Umsetzung der KRINKO-Empfehlungen zur Infektionsprävention und –kontrolle bei Patienten mit Mukoviszidose (Cystische Fibrose) : Ergebnisse eines Surveys in 35 deutschen Kliniken

Hintergrund: Die Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) hat 2012 Empfehlungen zur Infektionsprävention und –kontrolle (IPC) bei der medizinischen Behandlung von Patienten mit Cystischer Fibrose (CF) veröffentlicht. Ziel der vorliegenden Dissertation ist es, zu evaluieren, inwiefern diese Empfehlungen von deutschen Mukoviszidose-Zentren umgesetzt werden. Methoden: Es wurde ein Online-Fragebogen basierend auf den KRINKO Empfehlungen erstellt, der die Umsetzung der Empfehlungen erfasst. Die gewonnenen Daten wurden auf Korrelation mit Zentrumsgröße und Altersverteilung des Patientenguts untersucht. Ergebnisse: Insgesamt nahmen 35 CF Zentren teil (Antwortrate 32,7%). 37% davon behandeln mehr als 100 CF Patienten; 44% behandeln hauptsächlich Erwachsene. 86% bieten IPC Fortbildungen für medizinisches Personal und 89% für Patienten und ihre Familien an. 51% verwenden zusätzlich schriftliches Material (nur 6% beteiligen Patienten an der Erstellung von Konzepten). Kliniken für erwachsene Patienten berichten über einen Mangel an qualifiziertem Personal für intensivierte Umgebungsreinigung. Manche Kliniken haben Schwierigkeiten, Einzelzimmer mit separaten Sanitäranlagen anzubieten, um CF Patienten strikt zu segregieren. Im Gegensatz zu pädiatrischen Krankenhäusern implementieren manche Einrichtungen für Erwachsene keine Isolationsmaßnahmen bei Patienten mit multiresistenten (aber Carbapenem-sensitiven) gram-negativen Erregern. Die meisten Zentren führen mindestens einen Dekolonisationsversuch (einschließlich systemischer und inhalativer Antibiotika) bei Patienten, die mit MRSA besiedelt sind, durch. Fazit: Die KRINKO Empfehlungen zur Infektionsprävention werden von den zuständigen Ärzten als hilfreich empfunden und werden sorgfältig implementiert. Es gibt Verbesserungspotential bei der Segregierung von stationären CF Patienten in Einzelzimmern, insbesondere in großen CF Zentren, die hauptsächlich erwachsene Patienten behandeln.Background: The Commission for Hospital Hygiene and Infection Prevention (KRINKO) published guidelines for infection prevention and control (IPC) regarding Cystic Fibrosis (CF) in 2012. The goal of this dissertation was to evaluate whether these guidelines have been implemented into clinical practice in German CF centers. Methods: Based on the KRINKO guidelines, an online survey was created in order to acquire data about implementation of the guidelines. The acquired data was analyzed for correlation within size of the center and age distribution within the patient population. Results: Overall, 35 CF centers participated (response rate 32,7%). Of those, 37% treat more than 100 CF patients; 44% treat mainly adults. 86% offer IPC training to their medical staff and 89% offer training to patients and their families. 51% use mainly written material (only 6% include patients in concept creation). Clinics for adult CF patients report a shortage of qualified personnel for intensified environmental cleaning. Some hospitals struggle to provide single patient rooms with an adjacent sanitary area to segregate CF patients strictly. In contrast to pediatric clinics, some clinics for adult patients do not take isolation measures for patients with multiresistant (but carbapenem-sensitive) gram-negative pathogens. Most centers offer at least one decolonization cycle (including systemic and inhalative antibiotics) to patients colonized with MRSA. Conclusion: In CF centers in Germany, the KRINKO IPC recommendations are considered helpful by the attending physicians and thoroughly implemented. There is room for improvement concerning strict segregation of inpatients with CF in single patient rooms, in particular large CF centers mainly caring for adults

Transcriptomic changes arising during light-induced sporulation in Physarum polycephalum

