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Zusammenfassung. Feuerwerkskörper werden häufig zum Feiern von nationalen, kulturellen oder religiösen Anlässen verwendet. Trotz strenger gesetzlicher Regelungen geschehen immer wieder Unfälle im Zusammenhang mit Feuerwerk. Besonders die unvorsichtige Handhabung von Sprengkörpern stellt ein grosses Verletzungsrisiko dar. Methode: Dies ist eine retrospektive Studie basierend auf Daten des UNZ Inselspital Bern im Zeitraum 1. Januar 2013 bis 31. Dezember 2019. Es wurden unter anderem folgende Parameter analysiert: Geschlecht, Alter, Verletzungsmuster und Therapie. Resultate: Es konnten 59 Patientinnen und Patienten in die Studie eingeschlossen werden. Davon waren 81,4 % männlich, das Durchschnittsalter betrug 31 Jahre (Range 16–73; SD = 11,3). Ein Grossteil der Fälle (83,6 %) betraf den Kopf mit Beeinträchtigung der Ohren/des Gehörs sowie Verletzungen der Augen und des Gesichts. Die meisten Verletzungen waren Monotraumata, nur 6,8 % der Verletzungen betrafen mehrere Körperregionen. Insgesamt mussten neun Patienten aufgrund schwerwiegender Verletzungen hospitalisiert werden. Hiervon betraf eine Verletzung die Augen, die restlichen acht Verletzungen betrafen die Hände. Ausschliesslich bei diesen acht Patienten war eine operative Versorgung der Verletzungen nötig. Schlussfolgerung: Feuerwerkskörper sind mit einem beträchtlichen Verletzungsrisiko verbunden, vor allem bei unsicherer Handhabung. Unsere Studie zeigte, dass schwere Verletzungen vor allem die Hände betreffen. Zur Vermeidung solcher Verletzungen wäre eine systematische Datenerhebung von Verletzungen mit Feuerwerkskörpern nötig, da viele Verletzte in kleineren, peripheren Krankenhäusern oder gar nicht vorstellig werden. Anhand dieser Daten liessen sich umfassendere und detaillierte Präventionsstrategien entwickeln, die Verletzungen durch Feuerwerkskörper vorbeugen könnten.

Background Ambulance accidents are an unfortunate indirect result of ambulance emergency calls, which create hazardous environments for personnel, patients, and bystanders. However, in European German-speaking countries, factors contributing to ambulance accidents have not been optimally researched and analyzed. Objective The objective of this study was to extract, analyze, and compare data from online newspaper articles on ambulance accidents for Austria, Germany, and Switzerland. We hope to highlight future strategies to offset the deficit in research data and official registers for prevention of ambulance and emergency vehicle accidents. Methods Ambulance accident data were collected from Austrian, German, and Swiss free web-based daily newspapers, as listed in Wikipedia, for the period between January 2014 and January 2019. All included newspapers were searched for articles reporting ambulance accidents using German terms representing “ambulance” and “ambulance accident.” Characteristics of the accidents were compiled and analyzed. Only ground ambulance accidents were covered. Results In Germany, a total of 597 ambulance accidents were recorded, corresponding to 0.719 (95% CI 0.663-0.779) per 100,000 inhabitants; 453 of these accidents left 1170 people injured, corresponding to 1.409 (95% CI 1.330-1.492) per 100,000 inhabitants, and 28 of these accidents caused 31 fatalities, corresponding to 0.037 (95% CI 0.025-0.053) per 100,000 inhabitants. In Austria, a total of 62 ambulance accidents were recorded, corresponding to 0.698 (95% CI 0.535-0.894) per 100,000 inhabitants; 47 of these accidents left 115 people injured, corresponding to 1.294 (95% CI 1.068-1.553) per 100,000 inhabitants, and 6 of these accidents caused 7 fatalities, corresponding to 0.079 (95% CI 0.032-0.162) per 100,000 inhabitants. In Switzerland, a total of 25 ambulance accidents were recorded, corresponding to 0.293 (95% CI 0.189-0.432) per 100,000 inhabitants; 11 of these accidents left 18 people injured, corresponding to 0.211(95% CI 0.113-0.308) per 100,000 inhabitants. There were no fatalities. In each of the three countries, the majority of the accidents involved another car (77%-81%). In Germany and Switzerland, most accidents occurred at an intersection. In Germany, Austria, and Switzerland, 38.7%, 26%, and 4%, respectively, of ambulance accidents occurred at intersections for which the ambulance had a red light (P Conclusions This study draws attention to much needed auxiliary sources of data that may allow for creation of a contemporary registry of all ambulance accidents in Austria, Germany, and Switzerland. To improve risk management and set European standards, it should be mandatory to collect standardized goal-directed and representative information using various sources (including the wide range presented by the press and social media), which should then be made available for audit, analysis, and research.

