In-herd prevalence of Fasciola hepatica and Calicophoron / Paramphistomum spp. infections in German dairy cows with comparison of two coproscopical methods and establishment of real-time pyrosequencing for rumen fluke species differentiation.

Infections with liver and rumen flukes are among the most frequent parasitic diseases in cattle worldwide. In Europe, the predominant liver fluke species is Fasciola hepatica, and the recently rapidly spreading rumen flukes are mostly Calicophoron daubneyi and occasionally Paramphistomum leydeni. In this study, 1638 faecal samples from individual dairy cows from 24 northern and 18 southern German farms as well as one central German farm, all preselected for potential F. hepatica infection, were examined to determine in-herd prevalences of liver and rumen fluke infections. Furthermore, individual faecal egg counts (FECs) were determined in the northern and central German cows. On farms with patent F. hepatica infections, the mean in-herd prevalence was 15.8% in northern Germany, 41.6% in southern Germany and 14.0% in the central German farm. Rumen fluke infections resulted in high in-herd prevalences in all regions with a mean prevalence of 46.0% in northern, 48.4% in southern and 40.0% in central Germany. Individual FECs varied between 0.1 and 4.1 (mean 0.4) eggs per gram faeces (EPG) for F. hepatica and between 0.1 and 292.4 (mean 16.9) EPG for rumen flukes. Mean in-herd prevalence and mean FECs did not differ significantly between mono- and coinfected farms for either fluke species. Comparison of the classical sedimentation technique and the Flukefinder® method on a subset of 500 faecal samples revealed a similar number of positive samples, however, Flukefinder® mean FECs were three to four times higher for liver and rumen fluke eggs, respectively, with an increasing gap between EPG levels with rising egg counts. Fluke egg size measurement confirmed P. leydeni eggs on average to be larger in length and width (161.0 µm x 87.1 µm) than those of C. daubneyi (141.8 µm x 72.9 µm). However, due to overlap of measurements, morphological species identification based on egg size proved unreliable. For accurate identification, a real-time pyrosequencing approach was established, offering the advantage over classical Sanger sequencing of unambiguously identifying rumen fluke mixed species infections. Real-time pyrosequencing confirmed C. daubneyi (78.1% [50/64]) as the predominant rumen fluke species in Germany, while P. leydeni was detected in 12.5% (8/64) of sampled cows. A total of 9.4% (6/64) cows were infected with both C. daubneyi and P. leydeni, representing the first finding of a mixed infection in domestic ruminants in Europe to date.

Genomic Selection for Dairy Cattle Behaviour Considering Novel Traits in a Changing Technical Production Environment.

Cow behaviour is a major factor influencing dairy herd profitability and is an indicator of animal welfare and disease. Behaviour is a complex network of behavioural patterns in response to environmental and social stimuli and human handling. Advances in agricultural technology have led to changes in dairy cow husbandry systems worldwide. Increasing herd sizes, less time availability to take care of the animals and modern technology such as automatic milking systems (AMSs) imply limited human-cow interactions. On the other hand, cow behaviour responses to the technical environment (cow-AMS interactions) simultaneously improve production efficiency and welfare and contribute to simplified "cow handling" and reduced labour time. Automatic milking systems generate objective behaviour traits linked to workability, milkability and health, which can be implemented into genomic selection tools. However, there is insufficient understanding of the genetic mechanisms influencing cow learning and social behaviour, in turn affecting herd management, productivity and welfare. Moreover, physiological and molecular biomarkers such as heart rate, neurotransmitters and hormones might be useful indicators and predictors of cow behaviour. This review gives an overview of published behaviour studies in dairy cows in the context of genetics and genomics and discusses possibilities for breeding approaches to achieve desired behaviour in a technical production environment.

Unmapped short reads from whole-genome sequencing indicate potential infectious pathogens in german black Pied cattle.

When resequencing animal genomes, some short reads cannot be mapped to the reference genome and are usually discarded. In this study, unmapped reads from 302 German Black Pied cattle were analyzed to identify potential pathogenic DNA. These unmapped reads were assembled and blasted against NCBI's database to identify bacterial and viral sequences. The results provided evidence for the presence of pathogens. We found sequences of Bovine parvovirus 3 and Mycoplasma species. These findings emphasize the information content of unmapped reads for gaining insight into bacterial and viral infections, which is important for veterinarians and epidemiologists.

Genetic evaluations for endangered dual-purpose German Black Pied cattle using 50K SNPs, a breed-specific 200K chip, and whole-genome sequencing.

