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Background Global warming has increased the frequency of heat stress in livestock. Although heat stress directly leads to negative effects on production and reproduction traits in dairy cattle, the transgenerational transition of these changes is poorly understood. We hypothesized that heat stress in pregnant cows might induce epigenetic modifications in the developing embryo germ cells, which, in turn, might lead to phenotypic effects in the offspring. Here, we examined whether transgenerational effects of heat stress contribute to the phenotypic expression of economic traits in Israel dairy cattle. Since heat stress in Israel occurs specifically between June and October, first we examined the association of the month of birth of F1 cows (pregnancy of the F0 dam) with the performance of the F2 and F3 female offspring. Then, we calculated an annual heat stress index and examined the association of the heat stress index during the pregnancy of the F0 dam with the performance of her F2 and F3 offspring. Finally, we examined intergenerational interactions of heat stress by comparing the performance of F3 cows according to the pregnancy seasons of the F0 and F1 animals. Results We found a significant association of the month of birth, season of pregnancy, and heat stress index of F0 females, with the performance of their F2 and F3 progenies, which suggests a true transgenerational effect. The most significant transgenerational effects were on fat yield and concentration, dystocia, still-birth, and maturation. Conclusions These findings suggest that heat stress during pregnancy affects the performance of offspring, regardless of life circumstances in at least the last three generations. Therefore, heat stress can reduce selection efficiency in breeding programs and may have economic significance in livestock.

Background Pasteurellosis (Pasteurella infection) is one of the most common bacterial infections in rabbits on commercial farms and in laboratory facilities. Curative treatments using antibiotics are only partly efficient, with frequent relapses. Breeding rabbits for improved genetic resistance to pasteurellosis is a sustainable alternative approach. In this study, we infected 964 crossbred rabbits from six sire lines experimentally with Pasteurella multocida. After post-mortem examination and bacteriological analyses, abscess, bacteria, and resistance scores were derived for each rabbit based on the extent of lesions and bacterial dissemination in the body. This is the first study to use such an experimental design and response traits to measure resistance to pasteurellosis in a rabbit population. We investigated the genetic variation of these traits in order to identify potential selection criteria. We also estimated genetic correlations of resistance to pasteurellosis in the experimental population with traits that are under selection in the breeding populations (number of kits born alive and weaning weight). Results Heritability estimates for the novel response traits, abscess, bacteria, and resistance scores, ranged from 0.08 (± 0.05) to 0.16 (± 0.06). The resistance score showed very strong negative genetic correlation estimates with abscess (− 0.99 ± 0.05) and bacteria scores (− 0.98 ± 0.07). A very high positive genetic correlation of 0.99 ± 0.16 was estimated between abscess and bacteria scores. Estimates of genetic correlations of the resistance score with average daily gain traits for the first and second week after inoculation were 0.98 (± 0.06) and 0.70 (± 0.14), respectively. Estimates of genetic correlations of the disease-related traits with average daily gain pre-inoculation were favorable but with high standard errors. Estimates of genetic and phenotypic correlations of the disease-related traits with commercial selection traits were not significantly different from zero. Conclusions Disease response traits are heritable and are highly correlated with each other, but do not show any significant genetic correlations with commercial selection traits. Thus, the prevalence of pasteurellosis could be decreased by selecting more resistant rabbits on any one of the disease response traits with a limited impact on the selection traits, which would allow implementation of a breeding program to improve resistance to pasteurellosis in rabbits.

Es wurde ein Patient mit rheumatoider Arthritis (RA) vorgestellt, der unter der Therapie mit dem Januskinase-1/2-Inhibitor Baricitinib eine Infektion mit dem Hepatitis-E-Virus (HEV) entwickelte. Unser Patient hatte bei seiner vierteljährlichen Routineuntersuchung deutlich erhöhte Transaminasen bei einer unauffälligen körperlichen Untersuchung. Es fanden sich Antikörper der IgM- und IgG-Klasse gegen HEV und ein erhöhtes C‑reaktives Protein (CRP) sowie HEV-RNA mittels Real-Time-PCR, was auf eine frische HEV-Infektion hinwies. Baricitinib wurde sofort abgesetzt. Die ausführliche Anamnese ergab, dass der Patient Tage vor der Konsultation Rindertartar verzehrt hatte, ohne dass gastrointestinale Symptome oder Fieber aufgetreten waren. Im weiteren Verlauf erholte sich der Patient vollständig, und die Leberfunktionstests und das CRP normalisierten sich innerhalb von 3 Monaten. Baricitinib wurde daraufhin wieder eingenommen. Bisher wurden nur wenige Daten zu HEV-Infektionen bei RA-Patienten, die mit JAK-Inhibitoren behandelt wurden, publiziert. A patient with rheumatoid arthritis (RA) was presented, who developed an infection with the hepatitis E virus (HEV) under treatment with the Janus kinase (JAK) 1 and 2 inhibitor baricitinib. In the 3‑month routine check-up the patient had clearly elevated transaminase levels with an inconspicuous physical examination. The investigations detected antibodies of IgM and IgG classes against HEV and an elevated C‑reactive protein (CRP) level as well as HEV-RNA by real-time PCR, which is indicative of a recent HEV infection. Baricitinib was immediately discontinued. The extensive anamnesis revealed that the patient had eaten beef tartar some days before the consultation, without the occurrence of gastrointestinal symptoms or fever. In the further course the patient completely recovered and the liver function tests and the CRP levels normalized within 3 months. Baricitinib was then restarted. So far only few reports have been published on HEV infections in RA patients who have been treated with JAK inhibitors.

Zusammenfassung Ziel der Studie Die alveoläre Echinokokkose (AE) ist in Österreich, der Schweiz und Deutschland (DACh) eine seltene Erkrankung, welche durch eine Infektion mit dem Parasiten Echinococcus multilocularis hervorgerufen werden kann. Ziel der Arbeit ist die Darstellung von Unterschieden im Erfassungs- und Meldesystem der alveolären Echinokokkose in Österreich, der Schweiz und Deutschland und der Beschreibung der epidemiologischen Entwicklungen und deren Trends. Methodik Im Rahmen eines Epidemiologischen Updates am 06. September 2019 in Ulm, Deutschland diskutierten Experten und Repräsentanten über Unterschiede im Melde- und Erfassungssystem sowie über die aktuelle epidemiologische Situation. Ergebnisse In Österreich besteht seit 2004 nach §1 Abs. 1 eine namentliche Meldepflicht nach dem Epidemiegesetz 1950 (EpidemieG) und der Verordnung gemäß der anzeigepflichtig übertragbarer Krankheiten für Verdachts-, Erkrankungs- und Todesfälle für eine alveoläre Echinokokkose. Nach §7 Abs. 3 Infektionsschutzgesetz (IfSG) besteht für Deutschland seit 2001 ebenfalls eine Meldepflicht, allerdings nichtnamentlich. Zusätzlich stehen in beiden Ländern nationale Register bereit, welche für die Beantwortung wissenschaftlicher Fragen genutzt werden können. In der Schweiz besteht seit 1997 keine Meldepflicht mehr für die humane alveoläre Echinokokkose. Derzeit bestehen Bestrebungen für die zeitnahe Implementierung eines nationalen Registers für die alveoläre Echinokokkose in der Schweiz. Trotz unterschiedlicher Melde- und Erfassungssysteme zeigt sich für DACh ein ähnlicher epidemiologischer Trend. Schlussfolgerungen In Österreich, der Schweiz und Deutschland zeigt sich ein leicht steigender Trend von humanen Erkrankungsfällen mit alveolärer Echinokokkose. Die direkte Vergleichbarkeit ist aufgrund unterschiedlicher Meldepflichten und deren Strukturen eingeschränkt und erlaubt häufig nicht die gemeinschaftliche Beantwortung wissenschaftlicher Fragestellungen zur Diagnostik, Behandlung und Versorgung.

Die Diagnostik neuroendokriner Neoplasien des Pankreas (PanNEN) hat in den letzten Jahren v. a. im Bereich der WHO-Klassifikation, der TNM-Einteilung sowie der Gradierung Veränderungen erfahren. Zudem wurden einzelne neue diagnostische sowie prädiktive immunhistochemische Marker eingeführt. Die meisten Fortschritte wurden auf der Ebene der molekularen Pathogenese von PanNEN erzielt. Mittels „next generation sequencing“ wurden der „mammalian target of rapamycin (mTOR) pathway“, Hypoxie, aber auch epigenetische Veränderungen als wichtige tumorigene Mechanismen identifiziert. Im vorliegenden Artikel werden die wichtigsten Entwicklungen in der morphologischen und immunhistochemischen Diagnostik von PanNEN und deren molekularer Hintergrund beleuchtet., The diagnostics of pancreatic neuroendocrine tumors (PanNEN) have changed in recent years especially concerning the World Health Organization (WHO) classification, TNM staging and grading. Furthermore, some new prognostic and predictive immunohistochemical markers have been introduced. Most progress, however, has been made in the molecular pathogenesis of these neoplasms. Using next generation sequencing techniques, the mammalian target of rapamycin (mTOR) pathway, hypoxia and epigenetic changes were identified as key players in tumorigenesis. In this article the most important developments of morphological as well as immunohistochemical diagnostics together with the molecular background of PanNEN are summarized.

