no clear association with thin catheter type was found.

HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage.

Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component.

Intellectual disability in children aged less than seven years born moderately and late preterm compared with very preterm and term-born children - a nationwide birth cohort study.

BACKGROUND: Prematurity has been shown to be associated with an increased risk of intellectual disability (ID). METHOD: The aim was to establish whether the prevalence of ID, defined as significant limitations in both intellectual (intelligence quotient below 70) and adaptive functioning among moderately preterm (MP; 32+0 -33+6  weeks) and late preterm (LP; 34+0 -36+6  weeks) infants, is increased compared with that in term infants (≥37+0  weeks). Antenatal and neonatal risk factors for ID among gestational age groups were sought. The national register study included all live-born infants in Finland in 1991-2008, excluding those who died before one year age, or had any major congenital anomaly or missing data. A total of 1 018 256 infants (98.0%) were analysed: very preterm (VP; <32+0  weeks, n = 6329), MP (n = 6796), LP (n = 39 928) and term (n = 965 203). RESULTS: By the age of seven years, the prevalence of ID was 2.48% in the VP group, 0.81% in the MP group, 0.55% in the LP group and 0.35% in the term group. Intracranial haemorrhage increased the ID risk in all groups. Male sex and born small for gestational age predicted an increased risk in all but the MP group. CONCLUSIONS: The prevalence of ID decreased with increasing gestational age. Prevention of intracranial haemorrhages may have a beneficial effect on the neurodevelopmental outcomes of neonates.

Adipokines played a limited role in predicting temporary growth differences between very low birthweight infants with and without bronchopulmonary dysplasia.

AIMS: This study explored whether growth was poorer among very low birthweight (VLBW) infants with bronchopulmonary dysplasia (BPD) and assessed adipokine levels as predictors of early growth. METHODS: We studied 53 VLBW infants born in Tampere University Hospital up to 12 months of corrected age (CA). The median gestational age of the 21 infants with BPD and 32 infants without BPD was 29 weeks, and the median birthweights were 930 (635-1470) and 1185 (650-1470) grams. Growth parameters, macronutrients intake and plasma levels of adipokines were measured. RESULTS: Bronchopulmonary dysplasia infants were lighter than controls until 36 weeks of CA, with catch-up growth achieved by three months of CA. Adipsin levels were lower in BPD infants at 28 days of postnatal age. High leptin levels seemed protective for low weight for height at nine months of CA. The duration of ventilator therapy predicted low weight for height, length for age and body mass index and BPD predicted low length for age at 12 months of CA. CONCLUSIONS: Catch-up growth in VLBW infants with BPD was achieved by three months of CA, but adipokines played a limited role in predicting growth. Shortening ventilator therapy could help growth in VLBW infants.

Adult height and glucose tolerance: a re-appraisal of the importance of body mass index.

AIM: To study both the association between adult height and glucose regulation based on findings from a 75-g oral glucose tolerance test, and the combined effect of height and adiposity on glucose values. METHODS: We conducted a population-based, cross-sectional study among apparently healthy people with high cardiovascular risk living in south-western Finland. The study included 2659 participants aged 45-70 years, who had at least one cardiovascular risk factor but no previously diagnosed diabetes or manifested cardiovascular disease. An oral glucose tolerance test was performed in all participants. Height and weight were measured and BMI was calculated. The participants were divided into five height groups based on normal distribution. For further analysis of the association between height and glucose concentrations the participants were divided into four BMI groups (<25.0 kg/m2 ; 25-29.9 kg/m2 ; 30-34.9 kg/m2 ; ≥35 kg/m2 ). Data were analysed using age-adjusted linear regression models. RESULTS: Height was inversely associated with 2-h plasma glucose, but not with fasting plasma glucose concentration. No gender difference was observed. The 2-h plasma glucose values increased with an increase in BMI, so that height was inversely associated with 2-h plasma glucose in the three lowest BMI groups, but not in the highest BMI group (P=0.33). CONCLUSIONS: Taller people had lower 2-h plasma glucose concentrations than shorter people, up to a BMI of 35 kg/m2 . Adjustment for height and BMI is needed for accurate interpretation of oral glucose tolerance tests.

Custom-Shaped Organic Photovoltaic Modules-Freedom of Design by Printing.

Freedom of design that was introduced as organic photovoltaic (OPV) modules were fabricated by printing. As proof-of-concept, we show OPV leaf fabrication in A5 size using gravure and rotary screen printing processes for the main active layers of the OPV structure. These printing methods allow direct printing of any kind of arbitrary, two-dimensional shapes including patterning of the electric contacts thus post-patterning stages are not needed. Fabrication of custom-shaped OPV modules requires detailed information about the technical boundaries set by the manufacturing process and materials which in turn influence the layout design and R2R upscaling. In this paper, we show custom-shaped OPV modules, patterned directly in a shape of a tree leaf with an overall size of 110 cm2 and an active area of 50 cm2 providing a power conversion efficiency of 2.0% and maximum power of 98 mW.

