Doktora başvuru ikilemi: Poliklinik hastalarında veri güvenilirliğinin irdelenmesi

The aim of the study is to investigate the nature of outpatient-based visits to speciality care physicians in outpatient departments of a teaching hospital. A questionnaire which was in a sense “an after-visit summary” that contained patient age, gender and doctor’s major office contact reason was developed. Physicians from different medical disciplines completed the questionnaire on randomly selected visits. Data was analysed statistically by descriptive analysis and cross tabulation. 1184 adult patients were analysed; 587 [49.6 (%)] of them were visited by medicine specialists, and 597 [50.4 (%)] by surgeons. Among all adult admissions, first patients comprised less than half of the workload, 40.8 (%) in surgery and 43.5 (%) in medicine. There was a significant difference between the number of patient contacts in medical and surgical specialities in terms of major visit categories. Compared to first visit, numbers of established patients, office consultation and reporting were significantly higher, whereas number of prehospitalizations was significantly lower in medicine than surgery. As shown in the study, per capita doctors’ visit data is not very reliable, nor is it uniform in OECD database, disabling the comparison between countries.Bu çalışmanın amacı, bir eğitim araştırma hastanesinin farklı polikliniklerine başvuran ayaktan hastaların başvuru nedenlerini incelemektir. Araştırmamızda farklı polikliniklerden hekimler tarafından doldurulan, hastanın yaşı, cinsiyeti ve başvuru nedenini içeren; bir bakıma “muayene sonrası özeti” olan bir çizelge geliştirilmiştir. Hekimler çizelgeyi rastgele seçilen muayeneler arasından tamamlamışlardır. Elde edilen verilerden çapraz tablolar oluşturulmuş ve tanımlayıcı istatistik ile analiz edilmiştir. 1184 yetişkin hasta analiz edilmiş olup; 587'si (%49,6) dahili klinikleri, 597'si (%50,4) cerrahi klinikleri hekimlerince muayene edilmiştir. Tüm yetişkin başvuruları arasındaki hastaların yarısından azı hem dahili [40,84 (%)] hem de cerrahi [43,55 (%)] polikliniklerde ilk kez hekime başvuru yapan hastalardır. Dahili ve cerrahi polikliniklere yapılan hasta başvuru nedenleri arasında önemli bir farklılık bulunmaktadır. İlk muayeneleri kıyasladığımızda dahili branşlarda, takipli hasta sayısı, konsültasyon ve rapor yazdırma sayıları cerrahi branşlara göre önemli ölçüde daha yüksekken, hastaneye yatış öncesi yapılan muayene sayısı cerrahi branşlara göre önemli ölçüde daha düşük çıkmıştır. Çalışmada gösterildiği gibi, doktor başına düşen muayene verileri güvenilir olmamakla birlikte OECD veri tabanında bu konuda tam bir tanım birliği bulunmamaktadır, bu da ülkeler arasındaki karşılaştırma yapılmasını engellemektedir

A small molecule screen identifies novel inhibitors of mechanosensory nematocyst discharge in Hydra

Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense. Nematocyst discharge is controlled by a mechanosensory apparatus with analogies to vertebrate hair cells. Members of the transient receptor potential (TRPN) ion channel family are supposed to be involved in the transduction of the mechanical stimulus. A small molecule screen was performed to identify compounds that affect nematocyst discharge in Hydra. We identified several [2.2]paracyclophanes that cause inhibition of nematocyst discharge in the low micro-molar range. Further structure–activity analyses within the compound class of [2.2]paracyclophanes showed common features that are required for the inhibitory activity of the [2.2]paracyclophane core motif. This study demonstrates that Hydra can serve as a model for small molecule screens targeting the mechanosensory apparatus in native tissues

Expression of Pancreatitis-Associated Protein after Traumatic Brain Injury: A Mechanism Potentially Contributing to Neuroprotection in Human Brain

