HEALTH MANAGEMENT AT THE THRESHOLD OF THE NEW MILLENNIUM

Socio-economic, demographic, and political changes in Europe create new challenges facing the organization and management of public health. These issues were interpreted during the conference of the European Health Management Association held in June, 1998, in Dublin (Ireland). Over 250 participants from 30 countries discussed the problems of health care reforms, health policy and management, new information technologies and their application in public health and quality management. A special attention was paid to the reforms in Central and Eastern Europe as well as to the university education in health management. Through a specially performed questionnaire-based investigation, the participants outlined the profile of health care systems in the beginning of the new millenium. It was expected that the relative share of the taxes provided for public health financing would be of approximately 29 per cent, that one of the insurance money - of about 33 per cent, but of co-payment financing - of about 38 per cent. Experts' opinion was united around the statement that on the background of the tendency towards continuous increasing of public health expenditures one should look for the way out in resource redistribution (according to 84 per cent of the interviewed experts). An enhancement of the state financing was not expected as the future role of the state would mainly consist in the regulation (according to 69 per cent of the experts). More than 80 per cent of them considered the competition capable to find the proper way for co-work and collaboration facing both professional and institutional borderlines

MODERN STATISTIC METHODS FOR RATING OF HEALTH CONDUCT

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Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction.

Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. We report here the whole-genome sequences of the human-infective Trichuris trichiura and the mouse laboratory model Trichuris muris. On the basis of whole-transcriptome analyses, we identify many genes that are expressed in a sex- or life stage-specific manner and characterize the transcriptional landscape of a morphological region with unique biological adaptations, namely, bacillary band and stichosome, found only in whipworms and related parasites. Using RNA sequencing data from whipworm-infected mice, we describe the regulated T helper 1 (TH1)-like immune response of the chronically infected cecum in unprecedented detail. In silico screening identified numerous new potential drug targets against trichuriasis. Together, these genomes and associated functional data elucidate key aspects of the molecular host-parasite interactions that define chronic whipworm infection

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

Different pharynx closure techniques in laryngectomy as a risk for pharyngocutaneous fistula

Introduction: One of the most frequent and troublesome complication following laryngectomy is pharyngocutaneous fistula (PCF). There are a lot of different risk factors for PCF suspected and evaluated, but only few proven.Objective: Evaluation the role of different pharynx closure techniques on PCF-incidence.Material and method: The charts of 92 patients, treated for carcinoma of the larynx with laryngectomy at MBAL "Sv. Marina" between july 2007 and december 2014 (86 males, 6 females, aged 61.9 +/- 8.2 years; T4=39, T3=53; N0=71 and N+ =21) were evaluated retrospectively. Three types of closure of the neohypopharynx were used: linear plasty in 31 cases, Y-shaped plasty in 46 cases and atypical type of closure with local tissues being stretched beyond the midline in the remaining 6 cases (called ZZ, TL or L). The primary endpoint was development of clinically evident PCF. The analysis was performed via Student's t-test.Results: The overall incidence of PCF was 7.53%. 1/46 (2.17%) in the Y-plasty group, 3/31 (9.68%) in the I-plasty group and 1/6 (16.67%) in the atypical plasty group developed PCF. The statistical result of the analysis does not find significance in the development of PCF between the groups.Conclusion: The type of the suture line for closure of the neohypopharynx in previously unirradiated patients with otherwise uniform surgical technique does not appear to be a risk factor for PCF.Der Erstautor gibt keinen Interessenkonflikt an

The Pannexin 1 Channel and the P2X7 Receptor Are in Complex Interplay to Regulate the Release of Soluble Ectonucleotidases in the Murine Bladder Lamina Propria

The bladder urothelium releases ATP into the lamina propria (LP) during filling, which can activate P2X receptors on afferent neurons and trigger the micturition reflex. Effective ATP concentrations are largely dependent on metabolism by membrane-bound and soluble ectonucleotidases (s-ENTDs), and the latter are released in the LP in a mechanosensitive manner. Pannexin 1 (PANX1) channel and P2X7 receptor (P2X7R) participate in urothelial ATP release and are physically and functionally coupled, hence we investigated whether they modulate s-ENTDs release. Using ultrasensitive HPLC-FLD, we evaluated the degradation of 1,N6-etheno-ATP (eATP, substrate) to eADP, eAMP, and e-adenosine (e-ADO) in extraluminal solutions that were in contact with the LP of mouse detrusor-free bladders during filling prior to substrate addition, as an indirect measure of s-ENDTS release. Deletion of Panx1 increased the distention-induced, but not the spontaneous, release of s-ENTDs, whereas activation of P2X7R by BzATP or high concentration of ATP in WT bladders increased both. In Panx1−/− bladders or WT bladders treated with the PANX1 inhibitory peptide 10Panx, however, BzATP had no effect on s-ENTDS release, suggesting that P2X7R activity depends on PANX1 channel opening. We concluded, therefore, that P2X7R and PANX1 are in complex interaction to regulate s-ENTDs release and maintain suitable ATP concentrations in the LP. Thus, while stretch-activated PANX1 hinders s-ENTDS release possibly to preserve effective ATP concentration at the end of bladder filling, P2X7R activation, presumably in cystitis, would facilitate s-ENTDs-mediated ATP degradation to counteract excessive bladder excitability