Wir brauchen eine Pflegerevolution!

WIR BRAUCHEN EINE PFLEGEREVOLUTION! Wir brauchen eine Pflegerevolution! / Zimmermann, Pia (Rights reserved) ( -

Untersuchungen der genetischen Varianz aktueller Isolate des porzinen Parvovirus

Studies on the genetic variability of recent isolates of porcine parvovirus The aim of this study was to review the antigenetic variability of porcine parvovirus and to examine the role of porcine parvovirus in reproductive failure. Organ specimens of 500 fetuses and stillborn piglets from a total of 172 farms were analysed. Total DNA was isolated from the explants and quantitative as well as qualitative PCR was subsequently carried out. In 82 samples (15,8%) out of 28 farms (16,3%), PPV was diagnosed. In this study, we were able to show that rectal swabs are suitable substrates from which to detect porcine parvovirus in sows using a PCR analysis. In 12 out of 19 rectal swabs PPV genome was amplified. In one PPV-positive sample the sow was infected a minimum of 45 days before the rectal swab was collected. An attempt was made to cultivate porcine parvovirus out of 22 PPV-positive organ specimens of different origin. However, only 5 isolates could be cultivated and the production of progeny virus was very low in two of these isolates. Although multiple passages were performed, the virus yield did not increase. As the viral capsid is the target of host protective immunity against PPV, the complete gene of the structural protein of 7 field isolates was amplified and sequenced. The obtained sequences were aligned with the porcine parvovirus-strains NADL-2, Kresse, one challenge-virus of the year 1986 and with the vaccine strain of IDT. The sequence homology among the isolates sequenced is very high (on the level of nucleotide acids minimum 98,7%, on the level of amino acids minimum 97,7). Phylogenetic analysis revealed that there is only a distant relationship between NADL-2, Kresse and the challenge-virus on the hand and the field isolates on the other hand. A comparison of the aligned PPV-sequences from field isolates with the published sequence of two primers recommended for diagnostic PCR revealed single nucleotide differences. Therefore, it appears possible that the primer sequences published may not be suitable for a diagnostic PPV-PCR in the field. Taken as a whole, these data suggest that the porcine parvovirus may have altered antigenetically. Furthermore, the obtained sequences from field isolates of PPV now permit the examination of the antigenetic consequence of this evolution to develop effective vaccines against the PPV strains now present in the field.Ziel der vorliegenden Arbeit war die Beurteilung der antigenetischen Variabilität des porzinen Parvovirus (PPV). Gleichzeitig erfasst diese Studie den Anteil von porzinem Parvovirus an Fruchtbarkeitsstörungen in Süddeutschland. Dazu wurde Gewebematerial von 500 Schweinen aus 172 Betrieben auf PPV untersucht. Aus den Gewebeproben wurde die Gesamtnukleinsäure isoliert und anschließend mittels quantitativer und qualitativer PCR amplifiziert. 82 Proben (15,8%) aus 28 Betrieben (16,3%) waren positiv. Im Rahmen der diagnostischen PCR konnte gezeigt werden, dass Rektumtupfer geeignetes Untersuchungsmaterial sind, um PPV nachzuweisen. In 12 von 19 untersuchten Proben gelang der Virusnachweis. In einem untersuchten positiven Fall lag die Infektion gesichert mindestens 45 Tage zurück. Aus 22 in der PCR PPV-positiv getesteten Gewebeproben verschiedener Herkunft, wurde eine Virusanzucht versucht. Dies gelang nur bei 5 Isolaten. Zwei dieser Isolate zeigten dabei nur eine sehr niedrige Replikationsrate. Auch durch mehrfache Passagierung ließen sich nicht mehr Isolate anzüchten. Da das Kapsid für die Immunantwort verantwortlich gemacht wird, wurde aus positiven Gewebeproben das vollständige Gen des Kapsidproteins (VP1) von 7 Feldisolaten amplifiziert und sequenziert. Die gewonnenen Sequenzen wurden mit den Stämmen PPVNADL-2, PPV-Kresse, einem PPV-Challenge-Virus von 1986 und mit dem PPV-Impfstamm von IDT verglichen. Es konnte gezeigt werden, dass alle Isolate eine sehr hohe Homologie aufweisen (auf Nukleinsäurenebene zu 98,7%, auf Aminosäurenebene 97,7%. Eine phylogenetische Analyse erbrachte, dass die verwandtschaftliche Beziehung von NADL-2, Kresse und dem Challenge-Virus zu den 7 Feldisolaten relativ gering ist. Der Nukleinsäurensequenz-Vergleich zeigte, dass für 2 publizierten Methoden zum PPVNachweis mittels PCR, Punktmutationen auf der Zielsequenz einzelner Primer bei einzelnen Feldisolaten entstanden sind, und die Eignung dieser PCRs zum Nachweis eines breiten Isolatspektrums eingeschränkt sein könnte. Insgesamt implizieren die gewonnen Daten, dass sich das porzine Parvovirus antigenetisch verändert haben könnte. Die gewonnen Isolate erlauben nun die gezielte Untersuchung der Konsequenz dieser Evolution für die Entwicklung wirksamer Vakzine

