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Joseph Ross,1 Crystal Schatz,1 Kendall Beaugrand,1 Sjoert Zuidhof,2 Brenda Ralston,3 Nick Allan,1 Merle Olson4 1Chinook Contract Research Inc., Airdrie, AB, Canada; 2Sjoert Zuidhof Consulting, Okotoks, AB, Canada; 3Alberta Agriculture and Forestry, Airdrie, AB, Canada; 4Alberta Veterinary Laboratories Ltd., Calgary, AB, CanadaCorrespondence: Joseph Ross Email joe.ross@ccr01.comPurpose: Neonatal calf diarrhea (NCD) is a major cause of death and economic loss in the cattle industry. Although NCD is caused by a variety of nutritional factors and non-bacterial pathogens, treatment typically includes systemic antimicrobial therapy, even for non-severe cases that are more likely to have non-bacterial causes. Novel, non-antimicrobial therapies are needed to reduce antimicrobial use and optimize production efficiency.Methods: This production-level study compared the efficacy of activated charcoal to that of an antimicrobial regimen for treating mild-to-moderate cases of NCD, and identified the most common etiological agents. Calves diagnosed with non-severe diarrhea were randomly allocated into 3 treatment groups (n = 86 per group): group A received a standard antimicrobial regimen, B received both antimicrobials and activated charcoal, and C received activated charcoal only. Animals were monitored over the course of 7 days for mortality and recovery from diarrhea. Fecal samples were collected upon enrollment (day 0) and on day 7 to assess the presence of major NCD-causing pathogens.Results: Mortality was higher for groups B and C relative to A, although this difference was only statistically significant for group B vs A. No significant difference in the number of recovered animals was observed among the treatment groups, although group C was significantly slower to recover than A or B. The vast majority of day 0 samples were positive for non-bacterial organisms (mainly rotavirus and Cryptosporidium parvum), which decreased significantly by day 7 regardless of treatment group.Conclusion: Antimicrobials only moderately improved outcomes for non-severe diarrhea cases relative to activated charcoal. Thus, systemic antimicrobial treatment is likely unnecessary for the majority of NCD cases and should be limited to severe cases.Keywords: antimicrobial stewardship, activated charcoal, scours, non-bacterial, rotavirus, cryptosporidium

Suzana Bracic Tomazic,1,2,* Christoph Schatz,3,* Johannes Haybaeck3,4 1Department of Pathology, Hospital Graz II, Graz, 8020, Austria; 2Faculty of Medicine, University of Maribor, Maribor, 2000, Slovenia; 3Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, 6020, Austria; 4Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology, Medical University Graz, Graz, 8010, Austria*These authors contributed equally to this workCorrespondence: Johannes HaybaeckInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Müllerstraße 44, Innsbruck, 6020, AustriaTel +43 512 9003 71300Fax +43 512 9003 73301Email johannes.haybaeck@i-med.ac.atAbstract: The mortality of hepatocellular carcinoma (HCC) is distributed unevenly worldwide. One of the major causes is hepatitis B or hepatitis C virus infection and the development and progression of liver cirrhosis. The carcinogenesis of HCC is among others regulated via the mTOR (mechanistic target of rapamycin) signaling pathway and represents a possible method of targeted treatment. The aim of our article was to address the most recent clinical advances and findings of basic studies on the mTOR signaling pathway and the involved factors. Risk factors play a key role in dysregulation of the signaling pathway, where both mTORCs are upregulated and protein synthesis is altered. eIFs and, to a lesser extent, eEFs play an essential role in this process. Whether the factor will be upregulated or downregulated, among others, depends on hepatitis B/C virus infection. The amount of a particular factor in a patient sample lets us know whether HCC recurrence will occur, what is the likelihood of chemoresistance, and what outcome is predicted for patients with an increased value. Our analysis shows that in addition to mTOR, eIF3, eIF4, and eIF5 play an important role, as they can serve as biomarkers for non- and virus-related HCC.Keywords: mTOR, virus related HCC, non-virus related HCC, cancer, translation initiation, liver

Dominique Bremond-Gignac,1,2 Riadh Messaoud,3 Sihem Lazreg,4 Claude Speeg-Schatz,5 Didier Renault,6 Frédéric Chiambaretta7,8 On behalf of the Azithromycin Pediatric Study Group 1Ophthalmology Department, Centre St Victor, University Hospital of Amiens, Picardie Jules Verne University, Amiens, France; 2CNRS FR3636, Paris V University, France; 3Ophthalmology Department, Tahar Sfar University Hospital, Mahdia, Tunisia; 4Dar El Beida, Blida, Algeria; 5Ophthalmology Department, University Hospital of Strasbourg, Strasbourg, France; 6Laboratoires THÉA, Clermont-Ferrand, France; 7Ophthalmology Department, University Hospital of Clermont-Ferrand, Gabriel Montpied Hospital, Clermont-Ferrand, France; 8EA 7281 R2D2, Auvergne University, Clermont-Ferrand, France Purpose: To compare the efficacy of azithromycin 1.5% versus tobramycin 0.3% eyedrops on clinical ocular signs and symptoms of bacterial conjunctivitis in children and to assess the parents’ satisfaction regarding the dosing regimen.Patients and methods: An international, multicenter, randomized, investigator-masked, controlled clinical trial conducted in children (1 day to 18 years old) with bulbar conjunctival hyperemia and purulent discharge. Azithromycin 1.5% was administered as 1 drop twice daily for 3 days, and tobramycin 0.3% as 1 drop every 2 hours for 2 days, then 4 times daily for 5 days.Results: A total of 286 patients (mean age: 3.2 years) were enrolled. In children with bacteriologically positive cultures (N=203), azithromycin produced a significantly greater improvement in conjunctival discharge (P