Genetic evaluations of local cattle breeds are hampered due to small reference groups or biased due to the utilization of SNP effects estimated in other large populations. Against this background, there is a lack of studies addressing the possible advantage of whole-genome sequences (WGS) or consideration of specific variants from WGS data in genomic predictions for local breeds with small population size. Consequently, the aim of this study was to compare genetic parameters and accuracies of genomic estimated breeding values (GEBV) for 305-d production traits, fat-to protein ratio (FPR), and somatic cell score (SCS) at the first test date after calving and confirmation traits of the endangered German Black Pied cattle (DSN) breed using 4 different marker panels: (1) the commercial 50K Illumina BovineSNP50 BeadChip, (2) a customized 200K chip designed for DSN (DSN200K) which considers the most important variants for DSN from WGS, (3) randomly generated 200K chips based on WGS data, and (4) a WGS panel. The same number of animals was considered for all marker panel analyses (i.e., 1,811 genotyped or sequenced cows for conformation traits, 2,383 cows for lactation production traits, and 2,420 cows for FPR and SCS). Mixed models for the estimation of genetic parameters directly included the respective genomic relationship matrix from the different marker panels plus the trait-specific fixed effects. For the calculation of GEBV accuracies, we applied repeated random subsampling validation. In the process of separate cross-validations per trait, we created a validation set including 20% of cows with masked phenotypes, and a training set comprising 80% of the cows. The cows were selected randomly in a procedure with 10 replicates considering replacements in the different scenarios. The accuracy was defined as the correlation between the direct GEBV and the phenotypes with subtracted corresponding fixed effects for the cows in the validation set. For FPR and SCS, as well as for lactation production traits, heritabilities were largest based on WGS data, but the increase compared with the 50K or DSN200K applications was quite small in the range from 0.01 to 0.03. Also, for most of the conformation traits, heritabilities were largest based on WGS and DSN200K data, but the increase was in the range of the corresponding standard error. Accordingly, GEBV accuracies for most of the studied traits were highest based on WGS data or when utilizing the DSN200K chip, but the accuracy differences across the marker panels were quite small and nonsignificant. In conclusion, WGS data and the DSN200K chip only contributed to minor improvements in genomic predictions, still justifying the use of the commercial 50K chip. Nevertheless, WGS and the 200KDSN chip harbor breed-specific variants, which are valuable for studying causal genetic mechanisms in the endangered DSN population.

A Case Report of Acute Hepatitis Involving the Medicinal Herb Tinospora cordifolia Along with Other Variables.

This is a 54-year-old woman from Germany of central European origin who developed an acute hepatitis while orally taking Ayurvedic herbal remedies, among those was the medicinal herb Tinospora cordifolia. She took the plant powders from July 1, 2021, to October 1, 2021, with the intention of relieving the symptoms of her subjectively irritated gastrointestinal tract. The patient's main symptoms of acute hepatitis were progressively increasing general fatigue, nausea, and exhaustion. During an inpatient hospital admission from November 4, 2021, to November 9, 2021, she was under clinical observation, but no specific therapeutic measures were deemed necessary; however, blood chemistry showed an acute toxic hepatitis. There was no clinical or laboratory evidence of acute liver failure. Aminotransferase values decreased to normal values on December 14, 2021, by themselves. This case report contributes to the ongoing discussion about the potential risks of triggering an acute hepatitis due to the intake of herbal remedies from the Tinospora genus in rare cases, differentiating other involved risk factors. The case also shows that causality assignments are not trivial in the context of multivariate clinical scenarios. In the case of known hepatic metabolism-associated risk factors, T. cordifolia should be used with more caution based on available case reports. At the same time, no hasty and exaggerated prejudgments should be made about this medicinal herb, which has been very successfully used in traditional South Asian systems of medicine for many centuries.

Whole-Genome Sequencing Data Reveal New Loci Affecting Milk Production in German Black Pied Cattle (DSN).

German Black Pied (DSN) is considered an ancestral population of the Holstein breed. The goal of the current study was to fine-map genomic loci for milk production traits and to provide sequence variants for selection. We studied genome-wide associations for milk-production traits in 2160 DSN cows. Using 11.7 million variants from whole-genome sequencing of 304 representative DSN cattle, we identified 1980 associated variants (-log10(p) ≥ 7.1) in 13 genomic loci on 9 chromosomes. The highest significance was found for the MGST1 region affecting milk fat content (-log10(p) = 11.93, MAF = 0.23, substitution effect of the minor allele (ßMA) = -0.151%). Different from Holstein, DGAT1 was fixed (0.97) for the alanine protein variant for high milk and protein yield. A key gene affecting protein content was CSN1S1 (-log10(p) = 8.47, MAF = 049, ßMA = -0.055%) and the GNG2 region (-log10(p) = 10.48, MAF = 0.34, ßMA = 0.054%). Additionally, we suggest the importance of FGF12 for protein and fat yield, HTR3C for milk yield, TLE4 for milk and protein yield, and TNKS for milk and fat yield. Selection for favored alleles can improve milk yield and composition. With respect to maintaining the dual-purpose type of DSN, unfavored linkage to genes affecting muscularity has to be investigated carefully, before the milk-associated variants can be applied for selection in the small population.

