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Three dogs developed severe adverse events. Laboratory findings showed marked changes up to grade 4. Diarrhoea and anaemia were the most often observed adverse events (6), followed by dermatitis (4), alopecia (3) and pneumonia (3). Including blood chemistry changes (13), 50 adverse events were found in total. CONCLUSION Treatment with CA and glucocorticoids resulted in clinical remission in 10/12 dogs, but a high incidence of adverse events occurred requiring additional measures. All adverse events could be managed successfully in all cases. © British Veterinary Association 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.Sarah Mason planned to be a scientist. Working as a researcher, her interest in clinical work was piqued and, as an animal lover, she chose veterinary medicine and swiftly found that she wanted to specialise. British Veterinary Association.A much-loved small animal practitioner in Glasgow, he was a character and a real advocate for animals - it was he that brought contagious leukaemia in cats to the attention of researchers at the vet school. British Veterinary Association.After working in a successful small animal practice, he joined the pharmaceutical industry. He became an author of books for pet owners and the profession, and set up the Pet Health Counsellor programme. British Veterinary Association.Charities are highlighting the potential impact of Brexit on wildlife and the environment. Kathryn Clark reports. British Veterinary Association.Studies on myotonic dystrophy type 1 (DM1) have led to the RNA-mediated disease model for hereditary disorders caused by noncoding microsatellite expansions. This model proposes that DM1 disease manifestations are caused by a reversion to fetal RNA processing patterns in adult tissues due to the expression of toxic CUG RNA expansions (CUGexp) leading to decreased muscleblind-like, but increased CUGBP1/ETR3-like factor 1 (CELF1), alternative splicing activities. Here, we test this model in vivo, using the mouse HSA LR poly(CUG) model for DM1 and recombinant adeno-associated virus (rAAV)-mediated transduction of specific splicing factors. Surprisingly, systemic overexpression of HNRNPA1, not previously linked to DM1, also shifted DM1-relevant splicing targets to fetal isoforms, resulting in more severe muscle weakness/myopathy as early as 4 to 6 wk posttransduction, whereas rAAV controls were unaffected. Overexpression of HNRNPA1 promotes fetal exon inclusion of representative DM1-relevant splicing targets in differentiated myoblasts, and HITS-CLIP of rAAV-mycHnrnpa1-injected muscle revealed direct interactions of HNRNPA1 with these targets in vivo. Similar to CELF1, HNRNPA1 protein levels decrease during postnatal development, but are elevated in both regenerating mouse muscle and DM1 skeletal muscle. Our studies suggest that CUGexp RNA triggers abnormal expression of multiple nuclear RNA binding proteins, including CELF1 and HNRNPA1, that antagonize MBNL activity to promote fetal splicing patterns. Copyright © 2020 the Author(s). Published by PNAS.We sought to define the landscape of alternative pre-mRNA splicing in prostate cancers and the relationship of exon choice to known cancer driver alterations. [https://www.selleckchem.com/products/azd5363.html Selleckchem Capivasertib] To do so, we compiled a metadataset composed of 876 RNA-sequencing (RNA-Seq) samples from five publicly available sources representing a range of prostate phenotypes from normal tissue to drug-resistant metastases. We subjected these samples to exon-level analysis with rMATS-turbo, purpose-built software designed for large-scale analyses of splicing, and identified 13,149 high-confidence cassette exon events with variable incorporation across samples. We then developed a computational framework, pathway enrichment-guided activity study of alternative splicing (PEGASAS), to correlate transcriptional signatures of 50 different cancer driver pathways with these alternative splicing events. We discovered that Myc signaling was correlated with incorporation of a set of 1,039 cassette exons enriched in genes encoding RNA binding proteins. Using a human prostate epithelial transformation assay, we confirmed the Myc regulation of 147 of these exons, many of which introduced frameshifts or encoded premature stop codons. Our results connect changes in alternative pre-mRNA splicing to oncogenic alterations common in prostate and many other cancers. We also establish a role for Myc in regulating RNA splicing by controlling the incorporation of nonsense-mediated decay-determinant exons in genes encoding RNA binding proteins. Copyright © 2020 the Author(s). Published by PNAS.OBJECTIVES To estimate (1) the proportion of children not adhering to the Advisory Committee on Immunization Practices (ACIP) recommended early childhood immunization schedule and (2) associations between schedule adherence, sociodemographic characteristics, and up-to-date immunization status by 19 to 35 months of age. METHODS We used 2014 National Immunization Survey provider-verified vaccination data to classify vaccination patterns as "recommended" (ie, in line with ACIP dose- and age-specific recommendations), "alternate" (ie, in line with either limiting the number of shots per visit or skipping at least 1 vaccine series), or "unknown or unclassifiable" (ie, not in line with ACIP recommendations or clearly limiting shots per visit or vaccine series). We evaluated the association between vaccination patterns and up-to-date status for all ACIP-recommended vaccinations (including rotavirus and hepatitis A vaccines) using Poisson regression. RESULTS The majority of children's patterns were classified as "recommended" (63%), with 23% and 14% following alternate or unknown or unclassifiable patterns, respectively; 58% of children were up-to-date with all ACIP-recommended immunizations by 19 to 35 months. Not being up-to-date was associated with alternate (prevalence ratio = 4.2, 95% confidence interval 3.9-4.5) and unknown or unclassifiable (prevalence ratio = 2.4, 95% confidence interval 2.2-2.7) patterns. CONCLUSIONS High vaccine coverage by 19 to 35 months of age may miss nonadherence to the recommended immunization schedule in the first 18 months of life, leaving children vulnerable to preventable diseases. With more than one-third of US children not following the ACIP schedule, targeted interventions are needed to minimize vaccine delays and disease susceptibility. Copyright © 2020 by the American Academy of Pediatrics.