Perturbations in intermediary metabolism contribute to the pathogenesis of acute myeloid leukemia (AML) and can produce therapeutically actionable dependencies. Here, we probed whether alpha-ketoglutarate (aKG) metabolism represents a specific vulnerability in AML. Using functional genomics, metabolomics, and mouse models, we identified the aKG dehydrogenase complex, which catalyzes the conversion of aKG to succinyl CoA, as a molecular dependency across multiple models of adverse-risk AML.
View Article and Find Full Text PDFBy definition, ill and injured animals are on the negative valence of animal welfare. For beef cattle kept in feedlot settings, advances in cattle health management have resulted in a greater understanding and prevention of illness and injury. However, the management of cattle once they become ill and injured is an understudied area, and there are gaps in knowledge that could inform evidence-based decision-making and strengthen welfare for this population.
View Article and Find Full Text PDFAcute myeloid leukemia is the most common form of leukemia and can present with a wide variety of signs and symptoms. This article presents a case of a middle-aged male who presented with ongoing upper respiratory cold-like symptoms and was then found to be severely pancytopenic. A diagnosis of acute myeloid leukemia was made after a bone marrow biopsy, and the patient underwent induction chemotherapy.
View Article and Find Full Text PDFSpatial abilities of hens are particularly sensitive to development during early life. Experiences in pullet housing may have lasting consequences on adult hens' movements in cage-free environments. We tested whether opportunities to access elevated spaces during rearing improved hens' use of a multitiered aviary.
View Article and Find Full Text PDFThe objective of this study was to validate standing and locomotion lameness scoring, mechanical nociceptive threshold testing, and behavioral profile tools for the diagnosis of naturally occurring lameness etiologies in pigs. A total of 55 crossbred gilts and sows obtained from a commercial farm were enrolled in the study; with sound pigs classified as controls (8) and the remainder as lame due to integumentary (20), musculoskeletal (15), and combinations of integumentary and musculoskeletal (12) etiologies. Standing and locomotion lameness, mechanical nociceptive threshold (MNT) test, pig-human interventions, and latency to complete an obstacle course were evaluated.
View Article and Find Full Text PDFMetabolic rewiring and cellular reprogramming are trademarks of neoplastic initiation and progression in acute myeloid leukemia (AML). Metabolic alteration in leukemic cells is often genotype specific, with associated changes in epigenetic and functional factors resulting in the downstream upregulation or facilitation of oncogenic pathways. Targeting abnormal or disease-sustaining metabolic activities in AML provides a wide range of therapeutic opportunities, ideally with enhanced therapeutic windows and robust clinical efficacy.
View Article and Find Full Text PDFMucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B; OMIM #252920) is a lethal, pediatric, neuropathic, autosomal recessive, and lysosomal storage disease with no approved therapy. Patients are deficient in the activity of N-acetyl-alpha-glucosaminidase (NAGLU; EC 3.2.
View Article and Find Full Text PDFIn the United States swine industry, preweaning mortality represents the highest mortality rate of any production phase, nearly half attributed to crushing. The overarching aim of this study was to determine if enrichment ropes would entice neonatal piglets away from the sow and reduce preweaning mortality. Rope enrichments were provided to 161 piglets from 26 sows after farrowing.
View Article and Find Full Text PDFCoronavirus Disease 2019 (COVID-19) was declared a global pandemic on March 11, 2020 by the World Health Organization and its impact on animal agriculture in the United States was undeniable. By April, COVID-19 resulted in the simultaneous closure or reduced operations of many meat processing plants in the upper Midwest, leading to supply chain disruptions. In Iowa, the leading pork production and processing state, these disruptions caused producer uncertainty, confusion, and stress, including time-sensitive challenges for maintaining animal care.
View Article and Find Full Text PDFObjectives of this study were to evaluate an equine assisted learning (EAL) curriculum designed for medical students and resident physicians, and to determine impacts of the curriculum on participant perceptions of burnout and well-being. The EAL curriculum incorporated evidence-based skills and concepts to increase happiness and/or resilience. A pre/post intervention design was used, with 18 EAL participants receiving the curriculum within their month-long community based primary care clerkship elective, and 10 control (CTL) participants who did not receive the curriculum within their clerkship elective.
