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Background Matrix metalloproteinase 8 (MMP-8) is the most potent type-I collagen protease. Such collagen mainly constitutes the transient fibrosis in takotsubo cardiomyopathy (TTC) endomyocardial biopsies. High MMP-8 and tissue-inhibitor of matrix metalloproteinase-1 (TIMP-1) levels are implicated in acute coronary syndrome (ACS). We compared MMP-8 and TIM P-1 levels in consecutive TTC and ACS patients, and their association to TTC severity. Methods and results In 45 acute serum samples of TTC, 2072 ACS and 1000 controls, TI MP-1 differed between ACS 146.7ng/mL (115.0-186.3) (median (interquartile range)), TTC 115.7 (94.3-137.7) and controls 80.9 (73.2-90.4), (p Conclusions Even with other differing factors considered, TIMP-1 differentiated TTC from ACS better than TnT. In TTC, the low MMP-8/TIM P-1 molar ratio may reflect decreased proteolysis and increased transient fibrosis, perhaps in part explaining the left-ventricle impairment.

Background: To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. Methods: Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. Results: Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis <37 weeks of gestation) and 13 of them had early-onset pre-eclampsia (diagnosis <34 weeks of gestation). They had lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (% hCG-h) than controls. In receiver-operating characteristics (ROC) curve analysis, the area under the curve (AUC) for the combination of PlGF, PAPP-A, % hCG-h, nulliparity and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699-0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750-0.988) for early-onset pre-eclampsia. Without % hCG-h the AUC values were 0.756 (95% CI 0.651-0.861) and 0.810 (95% CI 0.682-0.938) respectively. For prediction of gestational hypertension, the AUC for % hCG-h was 0.708 (95% CI 0.608-0.808), but for other markers the AUC values were not significant. None of the AUC values were significant for the prediction of SGA infants in normotensive women. Conclusions: First trimester maternal serum % hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors.

Scientific findings have suggested a two-fold structure of the cognitive process. By using the heuristic thinking mode, people automatically process information that tends to be invariant across days, whereas by using the explicit thinking mode people explicitly process information that tends to be variant compared to typical previously learned information patterns. Previous studies on creativity found an association between creativity and the brain regions in the prefrontal cortex, the anterior cingulate cortex, the default mode network and the executive network. However, which neural networks contribute to the explicit mode of thinking during idea generation remains an open question. We employed an fMRI paradigm to examine which brain regions were activated when participants (n = 16) mentally generated alternative uses for everyday objects. Most previous creativity studies required participants to verbalize responses during idea generation, whereas in this study participants produced mental alternatives without verbalizing. This study found activation in the left anterior insula when contrasting idea generation and object identification. This finding suggests that the insula (part of the brain's salience network) plays a role in facilitating both the central executive and default mode networks to activate idea generation. We also investigated closely the effect of the serial order of idea being generated on brain responses: The amplitude of fMRI responses correlated positively with the serial order of idea being generated in the anterior cingulate cortex, which is part of the central executive network. Positive correlation with the serial order was also observed in the regions typically assigned to the default mode network: the precuneus/ cuneus, inferior parietal lobule and posterior cingulate cortex. These networks support the explicit mode of thinking and help the individual to convert conventional mental models to new ones. The serial order correlated negative

Parkinson's disease (PD) is a progressive neurodegenerative disorder causing movement disabilities and several non-motor symptoms in afflicted patients. Recent studies in animal models of PD and analyses of brain specimen from PD patients revealed an increase in the level and activity of the non-receptor tyrosine kinase Abelson (c-Abl) in dopaminergic neurons with phosphorylation of protein substrates, such as alpha-synuclein and the E3 ubiquitin ligase, Parkin. Most significantly inhibition of c-Abl kinase activity by small molecular compounds used in the clinic to treat human leukemia have shown promising neuroprotective effects in cell and animal models of PD. This has raised hope that similar beneficial outcome may also be observed in the treatment of PD patients by using c-Abl inhibitors. Here we highlight the background for the current optimism, reviewing c-Abl and its relationship to pathophysiological pathways prevailing in PD, as well as discussing issues related to the pharmacology and safety of current c-Abl inhibitors. Clearly more rigorously controlled and well-designed trials are needed before the c-Abl inhibitors can be used in the neuroclinic to possibly benefit an increasing number of PD patients.