Understanding the uptake of diagnostics for sustainable gastrointestinal nematode control by European dairy cattle farmers: a multi-country cross-sectional study.

To mitigate emerging anthelmintic resistance (AR) in cattle, sustainable gastrointestinal nematode control strategies should be adopted. A multi-centre study was set up to understand the factors affecting European dairy cattle farmers' adoption of diagnostics and to gauge for differences between regions. The data were collected through a multi-lingual survey by participating countries of the European Co-operation in Science and Technology (COST) action COMbatting Anthelmintic Resistance in ruminants (COMBAR). Four countries provided sufficient data to be included in the data analysis: Norway, Italy, Germany and Austria. Three models were estimated and validated through structural equation modelling. Norway, along with Germany and Austria (pooled dataset) showed similar trends that align with previous studies. AR risk perception had no influence on the adoption intention of diagnostics, a positive influence was found for attitude towards diagnostics and subjective norms (i.e., perceived opinion of others), and a negative influence of attitudes towards anthelminthics. Additionally, routine (i.e., perception of the current treatment) had an indirect effect on adoption intention through attitudes. Italy's data deviated from these findings, presenting a positive effect of the perceived severity of AR, and perceived behavioural control (i.e., perceived ability to perform a specific behaviour) on adoption intention of diagnostics. Finally, Norway's data set allowed for inclusion of a measurement of current behaviour in the model, identifying a direct positive effect of the perceived actual behaviour of other farmers on their own behaviour.

Title: Comprendre l'adoption des diagnostics pour le contrôle durable des nématodes gastro-intestinaux par les producteurs laitiers européens : une étude transversale multi-pays. Abstract: Pour atténuer la résistance émergente aux anthelminthiques (RA) chez les bovins, des stratégies durables de contrôle des nématodes gastro-intestinaux devraient être adoptées. Une étude multicentrique a été réalisée pour comprendre les facteurs affectant l'adoption des diagnostics par les éleveurs de bovins laitiers européens, et pour évaluer les différences entre les régions. Les données ont été recueillies au moyen d'une enquête multilingue menée par les pays participants à l'action de European Co-operation in Science and Technology (COST) COMbatting Anthelmintic Resistance in ruminants (COMBAR). Quatre pays ont collecté suffisamment de données pour être inclus dans l'analyse statistique : la Norvège, l'Italie, l'Allemagne et l'Autriche. Trois modèles ont été estimés et validés par modélisation d'équations structurelles. La Norvège, et d'autre part l'Allemagne et l'Autriche (données regroupées) ont montré des tendances similaires qui correspondent aux études précédentes. La perception de la RA n'avait aucune influence sur l'intention d'adoption des diagnostics, une influence positive a été trouvée pour l'attitude envers les diagnostics et les normes subjectives (c'est-à-dire l'opinion perçue des autres), et une influence négative des attitudes envers les anthelminthiques. De plus, la routine (c'est-à-dire la perception du traitement actuel) a eu un effet indirect sur l'intention d'adoption par le biais des attitudes. Les données de l'Italie s'écartaient des résultats précédents, présentant un effet positif de la gravité perçue du risque de la RA, et du contrôle comportemental perçu (c'est-à-dire la capacité perçue à adopter un comportement spécifique) sur l'intention d'adoption de diagnostic. Enfin, l'ensemble de données de la Norvège a permis d'inclure une mesure du comportement actuel dans le modèle, identifiant un effet positif direct du comportement réel perçu des autres agriculteurs sur son propre comportement.

Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography.

