Serum caspase-cleaved cytokeratin-18 fragment as a prognostic biomarker in hematological patients with febrile neutropenia

The study aim was to determine the benefit of the measurement of serum caspase-cleaved cytokeratin-18 (CK-18) fragment as a prognostic marker of febrile neutropenia (FN) in hematological patients. The study population consisted of 86 consecutive patients with FN who received intensive chemotherapy for hematological malignancy at the adult hematology ward of Kuopio University Hospital. Twenty-three patients (27%) had acute myeloid leukemia, and 63 patients (73%) were autologous stem cell transplant recipients. Serum caspase-cleaved CK-18 fragment M30, C-reactive protein (CRP) and procalcitonin (PCT) were measured at the onset of FN (d0), on day 1 (d1), and on day 2 (d2). Eight patients (9%) developed severe sepsis, including three patients with septic shock. Eighteen patients (21%) had a blood culture-positive infection. Serum CK-18 fragment peaked on the first day after fever onset in patients with severe sepsis. Higher CK-18 level was associated with severe sepsis, intensive care unit treatment, and fatal outcome, but not with blood culture positivity. In ROC curve analysis, d1 serum CK-18 fragment predicted severe sepsis with an area under the curve (AUC) of 0.767, CRP with an AUC of 0.764, and PCT with an AUC of 0.731. On d2, the best predictive capacity was observed for CRP with an AUC of 0.832. The optimal cutoff of caspase-cleaved CK-18 fragment M30 for predicting severe sepsis was 205 U/L on d1. In hematological patients, serum CK-18 fragment was found to be a potential prognostic marker of severe sepsis at early stages of FN.Peer reviewe

Fat oxidation at rest and during exercise in male monozygotic twins

Purpose We aimed to investigate if hereditary factors, leisure-time physical activity (LTPA) and metabolic health interact with resting fat oxidation (RFO) and peak fat oxidation (PFO) during ergometer cycling. Methods We recruited 23 male monozygotic twin pairs (aged 32-37 years) and determined their RFO and PFO with indirect calorimetry for 21 and 19 twin pairs and for 43 and 41 twin individuals, respectively. Using physical activity interviews and the Baecke questionnaire, we identified 10 twin pairs as LTPA discordant for the past 3 years. Of the twin pairs, 8 pairs participated in both RFO and PFO measurements, and 2 pairs participated in either of the measurements. We quantified the participants' metabolic health with a 2-h oral glucose tolerance test. Results Fat oxidation within co-twins was correlated at rest [intraclass correlation coefficient (ICC) = 0.54, 95% confidence interval (CI) 0.15-0.78] and during exercise (ICC = 0.67, 95% CI 0.33-0.86). The LTPA-discordant pairs had no pairwise differences in RFO or PFO. In the twin individual-based analysis, PFO was positively correlated with the past 12-month LTPA (r = 0.26, p = 0.034) and the Baecke score (r = 0.40, p = 0.022) and negatively correlated with the area under the curve of insulin (r = - 0.42, p = 0.015) and glucose (r = - 0.31, p = 0.050) during the oral glucose tolerance test. Conclusions Hereditary factors were more important than LTPA for determining fat oxidation at rest and during exercise. Additionally, PFO, but not RFO, was associated with better metabolic health.Peer reviewe

Reproducibility of Brain Responses: High for Speech Perception, Low for Reading Difficulties

Neuroscience findings have recently received critique on the lack of replications. To examine the reproducibility of brain indices of speech sound discrimination and their role in dyslexia, a specific reading difficulty, brain event-related potentials using EEG were measured using the same cross-linguistic passive oddball paradigm in about 200 dyslexics and 200 typically reading 8-12-year-old children from four countries with different native languages. Brain responses indexing speech and non-speech sound discrimination were extremely reproducible, supporting the validity and reliability of cognitive neuroscience methods. Significant differences between typical and dyslexic readers were found when examined separately in different country and language samples. However, reading group differences occurred at different time windows and for different stimulus types between the four countries. This finding draws attention to the limited generalizability of atypical brain response findings in children with dyslexia across language environments and raises questions about a common neurobiological factor for dyslexia. Our results thus show the robustness of neuroscience methods in general while highlighting the need for multi-sample studies in the brain research of language disorders

Does unemployment in family affect pregnancy outcome in conditions of high quality maternity care?

BACKGROUND: The influence of unemployment in the family on pregnancy outcome is controversial. Only a few studies have involved investigation of the effect of unemployment of the father on pregnancy. The objective of this study was to assess the effects of unemployment of one or both parents on obstetric outcome in conditions of free antenatal care attended by the entire pregnant population. METHODS: The data of 24 939 pregnancies included maternal risk factors, pregnancy characteristics and outcome, and was based on a self administered questionnaire at 20 weeks of pregnancy and on clinical records. RESULTS: Unemployment was associated with adolescent maternal age, unmarried status and overweight, anemia, smoking, alcohol consumption and prior pregnancy terminations. Multivariate logistic regression analysis indicated that after controlling for these maternal risk factors small differences only were found in pregnancy outcomes between unemployed and employed families. Unemployed women had significantly more often small-for-gestational-age (SGA) infants, at an OR of 1.26 (95% CI: 1.12 – 1.42) whereas, in families where both parents were unemployed, the risk of SGA was even higher at an OR of 1.43 (95% CI: 1.18 – 1.73). Otherwise, pregnancy outcome was comparable in the groups studied. CONCLUSION: Free antenatal care was unable to fully overcome the adverse pregnancy outcomes associated with unemployment, SGA risk being highest when both parents are unemployed

Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism

Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37(-/-)) model for MUL. Trim37(-/-) mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37(-/-) mice as compared with wildtype. Both male and female Trim37(-/-) mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37(-/-) mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37(-/-) mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37(-/-) mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37(-/-) mice. The most consistently seen phenotypes in Trim37(-/-) mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37(-/-) mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis.Peer reviewe