Understanding Haemonchus contortus Better Through Genomics and Transcriptomics.

Parasitic roundworms (nematodes) cause substantial mortality and morbidity in animals globally. The barber's pole worm, Haemonchus contortus, is one of the most economically significant parasitic nematodes of small ruminants worldwide. Although this and related nematodes can be controlled relatively well using anthelmintics, resistance against most drugs in common use has become a major problem. Until recently, almost nothing was known about the molecular biology of H. contortus on a global scale. This chapter gives a brief background on H. contortus and haemonchosis, immune responses, vaccine research, chemotherapeutics and current problems associated with drug resistance. It also describes progress in transcriptomics before the availability of H. contortus genomes and the challenges associated with such work. It then reviews major progress on the two draft genomes and developmental transcriptomes of H. contortus, and summarizes their implications for the molecular biology of this worm in both the free-living and the parasitic stages of its life cycle. The chapter concludes by considering how genomics and transcriptomics can accelerate research on Haemonchus and related parasites, and can enable the development of new interventions against haemonchosis.

How to assess kidney function in outpatient clinics.

BACKGROUND: In 2002, a new definition and classification of chronic kidney disease was published, and glomerular filtration rate < 60 ml/min/1.73 m(2) for 3 months or more was adapted to define chronic kidney disease irrespective of other signs of kidney damage. AIMS: To discuss different ways to assess kidney function in outpatient clinics and especially in primary care. METHODS: The PubMed database was searched for relevant articles. RESULTS: The estimated glomerular filtration rate equations which take into account plasma creatinine, age, sex, race and body size have been developed to identify patients with chronic kidney disease formerly overlooked if the renal function had been assessed by plasma creatinine alone. Cystatin C-based equations have also been developed to enhance accuracy for individuals with whom creatinine-based estimates for kidney function are acknowledged to be less accurate. DISCUSSION: The characteristics of the patients to whom the diagnostic test is applied can influence the sensitivity of the test. Thus, there is nowadays controversy over the best method to assess kidney function in general population. CONCLUSION: In the overwhelming majority of patients currently treated in primary care, the CKD-EPI creatinine equation is suitable for estimating renal function. The CKD-EPIcr-cys equation would provide further reliability in individuals with a CKD-EPI creatinine eGFR of 45-59 ml/min/1.73 m(2) , but the cost of serum cystatin C analysis limits its use in everyday general practice.

Patients with resistant hypertension have more peripheral arterial disease than other uncontrolled hypertensives.

The aim of this study was to investigate whether resistant hypertension differs from uncontrolled and controlled hypertension in terms of target organ damage. Hypertensive subjects with antihypertensive medication (n=385) were identified in a population survey conducted in southwestern Finland. None of the study subjects had previously diagnosed cardiovascular or renal disease or diabetes. Ankle-brachial index, estimated glomerular filtration rate, electrocardiogram-determined left ventricular hypertrophy and cardiometabolic risk factors were assessed. The prevalence of peripheral arterial disease among subjects with resistant, uncontrolled and controlled hypertension was 6/37 (16%), 22/275 (8%) and 0/73 (0%), respectively (P=0.006). There were no differences in the prevalence of renal insufficiency, left ventricular hypertrophy or metabolic parameters between the groups. Resistant hypertension affects vasculature more than uncontrolled hypertension, and thus it can be regarded as a marker of more severe disease.

Pulse pressure and subclinical peripheral artery disease.

Ankle-brachial index (ABI) measurement offers an easily available method to diagnose peripheral artery disease (PAD) and systemic atherosclerosis in early stage and thus to identify high-risk individuals for preventive interventions. The objective of this study was to assess the most practical criteria for the measurement of ABI in subjects with high cardiovascular risk. We examined 972 asymptomatic, middle-aged high-risk subjects without manifested cardiovascular disease or previously diagnosed diabetes. The prevalence of PAD (defined as ABI0.90) and borderline PAD (0.91-1.00) were 5% (95% confidence interval (CI) 4-7%) (49/972) and 20% (95% CI 18-23%) (192/972), respectively. In multivariate analysis, female gender (odds ratio (OR) 0.71 (95% CI 0.53-0.97)), current smoking (OR 2.14 (95% CI 1.47-3.11)) and pulse pressure (OR 1.03 for each increase of 1 mm Hg (95% CI 1.01-1.04)) were associated with low ABI. Measuring ABI in subjects who smoke or have pulse pressure >65 mm Hg seems to be worthwhile.

Correcting overall survival for the impact of crossover via a rank-preserving structural failure time (RPSFT) model in the RECORD-1 trial of everolimus in metastatic renal-cell carcinoma.

