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Reasons for performing study Early detection of recurrent laryngeal neuropathy ( RLN) is of considerable interest to the equine industry. Objectives To describe two imaging modalities, transoesophageal ultrasound ( TEU) and computed tomography ( CT) with multiplanar reconstruction to assess laryngeal muscle geometry, and determine the relationship between cricoarytenoid dorsalis ( CAD) geometry and function. Study design Two-phase study evaluating CAD geometry in experimental horses and horses with naturally occurring RLN. Methods Equine CAD muscle volume was determined from CT scan sets using volumetric reconstruction with LiveWire. The midbody and caudal dorsal-ventral thickness of the CAD muscle was determined using a TEU in the same horses; and in horses with a range of severity of RLN (n = 112). Results Transoesophageal ultrasound was able to readily image the CAD muscles and lower left:right CAD thickness ratios were observed with increasing disease severity. Computed tomography based muscle volume correlated very closely with ex vivo muscle volume (R2 = 0.77). Conclusions Computed tomography reconstruction can accurately determine intrinsic laryngeal muscle geometry. A relationship between TEU measurements of CAD geometry and laryngeal function was established. These imaging techniques could be used to track the response of the CAD muscle to restorative surgical treatments such as nerve muscle pedicle graft, nerve anastomosis and functional electrical stimulation. [ABSTRACT FROM AUTHOR]

Gastrointestinal colic is the most common primary care equine emergency and affects nearly one of four horses per year. Colic is a significant welfare concern for equine patients and a financial and emotional burden for owners. The primary care practitioner is instrumental in identifying critical cases quickly and making appropriate management recommendations to improve patient outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endoparasitism is a major cause of morbidity and mortality in alpacas (Lama pacos), with growing emergence of anthelmintic resistance. The purpose of the study was to correlate nematode worm burden and selected host phenotypic characteristics, such as age and weight, with the composition of the intestinal microbiota of adult alpacas. Fecal samples were collected per rectum from 102 healthy adult (2.1-11.2 years) alpacas at 3 separate timepoints (pre- and post-treatment with 8.8 mg/kg oral Levamisole HCL, and 4.6 months later) at a single farm. The profile of the fecal bacterial microbiota was characterized using 16S amplicon sequencing. Serial clinical exams and fecal egg counts were compared using related-samples analyses. The fecal microbiota of identically managed, healthy alpacas was characterized by a high level of temporal stability, as both α and β-diversity significantly correlated between sampling timepoints. Pairwise β-diversity between samples collected at each timepoint was low, ranging from 0.16-0.21 UniFrac distance units. The intensity of strongylid nematode infection (including Haemonchus, Ostertagia, Trichostrongylus) was only significantly correlated with microbiota composition in samples collected 14 days after treatment with levamisole. Analysis of similarity revealed no clustering of microbiota from anthelmintic responders or non-responders. Alpaca age explained the largest proportion of fecal microbiota variation and was the only consistently significant predictor of fecal microbiota taxonomic composition, by impacting the ratio of relative Bacteroidetes and Firmicutes abundance. Firmicutes, mostly Clostridiales, was the most abundant taxon across all collections., Competing Interests: The authors have declared that no competing interests exist.

Serum biochemistry results and presence of fibrosis on liver biopsies are frequently used as prognostic indicators in horses with liver dysfunction. The objective of this retrospective multicenter study was to determine if the magnitude of abnormal liver specific biochemical tests such as bile acids (BA), direct bilirubin and gamma-glutamyltransferase (GGT), or the presence of fibrosis reported on liver biopsies was associated with prognosis in horses with liver dysfunction. Eighty-two horses older than one year, examined at four referral hospitals in the eastern United States, with BA values greater than 30 µmol/L and having 6-months or more follow-up were included in the study. The association of the maximal BA, GGT and direct bilirubin values of each horse with survival was determined by logistic regression analysis. The presence or absence of fibrosis (non-quantitated) on a liver biopsy was compared between survivors and non-survivors by chi square test. The degree of increase in BA concentration and GGT activity was not related to outcome (OR 0.9999, 95% CI 0.9923 - 1.007, P = 0.97, and OR 1.0, 95% CI 0.9997 - 1.001, P = 0.31 respectively). Direct bilirubin concentration was positively associated with non-survival (OR 1.95, 95% CI 1.34-3.19, P = 0.0023). The presence of fibrosis was not associated with outcome (P = 0.37). These findings suggest that the magnitude of GGT and BA values or the mere presence of fibrosis on liver histopathology should not be used as prognostic indicators. In this study, direct bilirubin values were a better predictor of outcome., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To describe refeeding syndrome in an equid without a history of recognized risk factors., Case Summary: Refeeding syndrome with marked hypophosphatemia developed in an aged miniature donkey gelding during treatment of suspected enterocolitis. Hypophosphatemia (manifested clinically as ileus and neuromuscular weakness) developed despite a short (3 day) history of hyporexia, increased body condition (7/9), and adherence to nutritional recommendations for critically ill equids. Nutritional support included nasogastric enteral feeding with a commercial equine nutrition product claiming to provide 100% of the National Research Council's daily recommended protein, vitamin, and mineral requirements for equids. Hypophosphatemia developed despite this enteral supplementation and was ultimately corrected by intravenous administration of sodium phosphate solution., New or Unique Information Provided: This case report suggests that risk factors for refeeding syndrome in equids may be broader than previously recognized. Specifically, critically ill equids at risk for insulin dysregulation may have unique nutritional co-morbidities and requirements. This report highlights the need for both broader recognition of risk factors for refeeding syndrome, and revised best-practice nutritional guidelines and supplementation products to improve equine critical care., (© Veterinary Emergency and Critical Care Society 2021.)