View Article and Find Full Text PDFWe conducted a genome-wide association study of 1320 centenarians from the New England Centenarian Study (median age = 104 years) and 2899 unrelated controls using >9 M genetic variants imputed to the HRC panel of ~65,000 haplotypes. The genetic variants with the most significant associations were correlated to 4131 proteins that were profiled in the serum of a subset of 224 study participants using a SOMAscan array. The genetic associations were replicated in a genome-wide association study of 480 centenarians and ~800 controls of Ashkenazi Jewish descent.
View Article and Find Full Text PDFObtaining accurate blood pressure measurements in cats is challenging due to the stressful nature of clinic visits. The objective of this study was to evaluate the effects of veterinary clinic waiting experiences and a feline pheromone spray on blood pressure in the cat. We hypothesized that reduced stress associated with bypassing the waiting room and use of synthetic feline facial pheromone (FFP) spray would result in lower blood pressure.
View Article and Find Full Text PDFThere is a strong industry demand for technically simple and highly efficacious alternatives to heat cautery disbudding in goat kids that can be performed as a stand-alone procedure without adjunct anesthesia, and that result in improved overall welfare through reduced acute pain, reduced tissues healing interval, and a consistent safety record. The objective of this study was to consider the net effect of disbudding techniques on goat welfare by examining vocalization frequency, long-term efficacy and animal safety associated with four alternative caprine disbudding methods against sham-disbudded and heat-cautery controls. Sixty-five commercial male dairy kids were disbudded at 3-10 days of age with one of six disbudding treatments (clove oil injection, caustic paste, two cryosurgical methods, heat-cautery, and sham procedure).
View Article and Find Full Text PDFCancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK-an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6-as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity is required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects.
View Article and Find Full Text PDFWith different cage-free (CF) housing styles and management schemes, retailers have developed their own CF criteria. One highly debated aspect is if hens may be kept inside the system for part of the day-during the first few hours after lights-on. Research is lacking regarding the impacts of such a practice on hen welfare, incidence of eggs laid on the litter floor, litter condition, and air quality.
View Article and Find Full Text PDFAcidification is a practical way of preserving the bacteriological quality of milk so that it can be fed to calves under free-access conditions. The objectives of this study were to evaluate how milk replacer acidification and free-access feeding affect dairy calf behavior during the first week of life. Sixteen Holstein male calves were purchased at birth and transported to the University of Guelph Kemptville Campus Dairy Education and Research Centre.
View Article and Find Full Text PDFResearch on the assessment and management of pain in cows following difficult or assisted calving is still limited, especially on the effects of analgesics intended to mitigate this pain. The purpose of this study was to assess the effects of flunixin meglumine on the health and production of Holstein cows after calving. In total, 34 flunixin-treated and 38 placebo-treated animals were enrolled in a precalving treatment trial.
View Article and Find Full Text PDFThe objectives of this study were to evaluate the effects of free-access acidified milk replacer feeding on the pre- and postweaning health of dairy and veal calves. Individually housed calves were systematically assigned at birth to 1 of 2 feeding programs: free-access feeding (ad libitum) of acidified milk replacer (ACD, n=249) or traditional restricted feeding (3L fed twice daily) of milk replacer (RES, n=249). Calves were fed milk replacer containing 24% crude protein and 18% fat.
View Article and Find Full Text PDFThe objective of this study was to investigate the effects of carprofen administered immediately before cautery dehorning on nociception and stress. Forty Holstein calves aged approximately 6 to 8 wk old were either placebo treated and sham dehorned ( = 10) or cautery dehorned following administration of carprofen (1.4 mg/kg) subcutaneously ( = 10) or orally ( = 10) or a subcutaneous and oral placebo ( = 10) in a randomized, controlled trial.
View Article and Find Full Text PDFThe egg industry is moving away from the use of conventional cages to enriched cage and noncage laying hen housing systems because of animal welfare concerns. In this study, the prevalence and severity of lesions in noncage laying hens from commercial farms in two of the largest egg-producing states, California and Iowa, were evaluated by postmortem examination. Hens that died or were culled were collected during early, mid, and late stages of the laying cycle from 16 houses on three farms.
View Article and Find Full Text PDFAccurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures.
View Article and Find Full Text PDFPerioperative analgesic effects of oral firocoxib following cautery disbudding were investigated in preweaned calves. Twenty Holstein calves approximately 4 to 6wk old received a single oral dose of firocoxib, a nonsteroidal antiinflammatory, at 0.5mg/kg (n=10) or placebo (n=10) in a randomized controlled clinical trial.
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