Clinical trials in oncology often allow patients randomized to placebo to cross over to the active treatment arm after disease progression, leading to underestimation of the treatment effect on overall survival as per the intention-to-treat analysis. We illustrate the statistical aspects and practical use of the rank-preserving structural failure time (RPSFT) model with the Fleming-Harrington family of tests to estimate the crossover-corrected treatment effect, and to assess its sensitivity to various weighting schemes in the RECORD-1 trial. The results suggest that the benefit demonstrated in progression-free survival is likely to translate into a robust overall survival benefit.

Characterization of a novel transgenic rat carrying human tau with mutation P301L.

We have established a novel transgenic rat line carrying human microtubule-associated protein Tau-40 with mutation P301L. hTau-40/P301L transgenic male and female rats were followed up to 2 years of age. The hTau-40/P301L rats expressed human tau mRNA and protein in the limbic cortex and associated white matter, hippocampus and spinal cord. With increasing age, the staining density for phosphorylated tau increased in all these areas. Neither silver stains nor Fluoro-Jade staining indicated the presence of dying neurons, or axonal degeneration, and there was no evidence of increased gliosis or inflammation. However, some neurons did display dendritic abnormalities, and immunoblots revealed the presence of sarcosyl insoluble tau. A large test battery revealed no behavioral abnormalities in these rats, except a mild hyperactivity in the elevated plus maze. In conclusion, this transgenic tau rat may be a useful model for 'pretangle' pathology, although in this study conditions were not sufficient to induce significant neuronal loss or behavioral deficits.

High-sensitivity C-reactive protein and ankle brachial index in a finnish cardiovascular risk population.

High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = -0.077, p = 0.014), leukocyte count (r = -0.107, p = 0.001), and SCORE (r = -0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p < 0.0001) and waist circumference (r = 0.325, p < 0.0001). When we excluded subjects with hsCRP >10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue-driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease.

Hypertensive women with the metabolic syndrome are at risk of renal insufficiency more than men in general population.

The prevalence of renal insufficiency in hypertensive participants without comorbidities affecting renal function is unknown. The objective of this study was to assess the prevalence and predictors of renal insufficiency in general hypertensive population. We examined 994 hypertensive participants aged 45-70 years without previously diagnosed diabetes, cardiovascular disease or chronic kidney disease. Renal insufficiency was defined as estimated glomerular filtration rate <60 ml min(-1) per 1.73 m(2) by the Modification of Diet in Renal Disease formula. The metabolic syndrome was defined according to the International Diabetes Federation and the US National Cholesterol Education Program Third Adult Treatment Panel criteria. Glucose homoeostasis was assessed with an oral glucose tolerance test. The prevalence of renal insufficiency was 6.7% (95% confidence interval (CI) 5.3-8.5). In a multivariate model, the presence of renal insufficiency was predicted by female gender (odds ratio (OR) 3.57 (95% CI 1.90-6.72)), older age (OR 1.13 (95% CI 1.07-1.18)), use of diuretics (OR 2.13 (95% CI 1.19-3.82)) and metabolic syndrome (OR 2.79 (95% CI 1.34-5.79)). Newly diagnosed diabetes or prediabetes did not predict renal insufficiency. The prevalence of renal insufficiency was found to be lower than previously reported in hypertensive general population. Metabolic syndrome, but not newly diagnosed diabetes or prediabetes per se, was strongly associated with renal insufficiency especially in women. Renal insufficiency was also associated with the use of diuretics, but the clinical relevance of this finding needs to be clarified.

Bone mineral density and lipid changes during 5 years of follow-up in a study of prevention of breast cancer with toremifene in healthy, high-risk pre- and post-menopausal women.

A double-blind, randomised, placebo-controlled pilot study was initiated to evaluate the feasibility of chemoprevention with toremifene 60 mg/day in healthy women at high risk for breast cancer. Enrolment in the study was terminated earlier than planned because of slow patient accrual, although 13% of patients continued for 5 years. The revised efficacy outcomes were change in bone mineral density (BMD) from baseline at four skeletal sites, plus effects on serum lipids. In premenopausal women there was a trend for sustained increase in BMD during toremifene therapy after year 1 in lumbar spine. In postmenopausal women, toremifene had little or no effect on BMD trends. Levels of total and low-density lipoprotein (LDL) cholesterol were largely unchanged from baseline in premenopausal women treated with toremifene but were often slightly lower than in the placebo group during follow-up. Total and LDL cholesterol levels declined slightly from baseline in the postmenopausal women and were, at several points during the first 3 years, significantly lower than in the corresponding placebo group (p < 0.01). We conclude that: (a) assessment of toremifene 60 mg/day in chemoprevention will require further clinical trials; (b) toremifene 60 mg/day has no substantive negative effects on BMD in pre- or postmenopausal women and may exert a minor favourable influence (in particular, the effects of toremifene 60 mg/day on BMD in premenopausal women may make the drug an attractive alternative to tamoxifen 20 mg/day for that patient subset); (c) lipid effects of toremifene 60 mg/day are, at minimum, neutral and may be modestly favourable for reducing cardiovascular risk.