SERPINB2 and miR-146a/b are coordinately regulated and act in the suppression of psoriasis-associated inflammatory responses in keratinocytes

Psoriasis is a chronic inflammatory skin disease with numerous involved factors. miR-146a and miR-146b (miR-146a/b) are anti-inflammatory miRNAs that are increased in psoriatic skin. SERPINB2 has been shown to be upregulated in the inflammation and infections. Here we aimed to study the relationship between miR-146a/b and SERPINB2 and to delineate the role of SERPINB2 in association of plaque psoriasis. We report increased SERPINB2 expression in the skin of psoriasis patients, which was in a positive relationship with psoriasis severity and in a negative relationship with miR-146a/b in psoriatic lesions. In cultured keratinocytes, both cellular and secreted SERPINB2 levels were strongly induced in response to IFN-γ and TNF-α. Interestingly, SERPINB2 mRNA was downregulated by IL-17A and the combination of TNF-α and IL-17A at time points when miR-146a was increased. The predicted binding site for miR-146a/b in 3’ untranslated region of SERPINB2 revealed no activity in luciferase assay, while siRNA silencing of miR-146a/b direct targets IRAK1 and CARD10 resulted in reduced expression of SERPINB2, suggesting that miR-146a/b indirectly control SERPINB2 expression in the skin. The siRNA silencing of SERPINB2 increased the expression of IL-8, CXCL5 and CCL5 and migration of neutrophils revealing its anti-inflammatory role in keratinocytes. Our data together suggest that SERPINB2 and miR-146a/b are part of disease-related network of molecules that are coordinately regulated and act in controlling the inflammatory responses in psoriatic skin.     

Cat odour exposure decreases exploratory activity and alters neuropeptide gene expression in CCK(2) receptor deficient mice, but not in their wild-type littermates

An attempt was made to establish whether the anxiogenic effect of cat odour differs in female wild-type and CCK(2) receptor deficient mice, having different exploratory activity in the elevated plus-maze. The exposure of wild-type and homozygous CCK(2) receptor deficient mice to cat odour did not reveal substantial differences between the two genotypes. The number of contacts with the cat odour impregnated cloth was reduced and the frequency of stretch-attend postures was increased similarly in wild-type and homozygous mice. However, the following exposure of mice to the elevated plus-maze established differences as homozygous mice displayed increased exploratory activity in the plus-maze. The cat odour exposure significantly reduced exploratory activity only in homozygous mice. Together with the increased exploratory activity we established in homozygous mice significantly increased expression of the Oprm1 gene in the frontal cortex and mesencephalon. The exposure of mice to cat odour caused only minor changes in the gene expression of wild-type mice, whereas in homozygous animals a significantly increased expression of the Mc3r gene in the frontal cortex and temporal lobe, and the Pomc1 gene in the temporal lobe, mesencephalon and mesolimbic area was established. In conclusion, CCK(2) receptor deficient mice displayed reduced anxiety compared to their wild-type littermates in the plus-maze test. This behavioural effect seems to be related, at least partly, to an increased tone of opioid system in the brain. Moreover, homozygous mice respond to the exposure of cat odour with an increased anxiety. This effect seems to be related to the increased function of the melanocortin system in the brain structures of genetically modified mice.     

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies

Introduction

Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions.

Politics and technology in health information systems development: a discourse analysis of conflicts addressed in a systems design group

Different types of disagreements must be managed during the development of health information systems. This study examines the antagonisms discussed during the design of an information system for 175,000 users in a public health context. Discourse analysis methods were used for data collection and analysis. Three hundred and twenty-six conflict events were identified from four design meetings and divided into 16 categories. There were no differences regarding the types of conflicts that the different participants brought into the design discussions. Instead, conflict occurrence was primarily affected by the agendas that set the stage for examinations and debates. The results indicate that the selection of design method and the structure used for the meetings are important factors for the manner in which conflicts are brought into consideration during health information system design. Further studies comparing participatory and non-participatory information system design practices in health service settings are warranted.     

The potential of smart homes for injury prevention among the elderly

Smart homes promise to make the lives of elderly people more comfortable and safe. Today, there is a significant interest from industry and policy makers in developing these technologies. In theory, the emerging technologies make it possible to provide a new range of services. So far, however, the goal has often been to develop new services for young people rather than assisting old people to improve their quality of life. Especially important is the potential for using these technologies to promote safety and prevent injury among old people because this group is at home more than the other age groups. Networked devices can collect data from sensors and aid decision-making on intervention and other measures. Furthermore, these devices can instruct and remind individuals about safety-related issues.     

Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system

Tissue plasminogen activator (tPA) is increasingly recognized to play important roles in various physiological and pathological processes in the central nervous system (CNS). Much of the data on the involvement of plasminogen activators in neurophysiology and -pathology have been derived from studies on experimental animals. We have now performed a systematic characterization of the expression of tPA and its inhibitor, neuroserpin, in normal human CNS. Brain and spinal cord samples from 30-36 anatomic locations covering all major brain regions were collected at 9 autopsies of donors with no neurological disease. Tissues were embedded in paraffin and tissue arrays were constructed. In two cases parallel samples were snap-frozen for biochemical analysis. Expression and activity profiling of tPA and neuroserpin were performed by immunohistochemistry, in situ hybridization, immunocapture and zymography assays. In the adult CNS, tPA was expressed at the mRNA and protein levels in many types of neurons, in particular in thalamus, cortex of cerebellum, pontine nuclei, neocortex, limbic system, and medulla oblongata. Interestingly, tPA was often co-expressed with its CNS inhibitor, neuroserpin. Despite overlapping expression of tPA and neuroserpin, zymography and immunocapture assays demonstrated that human neural tissue is a rich source of active tPA. Our analysis documents a detailed map of expression of tPA and its inhibitor in the human CNS and is compatible with the view that tPA is a key player in CNS physiology and pathology.     

A Theory for Classification of Health Care Organizations in the New Economy

Most of the available studies into information technology (IT) have been limited to investigating specific issues, such as how IT can support decision makers distributing the information throughout health care organization, or how technology impacts organizational performance. In this study, for use in the planning of information system development projects, a theoretical model for the classification of health care organizations is proposed. We try to reflect the development in the contemporary digital economy by theoretically classifying health care organizations into three types, namely traditional, developing, and flexible. We describe traditional health care organizations as organizations with a centralized system for management and control. In developing health care organizations, IT is spread over the horizontal dimension and is used for coordinating the different parties throughout the organization. Finally, flexible health care organizations are those which work actively with the design of new health care organizational structure while they are designing the information system.     

Incidence of Parkinson's disease in estonia

The incidence of Parkinson's disease (PD) was studied over a 9-year period (1990-1998) in Tartu county, Estonia, with a mean population of 156,417. Based on 264 patients, the average crude incidence rate of PD was 18.8 per 100,000 person-years. The age-adjusted incidence was 16.8/100,000; 18.3 for the urban group and 14.0 for the rural group; 16.6 for men and 17.1 for women. The age-specific incidence was 1.0/100,000 in the age range 30-39 years, reached a maximum of 117.2/100,000 in the age range 70-79 years and declined in the elderly. The incidence of PD was comparable with that found in developed countries, except for a slightly higher (not significant) incidence rate in the urban compared with the rural population in Estonia.