Correction to: Flow-through experiments on the interaction of sandstone with Ba-rich fluids at geothermal conditions

Abstract After publication of the article (Orywall et al. 2017), it has been brought to our attention that there are a number of errors. The authors have listed them below

Simulation Experiment Schemas - Beyond Tools and Simulation Approaches: Software appendix [research data]

This archive contains the software described in the paper "Simulation Experiment Schemas - Beyond Tools and Simulation Approaches" published at the Winter Simulation Conference 2019. The tool guides users through the simulation experiment specification process via a graphical user interface. The entered information is used in the generation of backend-independent experiment specifications in the JSON format. The JSON-based specifications can be mapped to different simulation backends. Currently, two domains of modeling and simulation are supported: stochastic discrete-event simulation, and finite element simulation for electromagnetics. For both domains, basic simulation runs are supported as well as complex experiment designs such as sensitivity analyses based on full factorial designs

Missing Selectivity of Targeted 4 beta-Phorbol Prodrugs Expected to be Potential Chemotherapeutics

Targeting cytotoxic 4 beta-phorbol esters toward cancer tissue was attempted by conjugating a 4 beta-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors was envisioned to release lipophilic cytotoxins, which subsequently penetrate into cancer cells. The 4 beta-phorbol esters were prepared from 4 beta-phorbol isolated from Croton tiglium seeds, while the peptides were prepared by solid-phase synthesis. Cellular assays revealed activation of PKC by the prodrugs and efficient killing of both peptidase positive as well as peptidase negative cells. Consequently no selectivity for enzyme expressing cells was found.Peer reviewe

Cowpox Virus Transmission from Pet Rats to Humans, Germany

We describe a cluster of cowpox virus (CPXV) infections in humans that occurred near Munich, Germany, around the beginning of 2009. Previously, only sporadic reports of CPXV infections in humans after direct contact with various animals had been published. This outbreak involved pet rats from the same litter

The Acute Optic Neuritis Network (ACON): Study protocol of a non-interventional prospective multicenter study on diagnosis and treatment of acute optic neuritis

Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days-to-Rx). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON

The Acute Optic Neuritis Network (ACON): Study protocol of a non-interventional prospective multicenter study on diagnosis and treatment of acute optic neuritis

Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days-to-Rx). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON. Trial registration: ClinicalTrials.gov, identifier: NCT05605951

An expression signature of syndecan-1 (CD138), E-cadherin and c-met is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ

INTRODUCTION: Heparan sulphate proteoglycan syndecan-1 modulates cell proliferation, adhesion, migration and angiogenesis. It is a coreceptor for the hepatocyte growth factor receptor c-met, and its coexpression with E-cadherin is synchronously regulated during epithelial-mesenchymal transition. In breast cancer, changes in the expression of syndecan-1, E-cadherin and c-met correlate with poor prognosis. In this study we evaluated whether coexpression of these functionally linked prognostic markers constitutes an expression signature in ductal carcinoma in situ (DCIS) of the breast that may promote cell proliferation and (lymph)angiogenesis. METHODS: Expression of syndecan-1, E-cadherin and c-met was detected immunohistochemically using a tissue microarray in tumour specimens from 200 DCIS patients. Results were correlated with the expression patterns of angiogenic and lymphangiogenic markers. Coexpression of the three prognostic markers was evaluated in human breast cancer cells by confocal immunofluorescence microscopy and RT-PCR. RESULTS: Coexpression and membrane colocalization of the three markers was confirmed in MCF-7 cells. E-cadherin expression decreased, and c-met expression increased progressively in more aggressive cell lines. Tissue microarray analysis revealed strong positive staining of tumour cells for syndecan-1 in 72%, E-cadherin in 67.8% and c-met in 48.6% of DCIS. E-cadherin expression was significantly associated with c-met and syndecan-1. Expression of c-met and syndecan-1 was significantly more frequent in the subgroup of patients with pure DCIS than in those with DCIS and a coexisting invasive carcinoma. Levels of c-met and syndecan-1 expression were associated with HER2 expression. Expression of c-met significantly correlated with expression of endothelin A and B receptors, vascular endothelial growth factor (VEGF)-A and fibroblast growth factor receptor-1, whereas E-cadherin expression correlated significantly with endothelin A receptor, VEGF-A and VEGF-C staining. CONCLUSION: Syndecan-1, E-cadherin and c-met constitute a marker signature associated with angiogenic and lymphangiogenic factors in DCIS. This coexpression may reflect a state of parallel activation of different signal transduction pathways, promoting tumour cell proliferation and angiogenesis. Our findings have implications for future therapeutic approaches in terms of a multiple target approach, which may be useful early in breast cancer progression

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points