Despite the high prevalence and mortality of lung cancer and proven effectiveness of low-dose computed tomography (LDCT) to reduce mortality, Germany still lacks a national screening program. The German Institute for Quality and Efficiency in Health Care (IQWiG) and the Federal Office for Radiation Protection (BfS) both published positive scientific evaluations recommending a quality-controlled national screening program. IQWiG underlined the importance of a clear risk definition, integrated smoking cessation programs, and quality assurance, highlighting the necessity of procedural optimization.In the HANSE study, former and current smokers aged 55-79 years are assessed for their lung cancer risk by the NELSON and PLCOM2012 risk scores. 5000 high-risk participants, defined as PLCOM2012 6-year risk ≥ 1.58 % or fulfilling NELSON risk inclusion criteria, will be screened by LDCT at baseline and after 12 months. Lung nodules are analyzed by a modified Lung-RADS 1.1 score of the HANSE study, and values of emphysema and coronary calcium are determined and randomly reported to the participants. 7100 low-risk participants serve as a control. All patients are followed-up for up to 10 years. The sensitivity and specificity of the two risk assessments and LDCT screening, effects of the randomized LDCT reporting, efficiency of lung nodule management, and several other factors are assessed to analyze the success and quality of the holistic screening program.The HANSE study is designed as a holistic lung cancer screening study in northern Germany to answer pressing questions for a successful implementation of an effective German lung cancer screening program. · HANSE is designed to address pressing questions for the implementation of lung cancer screening in Germany.. · HANSE compares NELSON and PLCOM2012 risk assessments for optimal definition of the high-risk group. . · HANSE integrates cardiac calcium and pulmonary emphysema scoring in a holistic screening approach.. CITATION FORMAT: · Vogel-Claussen J, Lasch F, Bollmann B et al. Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography. Fortschr Röntgenstr 2022; 194: 1333 - 1345.

Prediction of R Status in Resections for Pancreatic Cancer Using Simplified Radiological Criteria.

OBJECTIVE: Predicting R status before surgery for pancreatic cancer (PDAC) patients with upfront surgery and neoadjuvant therapy. SUMMARY BACKGROUND DATA: Negative surgical margins (R0) are a key predictor of long-term outcomes in PDAC. METHODS: Patients undergoing pancreatic resection with curative intent for PDAC were identified. Using the CT scans from the time of diagnosis, the 2019 NCCN borderline resectability criteria were compared to novel criteria: presence of any alteration of the superior mesenteric-portal vein (SMPV) and perivascular stranding of the superior mesenteric artery (SMA). Accuracy of predicting R status was evaluated for both criteria. Patient baseline characteristics, surgical, histopathological parameters, and long-term overall survival (OS) after resection were evaluated. RESULTS: A total of 593 patients undergoing pancreatic resections for PDAC between 2010 and 2018 were identified. Three hundred and twenty-five (54.8%) patients underwent upfront surgery, whereas 268 (45.2%) received neoadjuvant therapy. In upfront resected patients, positive SMA stranding was associated with 56% margin positive resection rates, whereas positive SMA stranding and SMPV alterations together showed a margin positive resection rate of 75%. In contrast to these criteria, the 2019 NCCN borderline criteria failed to predict margin status. In patients undergoing neoadjuvant therapy, only perivascular SMA stranding remained a predictor of margin positive resection, leading to a rate of 33% R+ resections. Perivascular SMA stranding was related to higher clinical T stage (P = 0.003) and clinical N stage (P = 0.043) as well as perineural invasion (P = 0.022). SMA stranding was associated with worse survival in both patients undergoing upfront surgery (36 vs 22 months, P = 0.002) and neoadjuvant therapy (47 vs 34 months, P = 0.050). CONCLUSIONS: The novel criteria were accurate predictors of R status in PDAC patients undergoing upfront resection. After neoadjuvant treatment, likelihood of positive resection margins is approximately halved, and only perivascular SMA stranding remained a predictive factor.

Genomic analyses of claw disorders in Holstein cows: Genetic parameters, trait associations, and genome-wide associations considering interactions of SNP and heat stress.