Background: Rhabdomyolysis is a potentially fatal condition that can be triggered by a variety of inciting events, including excessive muscular exertion.The purpose of this study was to investigate the causes of creatine kinase elevation (CK≥1000U/L) to determine what percentage result from exRML, the etiology, and kinetics of CK levels, as well as the complications of exRML and comorbidities that may predispose an individual to this condition.Methods: We performed a cross-sectional analysis of the emergency department database for patients with CK≥1000U/L between 2012 and 2017. In total, there were 1957 cases of rhabdomyolysis diagnosed based on laboratory data and documentation. Trauma was the most common cause for rhabdomyolysis (n = 726/1957; 37.1%, respectively).Results: ExRML was identified in 2.1% (n = 42/1957) of the total cases. Patients with ExRML were significantly younger (30.1 ± 10.6 years) with a significantly higher maximal level of CK compared to the non-exertional causes of rhabdomyolysis, (CK = 16,884.4 ± 41,645.6U/L; both p < 0.005). The far majority of cases were sport or exercise related (n = 35/42; 83.3%), with strength training at the gym making up the largest group of athletes (n = 16/42; 38.1%). The main complication amongst the ExRML group was acute kidney insufficiency, which was observed in 42.9% of patients. The CK levels of the patients in the ExRML cohort steadily decreased after initiation of aggressive hydration.Conclusion: ExRML may be more prevalent than the current literature predicts, which is important to recognize as it has the potential to cause kidney failure, irregular heart rhythm, and death. Therefore, physicians and active individuals should be sensitized to the signs and symptoms that may lead to earlier recognition and proper treatment in exercising individuals.

Zusammenfassung. Gartenarbeit ist eine beliebte Freizeitaktivität in der Schweiz. Pro Jahr werden ungefähr eine Million Nichtberufsunfälle registriert, davon ereignen sich etwa 600 000 zu Hause oder während der Ausübung eines Hobbies, einschliesslich 16 000 Unfällen bei der Gartenarbeit. Ziel dieser retrospektiven Analyse ist die Untersuchung von Gartenarbeitsunfällen. Die Daten wurden aus der elektronischen Datenbank des Universitären Notfallzentrums des Inselspitals Bern gesammelt und retrospektiv ausgewertet. Patienten im Alter von 16 Jahren oder älter, die einen Unfall während der Gartenarbeit als Freizeitaktivität erlitten, wurden in die Analyse eingeschlossen. Jüngere Patienten wurden in einem separaten Notfallzentrum für Kinder und Jugendliche behandelt und somit nicht ausgewertet. Anschliessend wurden die Daten nach Alter, Geschlecht, Triagekategorie, Unfallmechanismus, unfallverursachendem Objekt, betroffenen Körperregionen, Diagnosen, Schweregrad der Verletzung (monotraumatisch, kombiniert mit mehr als einer betroffenen Körperregion oder Polytrauma) und ambulanter oder stationärer Behandlung analysiert. Unfälle bei der privaten Gartenarbeit ereigneten sich vorwiegend bei Erwachsenen im Alter von 40–69 Jahren. Dabei waren Männer häufiger als Frauen betroffen. Die Patienten zogen sich vorwiegend Augenverletzungen und Hautwunden zu. Exponierte Körperstellen wie Augen, Finger, Kopf und Gesicht waren am häufigsten betroffen. Es handelte sich vorwiegend um monotraumatische Verletzungen, die ambulant behandelt werden konnten. Stürze und ähnliche Ereignisse wie Stolpern führten häufig zu Unfällen. Unfälle wurden hauptsächlich durch organisches Material oder durch die fehlerhafte und nachlässige Anwendung von Werkzeugen verursacht. Die Datenanalyse zeigte, dass ein Grossteil der Unfälle durch einfache Präventionsmassnahmen verhindert werden könnten.

