Robust and time-effcient determination of perfusion parameters using time-encoded Arterial Spin Labeling MRI

In clinical routine, arterial spin labeling (ASL) faces many challenges, such as time pressure, patient- and disease-specific artifacts, e.g., in steno-occlusive and Moya-Moya disease. In addition, individually tailored parametrization of the MR pulse-sequence is frequently required. Time-encoded ASL-techniques like Hadamard time-encoded pseudocontinuous ASL (H-pCASL) offers a time and signal efficient way to measure accurately both perfusion and arterial transit-times. However, it relies on the decoding of a series of volumes. If even a single volume is corrupted this might, via the decoding process, lead to artifacts in the entire dataset and in the worst case result in the loss of the data. In this thesis a general introduction to time encoded ASL is given and three methods are introduced to increase the robustness of time-encoded ASL against image artifacts and to detect corrupted images. The first method is Walsh-ordered time-encoded H-pCASL (WH-pCASL). It proposes the Walsh-ordering of Hadamard encoding-matrices. In contrast to conventional H-pCASL, this makes perfusion-weighted images accessible during a running experiment and even from incomplete sets of encoded images. An optional additional averaging strategy is based on a mirrored matrix and results in more perfusion-weighted images without any penalty in time. The feasibility of the method is shown using five volunteer datasets. As a second method non-decoded time-encoded ASL is introduced. This novel model-based approach to quantification avoids the decoding step altogether. It models the non-decoded time encoded signal. Therefore it uses the convolution of the tissue response function with a model of the true encoded arterial input function, which is determined by the employed encoding matrix. The model was implemented in a Bayesian model-based ASL analysis framework to fit maps for hemodynamic parameters. The feasibility of the method is demonstrated in a study with five volunteers. The last method is an algorithm for the automated detection of outliers and corrupted images, which is based on variational Bayesian inference (VB). Using the variance of the posterior normal distributions, the algorithm measures the quality of a fit directly and without the need for a separate reference dataset. Its performance and feasibility is demonstrated using volunteer data and a clinical dataset

Incidence of anthelmintic resistance in cattle farms in Northern Germany – first results

Anthelmintic resistance (AR) is an increasing problem worldwide especially for small ruminants and it is also rising in cattle. To maintain the efficacy of anthelmintics is an important objective. The current project aims at the investigation of the current efficacy of macrocyclic lactone anthelmintics for strongylid nematodes in first season grazing (FSG) calves in Northern Germany. On 8 participating farms in Northern Germany faecal egg count reduction tests (FECRT) with ivermectin (IVM) were performed. On 3 farms the efficacy of IVM was found to be ≤90% and on only 4 farms it was > 95% at 14 days post treatment (d.p.t.). Only 2 farms showed a reduction ≥ 95% at 21 d.p.t.. This survey reveals a rising problem of AR. The problem of drug resistance places the welfare of animals at risk. In organic farming, without a preventive treatment, livestock may harbour high worm counts. Therefore it is necessary to maintain powerful anthelmintic drugs to guarantee the welfare of animals that need salvage treatment. To investigate the AR problem in cattle more surveys with different anthelmintic drug classes are urgently needed

Stimulation pro-fibrotischer und pro-inflammatorischer Signalwege im kardialen Remodeling durch den orphan Rezeptor GPRC5B