The aim of the present study was an in-depth genomic analysis to understand the genomic mechanisms of the 3 claw disorders dermatitis digitalis (DD), interdigital hyperplasia (HYP), and sole ulcer (SU). In this regard, we estimated genetic parameters based on genomic relationship matrices, performed genome-wide association studies, annotated potential candidate genes, and inferred genetic associations with breeding goal traits considering the most important chromosomal segments. As a further novelty of this study, we inferred possible SNP × heat stress interactions for claw disorders. The study consisted of 17,264 first-lactation Holstein Friesian cows kept in 50 large-scale contract herds. The disease prevalence was 15.96, 2.36, and 8.20% for DD, HYP, and SU, respectively. The remaining breeding goal traits consisted of type traits of the feet and leg composite, female fertility, health traits, and 305-d production traits. The final genotype data set included 44,474 SNPs from the 17,264 genotyped cows. Heritabilities for DD, HYP, and SU were estimated in linear and threshold models considering the genomic relationship matrix (G matrix). Genetic correlations with breeding goal traits based on G were estimated in a series of bivariate linear models, which were verified via SNP effect correlations for specific chromosome segments (i.e., segments harboring potential candidate genes for DD, HYP, and SU). Genome-wide association studies were performed for all traits in a case-control design by applying a single SNP linear mixed model. Furthermore, for DD, HYP, and SU, we modeled SNP × heat stress interactions in genome-wide association studies. Single nucleotide polymorphism-based heritabilities were 0.04 and 0.08 for DD, 0.03 and 0.10 for SU, and 0.03 and 0.23 for HYP from linear and threshold models, respectively. The genetic correlations between DD, HYP, and SU with conformation traits from the feet and leg composite were positive throughout, indicating the value of indirect selection on conformation traits to improve claw health. Genetic correlations between DD, SU, and HYP with other breeding goal traits indicated impaired female fertility, impaired udder health status, and productivity decline of diseased cows. Genetic correlations among DD, SU, and HYP were moderate to large, indicating that different claw disorders have similar genetic mechanisms. Nevertheless, we identified disease-specific potential candidate genes, and genetic associations based on the surrounding SNPs partly differed from the genetic correlations. Especially for candidate genes contributing to 2 traits simultaneously, correlations based on SNP effects from the respective chromosome segment were close to 1 or to -1. In this regard, we annotated the candidate genes KRT33A and KRT33B for HYP and DD, KIF27 for HYP and calving to first insemination, and MAN1A1 for SU and the production traits. For SNP × heat stress interactions, we identified significant SNPs on BTA 2, 4, 5, 7, 8, 9, 13, 22, 25, and 28, and we annotated the potential candidate genes FSIP2, CLCN1, ADGRV1, DOP1A, THBD, and RHOBTB1. Results indicate gene-specific mechanisms of the claw disorders only in specific environments.

Key parameters of head-heart electrical stunning need to be adapted to improve stunning effectiveness and meat quality in pigs of different genetic lines.

Adjustment of key parameters of electrical stunning of pigs is necessary to better respect animal welfare and avoid impairments of meat quality. In the present study, we analysed the effect of genetic line, stunning program and genetic line × stunning program interactions on stunning effectiveness, carcass and meat quality traits in 10,338 pigs from five different genetic lines in a German slaughterhouse using electrical stunning (two-cycle method head/heart current). Genetic line, stunning program and its interaction significantly influenced stunning effectiveness and pH in the semimembranosus muscle. Backup stunning rates ranged from 1.59 to 5.01% in the five genetic lines, and were significantly decreased (2.85%) in program 1 using a current of 1.3 to 1.35 A, 800 Hz and 1 s for the head-cycle compared to program 2 (4.73%) with 1.8 A, 100 Hz and 4.5 s. We suggest to consider genetic line × stunning program interactions when adjusting officially defined stunning parameters for head-heart electrical stunning.

[An Unexpected Complication: Contralateral Tension Pneumothorax following Transbronchial Forceps Biopsy]. / Eine unerwartete Komplikation: Kontralateraler Spannungspneumothorax nach transbronchialer Zangenbiopsie.

Ipsilateral pneumothoraces are a common complication after transbronchial forceps biopsy. In this case report, a contralateral tension pneumothorax and a pneumoperitoneum occurred following transbronchial forceps biopsy in addition to an ipsilateral pneumothorax.

Pasture rewetting in the context of nature conservation shows no long-term impact on endoparasite infections in sheep and cattle.

BACKGROUND: Nature conservation with reduced drainage of pastures has been increasingly promoted in agriculture in recent years. However, moisture on pastures is a crucial factor for the development of free-living stages of many parasite species in ruminants. Hence, for the first time, we conducted a field study between 2015 and 2017 at the German North Sea coast to investigate the long-term effect of pasture rewetting (since 2004) on endoparasite infections in sheep and cattle. METHODS: We examined faecal samples of 474 sheep and 646 cattle from five farms in spring, summer and autumn each year for the presence of endoparasite infections. Animals were kept on conventionally drained, undrained and rewetted pastures. The association between pasture rewetting and endoparasite infection probability was analysed in generalized linear mixed models and including further potential confounders. RESULTS: Infection frequencies for gastrointestinal strongyles, Eimeria spp. and Strongyloides papillosus were significantly higher in sheep (62.9%, 31.7% and 16.7%) than in cattle (39.0%, 19.7% and 2.6%). Fasciola hepatica was detected with a frequency of 13.3% in sheep and 9.8% in cattle, while rumen fluke frequency was significantly higher in cattle (12.7%) than in sheep (3.8%). Nematodirus spp., lungworms (protostrongylids, Dictyocaulus viviparus), Moniezia spp., Trichuris spp. and Dicrocoelium dendriticum were identified in less than 7% of samples. Co-infection with more than three endoparasite taxa was present significantly more often in sheep than in cattle. We identified significant positive correlations above 0.2 for excretion intensities between S. papillosus with strongyles, Eimeria spp. and Nematodirus spp. in sheep and between strongyles and Nematodirus spp. in cattle. Pasture rewetting had no long-term effect on endoparasite infections, neither in sheep nor in cattle. Interestingly, F. hepatica infections decreased significantly in sheep and cattle from 2015 (10.9% and 13.9%) to 2017 (1.4% and 2.1%). CONCLUSIONS: Pasture rewetting for nature conservation did not increase endoparasite infection probability in ruminants in the long term. This finding should be confirmed in ongoing studies aimed at further animal welfare parameters. The rapid decrease in F. hepatica infections over 3 years may suggest climatic impact or competition with rumen flukes in addition to potential anthelmintic treatment after feedback of the results to the farmers.