Zusammenfassung: Primär kutane Lymphome sind die zweithäufigste Gruppe der extranodalen Non-Hodgkin-Lymphome. In den letzten Jahren sind zahlreiche neue Varianten und Entitäten beschrieben worden, wobei diese z.T. noch keinen Eingang in die aktuelle WHO-Klassifikation gefunden haben. Dazu gehören Formen der Mycosis fungoides wie die granulomatöse Form, welche mit einer schlechteren Prognose einhergehen, aber auch die indolenten CD8-positiven Lymphoproliferationen im Kopfbereich und an akralen Lokalisationen. In der Gruppe der CD30-positiven lymphoproliferativen Erkrankungen werden bei der lymphomatoiden Papulose die neuen histologischen TypenD (epidermotrop, CD8+) und TypE (angioinvasiv) besprochen, welche aggressive Lymphome imitieren. Die kutanen peripheren T-Zell-Lymphome sind eine prognostisch heterogene Gruppe. Das kutane CD8+ aggressive epidermotrope zytotoxische Lymphom und das kutane gamma/delta-T-Zell-Lymphom sind ausgesprochen aggressive Erkrankungen, während das kutane CD4+ klein-/mittelgroßzellige T-Zell-Lymphom in seiner solitären und lokalisierten Form eine indolente Lymphomform darstellt, dessen Histogenese, Terminologie und Abgrenzung vom nodulären T-Zell-Pseudolymphom noch nicht geklärt sind. Bei den seltenen B-Zell-Lymphomen, welche sich primär oder sekundär in der Haut manifestieren, wird auf das Epstein-Barr-Virus(EBV)-assoziierte diffuse großzellige Lymphom des älteren Menschen und das EBV-assoziierte mukokutane Ulkus eingegangen. Diese Übersichtsarbeit beschreibt die klinischen, histologischen und immunphänotypischen Merkmale der neuen und seltenen Varianten und Entitäten kutaner Lymphome und zeigt den hohen Stellenwert der klinisch-pathologischen Korrelation in der Diagnostik auf.

There is a fundamental gap in our understanding of how horizontal gene transfer contributes to the enormous range of genetic variations that are observed among bacteria. Our model organism is Vibrio cholerae, the causative agent of cholera. V. cholerae enters a natural competence state for the uptake of DNA in response to environmental signals. Our objective is to better understand the regulatory circuits that drive competence in this organism and the mechanistic aspects of the DNA transfer and uptake process.

The aim of the vigilance system in Switzerland is the evaluation and classification of reported suspected adverse reactions of immunological veterinary medicines (IVMP), including suspected lack of expected efficacy. The Institute of Virology and Immunology (IVI) is the competent authority for marketing authorizations of immunological veterinary medicinal products in Switzerland and responsible for the vaccinovigilance system. In 2020, 130 adverse reaction reports were received (5% less compared to 2019). The reports mainly concerned dogs (41%) and cats (25%) followed by cattle (18%) and horses (7%). Many of the reports in dogs involved the application of combined vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza in combination with canine leptospira components, in cats against cat flu and feline panleukopenia in combination with feline leukaemia virus infection. Causality assessments were done according to the international ABON system. In 27% of the reported cases, the causality assessments between the vaccination and the reaction described were evaluated as being probable (ABON A), in 44% as possible (ABON B).Das Ziel des Vaccinovigilancemeldesystems ist die Erfassung und Klassifizierung von unerwünschten Arzneimittelwirkungen (UAW) nach der Anwendung von immunologischen Tierarzneimitteln (TAM) in der Schweiz. Dazu zählt auch eine vermutete ungenügende Wirksamkeit von Impfstoffen. Als Zulassungsstelle für immunologische TAM ist die Impfstoffkontrolle des Instituts für Virologie und Immunologie (IVI) auch zuständig für das Vaccinovigilancemeldesystem. 130 UAW Meldungen zu zugelassenen immunologischen TAM wurden im Jahr 2020 erfasst (5% weniger als 2019). Am häufigsten betrafen die Meldungen Kleintiere: Hunde (41%) und Katzen (25%), gefolgt von Rindern (18%) und Pferden (7%). Beim Hund basierten die meisten UAW auf der Anwendung von Impfstoffen gegen Staupe, Hepatitis, Parvovirose und Parainfluenza in Kombination mit Leptospirose, bei der Katze waren es Impfstoffe gegen Katzenschnupfen und -seuche kombiniert mit Feliner Leukämievirusinfektion. Die Meldungen wurden gemäss dem internationalen ABON System klassifiziert. In 27% aller eingegangenen Fälle wurde ein kausaler Zusammenhang zwischen der Impfung und der Impfreaktion als wahrscheinlich (ABON A), in 44% als möglich (ABON B) beurteilt.L’objectif du système de vaccinovigilance en Suisse est l’évaluation et la classification des effets indésirables suspectés signalés en rapport à des médicaments vétérinaires immunologiques, y compris le manque présumé d’efficacité attendue. L’Institut de virologie et d’immunologie (IVI) est l’autorité compétente pour les autorisations de mise sur le marché des médicaments immunologiques vétérinaires en Suisse et est responsable du système de vaccinovigilance. En 2020, 130 déclarations d’effets indésirables ont été reçues (5% de moins par rapport à 2019). Les signalements concernaient principalement les chiens (41%) et les chats (25%) suivis des bovins (18%) et des chevaux (7%). Chez les chiens, ces annonces impliquaient principalement l’application de vaccins combinés contre la maladie de Carré, l’hépatite, la parvovirose et la parainfluenza en combinaison avec la leptospirose, chez les chats contre le coryza et la panleucopénie féline en association avec la leucose féline. Les évaluations de causalité ont été effectuées selon le système international ABON. Dans 27% des cas rapportés, les évaluations de causalité entre la vaccination et la réaction décrite ont été évaluées comme probables (ABON A), dans 44% comme possibles (ABON B).Lo scopo del sistema di notifica di vaccinovigilanza è di identificare e classificare le reazioni avverse di un farmaco che possono sorgere dopo l’uso di medicamenti veterinari (MVet) immunologici in Svizzera. Questo include anche il sospetto di un’insufficiente efficacia dei vaccini. L’Istituto di Virologia e Immunologia (IVI), in qualità di ufficio di omologazione dei Mvet immunologici, è responsabile anche del sistema di notifica di vaccinovigilanza. Nel 2020 sono state registrate 130 notifiche di Mvet immunologici omologati (5% in meno del 2019). Le notifiche riguardavano per la maggior parte piccoli animali: cani (41%) e gatti (25%), seguiti da bovini (18%) e cavalli (7%). Nei cani la maggioranza delle reazioni avverse erano conseguenti all’uso di vaccini contro cimurro, epatite, parvovirosi e parainfluenza in combinazione con la leptospirosi, nei gatti invece le reazioni avverse erano in relazione a vaccini contro la rinite felina e la gastroenterite felina combinata con l’infezione virale della leucemia felina. Le notifiche sono state classificate secondo il sistema internazionale ABON. Nel 27% dei casi inoltrati è stata considerata una relazione causale tra la vaccinazione e la risposta alla vaccinazione come probabile (ABON A), e nel 44% come possibile (ABON B).

The etiopathogenesis of chronic otitis media epitympanalis/cholesteatoma and its proliferative destructive course with possible complications such as destruction of bony structures with hearing loss, vestibular dysfunction, facial nerve paralysis and intracranial complications are still unexplained. Surgery is still the way to go. New studies are increasingly looking at the innate immune system.Our studies were carried out in a mouse model in WT mice and immundeficient KO-mice, as well as in cholesteatoma and healthy ear canal skin and middle ear tissue, which was removed during ear surgery. The expression analyses were carried out at the gene and protein level using TNF as the major target for therapy evaluation. By means of TUNEL staining and immunohistochemistry the level of apoptosis was evaluated.The uncontrolled undirected cholesteatoma growth shows an immunomodulatory profile with up and down-regulation of various gene networks, especially those involved in TNF downstream and upstream signaling pathways. TNF in cholesteatoma is modulated both inflammatorily and apoptotically and therefore is suitable as a possible therapeutic approach in various models.Cholesteatoma might be immunomodulatory regulated.Die Ätiopathogenese der chronischen Otitis media epitympanalis bzw. des Cholesteatoms und ihr proliferierender destruierender Verlauf mit möglichen Komplikationen wie Destruktion der knöchernen Strukturen mit Hörverlust, vestibulärer Dysfunktion, Gesichtsnervenlähmung und intrakraniellen Komplikationen sind immer noch ungeklärt. Die Therapie der Wahl ist nach wie vor die operative Sanierung. Aktuelle Studien befassen sich immer mehr mit dem angeborenen Immunsystem.Unsere Untersuchungen erfolgten im Mausmodell an WT-Mäusen und immundefizienten KO-Mäusen sowie an Gewebeproben vom Cholesteatom, gesunder Gehörgangshaut und gesunder Mittelohrschleimhaut, die während sanierenden Ohroperationen entnommen wurden. Die Expressionsanalysen erfolgten auf Gen- und Proteinebene mit TNF als Major Target zur Therapieevaluation. Mittels TUNEL-Färbung und Immunhistochemie an Kryoschnitten wurde die Apoptose-Rate durch TNF bestimmt.Das ungerichtet-expansive Cholesteatomwachstum zeigt ein immunmodulatorisches Profil mit Hoch- und Runterregulation von verschiedenen Gen-Netzwerken, vor allem Molekülen der TNF-Down- und -Upstream-Signalwege. Dabei wird TNF sowohl inflammatorisch als auch apoptotisch moduliert und eignet sich als möglicher Therapieansatz in verschiedenen Modellen.Es gibt Hinweise auf eine immunmodulatorische Regulation im Cholesteatom.