Neuronal cell death after severe traumatic brain injury (TBI) is caused by a complex interplay of pathological mechanisms including excitotoxicity, oxidative stress, mitochondrial dysfunction, extensive neuroinflammation, and ischemia-reperfusion injury. Pancreatitis-associated protein I (PAP I/reg2) was reported to be a survival factor for peripheral neurons, particularly sensory and motor neurons. In rat brains, by experimental TBI as well as by kainic acid induced brain seizure, PAP I and PAP III were found to be up-regulated in central neurons. In this study, we performed immunohistochemical staining in postmortem human brain from patients who died after severe TBI to demonstrate PAP expression on protein level in cerebellar Purkinje cells, pyramidal and granular neurons in cerebral cortex, and cortical neurons in the fore- and mid-brain. In primary cultures of rat brain cortical, hippocampal, and cerebellar neurons, we found neuroprotective effects for PAP I on H2O2-induced oxidative stress. Moreover, serum K+-deprivation induces apoptotic cell death in 55% of cerebellar granule neurons (CGN), whereas upon treatment with PAP I only 32% of CGN are apoptotic. Using Western blot analyses, we compared protein phosphorylation in neuronal signaling pathways activated by PAP I versus Interleukin-6 (IL-6). We found a rapid activation of Akt-kinase phosphorylation by PAP I with a peak at 15min, whereas IL-6 induces Akt-phosphorylation lasting longer than 30min. Phosphorylation of MAP-42/44 kinases is stimulated in a comparable fashion. Both, IL-6 and PAP I increase phosphorylation of NFκB for activation of gene transcription, whereas only IL-6 recruits STAT3 phosphorylation, indicating that STAT3 is not a target of PAP I transcription activation in brain neurons. Application of the Akt-inhibitor Wortmanin reveals only a partial inhibition of PAP I-dependent protection of CGN from H2O2-induced oxidative stress. Based on our findings, we suggest that PAP I is a long lasting neurotrophic signal for central neurons. The neuroprotective effects parallel those that have been described for effects of PAP I in ciliary neurotrophic factor (CNTF)-mediated survival of sensory and motor neurons. PAP I may act in autocrine and/or paracrine fashion and thus may contribute to endogenous protective mechanisms relevant under harmful conditions like oxidative stress, brain injury, or neurodegeneratio

Numerical Investigations of Mixed Convection of Incompressible Viscous Fluid in LNG Storage with a Various Locations of Input and Output Mass

The article shows the results of mathematical simulation of mixed convection in the low-temperature storage of liquefied natural gas with a regenerative cooling. The regimes of mixed convection in a closed area with the different arrangement of the input and output sections of the masses are investigated. Two-dimensional nonstationary problem in the model of the Navier-Stokes in dimensionless variables "vorticity - stream function - temperature" was examined. Are obtained distributions of the hydrodynamic parameters and temperatures, characteristic basic laws governing the processes being investigated. Detailed circulating currents and carried out analysis of the mechanism of vortices formation and the temperature distribution in the solution for mixed convection mode with low Reynolds and Grashof numbers (Gr=10{6}, 100<Re<1000). Is established the significant influence of the geometrical arrangement of the input and output mass sections and input stream velocity on the structure of liquid flow and temperature in the low temperature LNG storage tanks

Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity

Background: Wnt proteins are a family of secreted signaling molecules that regulate key developmental processes in metazoans. The molecular basis of Wnt binding to Frizzled and LRP5/6 co-receptors has long been unknown due to the lack of structural data on Wnt ligands. Only recently, the crystal structure of the Wnt8-Frizzled8-cysteine-rich-domain (CRD) complex was solved, but the significance of interaction sites that influence Wnt signaling has not been assessed. Results: Here, we present an extensive structure-function analysis of mouse Wnt3a in vitro and in vivo. We provide evidence for the essential role of serine 209, glycine 210 (site 1) and tryptophan 333 (site 2) in Fz binding. Importantly, we discovered that valine 337 in the site 2 binding loop is critical for signaling without contributing to binding. Mutations in the presumptive second CRD binding site (site 3) partly abolished Wnt binding. Intriguingly, most site 3 mutations increased Wnt signaling, probably by inhibiting Wnt-CRD oligomerization. In accordance, increasing amounts of soluble Frizzled8-CRD protein modulated Wnt3a signaling in a biphasic manner. Conclusions: We propose a concentration-dependent switch in Wnt-CRD complex formation from an inactive aggregation state to an activated high mobility state as a possible modulatory mechanism in Wnt signaling gradients

Hydra Mesoglea Proteome Identifies Thrombospondin as a Conserved Component Active in Head Organizer Restriction

Thrombospondins (TSPs) are multidomain glycoproteins with complex matricellular functions in tissue homeostasis and remodeling. We describe a novel role of TSP as a Wnt signaling target in the basal eumetazoan Hydra. Proteome analysis identified Hydra magnipapillata TSP (HmTSP) as a major component of the cnidarian mesoglea. In general, the domain organization of cnidarian TSPs is related to the pentameric TSPs of bilaterians, and in phylogenetic analyses cnidarian TSPs formed a separate clade of high sequence diversity. HmTSP expression in polyps was restricted to the hypostomal tip and tentacle bases that harbor Wnt-regulated organizer tissues. In the hypostome, HmTSP- and Wnt3-expressing cells were identical or in close vicinity to each other, and regions of ectopic tentacle formation induced by pharmacological β-Catenin activation (Alsterpaullone) corresponded to foci of HmTSP expression. Chromatin immunoprecipitation (ChIP) confirmed binding of Hydra TCF to conserved elements in the HmTSP promotor region. Accordingly, β-Catenin knockdown by siRNAs reduced normal HmTSP expression at the head organizer. In contrast, knockdown of HmTSP expression led to increased numbers of ectopic organizers in Alsterpaullone-treated animals, indicating a negative regulatory function. Our data suggest an unexpected role for HmTSP as a feedback inhibitor of Wnt signaling during Hydra body axis patterning and maintenance