Genomic diversity and relationship analyses of endangered German Black Pied cattle (DSN) to 68 other taurine breeds based on whole-genome sequencing.

German Black Pied cattle (Deutsches Schwarzbuntes Niederungsrind, DSN) are an endangered dual-purpose cattle breed originating from the North Sea region. The population comprises about 2,500 cattle and is considered one of the ancestral populations of the modern Holstein breed. The current study aimed at defining the breeds closest related to DSN cattle, characterizing their genomic diversity and inbreeding. In addition, the detection of selection signatures between DSN and Holstein was a goal. Relationship analyses using fixation index (FST), phylogenetic, and admixture analyses were performed between DSN and 68 other breeds from the 1000 Bull Genomes Project. Nucleotide diversity, observed heterozygosity, and expected heterozygosity were calculated as metrics for genomic diversity. Inbreeding was measured as excess of homozygosity (FHom) and genomic inbreeding (FRoH) through runs of homozygosity (RoHs). Region-wide FST and cross-population-extended haplotype homozygosity (XP-EHH) between DSN and Holstein were used to detect selection signatures between the two breeds, and RoH islands were used to detect selection signatures within DSN and Holstein. DSN showed a close genetic relationship with breeds from the Netherlands, Belgium, Northern Germany, and Scandinavia, such as Dutch Friesian Red, Dutch Improved Red, Belgian Red White Campine, Red White Dual Purpose, Modern Angler, Modern Danish Red, and Holstein. The nucleotide diversity in DSN (0.151%) was higher than in Holstein (0.147%) and other breeds, e.g., Norwegian Red (0.149%), Red White Dual Purpose (0.149%), Swedish Red (0.149%), Hereford (0.145%), Angus (0.143%), and Jersey (0.136%). The FHom and FRoH values in DSN were among the lowest. Regions with high FST between DSN and Holstein, significant XP-EHH regions, and RoH islands detected in both breeds harbor candidate genes that were previously reported for milk, meat, fertility, production, and health traits, including one QTL detected in DSN for endoparasite infection resistance. The selection signatures between DSN and Holstein provide evidence of regions responsible for the dual-purpose properties of DSN and the milk type of Holstein. Despite the small population size, DSN has a high level of diversity and low inbreeding. FST supports its relatedness to breeds from the same geographic origin and provides information on potential gene pools that could be used to maintain diversity in DSN.

Genomic loci and genetic parameters for uterine diseases in first-parity Holstein cows and associations with milk production and fertility.