Background Columnaris disease (CD) is an emerging problem for the rainbow trout aquaculture industry in the US. The objectives of this study were to: (1) identify common genomic regions that explain a large proportion of the additive genetic variance for resistance to CD in two rainbow trout (Oncorhynchus mykiss) populations; and (2) estimate the gains in prediction accuracy when genomic information is used to evaluate the genetic potential of survival to columnaris infection in each population. Methods Two aquaculture populations were investigated: the National Center for Cool and Cold Water Aquaculture (NCCCWA) odd-year line and the Troutlodge, Inc., May odd-year (TLUM) nucleus breeding population. Fish that survived to 21 days post-immersion challenge were recorded as resistant. Single nucleotide polymorphism (SNP) genotypes were available for 1185 and 1137 fish from NCCCWA and TLUM, respectively. SNP effects and variances were estimated using the weighted single-step genomic best linear unbiased prediction (BLUP) for genome-wide association. Genomic regions that explained more than 1% of the additive genetic variance were considered to be associated with resistance to CD. Predictive ability was calculated in a fivefold cross-validation scheme and using a linear regression method. Results Validation on adjusted phenotypes provided a prediction accuracy close to zero, due to the binary nature of the trait. Using breeding values computed from the complete data as benchmark improved prediction accuracy of genomic models by about 40% compared to the pedigree-based BLUP. Fourteen windows located on six chromosomes were associated with resistance to CD in the NCCCWA population, of which two windows on chromosome Omy 17 jointly explained more than 10% of the additive genetic variance. Twenty-six windows located on 13 chromosomes were associated with resistance to CD in the TLUM population. Only four associated genomic regions overlapped with quantitative trait loci (QTL) between both populations. Conclusions Our results suggest that genome-wide selection for resistance to CD in rainbow trout has greater potential than selection for a few target genomic regions that were found to be associated to resistance to CD due to the polygenic architecture of this trait, and because the QTL associated with resistance to CD are not sufficiently informative for selection decisions across populations. Electronic supplementary material The online version of this article (10.1186/s12711-019-0484-4) contains supplementary material, which is available to authorized users.

Despite numerous dendroclimatological investigations into different tree species from Bosnia and Herzegovina, information is lacking on intra-annual wood formation patterns, which would help us to interpret the climate signal in tree rings better. Using the pinning method and manual band dendrometers, we investigated the seasonal dynamics of radial growth of black pine (Pinus nigra Arnold) trees in two successive growing seasons: 2011 and 2012. The up to 60-year-old trees grew in a stand at the base of a hill in the western, mountainous part of the Balkan Peninsula. The seasonal dynamics of wood formation and final number of cells differed between the studied years. Wood formation started in both years in early to mid-March. Differences were noticed in the wood production culmination in 2011 it occurred at the end of May and beginning of June in 2012 and 2011, respectively. Xylem growth finished in 2012 in the middle of August and in 2011 in the middle of September. Based on the first derivative of the Gompertz function calculated rate of xylem growth was lowest in 2011. The dendrometers recorded a slow increment rate in spring, higher in summer and a decreasing rate again in the late summer in both growing seasons. In comparison with pinning, dendrometers showed a delay in the start of radial growth of up to 20 days in 2012. Additionally, dendrometers showed an increase in stem girth after the end of both growing seasons, when wood formation was already completed. Deviations between the two methods could be ascribed to the influence of water storage dynamics in the main stem and numerous structural processes in bark tissue, which are captured in dendrometer data. The influence of weather conditions on xylem phenology is also indicated by differences between the two studied years, although it is difficult to identify the influence of particular short-term weather events. Kljub velikemu številu dendroklimatoloških raziskav o različnih drevesnih vrstah iz Bosne in Hercegovine primanjkuje informacij o sezonskem nastajanju lesa, ki bi pripomogle k boljši interpretaciji klimatskega signala v branikah. Z uporabo metode pining in ročnih dendrometrov smo raziskali sezonsko dinamiko debelinske rasti dreves črnega bora (Pinus nigra Arnold) v dveh zaporednih rastnih sezonah: 2011 in 2012. Do 60 let stara drevesa so rastla v sestoju ob vznožju planote v zahodnem, goratem predelu Balkanskega polotoka. Med obema letoma je bilo zaznati razlike v sezonski dinamiki nastajanja lesa in končnem številu celic. V obeh letih se je les pričel nastajati v začetku oziroma sredi marca. Razlike so bile opažene v najvišji stopnji nastajanja lesa: v letu 2011 je nastopila na dan v letu (DVL) 153 in na DVL 145 v letu 2012 prav tako pa tudi v koncu ksilemske rasti: končala se je okoli DVL 223 v letu 2012 in okoli DVL 255 v letu 2011. Na podlagi prvega odvoda Gompertzove funkcije je bila stopnja ocenjene ksilemske rasti nižja v letu 2011. Dendrometri so v obeh rastnih sezonah zabeležili nizko stopnjo priraščanja spomladi, višjo poleti in ponovno nižjo jeseni. V primerjavi z metodo pining so dendrometri zabeležili zamik v začetku debelinskega priraščanja do 20 dni v letu 2012. Poleg tega so dendrometri zabeležili povečan obseg debla po koncu rastne sezone v obeh rastnih sezonah, ko se je nastajanje lesa že zaključilo. Razlike med obema metodama lahko pripišemo vplivu gibanja vode v ksilemu in floemu ter številnim strukturnim procesom v skorji, ki so zabeleženi v meritvah dendrometrov. Vpliv vremenskih razmer na nastajanje ksilema je prav tako povezan z razlikami med obema rastnima sezonama, čeprav je težko opredeliti posledice kratkotrajnih vremenskih pojavov

Ulnar humeral condyle fractures are rare paediatric elbow fractures, classified as Salter-Harris IV paediatric elbow injuries. Due to constant radiological changes in the elbow with varying manifestation of ossification centres as well as late ossification of the trochlea, diagnosis of these injuries is challenging. To avoid long-term complications, the treating surgeon should be familiar with the rare injury picture, diagnostics and adequate therapeutic measures.The present retrospective study includes data on all paediatric cases from 2002 to 2019 with primary or secondary treatment at a paediatric traumatology centre for ulnar condyle fracture with a minimum follow-up of 12 months. Range of motion, joint stability under valgus and varus stress as well as axial ratios of the injured and uninjured side were evaluated in a clinical follow-up examination. The Mayo Elbow Performance Score was used to objectify functional results.20 children, average age 8.6 years (4 - 13) and average follow-up time 25 months, were included. Radiological evaluation based on Jakob and Fowles classification revealed a type I fracture in three cases, a type II fracture in one case and a type III fracture in 16 cases. Three cases were treated nonoperatively with an upper arm cast. 17 children were treated with open reduction and internal fixation. Diagnosis of three fractures was delayed. No postoperative complications such as infections, nerve damage or nonunions. 15 children showed free elbow function. Three children showed slightly restricted elbow extension by less than 10° and two by 10°-20°. All children showed free pro/supination. 18 children showed a physiological and bilaterally identical arm axis compared to the uninjured side. Two children showed a slightly increased cubitus valgus with a 5 - 10° difference between sides. Radiologically, two children with delayed fracture treatment showed partial necrosis of the trochlea. The Mayo Elbow Score showed good (2) to excellent results in all children (18).Very good clinical and functional results can be expected if the injury is diagnosed without delay followed by adequate therapy. Misdiagnosis of ulnar condyle fractures can be associated with the development of nonunions and functional restrictions as well as, after operative therapy, trochlear necrosis. Children up to the age of 6 in particular are at risk of misdiagnosis due to faulty assessment of the cartilaginous trochlea.Die Fraktur des Condylus ulnaris humeri ist eine sehr seltene Salter-Harris-IV-Verletzung des kindlichen Ellenbogens. Aufgrund stetiger radiologischer Veränderungen am Ellenbogen mit unterschiedlichem Auftreten der Ossifikationskerne sowie einer späten Ossifikation der Trochlea ist die Diagnosestellung eine Herausforderung. Um Langzeitkomplikationen zu vermeiden, sollte dem behandelnden Chirurgen das seltene Krankheitsbild, die Diagnostik und adäquate Therapie bekannt sein.Im Rahmen einer retrospektiven Untersuchung wurden alle Kinder erfasst, die eine Condylus-ulnaris-Fraktur zwischen 2002 und 2019 erlitten haben und an einer einzelnen kindertraumatologischen Schwerpunktklinik primär oder sekundär behandelt wurden. Das Follow-up betrug mindestens 12 Monate. Im Rahmen einer klinischen Nachuntersuchung wurde der Bewegungsumfang, die Gelenkstabilität in Valgus- und Varusstress sowie die Achsenverhältnisse im Seitenvergleich überprüft. Zur Objektivierung der funktionellen Ergebnisse wurde der Mayo-Ellenbogen-Performance-Score verwendet.20 Kinder mit einem Durchschnittsalter von 8,6 Jahren (4 – 13) und einer durchschnittlichen Nachbeobachtungszeit von 25 Monaten konnten eingeschlossen werden. Die radiologische Auswertung anhand der Jakob-Fowles-Klassifikation ergab eine Typ-I-Fraktur in 3 Fällen, eine Typ-II-Fraktur in 1 Fall sowie eine Typ-III-Fraktur in 16 Fällen. Bei 3 Kindern wurde eine konservative Behandlung mit Oberarmgips durchgeführt, bei 17 Kindern eine offene Reposition und osteosynthetische Versorgung. Bei 3 Frakturen erfolgte eine verspätete Diagnosestellung. Es traten keine postoperativen Komplikationen wie Infekte, Nervenschäden oder Pseudarthrosen auf. 15 Kinder zeigten eine freie Funktion des Ellenbogens. Drei Kinder zeigten ein leichtes Streckdefizit von unter 10° und 2 Kinder ein Streckdefizit von 10 – 20°. Alle Kinder hatten eine freie Unterarmumwendbewegung. 18 Kinder zeigten eine physiologische und seitengleiche Armachse. Zwei Kinder zeigten einen leicht verstärkten Cubitus valgus mit 5 – 10° Seitendifferenz. Radiologisch zeigten 2 Kinder mit verspätet versorgten Frakturen eine partielle Nekrose der Trochlea. Der Mayo-Ellenbogen-Score zeigte gute (2) bis exzellente Ergebnisse bei allen Kindern (18).Wird die Diagnose ohne Verzögerung gestellt sowie eine adäquate Therapie durchgeführt, ist mit einem sehr guten klinisch-funktionellen Ergebnis zu rechnen. Das Nichterkennen einer Condylus-ulnaris-Fraktur kann mit der Entwicklung einer Pseudarthrose mit funktionellen Einschränkungen sowie nach operativer Therapie mit einer Trochleanekrose einhergehen. Kinder bis zum 6. Lebensjahr sind hier besonders betroffen aufgrund der Fehleinschätzung der noch knorpeligen Trochlea.