<p>Abstract</p> <p>Background</p> <p><it>Physarum polycephalum </it>is a free-living amoebozoan protist displaying a complex life cycle, including alternation between single- and multinucleate stages through sporulation, a simple form of cell differentiation. Sporulation in <it>Physarum </it>can be experimentally induced by several external factors, and <it>Physarum </it>displays many biochemical features typical for metazoan cells, including metazoan-type signaling pathways, which makes this organism a model to study cell cycle, cell differentiation and cellular reprogramming.</p> <p>Results</p> <p>In order to identify the genes associated to the light-induced sporulation in <it>Physarum</it>, especially those related to signal transduction, we isolated RNA before and after photoinduction from sporulation- competent cells, and used these RNAs to synthesize cDNAs, which were then analyzed using the 454 sequencing technology. We obtained 16,669 cDNAs that were annotated at every computational level. 13,169 transcripts included hit count data, from which 2,772 displayed significant differential expression (upregulated: 1,623; downregulated: 1,149). Transcripts with valid annotations and significant differential expression were later integrated into putative networks using interaction information from orthologs.</p> <p>Conclusions</p> <p>Gene ontology analysis suggested that most significantly downregulated genes are linked to DNA repair, cell division, inhibition of cell migration, and calcium release, while highly upregulated genes were involved in cell death, cell polarization, maintenance of integrity, and differentiation. In addition, cell death- associated transcripts were overrepresented between the upregulated transcripts. These changes are associated to a network of actin-binding proteins encoded by genes that are differentially regulated before and after light induction.</p

Perseverative Thinking in Depression and Anxiety

The current study investigated the impact of worry and brooding as moderators of the tripartite model of depression and anxiety (TMDA). We hypothesized that both types of perseverative thinking would moderate the association between negative affectivity (NA) and both anxiety and depression. Complete data sets for this questionnaire survey were obtained from 537 students. Participants’ ages ranged from 16 to 49 years with a mean age of 21.1 years (SD = 3.6). Overall, results from path analyses supported the assumptions of the TMDA, in that NA was a non-specific predictor for both depression and anxiety whilst lack of positive affectivity (PA) was related to depression only. Unexpectedly, perseverative thinking had an effect on the dependency of negative and positive affectivity. Worry was a significant moderator for the path NA–anxiety. All other hypothesized associations were only marginally significant. Alternative pathways as well as methodological implications regarding similarities and differences of the two types of perseverative thinking are discussed

Compressive hydrated nucleus pulposus extrusion in a dog

An 8-year-old female neutered Maltese Bichon Frise was presented to a small animal hospital for assessment of acute paraplegia. Diagnostic imaging including plain spinal radiographs and CT angiography was neither suggestive of an intervertebral disc extrusion nor any other abnormalities could be detected. The dog was referred to the emergency service of a specialty hospital for an MRI scan. The MRI showed features of a hydrated nucleus pulposus extrusion (HNPE) at L2-3. Subsequent hemilaminectomy identified a mixture of white gelatinous and partly firm material. Cytology and histology were consistent with a partially degenerated nucleus pulposus. Compressive HNPE of the lumbar spine was diagnosed. The dog was discharged 5 days postoperatively. At the last follow-up conducted by phone interview (2 months postoperatively), the owner reported normal ambulation without any signs of neurologic deficits

Prevalence, incidence and sex ratio of transsexualism in Germany established by counting applications of the german trassexuals`act during the period 1991 until 2000