Based on the clinical stage (e.g., vaginal discharge) and bacterial species, several forms of uterine diseases (UD) exist and can be classified as different traits [i.e., different stages of endometritis (EM) and metritis (MET)], which may differ in their genetic background and causal physiological mechanisms. Consequently, the present study aimed to study (1) the effect of UD on 305-d lactation and fertility, (2) the estimation of heritabilities for UD traits using pedigree- and SNP-based relationships, and (3) genome-wide associations to detect significant SNP markers and to infer candidate genes for UD traits. The data set contained herd manager and veterinarian recorded UD traits of 14,810 first-lactating genotyped Holstein cows from 63 large-scale contract herds. Binary defined UD traits (healthy or diseased) according to the clinical stage were endometritis catarrhalis (EM I), endometritis mucopurulenta (EM II), endometritis purulenta (EM III), pyometra (EM IV), endometritis (EM_SOD; superordinate diagnosis = no specific clinical stage defined), and MET. The binary defined trait UDall included all EM and MET diagnoses. The prevalence of UDall was 26.7%. The effect of UD on 305-d lactation and fertility was estimated via linear and generalized linear mixed models. We applied linear single-trait animal models and threshold models to estimate pedigree- and SNP-based heritabilities for UD traits, and bivariate linear models for genetic correlation estimations between UDall with 305-d lactation and fertility traits. A diagnosis for UDall had significant unfavorable effects on the female fertility traits calving interval, interval from calving to first service, days open, and nonreturn rate after 90 d, but was unrelated to 305-d lactation records for production traits milk yield, protein yield, and fat yield. Heritabilities for UDall and EM stages were close to zero, displaying maximal values of 0.05 for pedigree and 0.07 for SNP-based relationship matrices. For MET, pedigree- and SNP-based heritabilities were <0.001 and 0.07, respectively. Genetic correlations ranged from 0.20 to 0.31 between UDall with 305-d milk, protein, and fat yield, and from 0.17 to 0.40 with fertility traits. The GWAS revealed 5 SNP on bovine chromosomes (BTA) 1, 8, 10, 23 for UDall, 5 SNP on BTA 26 for EM I, 1 SNP on BTA 19 for EM II, 4 SNP on BTA 2, 18, 20, 25 for EM III, and 4 SNP on BTA 4, 16, 20 for EM IV above the significance threshold. For EM_SOD, we identified 15 significantly associated SNP on 4 chromosomes, and 4 significant SNP on BTA 3, 20, 22, 28 for MET. Marker associations for UD traits were annotated to 24 potential candidate genes using the ENSEMBL database. Six of these genes were previously reported to be involved in uterine defense mechanisms or in endometritis. Further detected genes contribute to immune response mechanisms during bacterial infections. Different SNP significantly influenced different UD stages, explaining the inter-individual variations in clinical severity of uterine infections.

Design and performance of a bovine 200 k SNP chip developed for endangered German Black Pied cattle (DSN).

BACKGROUND: German Black Pied cattle (DSN) are an endangered dual-purpose breed which was largely replaced by Holstein cattle due to their lower milk yield. DSN cattle are kept as a genetic reserve with a current herd size of around 2500 animals. The ability to track sequence variants specific to DSN could help to support the conservation of DSN's genetic diversity and to provide avenues for genetic improvement. RESULTS: Whole-genome sequencing data of 304 DSN cattle were used to design a customized DSN200k SNP chip harboring 182,154 variants (173,569 SNPs and 8585 indels) based on ten selection categories. We included variants of interest to DSN such as DSN unique variants and variants from previous association studies in DSN, but also variants of general interest such as variants with predicted consequences of high, moderate, or low impact on the transcripts and SNPs from the Illumina BovineSNP50 BeadChip. Further, the selection of variants based on haplotype blocks ensured that the whole-genome was uniformly covered with an average variant distance of 14.4 kb on autosomes. Using 300 DSN and 162 animals from other cattle breeds including Holstein, endangered local cattle populations, and also a Bos indicus breed, performance of the SNP chip was evaluated. Altogether, 171,978 (94.31%) of the variants were successfully called in at least one of the analyzed breeds. In DSN, the number of successfully called variants was 166,563 (91.44%) while 156,684 (86.02%) were segregating at a minor allele frequency > 1%. The concordance rate between technical replicates was 99.83 ± 0.19%. CONCLUSION: The DSN200k SNP chip was proved useful for DSN and other Bos taurus as well as one Bos indicus breed. It is suitable for genetic diversity management and marker-assisted selection of DSN animals. Moreover, variants that were segregating in other breeds can be used for the design of breed-specific customized SNP chips. This will be of great value in the application of conservation programs for endangered local populations in the future.

Genome-Wide Association Study Using Whole-Genome Sequence Data for Fertility, Health Indicator, and Endoparasite Infection Traits in German Black Pied Cattle.

This genome-wide association study (GWAS) aimed to identify sequence variants (SVs) and candidate genes associated with fertility and health in endangered German Black Pied cattle (DSN) based on whole-genome sequence (WGS) data. We used 304 sequenced DSN cattle for the imputation of 1797 genotyped DSN to WGS. The final dataset included 11,413,456 SVs of 1886 cows. Cow traits were calving-to-first service interval (CTFS), non-return after 56 days (NR56), somatic cell score (SCS), fat-to-protein ratio (FPR), and three pre-corrected endoparasite infection traits. We identified 40 SVs above the genome-wide significance and suggestive threshold associated with CTFS and NR56, and three important potential candidate genes (ARHGAP21, MARCH11, and ZNF462). For SCS, most associations were observed on BTA 25. The GWAS revealed 61 SVs, a cluster of 10 candidate genes on BTA 13, and 7 pathways for FPR, including key mediators involved in milk fat synthesis. The strongest associations for gastrointestinal nematode and Dictyocaulus viviparus infections were detected on BTA 8 and 24, respectively. For Fasciola hepatica infections, the strongest associated SVs were located on BTA 4 and 7. We detected 200 genes for endoparasite infection traits, related to 16 pathways involved in host immune response during infection.