Obesity, as a major risk factor of metabolic syndrome (MetS), represents a pandemic, especially in Western societies, and is considered a risk factor for malignancies. Helicobacter pylori (Hp), is a definite carcinogen with global distribution. We aimed to investigate, for the first time in Switzerland, the main gastric mucosa premalignant histological lesions of bariatric patients in correlation with MetS components and Hp Infection (Hp-I). By reviewing retrospectively 94304 patient cases, a total of 116 eligible patients having undergone bariatric surgery were identified. The mean patient age was 48.66 years. Hp(+) patients were 24% (28/116). Presence of gastric mucosa atrophy was documented in 8/28 Hp(+) patients (29%) and (2/88) Hp(−) ones (2%) (p = 0.006). Gastric mucosa intestinal metaplasia was observed in 14/28 (50%) Hp(+) patients versus 3/88 (3.4%) of Hp(-) group (p &lt, 0.0001). Hp(+) patients exhibited statistically higher arterial hypertension (p = 0.033). The homeostatic model of assessment insulin resistance was also statistically significantly higher for the Hp(+) group (p &lt, 0.001). In a multivariate analysis, including arterial hypertension, gastric mucosa atrophy, and intestinal metaplasia as variables, statistical significance remained only for intestinal metaplasia (p = 0.001). In conclusion, Hp-I is associated with premalignant gastric mucosa histologic lesions and MetS components, including arterial hypertension and IR. Further large-scale prospective studies are required to confirm these findings.

Nonalcoholic fatty liver disease (NAFLD) emerges as an important global burden and Helicobacter pylori infection (Hp-I) has been suggested as a risk factor of NAFLD, although controversy exists. This retrospective study aimed to investigate a potential impact of active Hp-I on NAFLD severity in morbidly obese patients, subjected to bariatric surgery and gastric biopsy for documentation of Hp-I. Of 64 eligible participants, 15 (23.4%) were diagnosed with active Hp-I, showing higher rates of nonalcoholic steatohepatitis (NASH) than those without Hp-I (86.7% vs. 26.5%, respectively, p &lt, 0.001). Concerning histological lesions, steatosis grade (p = 0.027), ballooning (p &lt, 0.001), lobular inflammation (p = 0.003), and fibrosis stage (p &lt, 0.001) were also more severe in Hp-I positive patients. Likewise, liver function tests, insulin resistance, dyslipidemia, and arterial hypertension were significantly higher in Hp-I positive patients. Hp-I was independently positively associated with NASH (beta = 3.27, p = 0.002), severe NASH (beta = 2.37, p = 0.018), and the presence of fibrosis (beta = 3.86, p = 0.001) in a binary regression model, after adjustment for potential confounders. In conclusion, active Hp-&Iota, was independently associated with NASH and fibrosis, findings offering potential clinical implication.