Die vorliegende Arbeit untersucht anhand aller bundesweit getroffenen Entscheidungen gemäß § 1 (Vornamensänderung) und § 8 (Personenstandsänderung) des Transsexuellen-gesetzes für die Zeit von 1991 bis 2000 die Inzidenz und Prävalenz transsexueller Geschlechtsidentitätsstörungen in Deutschland. Dabei konnte von der Prämisse ausgegangen werden, dass die Diagnose Transsexualität laut Gesetz von zwei Sachverständigen gestellt werden muss, bevor ein Antrag nach den §§ 1 oder 8 des Transsexuellengesetzes bewilligt wird. Dementsprechend wurden alle Anträge nach dem Transsexuellengesetz auf Vornamensänderung und auf Personenstandsänderung ausgewertet, die in den Jahren 1991 bis 2000 gestellt wurden. Die Untersuchung baut auf einer gleichartigen Erhebung von Osburg und Weitze (1993) für die Jahre 1981-1990 auf und hat so die Möglichkeit, einen Längsschnittvergleich anzustellen. Insgesamt kann nach Elimination der doppelten und der abgelehnten Anträge aus 3583 gestellten Anträgen auf eine Gesamtzahl von 2506 Transsexuellen geschlossen werden. Dies entspricht einer Zehnjahresprävalenzrate von 3,36 Transsexuellen pro 100.000 der deutschen Bevölkerung bzw. 4,14 MannzuFrau-Transsexuelle/ auf 100.000 der männlichen Bevölkerung und 2,63 FrauzuMann-Transsexuelle/ 100.000 der weiblichen deutsche Bevölkerung. Diese Zahlen liegen signifikant höher als die Zehnjahresprävalenzrate, die von Osburg und Weitze ermittelt wurde. Bezieht man die Daten von Osburg und Weitze mit ein, erhält man eine Prävalenzrate von 4,26/ 100.000 der deutschen Bevölkerung (MannzuFrau: 5,48/ 100.000 und FrauzuMann: 3,12/ 100.000). Die mittlere Inzidenzrate lag bei 0,34 Transsexuellen/ 100.000 der deutschen Gesamtbevölkerung/ Jahr bzw. bei 0,41 MannzuFrau-Transsexuellen/ 100.000 der männlichen deutschen Gesamtbevölkerung/ Jahr und 0,26 FrauzuMann-Transsexuellen/ 100.000 der weiblichen deutschen Gesamtbevölkerung/ Jahr. Im Vergleich der einzelnen Bundesländer konnte eine signifikant höhere Zehnjahres-prävalenz in den Stadtstaaten und eine signifikant niedrigere Zehnjahresprävalenz in den neuen Bundesländern nachgewiesen werden. Das Geschlechterverhältnis im Erhebungszeitraum lag bei 1,5:1 zugunsten der MannzuFrau-Transsexuellen und hat sich somit im Vergleich zur Vor-Dekade (wo es noch 2,3:1 betrug) deutlich einer Gleichverteilung angenähert. Das Durchschnittsalter bei Bewilligung der Anträge zur Vornamensänderung lag bei 33,0 Jahren. Dabei fand sich ein bemerkenswerter Unterschied zwischen MannzuFrau- und FrauzuMann-Transsexuellen: Das Durchschnittsalter der MannzuFrau-Transsexuellen war mit 35,6 Jahren (17-74 Jahre) signifikant höher als das der FrauzuMann-Transsexuellen mit 29,1 Jahren (18 - 72 Jahre). Im Vergleich zur vorhergehenden Dekade ergab sich in dieser Hinsicht kein Unterschied. Das Durchschnittsalter bei der Bewilligung von Anträgen zur Personenstandsänderung lag bei 33,8 Jahren (18-72 Jahre), entsprechend 35,9 Jahren (18-72 Jahre) für MannzuFrau- und 30,9 Jahren (20-66 Jahre) für FrauzuMann-Transsexuelle. Auch dieser Unterschied ist signifikant und ist auch größer als in der Untersuchung für die vorhergehende Dekade von Osburg und Weitze (1993). In Bezug auf die Art der Entscheidung fiel auf, dass insgesamt signifikant weniger Anträge als in der vorhergehenden Dekade abgelehnt wurden. Außerdem wurden signifikant weniger Anträge von FrauzuMann- als von MannzuFrau-Transsexuellen abgelehnt. Im Verlauf der zehn Jahre änderte sich die Ablehnungsrate nicht, während die Anzahl der Anträge signifikant stieg. Im Vergleich zur vorhergehenden Dekade hat die Zeit, die zwischen Anträgen auf Vornamens- und Personenstandsänderung verging, zugenommen. Insbesondere