The positive effects of light to moderately intensive physical activity during pregnancy are not in question. Corresponding exercise recommendations can be found in national and international guidelines, which show a relatively solid evidence base. However, there are large knowledge gaps with respect to training recommendations for ambitious amateur sportswomen and elite athletes. Therefore, among both athletes and their supporting staff there is a large degree of uncertainty, which sports activity and to what extent it can be maintained safely without risk to the mother and her unborn child. In addition to the consideration of contraindications, where sporting activities must be avoided, there are certain training-associated precautions (e.g. when training at high altitude or in hot conditions) that should be respected. Also, in view of the manifold physiological changes that pregnancy entails (e.g. anatomical, hormonal, metabolic, cardiovascular and pulmonary), competitive sports-oriented training should be directed individually under close observation of mother's and child's well-being.

Background: Little is known about idiopathic Epilepsy in Greater Swiss Mountain Dogs. Until now this breed is not listed as a predisposed breed for idiopathic epilepsy. The aim of this study was to estimate the prevalence of idiopathic epilepsy in Greater Swiss Mountain Dogs in Switzerland and to describe the clinical characteristics of epilepsy in this breed including seizures semiology and response to treatment. Material and Methods: Records of the Swiss Kennel Club for Greater Swiss Mountain Dogs were searched for reported cases of epileptic seizures between 1999-2019. The total number of reported cases and the signalment was reviewed. Furthermore, all owners of Greater Swiss Mountain Dogs registered to the breeding club were invited to complete an online questionnaire. Results: In total 600 Greater Swiss Mountain Dog's live in Switzerland: 70-90 puppies are born each year. Between 1999 and 2019 34 dogs (2%) were announced with seizures. Of the 400 owners invited to answer the questionnaire 128 completed the questionnaire. 20 of these 128 dogs were suffering from idiopathic epilepsy. The prevalence for idiopathic epilepsy based on the questionnaire was therefore 15,6%. All affected dogs showed generalized tonic-clonic seizures. Cluster seizures and status epilepticus occurred in 5 (41,6%) and 6 (50%) of the dogs. Long term seizure control was only achieved in 10% of the dogs. Five dogs (25%) died or were euthanized because of insufficient seizure control. Only one dog (5%) showed clinical remission. Conclusion: Prevalence of idiopathic epilepsy is higher in Greater Swiss Mountain Dogs in Switzerland compared to the general dog population. Seizure control seems to be difficult to achieve in this breed and remission-rate is low.Hintergrund: Bisher wird der Grosse Schweizer Sennenhund nicht unter den prädisponierten Rassen für idiopathische Epilepsie geführt. Allerdings liegen hierzu bisher auch nur wenige Daten und keine wissenschaftlichen Studien vor. Ziel dieser Studie ist es, die Häufigkeit der idiopathischen Epilepsie bei Grossen Schweizer Sennenhunden zu erheben und Anfallscharakteristik, Therapieprotokolle und -erfolge bei den betroffenen Hunden zu dokumentieren, um das Risiko für diese Erkrankung und den Verlauf besser einschätzen zu können. Material und Methoden: Es wurden Unterlagen des Schweizer Zuchtverbandes «Klub für Grosse Schweizer Sennenhunde» mit gemeldeten Fällen von epileptischen Anfällen ab Geburtsjahr 1999–2019 analysiert. Zusätzlich wurde eine Einladung zu einer Online-Umfrage zur idiopathischen Epilepsie (Einteilung Anfälle ja/nein, wenn ja; Angaben zu Anfallscharakteristik, Therapie, Therapieerfolge) an die Mitglieder des Zuchtverbandes verschickt. Ergebnisse: In der Schweiz besteht die Population aus ca. 600 Tieren, 70–90 Welpen werden pro Jahr geboren. Im Zeitraum zwischen 1999 und 2019 wurden dem Zuchtverband 34 Hunde mit Epilepsie in der Schweiz gemeldet, das entspricht einer Rate von an Epilepsie erkrankten Hunden von ca. 2%. 400 Tierbesitzer wurden zur Umfrage eingeladen und 128 nahmen teil. Die Prävalenz von idiopathischer Epilepsie beim Grossen Schweizer Sennenhund betrug mit 20 erkrankten Hunden 15,6%. Alle betroffenen Tiere zeigten generalisierte tonisch-klonische Anfälle. Bei 5 Tieren (41,6%) trat ein Status epilepticus auf. Bei 6/12 (50%) Hunden traten Clusteranfälle auf. Andauernde Therapieerfolge wurden nur bei 10% erzielt, 25% sind verstorben und Remission wurde ausschliesslich bei einem Hund (5%) erreicht. Schlussfolgerungen: Die Prävalenz der idiopathischen Epilepsie in Grossen Schweizer Sennenhunden in der Schweiz ist höher als in der durchschnittlichen Hundepopulation (0,6–0,75%). Status epilepticus und Clusteranfälle sind häufig, eine Remission ist sehr selten.Contexte: On sait peu de choses sur l’épilepsie idiopathique chez les Grands Bouviers Suisses. Jusqu’à présent, cette race n’est pas répertoriée comme une race prédisposée à l’épilepsie idiopathique. Le but de cette étude était d’estimer la prévalence de l’épilepsie idiopathique chez les Grands Bouviers Suisses en Suisse et de décrire les caractéristiques cliniques de l’épilepsie chez cette race, y compris la sémiologie des crises et la réponse au traitement. Matériel et méthodes: Les archives de l’association d’élevage «Club des Grands Bouviers Suisses» ont été étudiées pour les cas signalés de crises d’épilepsie entre 1999 et 2019. Le nombre total de cas signalés et le signalement ont été examinés. De plus, tous les propriétaires de Grands Bouviers Suisses inscrits au club d’élevage ont été invités à remplir un questionnaire en ligne. Résultats: Au total 600 Grands Bouviers Suisses vivent en Suisse et 70 à 90 chiots naissent chaque année. Entre 1999 et 2019, 34 chiens (2%) ont fait l’objet de crises d’épilepsie. Sur les 400 propriétaires invités à répondre au questionnaire, 128 ont rempli le questionnaire. 20 de ces 128 chiens souffraient d’épilepsie idiopathique. La prévalence de l’épilepsie idiopathique sur la base du questionnaire était donc de 15,6%. Tous les chiens atteints ont présenté des crises tonico-cloniques généralisées. Chez 5 animaux (41,6%) un status epilepticus est survenu et des crises en série chez 6 animaux (50%). Le contrôle à long terme des crises n’a été obtenu que chez 10% des chiens. Cinq chiens (25%) sont morts ou ont été euthanasiés en raison d’un contrôle insuffisant des crises. Un seul chien (5%) a présenté une rémission clinique. Conclusion: La prévalence de l’épilepsie idiopathique est plus élevée chez les Grands Bouviers Suisses en Suisse que dans la population canine générale. Le contrôle des crises semble difficile à réaliser dans cette race et le taux de rémission est faible.Stato dell’arte: L’epilessia idiopatica del grande bovaro svizzero è stata finora poco investigata. Attualmente questa razza non è inclusa nelle razze predisposte all’epilessia idiopatica. Lo scopo di questo studio è di investigare la prevalenza dell’epilessia idiopatica nel grande bovaro svizzero in una popolazione svizzera e descrivere le caratteristiche cliniche di questa patologia in questa razza canina includendo la semeiotica delle crisi epilettiche e la risposta clinica alla terapia. Materiali e metodi: le storie cliniche dei grandi bovari svizzeri iscritti al club cinofilo svizzero sono state ricercate in un intervallo temporale compreso tra il 1999–2019 al fine di segnalare casi affetti da epilessia idiopatica. Sono stati esaminati il numero totale dei casi e il relativo segnalamento. Inoltre, tutti i proprietari del grande bovaro svizzero registrati in allevamenti ufficiali sono stati invitati a compilare un questionario online. Risultati: in totale in Svizzera sono registrati 600 soggetti di grande bovaro svizzero: ogni anno nascono tra i 70 ed i 90 cuccioli. Tra il 1999 e il 2019 sono stati segnalati 34 soggetti (2%) affetti da crisi epilettiche. Il questionario online è stato compilato da 128 su 400 proprietari contattati. Venti proprietari su 128 hanno segnalato la presenza di crisi epilettiche di natura idiopatica. La relativa prevalenza dell’epilessia idiopatica riscontrata è risultata, dunque, pari al 15,6% basandosi sui dati derivati dal questionario. Tutti i soggetti affetti presentavano crisi epilettiche di tipo tonico-clonico. Cinque soggetti (41,6%) sono stati affetti da status epilepticus. Sei soggetti su dodici (50%) hanno presentato crisi di tipo cluster. Il controllo a lungo termine delle crisi è stato possibile solo nel 10% dei casi. Cinque soggetti (25%) sono deceduti, un solo soggetto (5%) ha presentato remissioni dei sintomi clinici. Conclusioni: la prevalenza dell’epilessia idiopatica nel grande bovaro svizzero in Svizzera è più grande se confrontata con quella generale nella popolazione canina. Lo stato epilettico e le crisi di tipo cluster sono comuni in questa razza, mentre la percentuale di soggetti che recuperano dai sintomi clinici è bassa.