Background: The annual number of international tourist arrivals has recently exceeded one billion, yet surprisingly few studies have characterized travelers' behavior, illness, and risk factors in a prospective setting. Particularly scarce are surveys of data spanning travel, return, and follow-up of the same cohort. This study examines behavior and illness among travelers while abroad, after return home, and at follow-up. Patterns of behavior connected to type of travel and illness are characterized so as to identify risk factors and provide background data for pre-travel advice. Methods: Volunteers to this prospective cohort study were recruited at visits to a travel clinic prior to departure. Data on the subjects' health and behavior were collected by questionnaires before and after journeys and over a three-week follow-up. In addition, the subjects were asked to fill in health diaries while traveling. Results: The final study population consisted of 460 subjects, 79 % of whom reported illness during travel or on arrival: 69 % had travelers' diarrhea (TD), 17 % skin problems, 17 % fever, 12 % vomiting, 8 % respiratory tract infection, 4 % urinary tract infection, 2 % ear infection, 4 % gastrointestinal complaints other than TD or vomiting, and 4 % other symptoms. Of all subjects, 10 % consulted a doctor and 0.7 % were hospitalized; 18 % took antimicrobials, with TD as the most common indication (64 %). Ongoing symptoms were reported by 25 % of all travelers upon return home. During the three-week follow-up (return rate 51 %), 32 % of respondents developed new-onset symptoms, 20 % visited a doctor and 1.7 % were hospitalized. Factors predisposing to health problems were identified by multivariable analysis: certain regions (Southern Asia, South-Eastern Asia, and Eastern Africa), female gender, young age, and long travel duration. Conclusions: Despite proper preventive measures like vaccinations, malaria prophylaxis, and travel advice, the majority of our subjects

One of the challenges of naturalistic neurosciences using movie-viewing experiments is how to interpret observed brain activations in relation to the multiplicity of time-locked stimulus features. As previous studies have shown less inter-subject synchronization across viewers of random video footage than story-driven films, new methods need to be developed for analysis of less story-driven contents. To optimize the linkage between our fMRI data collected during viewing of a deliberately non-narrative silent film 'At Land' by Maya Deren (1944) and its annotated content, we combined the method of elastic-net regularization with the model-driven linear regression and the well-established data-driven independent component analysis (ICA) and inter-subject correlation (ISC) methods. In the linear regression analysis, both IC and region-of-interest (ROI) time-series were fitted with time-series of a total of 36 binary-valued and one real-valued tactile annotation of film features. The elastic-net regularization and cross-validation were applied in the ordinary least-squares linear regression in order to avoid over-fitting due to the multicollinearity of regressors, the results were compared against both the partial least-squares (PLS) regression and the un-regularized full-model regression. Nonparametric permutation testing scheme was applied to evaluate the statistical significance of regression. We found statistically significant correlation between the annotation model and 9 ICs out of 40 ICs. Regression analysis was also repeated for a large set of cubic ROIs covering the grey matter. Both IC- and ROI-based regression analyses revealed activations in parietal and occipital regions, with additional smaller clusters in the frontal lobe. Furthermore, we found elastic-net based regression more sensitive than PLS and un-regularized regression since it detected a larger number of significant ICs and ROIs. Along with the ISC ranking methods, our regression analysis proved a

Background: Psychopathy, a severe disorder of personality, is well represented in the criminal and forensic psychiatric population and is significantly associated with increased risk of violence and crime. Fire-setting is a major source of property damage, injury, and death in many Western countries. The primary aim of this study was to evaluate psychopathic traits in a consecutive sample of Finnish male pretrial fire-setting offenders. Further, we wanted to investigate whether fire-setting recidivists show higher traits of psychopathy than one-time firesetters and whether exclusive firesetters show lower traits of psychopathy than those with criminal versatility. Methods: The forensic psychiatric examination statements for male firesetters who underwent a pretrial forensic psychiatric evaluation during a 10-year period (1989 - 1998) were reviewed. The sample comprised 129 firesetters with normal IQ, 41 of whom were fire-setting recidivists. Fifty men were exclusive firesetters. Assessment of psychopathy-like personality character was performed using the 20-item Hare Psychopathy Checklist-Revised. Results: Two individuals (1.6%, 95% CI: 0.0-3.7) scored >= 30 points and 19 (14.7%, 95% CI: 8.6-20.8) >= 25 points on the PCL-R. The mean PCL-R total score was 16.1 (SD 6.88), the mean Factor 1 score 5.0 (SD 3.41), and the mean Factor 2 score 9.9 (SD 3.86). No significant differences emerged between the recidivists and the one-time firesetters. The versatile firesetters exhibited significantly higher mean total and factor scores than the exclusive ones. Conclusion: Among firesetters, there is a subgroup of persons with significant psychopathic traits, which should be recognized in legal and health care organizations. Although psychopathy was associated with greater criminal versatility, it bore no relationship to fire-setting recidivism.

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.