Aim. To investigate the characteristics of Emergency Department (ED) presentations due to acute paracetamol intoxication. Methods. Retrospective observational study of patients presenting to the ED of Bern University Hospital between May 1, 2012, and October 31, 2018, due to a paracetamol overdose (defined as intake of >4 g/24 h). Cases were identified using the full-text search of the electronic patient database and were grouped into intentional (suicidal/parasuicidal) and unintentional intoxications (e.g., patient unaware of maximal daily dose). Results. During the study period, 181 cases were included and 143 (79%) of those were intentional. Compared to the patients in the unintentional group, patients in the intentional group were more often female (85% vs 45%, p<0.001) and younger (median age 23.0 vs 43.5 years, p<0.001), more frequently suffered from psychiatric comorbidities (93%, (including 49% with borderline personality disorder) vs 24%, p<0.001), and paracetamol was more often taken as a single dose (80% vs 13%, p<0.001). Although the median daily ingested dose was lower in the unintentional than in the intentional group (8.2 g vs 12.9 g, p<0.001), patients in the unintentional group presented later (29% vs 84% within 24 h of ingestion, p<0.001), included more cases of acute liver failure (nine (24%) vs six (4%), p<0.001), and were more often hospitalised (24% vs 52% treated as outpatients, p=0.002). There were no significant differences between the groups regarding drug-induced liver injury (seven cases (5%) in the intentional and one (3%) in the unintentional group) or fatalities (one in each group). Conclusions. The majority of presentations due to paracetamol poisoning were intentional, most commonly in female patients with borderline personality disorder. Patients with unintentional paracetamol intoxication had worse outcomes with respect to acute liver failure and hospitalisation. Future preventive measures should raise awareness of paracetamol toxicity in the general population and encourage particular attention and frequent follow-ups when prescribing paracetamol for vulnerable groups.

The consequences of mushroom poisoning range from mild, mostly gastrointestinal, disturbances to organ failure or even death. This retrospective study describes presentations related to mushroom poisoning at an emergency department in Bern (Switzerland) from January 2001 to October 2017. Gastrointestinal disturbances were reported in 86% of the 51 cases. The National Poisons Information Centre and mycologists were involved in 69% and 61% of the cases, respectively. Identification of the mushroom type/family was possible in 43% of the cases. The most common mushroom family was Boletaceae (n = 21) and the most common mushrooms Xerocomus chrysenteron (n = 7, four being part of a cluster), Clitocybe nebularis, Lepista nuda and Lactarius semisanguifluus (n = 5 each, four being part of a cluster). Poisonous mushrooms included Amanita phalloides (n = 3, all analytically confirmed), Boletus satanas (n = 3), Amanita muscaria (n = 2) and Amanita pantherina (n = 2). There were no fatalities and 80% of the patients were discharged within 24 h. Mushroom poisoning does not appear to be a common reason for emergency consultation and most presentations were of minor severity and related to edible species (e.g., due to incorrect processing). Nevertheless, poisonous mushrooms and severe complications were also recorded. Collaboration with a poison centre and/or mycologists is of great importance, especially in high risk cases.

Genetic and epigenetic alterations in the equine sarcoid, a locally invasive skin tumour of equids, are still poorly characterized. Numerous studies have provided reliable evidence for the relationship between the development of cancer and the loss of function of a number of tumour suppressor genes. In the present study, we assessed methylation levels in the promoter region of SFN, S100A14 and POU2F3 genes in sarcoid samples to clarify whether DNA methylation may be associated with previously identified changes in the expression level of these genes during the course of tumour progression. Using bisulfite sequencing and clone sequencing, we detected that lesional samples had a significantly higher rate of DNA methylation in the analyzed S100A14A region than the corresponding normal skin tissue. A frequent methylation of the SFN and POU2F3 promoter sequences were observed in both the tumour samples and the control skin tissues. Further studies are needed to evaluate the role of aberrant methylation in sarcoid progression and to understand the mechanisms involved in reduced expression of SFN, S100A14 and POU2F3 genes in the lesional tissues.

Thymic stromal lymphopoietin (TSLP) is a cytokine involved in lymphocyte development. In humans and mice, TSLP drives the differentiation of T helper 2 (Th2) cells and the development of allergic inflammation. The equine TSLP gene has been previously identified and characterized, but its role in the pathogenesis of equine allergic diseases is not known. Our objective was to assess the expression of TSLP in bronchoalveolar lavage (BAL) cells and in primary bronchial epithelial cells (BEC) isolated from horses with recurrent airway obstruction (RAO). RNA was isolated from BAL cells sampled from clinical cases of RAO (n=8) and from control horses (n=12). Furthermore, BAL samples were taken from an additional group of 8 RAO-susceptible and 8 control horses when on pasture (remission) and after 30 days of exposure to moldy hay (exacerbation). In order to study epithelial cells as a potential source of TSLP, cultures of primary bronchial epithelial cells (BEC) were established from 6 RAO-affected and 6 healthy horses and stimulated in vitro with hay dust solution (HDS). Expression of TSLP mRNA was assessed by quantitative real-time RT-PCR (qPCR). Clinical RAO-cases had higher TSLP expression in BAL than control horses (p