espanolEl objetivo de este articulo es doble: por un lado, se trata de refutar un topico de la literatura filosofica moderna y contemporanea sobre el presunto valor de la ceguera en cuanto vision mas profunda respecto a la vision fisica, una especie de sabiduria directa, intuitiva, espiritual. Dicha idea, en los ultimos dos siglos ha alimentado no solo una mitologia estetica (lo “espiritual en el arte”, la “visibilidad de lo invisible”, etc.) sino tambien una metafisica que se podria resumir en el desprecio gnoseologico del Aparecer, pues la verdad estaria siempre detras de los fenomenos, en la oscuridad de lo indeterminado, donde solo unos pocos tendrian acceso: esta es la tirania de la ceguera como paradigma cultural. La distorsion sistematica de la hermeneutica de los textos griegos, se ha introducido asi en el lenguaje cotidiano, deformando lentamente toda nuestra concepcion del valor teoretico de lo visual y a la vez del legado griego. Por esta razon, el segundo objetivo del articulo, en desmontar las razones de este constructo, sera el de ofrecer una lectura alternativa de la cultura visual griega, en este caso especialmente a traves de la obra de Sofocles “Edipo Rey”, donde la mayoria de estos topicos pretenden fundamentarse. EnglishThe aim of this article is twofold: on the one hand, it aims at a refutation of a modern topic in philosophical literature about the supposed value of blindness as a kind of sight, deeper than the physical one, a kind of direct, intuitive and spiritual wisdom. This idea, in the last two centuries, has nourished not only an aesthetic mythology (i.e. the “spiritual in art”, the “visibility of the invisible”, etc.) but also a specific kind of Metaphysics that we could summarize as the epistemological denigration of the Appearance, since the truth would always be behind the phenomena, in the darkness of the indeterminate, where only a few would have access: this is the tyranny of blindness as a cultural paradigm. Thus, the systematic hermeneutical distortion of the Greek texts has been introduced into everyday language, slowly deforming our entire conception of the theoretical value of the visual and at the same time of the Greek legacy. For this reason, by dismantling the argumentation for this construct, the second aim of the article will be to offer an alternative reading of Greek visual culture, in this case especially through the work of Sophocles “Oedipus Rex”, where the majority of these topics pretend to be grounded.

Background Information regarding the prevalence of PKU in the Middle East in comparison to other world regions is scarce, which might be explained by difficulties in the implementation of national newborn screening programs. Objective This study seeks for the first time to genotype and biochemically characterize patients diagnosed with hyperphenylalaninemia (HPA) at the Pediatric Metabolic Genetics Clinic at the King Hussein Medical Center, Amman, Jordan. Methods A total of 33 patients with HPA and 55 family members were investigated for pterins (neopterin and biopterin) and dihydropteridine reductase (DHPR) activity in dried blood spots. Patients with HPA were genotyped for phenylketonuria (PKU) and the genes involved in tetrahydrobiopterin (BH$_{4}$) metabolism. Results In total 20 patients were diagnosed with PKU due to phenylalanine hydroxylase (PAH) deficiency, 2 with GTP cyclohydrolase I (GTPCH) deficiency, 6 with DHPR deficiency, and 3 with the 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. Diagnosis was not possible in 2 patients. This study documents a high percentage of BH$_{4}$ deficiencies within HPA patients. With one exception, all patients were homozygous for particular gene variants. Conclusions This approach enables differentiation between PKU and BH$_{4}$ deficiencies and, thus, allows for critical selection of a specific treatment strategies.

Early ophthalmological care of patients in intensive care with SARS-CoV­2 (Severe-Acute-Respiratory-Syndrom-Corona-Virus-2) infections is very time-consuming; however, this approach might prevent other ophthalmological diseases, such as lagophthalmos. There is no difference in ophthalmological treatment between SARS-CoV­2 positive and other intensive care patients. Due to the small number of cases in our observational study, a specific ophthalmological clinical pattern related to SARS-CoV­2 infections cannot currently be identified; however, the increased occurrence of subconjunctival hemorrhage in intensive care SARS-CoV­2 patients is remarkable. It remains unclear how ocular symptoms in SARS-CoV­2 infections are related or how they occur in different stages of the disease. Therefore, further studies are necessary for representative statements.

In December 2019 a novel coronavirus was firstly encountered in Wuhan/China with a massive outbreak of fatal pneumonia leading to a pandemic declared by the World Health Organization in March 2020 (WHO Dashboard COVID-19. [WHO web site]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019), affecting mainly elderly adults with underlying co-morbidities. Clinical course in children below the age of 10 years is considered to be mild or even with subclinical signs (Sinha IP, Ha et al. The Lancet Respiratory medicine 2020;27;S2213–2600(20) 30152-1). We describe a 4 month old infant with co-infection of SARS CoV-2 and influenza A virus.

Twenty years ago, an enzyme homologous to the previously known angiotensin-converting enzyme (ACE) was identified, and subsequently named ACE2. In the renin-angiotensin system (RAS), ACE2 has counter-regulatory functions against the classical effector peptide angiotensin II, for example in blood pressure regulation and cardiovascular remodeling. However, ACE2 provides an initially unexpected interesting link between virology and cardiovascular medicine. That is, ACE2 represents the binding receptor for the cellular uptake of SARS-CoV and SARS-CoV-2 viruses. Thus, ACE2 is relevant for COVID-19. In this context, it was suspected that therapy with RAS blockers might promote transmission and complications of COVID-19 by upregulation of ACE2 expression. The aim of this short review is, to describe the link between the RAS, particularly ACE2, and COVID-19. Based on our analysis and evaluation of the available findings, we justify our conclusion: important drugs such as ACE inhibitors and angiotensin receptor blockers should continue to be prescribed according to guidelines to stable patients in the context of the COVID-19 pandemic.

Within the cytoplasm of NPC tumor cells Corona virus like particles have been described earlier. Controlling immunfluorescent studies using anti-Corona-rabbit serum revealed the antigen localization within the tumor cell cytoplasm. Vice versa the blood sera from NPC-patients reveal significatively higher Corona antibody titers than blood sera from other than NPC-patients. The results open the theory that next to the well known EBV-infection the Corona virus infection plays an important role in NPC tumor biology. The question remains open whether there is an interacting function between a RNA-virus infection (Corona) and a DNA-virus infection (EBV) in nasopharyngeal carcinoma.

Five carcinoma of the nasopharynx (four lymphoepithelial carcinoma of the Regaud type and one squamous cell carcinoma) were examined light and electron microscopically. In addition to the familiar histological and cytological features of these tumors, and because of an increased antibody titer against Epstein-Barr virus in all five patients, all those cytoplasmic and nuclear inclusions were examined which could be interpreted as indicative of a virus contact.The following structures were found:Particles and microtubules which correspond in diameter, shape and location to Corona viruses.Particles surrounded by a double membrane and resembling in form and diameter Onkorna viruses.Tubulo-reticular, coil-shaped cytoplasmic inclusions interpreted as an unspecific reaction of the host cell to viral attack.Spherical nuclear bodies, which are frequently observed in tumors and during viral infections.Intranuclear particles which correspond in diameter, structure and distribution to viruses of the herpes type such as have been described in cell cultures of Burkitt lymphoma and nasopharyngeal carcinoma. The fifth group particularly was discussed in detail with regard to differentiation between those particles and other structures which could simulate a virus structure.Together with the appearance of increased ribosomes and of particular chromatin distribution within the tumor cell nuclei, the particles we discussed have been interpreted as morphological indications of a virus etiology of the examined tumors.

Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals. Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals.