wurden weniger Anträge nach § 1 und § 8 Transsexuellengesetz gleichzeitig gestellt. Die Rate der Anträge auf Rückumwandlung des Vornamens- oder des Personenstandes nach § 6 Transsexuellengesetz lag bei 0,6 % der gesamten Transsexuellen und hat sich somit – verglichen zum Zeitraum von 1981 bis 1990 – trotz deutlich gestiegener Antragszahlen nicht verändert.Surveying applications for changing of the first name (§ 1 german trassexuals´act) or the sex status (§ 8 german trassexuals`act) at all german courts during the period from 1991 until 2000 the prevalence, the incidence and the sex ratio of transsexualism in Germany were surveyed. An important requirement for the permission of these applications is getting the diagnosis transsexualism confirmed by at least two experts. The basis for this survey was the examination by Weitze and Osburg (1996), who collected the same data for the period 1981-1990. That was the first period the german transsexuals´act (TSG) existed. So it was possible to examine a longitudinal section. After elaminating the double and the rejected applications from all 3583 applications there were left a number of 2506 transsexuals. This corresponds to a ten-year-prevalence of 3,36 transsexuals per 100.000 of the german population or rather 4,14 MF-transsexuals/ 100.000 of the male population und 2,63 FM-transsexuals/ 100.000 of the female german population. This is significantly higher then the established data of Weitze and Osburg (1996). If you additionally include the data of Osburg and Weitze, a prevalence of 4,26 per 100.000 of the german population can be estimated (MaletoFemale 5,48/ 100.000 and Femaletomale: 3,12/ 100.000). The avarage incidence was 0,34 transsexuals per 100.000 of the german population per year (0,41 MF-transsexuals/ 100.000 of the male german population per year and 0,26 FM-transsexuals/ 100.000 of the female german population per year. Comparing the different states there was provable a significant higher ten-year-prevalence in the federal city states and a significant lower ten-year-prevalence in the newly formed german states. The sex ratio was 1,5:1 in favor of the MF-transsexuals. Compared to the previous decade, where it was 2,3:1, it is getting nearer to a uniform distribution. The avarage age was 33,0 years, when the applications for changing of the first name were permitted. There was a remarkable difference between MF- and FM-transsexuals: The avarage age of the MF-transsexuals was 35,6 years (17-74 years) and thereby significantly higher than the average age of the FM-transsexuals, which was 29,1 years (18-72 years). Concerning to this there was no difference compared to the previous decade. The avarage age was 33,8 years (18-72 years), appopriate 35,9 years (18-72 years) for the MF- and 30,9 years (20-66 years) for FM-transsexuals, when the applications for changing of the sex status were permitted. Even this difference is significant and even higher than the difference in the previous dekade. Significantly less applications had been rejected compared with the previous decade. Additionally less applications of FM-transsexuals than applications of MF-transsexauls had been rejected. The rate of rejections did not change between the individual years, but the number of applications rised. Comparing the two decades the time between the application for the change of the first name and the sex status had rised. Especially less applications had been placed the same time. The rate of applications for the rechange of the first name or of the sex status (§ 6 german`s transsexual act) was 0,6 % of the whole transsexuals. It has not changend in comparison with the previous decade