Die Behandlung der chronischen Herzinsuffizienz stellt eine der größten Herausforderungen der modernen Medizin dar. An Ihrer Entstehung sind Inflammation, kardiale Fibrose und myokardialer Zellverlust sowie kardiomyozytäre Hypertrophie beteiligt. Diese Prozesse münden letztendlich in kardialem Remodeling, welches mit einer stark eingeschränkten Funktion des Herzens einhergeht, sodass dieses den Körper nicht mehr suffizient mit Blut versorgt. Eine Schlüsselrolle in der Pathogenese spielen dabei kardiale Fibroblasten, welche einen Großteil der kardialen Zellpopulation darstellen. GPRC5B, ein G-Protein-gekoppelter orphan Rezeptor, der pro-inflammatorische Eigenschaften in Adipozyten hat und in den Glukose- und Lipidstoffwechsel involviert ist, wird endogen in kardialen Fibroblasten exprimiert. Er wirkt vermutlich über die Aktivierung der NFκB-Signalkaskade. Hier wurde die Regulation und Funktion dieses Rezeptors in primären Rattenkardiofibroblasten und seine potentielle Bedeutung in der Pathogenese kardialen Remodelings untersucht. Die Expression des GPRC5B-Rezeptors wird durch TNFα, LPS und mechanischen Stress reguliert. In, frisch aus neonatalen Ratten isolierten, kardialen Fibroblasten zeigte sich im Western Blot nach 48h Stimulation mit TNFα (50 ng/ml) oder LPS (100 ng/ml) eine signifikante Hochregulierung von GPRC5B gegenüber unstimulierten Zellen. Diese Regulation von GPRC5B bestätigte sich auch auf mRNA-Ebene (qPCR). Des Weiteren zeigten Auswertungen der mRNA nach 24 stündiger mechanischer Belastung durch 18%ige Dehnung eine deutliche Hochregulation von GPRC5B gegenüber nicht-gedehnten Zellen. Bei adenoviral vermittelter Überexpression von GPRC5B in kardialen Fibroblasten (20 MOI) wurde ein Anstieg der basalen Transkriptionsrate von TNFα, IL-1ß, IL-6, MCP-1 und von MMP-9 beobachtet. Nach anschließender 24 stündiger Stimulation mit LPS (10 ng/ml) zeigte sich kein signifikanter Unterschied der IL-6 und MCP-1-mRNA-Niveaus im Vergleich zu den mit AdLacZ infizierten Kontrollzellen, die TNFα-, IL-1ß- und MMP-9-Transkriptionen stiegen hingegen signifikant an. Die Überepxression von GPRC5B hatte keinen Einfluss auf die Transkription von Kollagen-1A1 in vitro. Mittels spezifischer siRNA ließ sich in kardialen Fibroblasten ein Knockdown von GPRC5B auf Proteinebene auf 25% des endogenen Expressionsniveaus erreichen. In den Knockdown-Zellen war nach Transfektion mit anschließender 24 stündiger Stimulation mit LPS (10 ng/ml) eine Abnahme von IL-1ß- und von MMP-9-mRNA gegenüber den Kontrollzellen nachweisbar, während IL-6 und MCP-1 unbeeinflusst blieben. Der Knockdown von GPRC5B hatte einen signifikanten Anstieg von TNFα-mRNA zur Folge. Des Weiteren wurden im Western Blot die Proteinlysate von ganzen Herzen GPRC5B-überexprimierender Mäuse mit denen von Wildtypen verglichen. Dabei stellte sich heraus, dass erhöhte GPRC5B-Expression zu signifikanter Anreicherung von MMP-9 und signifikant erniedrigtem Gehalt von Kollagen-1A1 führte. Es konnte erstmalig gezeigt werden, dass die Expression von GPRC5B in kardialen Fibroblasten durch inflammatorische und Stress-induzierte Signalwege erhöht wird. Außerdem konnte demonstriert werden, dass GPRC5B die Transkription von inflammatorischen Zytokinen moduliert (TNFα, IL-1ß, IL-6, MCP-1) und in den Stoffwechsel der kardialen Extrazellulärmatrix eingreift (MMP-9, Kollagen-1A1). Insgesamt weisen diese Untersuchungsergebnisse auf eine funktionale Beteiligung des orphan Rezeptor GPRC5B an myokardialen Entzündungsprozessen und dem kardialen Remodeling hin

Heimatlieder und Gelegenheits-Gedichte eines Balten

https://www.ester.ee/record=b1513211*es

Die Ehrverletzung : nach dem Entwurf der Redakstionskommission des neuen Strafgesetzbuchs für Russland

Digiteeritud Euroopa Regionaalarengu Fondi rahastusel, projekti "Eesti teadus- ja õppekirjandus" (2014-2020.12.03.21-0848) raames.https://www.ester.ee/record=b4005938*es

In memoriam: Theodor Hiepe (1929–2022)—great German scholar of parasitology

Theodor Hiepe (1929-2022) was an outstanding researcher, a world-renowned scientist, a dedicated teacher and a great mentor. During his scientific career, which spanned over 60 years, he made major contributions to many different fields of parasitology. With the passing of Dr. h.c. mult. Theodor Hiepe in September 2022 the scientific community suffered a great loss

Epidemiological study on factors influencing the occurrence of helminth eggs in horses in Germany based on sent-in diagnostic samples

Gastrointestinal nematodes are ubiquitous parasites of grazing equines with Parascaris spp., and strongyles being the most relevant ones regarding the prevalence and potential disease severity. Despite their importance, epidemiological data regarding the presence and egg-shedding intensities of these parasites are scarce. Data from 1067 horse samples collected on German horse farms initially to compare diagnostic methods were used for epidemiological analyses. Due to its higher sensitivity, presence/absence data were based on a combined sedimentation/flotation technique while faecal egg counts were based on Mini-FLOTAC. For strongyles, 46.5% of the samples were positive and the median egg-shedding intensity was 40 (range 5–2590). In multivariate analyses, prevalence and egg-shedding intensity were significantly influenced by season, age group and sample type. The drug used for the last treatment and the number of foals on the yard only affected prevalence while the number of horses on the yard and sex were only significant for egg-shedding intensity. For Parascaris spp., a prevalence of 4.6% and a median egg-shedding intensity of 0 (range 5–905) were observed. In multivariate analyses, the age group, the time since the last anthelmintic treatment, presence and number of foals had significant effects on ascarid prevalence whereas egg-shedding intensity was significantly influenced by age group and season only. Parascaris occurred only on yards with foals, but with an increasing number of foals, Parascaris egg-shedding intensity decreased. Prevalence and egg-shedding intensity were influenced by different but partially overlapping variables for Parascaris and strongyles