Exercise testing in athletes is used to (a) evaluate baseline fitness and prescribe an exercise program or training zones, (b) evaluate continued progress after engaging in exercise training over a period of time, (c) diagnose cardiopulmonary conditions affecting exercise performance, and, (d) provoke arrhythmias or evaluate hemodynamic response to exercise in an athlete with a known cardiovascular condition to determine whether it is safe to participate in competitive sports. Exercise testing is not part of routine pre-participation (PPS) screening; however, it can supplement the clinical work-up of athletes with pathological findings during PPS and/or with symptoms. In several conditions associated with sudden cardiac death in athletes, exercise testing is helpful to reinforce the diagnosis. In the workup of exercise-related symptoms special attention should be given to closely reproducing the exercise demands of the respective sporting discipline. Exercise testing is an important and integrative diagnostic feature in the armamentarium of the sports cardiologist.

Leigh syndrome is one of the most common neurological phenotypes observed in pediatric mitochondrial disease presentations. It is characterized by symmetrical lesions found on neuroimaging in the basal ganglia, thalamus, and brainstem and by a loss of motor skills and delayed developmental milestones. Genetic diagnosis of Leigh syndrome is complicated on account of the vast genetic heterogeneity with >75 candidate disease-associated genes having been reported to date. Candidate genes are still emerging, being identified when "omics" tools (genomics, proteomics, and transcriptomics) are applied to manipulated cell lines and cohorts of clinically characterized individuals who lack a genetic diagnosis. NDUFAF8 is one such protein; it has been found to interact with the well-characterized complex I (CI) assembly factor NDUFAF5 in a large-scale protein-protein interaction screen. Diagnostic next-generation sequencing has identified three unrelated pediatric subjects, each with a clinical diagnosis of Leigh syndrome, who harbor bi-allelic pathogenic variants in NDUFAF8. These variants include a recurrent splicing variant that was initially overlooked due to its deep-intronic location. Subject fibroblasts were found to express a complex I deficiency, and lentiviral transduction with wild-type NDUFAF8-cDNA ameliorated both the assembly defect and the biochemical deficiency. Complexome profiling of subject fibroblasts demonstrated a complex I assembly defect, and the stalled assembly intermediates corroborate the role of NDUFAF8 in early complex I assembly. This report serves to expand the genetic heterogeneity associated with Leigh syndrome and to validate the clinical utility of orphan protein characterization. We also highlight the importance of evaluating intronic sequence when a single, definitively pathogenic variant is identified during diagnostic testing.

Cromosomes; Marcadors pronòstics Cromosomas; Marcadores de pronóstico Chromosomes; Prognostic markers Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy. This work was supported by grants from Instituto de Salud Carlos III (ISCIII) FIS/FEDER (PI12/01250; CP08/00223; PI16/00253; and CB16/12/00449), MINECO (SAF2013-48849-C2-1-R) to SP, BFU2015-68354 to THS, Breast Cancer Research Foundation (BCRF-17-008) to JA, AGL2014-52395-C2-2-R to DA, Worldwide Cancer Research, Red Temática de Investigación Cooperativa en Cáncer (RD012/0036/005), Fundación Científica de la Asociación Española contra el Cáncer, and Fundació La Marató TV3. THS was supported by institutional funding (MINECO) through the Centres of Excellence Severo Ochoa award and the CERCA Programme of the Catalan Government, and SS-B, by a Fundació La Caixa fellowship. We thank La Caixa Foundation and Cellex Foundation for provide research facilities and equipment. GV has received funding from the MINECO (a “Juan de la Cierva Incorporation” fellowship; IJCI-2014-20723). SP was a recipient of a Miguel Servet contract (ISCIII/FIS), and AI, JPC-C, LP-G, and GS-B are supported by contracts from Worldwide Cancer Research, Fundació La Marató TV3, Fundació FERO, and a FI Fellowship from the Generalitat de Catalunya, respectively.

A seven-year-old neutered male Labrador retriever was presented with behavioral changes and reduced vision. Neurological examination revealed blindness of the left eye with a positive pupillary light reflex and a decreased mental status. Blood and cerebrospinal fluid analyses showed no abnormalities. MRI revealed a deviant area located in the thalamic, hypothalamic and caudate nuclear regions. Invasion of the left optic nerve was also observed. The dog was euthanized after 38 days of palliative treatment. Necropsy showed a non-encapsulated extruding white lardaceous mass, with a diameter of 2 cm, in the white matter, located in the ventral thalamic region near the chiasma opticum, which extended along the left optic nerve. Histologically, neoplastic cells had a “fried egg” appearance. Immunolabelling for glial fibrillary acidic protein demonstrated the presence of numerous reactive astrocytes. The tumor was diagnosed as a low grade (II) intracranial oligodendroglioma with infiltration of the optic nerve.

Murine gammaherpesvirus 68 (MHV68) is a small-animal model suitable for study of the human pathogens Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus. Here, we have characterized the roles of the endosomal Toll-like receptor (TLR) escort protein UNC93B, endosomal TLR7, -9, and -13, and cell surface TLR2 in MHV68 detection. We found that the alpha interferon (IFN-α) response of plasmacytoid dendritic cells (pDC) to MHV68 was reduced in Tlr9 −/− cells compared to levels in wild type (WT) cells but not completely lost. Tlr7 −/− pDC responded similarly to WT. However, we found that in Unc93b −/− pDC, as well as in Tlr7 −/− Tlr9 −/− double-knockout pDC, the IFN-α response to MHV68 was completely abolished. Thus, the only pattern recognition receptors contributing to the IFN-α response to MHV68 in pDC are TLR7 and TLR9, but the contribution of TLR7 is masked by the presence of TLR9. To address the role of UNC93B and TLR for MHV68 infection in vivo , we infected mice with MHV68. Lytic replication of MHV68 after intravenous infection was enhanced in the lungs, spleen, and liver of UNC93B-deficient mice, in the spleen of TLR9-deficient mice, and in the liver and spleen of Tlr7 −/− Tlr9 −/− mice. The absence of TLR2 or TLR13 did not affect lytic viral titers. We then compared reactivation of MHV68 from latently infected WT, Unc93b −/− , Tlr7 −/− Tlr9 −/− , Tlr7 −/− , and Tlr9 −/− splenocytes. We observed enhanced reactivation and latent viral loads, particularly from Tlr7 −/− Tlr9 −/− splenocytes compared to levels in the WT. Our data show that UNC93B-dependent TLR7 and TLR9 cooperate in and contribute to detection and control of MHV68 infection. IMPORTANCE The two human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), can cause aggressive forms of cancer. These herpesviruses are strictly host specific, and therefore the homolog murine gammaherpesvirus 68 (MHV68) is a widely used model to obtain in vivo insights into the interaction between these two gammaherpesviruses and their host. Like EBV and KSHV, MHV68 establishes lifelong latency in B cells. The innate immune system serves as one of the first lines of host defense, with pattern recognition receptors such as the Toll-like receptors playing a crucial role in mounting a potent antiviral immune response to various pathogens. Here, we shed light on a yet unanticipated role of Toll-like receptor 7 in the recognition of MHV68 in a subset of immune cells called plasmacytoid dendritic cells, as well as on the control of this virus in its host.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer’s safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvβ6., Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ6.

The ADAMTS9 rs4607103 C allele is one of the few gene variants proposed to increase the risk of type 2 diabetes through an impairment of insulin sensitivity. We show that the variant is associated with increased expression of the secreted ADAMTS9 and decreased insulin sensitivity and signaling in human skeletal muscle. In line with this, mice lacking Adamts9 selectively in skeletal muscle have improved insulin sensitivity. The molecular link between ADAMTS9 and insulin signaling was characterized further in a model where ADAMTS9 was overexpressed in skeletal muscle. This selective overexpression resulted in decreased insulin signaling presumably mediated through alterations of the integrin β1 signaling pathway and disruption of the intracellular cytoskeletal organization. Furthermore, this led to impaired mitochondrial function in mouse muscle—an observation found to be of translational character because humans carrying the ADAMTS9 risk allele have decreased expression of mitochondrial markers. Finally, we found that the link between ADAMTS9 overexpression and impaired insulin signaling could be due to accumulation of harmful lipid intermediates. Our findings contribute to the understanding of the molecular mechanisms underlying insulin resistance and type 2 diabetes and point to inhibition of ADAMTS9 as a potential novel mode of treating insulin resistance.

Background: It is now generally accepted that obesity is a major risk factor for type 2 diabetes mellitus (T2DM). Hepatic steatosis in particular, as well as visceral and ectopic fat accumulation within tissues, is associated with the development of the disease. We recently presented the first study on isolated human pancreatic adipocytes and their interaction with islets [Gerst, F., Wagner, R., Kaiser, G., Panse, M., Heni, M., Machann, J., et al., 2017. Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion. Diabetologia 60(11):2240–2251.]. The results indicate that the function of adipocytes depends on the overall metabolic status in humans which, in turn, differentially affects islet hormone release. Scope of Review: This review summarizes former and recent studies on factors derived from adipocytes and their effects on insulin-secreting β-cells, with particular emphasis on the human pancreas. The adipocyte secretome is discussed with a special focus on its influence on insulin secretion, β-cell survival and apoptotic β-cell death. Major Conclusions: Human pancreatic adipocytes store lipids and release adipokines, metabolites, and pro-inflammatory molecules in response to the overall metabolic, humoral, and neuronal status. The differentially regulated adipocyte secretome impacts on endocrine function, i.e., insulin secretion, β-cell survival and death which interferes with glycemic control. This review attempts to explain why the extent of pancreatic steatosis is associated with reduced insulin secretion in some studies but not in others. Keywords: Fatty pancreas, Adipocytes, Paracrine signalling, Insulin secretion, β-cell mass, Type 2 diabetes mellitus (T2DM)

PurposeGlioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma.MethodsSOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively.ResultsHigher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells.ConclusionFrom our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells.