The Evolution of Extracellular Matrix

We present a perspective on the molecular evolution of the extracellular matrix (ECM) in metazoa that draws on research publications and data from sequenced genomes and expressed sequence tag libraries. ECM components do not function in isolation, and the biological ECM system or “adhesome” also depends on posttranslational processing enzymes, cell surface receptors, and extracellular proteases. We focus principally on the adhesome of internal tissues and discuss its origins at the dawn of the metazoa and the expansion of complexity that occurred in the chordate lineage. The analyses demonstrate very high conservation of a core adhesome that apparently evolved in a major wave of innovation in conjunction with the origin of metazoa. Integrin, CD36, and certain domains predate the metazoa, and some ECM-related proteins are identified in choanoflagellates as predicted sequences. Modern deuterostomes and vertebrates have many novelties and elaborations of ECM as a result of domain shuffling, domain innovations and gene family expansions. Knowledge of the evolution of metazoan ECM is important for understanding how it is built as a system, its roles in normal tissues and disease processes, and has relevance for tissue engineering, the development of artificial organs, and the goals of synthetic biology

Struktur- und Funktionsanalyse der zytokinbindenden Domäne des humanen Interleukin-6-Rezeptors

Die Familie der IL-6-Typ-Zytokine (IL-6, IL-11, CT-1, CNTF, LIF, OSM, BSF-3) ist durch eine vierhelikale Faltung gekennzeichnet. Alle Zytokine dieser Familie agieren über einen Rezeptorkomplex, der als gemeinsame Komponente mindestens ein Molekül gp130 enthält. IL-6 und IL-11 signalisieren über ein gp130-Homodimer, während CT-1, CNTF, LIF und OSM ein Heterodimer aus gp130 und dem strukturell verwandten LIFR oder, im Falle des OSM, auch OSMR verwenden. Die Rezeptoren der vierhelikalen Zytokine sind in ihrem extrazellulären Bereich modulartig aus Ig- und Fibronektin-Typ-III-ähnlichen Domänen aufgebaut. Sie besitzen als gemeinsame Struktureinheit ein zytokinbindendes Modul (CBM) aus zwei Fibronektin-Typ-III-ähnlichen Domänen, die durch vier konservierte Cysteine in der N-terminalen und ein konserviertes WSXWS-Motiv in der C-terminalen Domäne charakterisiert sind. Auf Zielzellen bindet IL-6 an den spezifischen IL-6 Rezeptor, worauf der Komplex aus IL-6/IL-6R mit dem Signaltransduktor gp130 assoziiert. Der IL-6R besteht in seinem extrazellulären Bereich aus drei Domänen. Die N-terminale Ig-ähnliche Domäne ist für die biologische Aktivität nicht notwendig. Die Domänen 2 und 3 bilden das CBM, welches auch in löslicher Form agonistisch wirkt. In der vorliegenden Arbeit wurden die strukturellen und funktionellen Eigenschaften der dritten extrazellulären Domäne des IL-6R untersucht. Das Protein läßt sich effizient in Bakterien exprimieren und in vitro renaturieren. Es konnte gezeigt werden, daß Domäne 3 für die Bindung an IL-6 ausreichend ist, der Komplex aus D3 und IL-6 jedoch nicht mehr mit dem gp130-Molekül assoziieren kann. Da der lösliche IL-6R (bestehend aus D2 und D3) in der Lage ist, an gp130 zu binden und ein biologisches Signal auszulösen, weisen diese Daten der C-terminalen CBM-Domäne (D3) eine ligandenbindende Funktion und der N-terminalen CBM-Domäne eine wichtige Rolle bei der Komplexbildung mit gp130 und Signalinduktion zu. Die gezeigte Expressions- und Renaturierungsstrategie für D3 wurde zur Markierung des Proteins mit 15N und 13C für die mehrdimensionale, heteronukleare NMR-Spektroskopie angewandt. Die hierdurch ermöglichte Strukturaufklärung von D3 als einer eindeutig in die Ligandenbindung involvierten Teilstruktur wird umfassendere strukturelle Informationen über den IL-6R-Komplex liefern, als es die bisherigen Mutations- bzw. Modellbaustudien konnten