A simple preoperative stratification tool predicting the risk of postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) can be associated with severe postoperative morbidity. This study aims to develop a preoperative POPF risk calculator that can be easily implemented in clinical routine. METHODS: Patients undergoing PD were identified from a prospectively-maintained database. A total of 11 preoperative baseline and CT-based radiological parameters were used in a binominal logistic regression model. Parameters remaining predictive for grade B/C POPF were entered into the risk calculator and diagnostic accuracy measures and ROC curves were calculated for a training and a test patient cohort. The risk calculator was transformed into a simple nomogram. RESULTS: A total of 242 patients undergoing PD in the period from 2012 to 2018 were included. CT-imaging-based maximum main pancreatic duct (MPD) diameter (p = 0.047), CT-imaging-based pancreatic gland diameter at the anticipated resection margin (p = 0.002) and gender (p = 0.058) were the parameters most predictive for grade B/C POPF. Based on these parameters, a risk calculator was developed to identify patients at high risk of developing grade B/C POPF. In a training cohort of PD patients this risk calculator was associated with an AUC of 0.808 (95%CI 0.726-0.874) and an AUC of 0.756 (95%CI 0.669-0-830) in the independent test cohort. A nomogram applicable as a visual risk scale for quick assessment of POPF grade B/C risk was developed. CONCLUSION: The preoperative POPF risk calculator provides a simple tool to stratify patients planned for PD according to the risk of developing postoperative grade B/C POPF. The nomogram visual risk scale can be easily integrated into clinical routine and may be a valuable model to select patients for POPF-preventive therapy or as a stratification tool for clinical trials.

Genomic Loci Affecting Milk Production in German Black Pied Cattle (DSN).

German Black Pied cattle (DSN) is an endangered population of about 2,550 dual-purpose cattle in Germany. Having a milk yield of about 2,500 kg less than the predominant dairy breed Holstein, the preservation of DSN is supported by the German government and the EU. The identification of the genomic loci affecting milk production in DSN can provide a basis for selection decisions for genetic improvement of DSN in order to increase market chances through the improvement of milk yield. A genome-wide association analysis of 30 milk traits was conducted in different lactation periods and numbers. Association using multiple linear regression models in R was performed on 1,490 DSN cattle genotyped with BovineSNP50 SNP-chip. 41 significant and 20 suggestive SNPs affecting milk production traits in DSN were identified, as well as 15 additional SNPs for protein content which are less reliable due to high inflation. The most significant effects on milk yield in DSN were detected on chromosomes 1, 6, and 20. The region on chromosome 6 was located nearby the casein gene cluster and the corresponding haplotype overlapped the CSN3 gene (casein kappa). Associations for fat and protein yield and content were also detected. High correlation between traits of the same lactation period or number led to some SNPs being significant for multiple investigated traits. Half of all identified SNPs have been reported in other studies, previously. 15 SNPs were associated with the same traits in other breeds. The other associated SNPs have been reported previously for traits such as exterior, health, meat and carcass, production, and reproduction traits. No association could be detected between DGAT1 and other known milk genes with milk production traits despite the close relationship between DSN and Holstein. The results of this study confirmed that many SNPs identified in other breeds as associated with milk traits also affect milk traits in dual-purpose DSN cattle and can be used for further genetic analysis to identify genes and causal variants that affect milk production in DSN cattle.

[IgG4-associated lung disease with granulomatous lesions : Coexistence of two entities or the spectrum of one disease?] / IgG4-assoziierte Lungenerkrankung mit granulomatösen Läsionen : Koexistenz zweier Entitäten oder das Spektrum einer Erkrankung?

A 54-year-old patient with a history of pulmonary tuberculosis and occupational exposure to dust in early adulthood presented with symptoms of coughing with sputum, weight loss, occasional night sweats, and thoracic pain. Non-necrotizing granulomatosis in lung and lymph-node biopsies indicated sarcoidosis. Combined immunosuppressive therapy did not lead to an improvement. An atypical lung resectate with fibroinflammatory changes and obliterative endothelialitis may finally lead to the diagnosis of IgG4-associated lung disease with a bronchovascular pattern of involvement. The question discussed here is whether this is a coexistence of IgG4-associated lung disease with sarcoidosis or the spectrum of one disease.