Preoperative/Neoadjuvant Therapy in Pancreatic Cancer: A Systematic Review and Meta-analysis of Response and Resection Percentages

Jörg Kleef and colleagues systematically reviewed studies on neoadjuvant therapy and tumor response, toxicity, resection, and survival percentages in pancreatic cancer and suggest that patients with locally nonresectable tumors should be included in neoadjuvant protocols

Quantitative automated microscopy (QuAM) elucidates growth factor specific signalling in pain sensitization

<p>Abstract</p> <p>Background</p> <p>Dorsal root ganglia (DRG)-neurons are commonly characterized immunocytochemically. Cells are mostly grouped by the experimenter's eye as "marker-positive" and "marker-negative" according to their immunofluorescence intensity. Classification criteria remain largely undefined. Overcoming this shortfall, we established a quantitative automated microscopy (QuAM) for a defined and multiparametric analysis of adherent heterogeneous primary neurons on a single cell base.</p> <p>The growth factors NGF, GDNF and EGF activate the MAP-kinase Erk1/2 via receptor tyrosine kinase signalling. NGF and GDNF are established factors in regeneration and sensitization of nociceptive neurons. If also the tissue regenerating growth factor, EGF, influences nociceptors is so far unknown. We asked, if EGF can act on nociceptors, and if QuAM can elucidate differences between NGF, GDNF and EGF induced Erk1/2 activation kinetics. Finally, we evaluated, if the investigation of one signalling component allows prediction of the behavioral response to a reagent not tested on nociceptors such as EGF.</p> <p>Results</p> <p>We established a software-based neuron identification, described quantitatively DRG-neuron heterogeneity and correlated measured sample sizes and corresponding assay sensitivity. Analysing more than 70,000 individual neurons we defined neuronal subgroups based on differential Erk1/2 activation status in sensory neurons. Baseline activity levels varied strongly already in untreated neurons. NGF and GDNF subgroup responsiveness correlated with their subgroup specificity on IB4(+)- and IB4(-)-neurons, respectively. We confirmed expression of EGF-receptors in all sensory neurons. EGF treatment induced STAT3 translocation into the nucleus. Nevertheless, we could not detect any EGF induced Erk1/2 phosphorylation. Accordingly, intradermal injection of EGF resulted in a fundamentally different outcome than NGF/GDNF. EGF did not induce mechanical hyperalgesia, but blocked PGE₂-induced sensitization.</p> <p>Conclusions</p> <p>QuAM is a suitable if not necessary tool to analyze activation of endogenous signalling in heterogeneous cultures. NGF, GDNF and EGF stimulation of DRG-neurons shows differential Erk1/2 activation responses and a corresponding differential behavioral phenotype. Thus, in addition to expression-markers also signalling-activity can be taken for functional subgroup differentiation and as predictor of behavioral outcome. The anti-nociceptive function of EGF is an intriguing result in the context of tissue damage but also for understanding pain resulting from EGF-receptor block during cancer therapy.</p

Hypomethylation and expression of BEX2, IGSF4 and TIMP3 indicative of MLL translocations in Acute Myeloid Leukemia

Background Translocations of the Mixed Lineage Leukemia (MLL) gene occur in a subset (5%) of acute myeloid leukemias (AML), and in mixed phenotype acute leukemias in infancy - a disease with extremely poor prognosis. Animal model systems show that MLL gain of function mutations may contribute to leukemogenesis. Wild-type (wt) MLL possesses histone methyltransferase activity and functions at the level of chromatin organization by affecting the expression of specific target genes. While numerous MLL fusion proteins exert a diverse array of functions, they ultimately serve to induce transcription of specific genes. Hence, acute lymphoblastic leukemias (ALL) with MLL mutations (MLLmu) exhibit characteristic gene expression profiles including high-level expression of HOXA cluster genes. Here, we aimed to relate MLL mutational status and tumor suppressor gene (TSG) methylation/expression in acute leukemia cell lines. Results Using MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification assay), methylation of 24 different TSG was analyzed in 28 MLLmu and MLLwt acute leukemia cell lines. On average, 1.8/24 TSG were methylated in MLLmu AML cells, while 6.2/24 TSG were methylated in MLLwt AML cells. Hypomethylation and expression of the TSG BEX2, IGSF4 and TIMP3 turned out to be characteristic of MLLmu AML cell lines. MLLwt AML cell lines displayed hypermethylated TSG promoters resulting in transcriptional silencing. Demethylating agents and inhibitors of histone deacetylases restored expression of BEX2, IGSF4 and TIMP3, confirming epigenetic silencing of these genes in MLLwt cells. The positive correlation between MLL translocation, TSG hypomethylation and expression suggested that MLL fusion proteins were responsible for dysregulation of TSG expression in MLLmu cells. This concept was supported by our observation that Bex2 mRNA levels in MLL-ENL transgenic mouse cell lines required expression of the MLL fusion gene. Conclusion These results suggest that the conspicuous expression of the TSG BEX2, IGSF4 and TIMP3 in MLLmu AML cell lines is the consequence of altered epigenetic properties of MLL fusion proteins