Recurrent airway obstruction (RAO) in horses is the result of an interaction of genetic and environmental factors and shares many characteristics with human asthma. Many studies have suggested that the interleukin-4 receptor gene (IL4R) is associated with this disease, and a QTL region on chromosome 13 containing IL4R was previously detected in one of the two Swiss Warmblood families. We sequenced the entire IL4R gene in this family and detected 93 variants including five non-synonymous protein-coding variants. The allele distribution at these SNPs supported the previously detected QTL signal. Subsequently, we investigated IL4R mRNA expression in bronchoalveolar lavage fluid cells. During exacerbation, IL4R expression was increased in RAO-affected offspring in the implicated family, but not in the other family. These findings support that IL4R plays a role in some cases of RAO.

Equine recurrent airway obstruction (RAO) is a chronic lower airway disease of the horse caused by hypersensitivity reactions to inhaled stable dust, including mould spores such as Aspergillus fumigatus. The goals of this study were to investigate whether total serum IgE levels and allergen-specific IgE and IgG subclasses are influenced by genetic factors and/or RAO and whether quantitative trait loci (QTL) could be identified for these parameters. The offspring of two RAO-affected sires (S1: n=56 and S2: n=65) were grouped by stallion and disease status, and total serum IgE levels and specific IgE, IgGa, IgGb and IgG(T) levels against recombinant Aspergillus fumigatus 7 (rAspf7) were measured by ELISA. A panel of 315 microsatellite markers covering the 31 equine autosomes were used to genotype the stallions and their offspring. A whole-genome scan using half-sib regression interval mapping was performed for each of the IgG and IgE subclasses. There was no significant effect of disease status or sire on total IgE levels, but there was a significant effect of gender and age. rAspf7-specific IgGa levels were significantly higher in RAO-affected than in healthy horses. The offspring of S1 had significantly higher rAspf7-specific IgGa and IgE levels than those of S2. Five QTLs were significant chromosome-wide (P

Summary Reasons for performing study: Sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. Infection by bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far. Hypothesis: Given the pathogenic role of BPV-1 and BPV-2 in sarcoid disease, we suggest that intralesional viral DNA concentration may reflect the degree of affection. Methods: Severity of disease was addressed by recording the tumour growth kinetics, lesion number and tumour type for 37 sarcoid-bearing horses and one donkey. Viral load was estimated via quantitative real-time PCR (qPCR) of the E2, E5, L1 and L2 genes from the BPV-1/-2 genome for one randomly selected lesion per horse and correlated with disease severity. Results: Quantitative PCR against E2 identified viral DNA concentrations ranging from 0-556 copies/tumour cell. Of 16 horses affected by quiescent, slowly growing single tumours or multiple mild-type lesions, 15 showed a viral load up to 1.4 copies per cell. In stark contrast, all equids (22/22) bearing rapidly growing and/or multiple aggressive sarcoids had a viral load between 3 and 569 copies per cell. Consistent results were obtained with qPCR against E5, L1 and L2. Conclusions: While tumours of the same clinical type carried variable virus load, confirming that viral titre does not determine clinical appearance, we identified a highly significant correlation between intralesional viral load and disease severity. Potential relevance: The rapid determination of BPV viral load will give a reliable markerfordisease severity and may also be considered when establishing a therapeutic strategy.

The aim of our study was to diagnose aneuploidy in equine spermatozoa by multicolour fluorescence in situ hybridization (FISH) technique using specific molecular probes for equine sex chromosomes and autosome pair four (EGFR probe) labeled by different fluorochromes. These were applied on decondensed spermatozoa of four stallions. In total, more than 8800 sperm cells were examined. The total frequency of aberrant cells was 0.496%: aneuploidy of XX (0.135%), YY (0.023%), XY (0.102%), diploidy (0.057%), lack of sex chromosome (0.18%). In one stallion the ratio of normal X- and Y-bearing cells was different from the expected 1:1 ratio (p = 0.0002), in all three other stallions this ratio was close to 1:1. The present study demonstrated that the FISH technique is a powerful method to identify sex chromosome aberrations in equine spermatozoa and allows for the determination of the ratio between X-Y-spermatozoa.