In silico analysis of the cyclophilin repertoire of apicomplexan parasites

<p>Abstract</p> <p>Background</p> <p>Cyclophilins (Cyps) are peptidyl <it>cis/trans </it>isomerases implicated in diverse processes such as protein folding, signal transduction, and RNA processing. They are also candidate drug targets, in particular for the immunosuppressant cyclosporine A. In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa. In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.</p> <p>Results</p> <p>BLAST and maximum likelihood analyses identified 16 different cyclophilin subfamilies within the genomes of <it>Cryptosporidium hominis</it>, <it>Toxoplasma gondii</it>, <it>Plasmodium falciparum</it>, <it>Theileria annulata</it>, <it>Theileria parva</it>, and <it>Babesia bovis</it>. In addition to good statistical support from the phylogenetic analysis, these subfamilies are also confirmed by comparison of cyclophilin domain architecture. Within an individual genome, the number of different Cyp genes that could be deduced varies between 7–9 for Cryptosporidia and 14 for <it>T. gondii</it>. Many of the putative apicomplexan cyclophilins are predicted to be nuclear proteins, most of them presumably involved in RNA processing.</p> <p>Conclusion</p> <p>The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi. The identification of Cyp subfamilies that are specific for lower eukaryotes, apicomplexa, or even the genus Plasmodium is of particular interest since these subfamilies are not present in host cells and might therefore represent attractive drug targets.</p

Investigation on the influence of nematophagous fungi as feed additive on nematode infection risk of sheep and goats on pasture

Gastrointestinal nematodes in small ruminants cause high economic losses. Thus on most farms anthelmintic treatment is required. In response to increasing problems with anthelmintic resistance, biological control, for example the use of nematophagous fungi, has received significant attention. The aim of this study was to investigate the effect of Duddingtonia flagrans orally applied to small ruminants on natural infection with gastrointestinal nematodes in a field study in Northern Germany. 20 goats and 20 sheep were fed daily for 3 months with 5x105 spores of D. flagrans per kg bodyweight. Differences in body weight, faecal egg count and larval development in faeces and on pasture in comparison with same-sized control groups were analysed. After 3 months the control goats showed significantly higher mean faecal egg count than the fungus-fed group. No significant difference was found between the two sheep groups. The maximum in larval reduction in faeces was 81.3 % in the sheep groups and 67.9 % in the goat groups (not significant). At the end of the study the body weight gain in the fungus-treated groups was 1.7 kg higher in goats and 0.7 kg higher in sheep than in the control groups (not significant). Regarding the first-year-grazing goats only, the bodyweights revealed significant differences (p<0.05). No statistically significant differences were observed in pasture larval counts. In the study presented here, no clear effect of fungus could be observed. A modified feeding regimen, perhaps with permanent release boluses or feed blocks, may improve the efficacy. Furthermore, it seems that climatic conditions during the study period could have influenced the results and displayed how sensitive the fungus application may be on such parameters

Immunization Trials with Recombinant Major Sperm Protein of the Bovine Lungworm Dictyocaulus viviparus

The lungworm Dictyocaulus viviparus is one of the most economically important bovine parasites in temperate climate regions. Following infection, D. viviparus induces a temporary protective immunity, and a vaccine based on attenuated, infective larvae is commercially available. However, due to several disadvantages of the live vaccine, the development of a recombinant subunit vaccine is highly desirable. Therefore, the major sperm protein (MSP), which is essential for the parasite’s reproduction, was tested as a recombinantly Escherichia coli-expressed glutathione-S-transferase (GST)-fused vaccine antigen in immunization trials with two different adjuvants, Quil A and Al(OH)3. Calves (N = 4 per group) were immunized on study day (SD) 0, 21 and 42 and given a challenge infection on SD 63–65. The two control groups received only the respective adjuvant. Based on geometric means (GM), a 53.64% reduction in larvae per female worm was observed in the rMSP Quil A group vs. its control group (arithmetic means (AM): 54.43%), but this difference was not statistically significant. In the rMSP Al(OH)3 group, the mean number of larvae per female worm was even higher than in the respective control group (GM: 9.24%, AM: 14.14%). Furthermore, male and female worm burdens and the absolute number of larvae did not differ significantly, while the Al(OH)3 control group harbored significantly longer worms than the vaccinated group. Vaccinated animals showed a rise in rMSP-specific antibodies, particularly IgG and its subclass IgG1, and the native protein was detected by immunoblots. Although rMSP alone did not lead to significantly reduced worm fecundity, it might still prove useful as part of a multi-component vaccine