Objective: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.Methods: Whole body ablation of Lumican (Lum(-/-)) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.Results: Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.Conclusions: These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome. (C) 2018 The Authors. Published by Elsevier GmbH.

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future. ispartof: ALLERGY vol:74 pages:3-25 ispartof: location:Denmark status: published

The extracellular matrix (ECM) is a network of di erent proteins and proteoglycans that controls di erentiation, migration, repair, survival, and development, and it seems that its remodeling is required for healthy adipose tissue expansion. Obesity drives an excessive lipid accumulation in adipocytes, which provokes immune cells infiltration, fibrosis (an excess of deposition of ECM components such as collagens, elastin, and fibronectin) and inflammation, considered a consequence of local hypoxia, and ultimately insulin resistance. To understand the mechanism of this process is a challenge to treat the metabolic diseases. This review is focused at identifying the putative role of ECM in adipose tissue, describing its structure and components, its main tissue receptors, and how it is a ected in obesity, and subsequently the importance of an appropriate ECM remodeling in adipose tissue expansion to prevent metabolic diseases.

The goal of this study was to analyse the frequency of ultrasonographic findings in 129 calves with bronchopneumonia and to determine how often multiple abnormalities occur in individual calves. The frequency of abnormal ultrasonographic findings ranged from 4 to 88%. Comet-tail artifacts were the most common finding (88%) followed in decreasing order by scattered echogenic foci (69%), air bronchograms (44%), superficial alveolograms (29%), pleural effusion (26%), hepatisation (23%), pleural lesions (18%), fluid bronchograms (14%), lung abscesses (6%) and fibrin deposits or fibrin strands (4%). Thoracic ultrasonography yielded a mean of 3.3 ± 1.55 abnormal findings (range, 1-6) per calf. Ultrasonography of the lungs in calves with bronchopneumonia is a useful adjunct to clinical examination and allows the determination of the type and severity of lesions.In der vorliegenden Arbeit wurde die Häufigkeit der bei 129 Kälbern mit Bronchopneumonie erhobenen Ultraschallbefunde retrospektiv ausgewertet. Ebenso wurde untersucht, wie oft bei einem Kalb mehrere Befunde gleichzeitig vorhanden waren. Die Häufigkeit abnormer Ultraschallbefunde variierte zwischen 4 und 88%. Kometenschweifartefakte stellten mit 88% den häufigsten abnormen Befund dar. Sie wurden in abnehmender Reihenfolge gefolgt von Luftreflexen (69%), Luftbronchogrammen (44%), oberflächlichen Alveologrammen (29%), Pleuraergüssen (26%), Hepatisation (23%), Pleuraveränderungen (18%), Flüssigkeitsbronchogrammen (14%), Lungenabszessen (6%) und Fibrin oder Fibrinspangen (4%). Im Durchschnitt wurden pro Kalb 3.3 ± 1.55 krankhafte Ultraschallbefunde ermittelt. Die ­Ultraschalluntersuchung der Lunge stellt bei Kälbern mit Bronchopneumonie eine wertvolle Ergänzung der klinischen Untersuchung dar. Sie ermöglicht es, die Art und den Schweregrad der bronchopneumonischen Veränderungen darzustellen und zu objektivieren.Dans la présente étude, la fréquence des constatations échographiques anormales recueillies sur 129 veaux souffrant de bronchopneumonie a été évaluée de manière rétrospective. Il a également été étudié combien de fois un veau présentait simultanément plusieurs découvertes. La fréquence des échographies anormales variait entre 4 et 88%. Des artefacts en queue de comète représentaient, avec 88%, les découvertes anormales les plus courantes. Ils étaient, par ordre décroissant, suivi par des réflexions de l’air (69%), des bronchogrammes aériens (44%), des alvéologrammes superficiels (29%), un épanchement pleural (26%), une hépatisation (23%), des altérations pleurales (18%), des bronchogrammes liquidiens (14%), des abcès pulmonaires (6%) et de la fibrine ou des ponts de fibrine (4%). En moyenne 3,3 ± 1,55 résultats d’échographie anormaux ont été déterminés par veau. L’examen échographique des poumons est, chez les veaux souffrant d’une bronchopneumonie, un complément précieux à l’examen clinique. Il permet de représenter la nature et la gravité des changements de bronchopneumonie et de les objectiver.In questo studio si è valutata retrospettivamente la frequenza dei risultati ecografici di 129 vitelli affetti da broncopolmonite e si è esaminato quanto spesso erano presenti contemporaneamente risultati anomali per lo stesso vitello. La frequenza dei risultati ecografici anomali si riscontrava tra il 4 e l’88%. Gli artefatti ecografici a “coda di cometa” erano nell’88% dei casi i risultati anomali più comuni. In ordine decrescente seguivano ecogenicità dell’aria (69%), broncogramma aereo (44%), alveogramma superficiale (29%), versamento pleurico (26%), epatizzazione (23%), lesioni pleuriche (18%), broncogrammi liquidi (14%), ascessi polmonari (6%) e fibrina o maglie di fibrina (4%). In media sono stati riscontrati 3.3 ± 1.55 esami ecografici anomali per ogni vitello. L’esame ecografico dei polmoni dei vitelli affetti da broncopolmonite è un valido esame complementare all’esame clinico e permette di determinare e ­evidenziare il tipo e la gravità delle lesioni broncopolmonari.

Zusammenfassung: Eine zerebrale Beteiligung bei Malaria mit Plasmodium vivax ist ungewöhnlich. Diese schwere Form der Malaria ist üblicherweise durch Plasmodium falciparum bedingt. Wir berichten über eine 18-jährige Patientin aus Pakistan mit langjähriger intermittierender Fieberanamnese, welche 4Monate nach Einreise in die Schweiz erstmals an einer zerebralen Vivax-Malaria erkrankt. Die eindrückliche neurologische Symptomatik mit Amaurosis und Bewusstseinsstörung bildete sich in diesem Fall unter Therapie in wenigen Tagen zurück. Jedoch sind Todesfälle bei zerebraler Malaria durch Plasmodium vivax beschrieben

Zusammenfassung: Typ-II-Endometriumkarzinome sind hoch aggressive Tumoren, die häufig mit einer Inaktivierung des Tumorsuppressor-Gens TP53 assoziiert sind. In einem Mausmodell mit endometriumspezifischer Deletion des Trp53-Gens zeigten sich anfangs dysplastische Veränderungen am Mausendometrium, identisch den bekannten Vorläuferläsionen des Typ-II-Endometriumkarzinoms beim Menschen. Im weiteren Verlauf fanden sich bei diesem Mausmodell in einem hohen Prozentsatz auch Endometriumkarzinome, entsprechend den gängigen Subtypen des Typ-II-Endometriumkarzinoms. Der mTORC1-Signalweg war dabei sowohl in den Vorläuferläsionen als auch in invasiven Karzinomen häufig aktiviert. Dies lässt auf eine Kooperation dieses Signalwegs mit der Trp53-Defizienz im Rahmen der Tumorentstehung schließen. Analog dazu konnte bei der Analyse von 521 humanen Endometriumkarzinomen ebenfalls häufig eine Aktivierung des mTORC1-Signalwegs in Typ-I- und -II-Endometriumkarzinomen nachgewiesen werden. Die Aktivierung des mTORC1-Signalwegs sowie die p53-Überexpression und/oder TP53-Mutation waren unabhängige negative Prognosefaktoren bei Patientinnen mit Endometriumkarzinom. Offenbar spielen molekulare Veränderungen in p53 und dem mTORC1-Signalweg zwar eine unterschiedliche Rolle bei der Entstehung der verschiedenen Subtypen des Endometriumkarzinoms, die Kombination aus p53-Inaktivierung und mTORC1-Signalwegaktivierung ist aber - unabhängig vom Subtyp - eine gemeinsame pathogenetische Eigenschaft fortgeschrittener und aggressiver Endometriumtumoren

Zusammenfassung: Die Arthrose des oberen Sprunggelenks (OSG) ist häufig mit einer Fehlstellung verbunden, dabei ist die Valgusarthrose seltener als die Varusarthrose. Die Ursachen für eine Valgusarthrose sind eine mediale Bandinstabilität, ein Pes planovalgus und posttraumatische Fehlstellungen z.B. nach Fibulafraktur oder Stauchung des lateralen Tibiaplateaus. Damit eine OSG-Prothese kurz- wie auch langfristig korrekt und schmerzfrei funktionieren kann, muss die Biomechanik entsprechend den Prinzipien der mechanischen Achse, deren Wichtigkeit in der Orthopädie allgemein akzeptiert ist, wiederhergestellt werden. Richtlinien sind dabei (1) ein anteriorer tibiotalarer Winkel von etwa 90° und (2) eine neutrale Rückfußstellung. Diese wird vorzugsweise mit der Rückfußaufnahme nach Saltzman gemessen. Dabei ist zu beachten, dass der normale Rückfuß in einer Neutralstellung bis 1-2° Varusposition und nicht wie bisher angenommen in einer Valgusstellung ist. Je nach Ausmaß und Lokalisation der Valgusdeformität werden in unterschiedlicher Reihenfolge (1) die OSG-Prothese implantiert, (2) supra- und (3) inframalleoläre Korrekturosteotomien/-Arthrodesen, (4) eine mediale Bandplastik, (5) eine Fibulaosteotomie (6) mit eventueller Rekonstruktion der Syndesmose durchgeführt