REASONS FOR STUDY: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor a chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required. METHODS: The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood halfsib families. Based on a history of clinical signs (coughing, nasal discharge, abnormal breathing and poor performance), horses were classified in a horse owner assessed respiratory signs index (HOARSI 1-4: from healthy, mild, moderate to severe signs). Four microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2-4) and Sire 2 (35 HOARSI 1 vs. 50 HOARSI 2-4), age 07 years. RESULTS: For both sires haplotypes could be established in the order AHT133-LEXO47-VHL47-ASB37. The distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans, respectively. Haplotype association with mild to severe clinical signs of chronic lower airway disease (HOARSI 2-4) was significant in the offspring of Sire 1 (P = 0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage analysis showed the ECA13q13 region containing IL4RA to be linked to equine chronic lower airway disease in one family (P

Recurrent airway obstruction (RAO) is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE) was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

Equine recurrent airway obstruction (RAO) is an inflammatory, obstructive airway disease induced by exposure of susceptible horses to inhaled organic dust particles. The immunological process underlying RAO is still unclear. Previous studies have shown that RAO is linked to the Interleukin-4 receptor (IL-4R) gene in one Warmblood family (F1), but not in another (F2). It has also been shown that in F1, but not in F2, RAO is associated with resistance against parasites, suggesting that this association may have an immuno-genetic basis. Therefore, we hypothesized that the T helper (h)1/Th2/regulatory (Treg) cytokine profiles of RAO-associated antigen- and parasite-antigen-stimulated peripheral blood mononuclear cells (PBMC) differ between RAO-affected and healthy horses depending on their genetic background. In our study, PBMC from 17 RAO-affected and 14 healthy control horses of F1 and F2 were stimulated for 24h with antigens relevant to RAO [hay dust extract (HDE), Aspergillus fumigatus extract (AFE) and lipopolysaccharids (LPS)]; cyathostomin extract (CE) and recombinant cyathostomin antigen (RCA) or with concanavalin A (ConA). Total mRNA levels of IL-4, IL-4R, IL-13, interferon (INF)-γ and IL-10 were examined by qRT-PCR. Stimulation with either HDE or RCA resulted in significant differences in IL-4R mRNA levels between RAO-affected and control horses in F1, but not in F2. For IL-10 mRNA expression, a significant difference between RAO-affected and control horses in F1 but not in F2 was observed only following stimulation with HDE. In contrast to HDE, stimulation with CE resulted in a significant difference of IL-10 mRNA expression level between RAO-affected horses of F2 and healthy horses of F1. No significant differences were detected upon stimulation with any of the other challenge agents. These findings indicate that the immunological response, specifically IL-4R expression, in response to hay dust and cyathostomin antigens, differs between RAO-affected and healthy horses depending on their genetic background. This study shows that analysis of PBMC reveals systemic changes associated with RAO and helps to elucidate immunological pathways involved in this disease.

It is widely accepted that equine sarcoid disease, the most common skin associated neoplasm in equids, is induced by bovine papillomavirus (BPV-1). Although BPV-1 DNA has been found in almost all examined sarcoids so far, its detailed impact on the horse's host cell metabolism is largely unknown. We used equine fibroblast cell lines originating from sarcoid biopsies to study BPV-1-associated changes on DNA methylation status and oxidative stress parameters. Sarcoid-derived fibroblasts manifested increased proliferation in vitro, transcriptional rDNA activity (NORs expression) and DNA hypomethylation compared to control cells. Cells isolated from equine sarcoids suffered from oxidative stress: the expression of antioxidant enzymes was decreased and the superoxide production was increased. Moreover, increased ploidy, oxidative DNA damage and micronuclei formation was monitored in sarcoid cells. We postulate that both altered DNA methylation status and redox milieu may affect genomic stability in BPV-1-infected cells and in turn contribute to sarcoid pathology.

Recurrent airway obstruction (RAO), or 'heaves', is a common performance-limiting allergic respiratory disease of mature horses. It is related to sensitization and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. In a previous study, we detected a QTL for RAO on ECA 13 in a half-sib family of European Warmblood horses. In this study, we genotyped additional markers in the family and narrowed the QTL down to about 1.5 Mb (23.7-25.2 Mb). We detected the strongest association with SNP BIEC2-224511 (24,309,405 bp). We also obtained SNP genotypes in an independent cohort of 646 unrelated Warmblood horses. There was no genome-wide significant association with RAO in these unrelated horses. However, we performed a genotypic association study of the SNPs on ECA 13 in these unrelated horses, and the SNP BIEC2-224511 also showed the strongest association with RAO in the unrelated horses (p(raw) = 0.00037). The T allele at this SNP was associated with RAO both in the family and the unrelated horses. Thus, the association study in the unrelated animals provides independent support for the previously detected QTL. The association study allows further narrowing of the QTL interval to about 0.5 Mb (24.0-24.5 Mb). We sequenced the coding regions of the genes in the critical region but did not find any associated coding variants. Therefore, the causative variant underlying this QTL is likely to be a regulatory mutation.

Recurrent airway obstruction (RAO), or heaves, is a naturally occurring asthma-like disease that is related to sensitisation and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. A genome-wide scanning approach using two half-sibling families was taken in order to locate the chromosome regions that contribute to the inherited component of this condition in these families. Initially, a panel of 250 microsatellite markers, which were chosen as a well-spaced, polymorphic selection covering the 31 equine autosomes, was used to genotype the two half-sibling families, which comprised in total 239 Warmblood horses. Subsequently, supplementary markers were added for a total of 315 genotyped markers. Each half-sibling family is focused around a severely RAO-affected stallion, and the phenotype of each individual was assessed for RAO and related signs, namely, breathing effort at rest, breathing effort at work, coughing, and nasal discharge, using an owner-based questionnaire. Analysis using a regression method for half-sibling family structures was performed using RAO and each of the composite clinical signs separately; two chromosome regions (on ECA13 and ECA15) showed a genome-wide significant association with RAO at P < 0.05. An additional 11 chromosome regions showed a more modest association. This is the first publication that describes the mapping of genetic loci involved in RAO. Several candidate genes are located in these regions, a number of which are interleukins. These are important signalling molecules that are intricately involved in the control of the immune response and are therefore good positional candidates.

BACKGROUND In humans, thymic stromal lymphopoietin (TSLP) plays a central role in the development of allergic inflammation, such as atopic dermatitis (AD), but it is unknown whether it is involved in the pathogenesis of canine AD (CAD). HYPOTHESIS/OBJECTIVES Our aim was to characterize canine TSLP and to assess its expression in CAD. METHODS Canine TSLP was identified based on sequence homology with human TSLP and the complementary DNA (cDNA) cloned by RT-PCR. Real-time quantitative RT-PCR was established to assess the expression of canine TSLP in cultured canine keratinocytes and in skin biopsy specimens from lesional and nonlesional skin of 12 dogs with CAD and eight healthy control dogs. RESULTS Partial canine TSLP cDNA was cloned and characterized. It contained four exons that shared 70 and 73% nucleotide identity with human and equine TSLP, respectively, encoding the signal peptide and full-length secreted protein. We found significantly increased TSLP expression in lesional and nonlesional skin of dogs with CAD compared with healthy control dogs (P < 0.05), whereas no difference was measured between lesional and nonlesional samples. In cultured primary canine keratinocytes, we found increased TSLP expression after stimulation with house dust mite allergen extract or Toll-like receptor ligands lipopolysaccharide and poly I:C. CONCLUSIONS AND CLINICAL IMPORTANCE Increased TSLP expression in the skin of dogs with CAD supports an involvement of TSLP in the pathogenesis of CAD similar to that in humans. Further studies should elucidate the function and therapeutic potential of TSLP in CAD.