Zusammenfassung: Die Immunhistochemie hat sich zu einem unverzichtbaren Hilfsmittel in der Prostatabiopsiediagnostik entwickelt. Da der Basalzellverlust als ein definierendes Kennzeichen von Malignität angesehen wird, können vor allem Basalzellmarker in der Differenzialdiagnose benigner und maligner Läsionen hilfreich sein. Basalzellzytokeratine und p63 haben daher schon lange einen festen Platz im diagnostischen Repertoire von Uropathologen. Wünschenswert wäre jedoch, diese Negativmarker durch zusätzliche komplementäre Positivmarker zu ergänzen, um die diagnostische Genauigkeit weiter zu erhöhen. Der am weitesten verbreitete Positivmarker ist die α-Methylazyl-CoA-Razemase (AMACR), die im Prostatakarzinom stark aufreguliert ist und sogar mit p63 in einer einzigen Immunfärbung kombiniert werden kann. Dieser Beitrag gibt einen kurzen und kritischen Überblick über gegenwärtige diagnostische Biomarker des Prostatakarzinoms und schlägt darüber hinaus Golgi-Phosphoprotein2" (GOLPH2) und "fatty acid synthase" (FASN) als zusätzliche diagnostische Marker vor

Zusammenfassung: Die mit einer chronischen therapieresistenten Obstipation verbundene Hypoganglionose macht 3-5% der bioptisch abzuklärenden gastrointestinalen Innervationsstörungen im Kindes- und Erwachsenenalter aus. Sie kann wie der M.Hirschsprung zu einem Megakolon führen und muss als wichtige Differenzialdiagnose berücksichtigt werden. Es lassen sich 3Hauptformen der Hypoganglionose unterscheiden: Die kongenitale hypoplastische Hypoganglionose tritt vorwiegend beim klassischen M.Hirschsprung proximal des aganglionären Segments auf. Sie zeigt kleine zellarme Ganglien mit großen interganglionären Abständen. Die oligoneuronale dysganglionäre Hypoganglionose manifestiert sich im Kindesalter und ist charakterisiert durch eine zunächst normale Zahl hypoplastischer Nervenzellen normal großer Ganglien des Plexus myentericus. Diese Form der Hypoganglionose kann progressiv verlaufen und in eine atrophische Hypoganglionose münden, die im Erwachsenenalter ein der Hirschsprung-assoziierten hypoplastischen Hypoganglionose ähnliches morphologisches Bild zeigt. Alle Formen äußern sich in einer verminderten Acetylcholinesterase-Aktivität der Nervenfasern der Muscularis propria. Über die Ätiologie der Hypoganglionose ist wenig bekannt: Bei den Hirschsprung assoziierten Formen sind vereinzelt Mutationen im RET- und GDNF-Gen nachgewiesen worden. Im heterozygoten GDNF+/--Tiermodell führt die GDNF-Mutation zur Hypoganglionose, was bei der isolierten Hypoganglionose des Menschen noch zu belegen ist

Zusammenfassung: In dieser Studie untersuchten wir, ob es sich bei Rezidiven von klassischen Hodgkin-Lymphomen (HL) um Rezidive im engeren Sinn oder aber um klonal unverwandte Sekundärtumoren handelt. Die Untersuchungen erfolgten an formalinfixierten, paraffineingebetteten Gewebeproben von 11Patienten. Hodgkin- bzw. Sternberg-Reed-Riesenzellen wurden nach immunhistochemischer Markierung mit CD30 mittels Laser mikrodisseziert und die Fragmentlängen des Schwerkettenimmunglobulin-Gens (IgH) unter Verwendung von FR3- und J-Konsensusprimern analysiert. Zwei Frührezidive nach einer HL-Erstdiagnose zeigten klonale Verwandschaft zu den Primärtumoren, während 3 von 4Frührezidiven nach einem Erst- oder Zweitrezidiv nicht mit dem vorangegangenen HL verwandt waren. Drei Spätrezidive waren mit dem ursprünglichen HL klonal unverwandt. Wir schließen daraus, dass es sich bei so genannten "Rezidiven" von HL z.T. um klonal unverwandte Zweitneoplasien handeln kann, was möglicherweise von therapeutischer Relevanz sein könnte

Zusammenfassung: Der Morbus Whipple ist eine seltene, ohne antibiotische Therapie schwer verlaufende, chronische Infektionserkrankung durch Tropheryma whipplei, ein ubiquitär vorkommendes, grampositives Bakterium. Der Erreger kann in den betroffenen Geweben und Körperflüssigkeiten durch histologischen Nachweis PAS-positiver Makrophagen, elektronenmikroskopisch und in der Polymerasekettenreaktion (PCR) nachgewiesen werden. Arthralgien und Arthritiden sind ein häufiges Primärsymptom dieser Multisystemerkrankung. Im Verlauf treten häufig Gewichtsverlust, Diarrhö und Abdominalschmerzen auf. In 10-40% der Krankheitsfälle bestehen zusätzlich neurologische Symptome. Wir berichten über einen 67-jährigen Patienten mit jahrzehntelanger Oligoarthritis, bei dem der Erreger mittels PCR ausschließlich in der Synovialflüssigkeit nachgewiesen werden konnte. Dieser Fall illustriert, dass der charakteristische Befund PAS-positiver Makrophagen und selbst die erregerspezifische PCR im Dünndarmgewebe negativ sein kann, sodass der Erregernachweis aus dem jeweils symptomatischen Organsystem angestrebt werden sollte. Die mehrmonatige bis mehrjährige Behandlung erfolgt möglichst mit liquorgängigen Antibiotika, typischerweise mit Ceftriaxon, gefolgt von Cotrimoxazol. Vor Abschluss der Therapie ist der Nachweis der Erregerfreiheit im Darm, Liquor bzw. im betroffenen Organ anzustreben

Zusammenfassung: Die pollenassoziierte Nahrungsmittelallergie beruht auf einer Struktur- und Sequenzähnlichkeit allergener Proteine in Pollen und pflanzlichen Nahrungsmitteln. Die primäre IgE-Antwort richtet sich bei betroffenen Patienten in der Regel primär gegen Epitope auf Pollenproteinen mit sekundärer Erkennung homologer Epitope auf Nahrungsmittelallergenen. So leiden z.B. in Zentral- und Nordeuropa bis zu 80% der Birkenpollenallergiker gleichzeitig unter einer Nahrungsmittelallergie insbesondere gegen Stein- und Kernobst sowie gegen verschiedene Nüsse und Gemüse. Die Hauptmanifestation der pollenassoziierten Nahrungsmittelallergie ist das orale Allergiesyndrom, eine Kontakturtikaria der Mundschleimhaut. Neben der Kontakturtikaria insbesondere der Hände bei Berührung der allergenen Nahrungsmittel entwickeln Patienten mit pollenassoziierter Nahrungsmittelallergie bei deren Einnahme v.a. generalisierte Urtikaria und Angioödeme als kutane Symptome. Der Einfluss einer pollenassoziierten Nahrungsmittelallergie auf die Ausprägung und den Verlauf des atopischen Ekzems ist bis heute noch nicht definitiv geklärt

Zusammenfassung: Die Verwendung rekombinanter Allergenkomponenten eröffnet mehrere diagnostische Möglichkeiten. So können krankheitsspezifische Sensibilisierungsmuster wie etwa bei der allergisch bronchopulmonalen Aspergillose ABPA identifiziert werden. Durch Bestimmung der Majorallergene wichtiger Pollen (Betv1, Ole1, Phlp1/Phlp5) kann eine präzisere Indikationsstellung im Hinblick auf eine allergenspezifische Immuntherapie ermöglicht werden, da Extrakte v.a. Majorallergene enthalten. Sensibilisierungen auf Nebenallergene wie Profiline und Polcalcine beeinflussen aufgrund der großen Kreuzreaktivität herkömmliche IgE-Tests, sind aber oft von untergeordneter klinischer Bedeutung. Bei Nahrungsmitteln können häufige Kreuzreaktionen etwa mit Birkenpollen über Betv1/PR-10-Proteine nachgewiesen werden. Zudem lassen Sensibilisierungen auf Speicherproteine etwa von Erdnuss (Arah2) oder Lipidtransferproteine von Pfirsich (Prup3) oder Haselnuss (Cora8) Rückschlüsse auf ein höheres Anaphylaxierisiko zu. Anstrengungsinduzierte Beschwerden (Tria19), unklare Latexsensibilisierungen oder Doppelpositivität bei Insektengiftallergien sind weitere aktuell sinnvolle Einsatzgebiete. Microarray-basierte Allergenchips erlauben bereits heute die Bestimmung von IgE gegen über 100Allergenen aus kleinsten Serummengen, bedürfen aber noch der Evaluation und Optimierung bezüglich Allergenauswahl und Sensitivität