Reasons for Performing Study: Although muscle mass strongly influences performance, there is currently no effective means to measure the 3-dimensional muscle mass of horses. We evaluated a 3-dimensional (3D) scanning methodology for its ability to quantify torso and hindquarter volumes as a proxy for regional muscle mass in horses., Objectives: Determine the repeatability of 3D scanning volume (V) measurements and their correlation to body weight, estimated body volume and muscle/fat ultrasound (US) depth., Methods: Handheld 3D photonic scans were performed on 16 Quarter Horses of known body weight 56 days apart (n = 32 scans) with each scan performed in duplicate (n = 32 replicates). Tail head fat, gluteal and longissimus dorsi muscle depths were measured using US. Processed scans were cropped to isolate hindquarter (above hock, caudal to tuber coxae) and torso (hindquarter plus dorsal thoracolumbar region) segments and algorithms used to calculate V. Torso and hindquarter volume were correlated with body weight and US using Pearson's correlation and with estimated torso volume (50% body weight / body density) with Bland-Altman analysis., Results: Scans took 2 min with < 3.5% error for duplicate scans. Torso volume (R = 0.90, P< 0.001) and hindquarter volume (R = 0.82, P< 0.001) strongly correlated with body weight and estimated BV (R = 0.91) with low bias. Torso volume moderately correlated to mean muscle US depth (R = 0.4, P< 0.05) and tail head fat (R = 0.42, P< 0.01). Mean muscle US depth moderately correlated to body weight (R = 0.50, P< 0.01)., Main Limitations: 3D Scans determine body volume not muscle volume., Conclusions: The hand-held 3D scan provided a rapid repeatable assessment of torso and hindquarter volume strongly correlated to body weight and estimated volume. Superimposition of regional scans and volume measures could provide a practical means to follow muscle development when tail head fat depth remain constant., Competing Interests: The authors have declared that no competing interests exist.

Background: A subset of horses deficient in alpha-tocopherol (α-TP) develop muscle atrophy and vitamin E-responsive myopathy (VEM) characterized by mitochondrial alterations in the sacrocaudalis dorsalis medialis muscle (SC)., Objectives: To quantify muscle histopathologic abnormalities in subclinical α-TP deficient horses before and after α-TP supplementation and compare with retrospective (r)VEM cases., Animals: Prospective study; 16 healthy α-TP-deficient Quarter Horses. Retrospective study; 10 retrospective vitamin E-responsive myopathy (rVEM) cases ., Methods: Blood, SC, and gluteus medius (GM) biopsy specimens were obtained before (day 0) and 56 days after 5000 IU/450 kg horse/day PO water dispersible liquid α-TP (n = 8) or control (n = 8). Muscle fiber morphology and mitochondrial alterations were compared in samples from days 0 and 56 and in rVEM cases., Results: Mitochondrial alterations more common than our reference range (<2.5% affected fibers) were present in 3/8 control and 4/8 treatment horses on day 0 in SC but not in GM (mean, 2.2; range, 0%-10% of fibers). Supplementation with α-TP for 56 days did not change the percentage of fibers with mitochondrial alterations or anguloid atrophy, or fiber size in GM or SC. Clinical rVEM horses had significantly more mitochondrial alterations (rVEM SC, 13% ± 7%; GM, 3% ± 2%) and anguloid atrophy compared to subclinical day 0 horses., Conclusions and Clinical Importance: Clinically normal α-TP-deficient horses can have mitochondrial alterations in the SC that are less severe than in atrophied VEM cases and do not resolve after 56 days of α-TP supplementation. Preventing α-TP deficiency may be of long-term importance for mitochondrial viability., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Efficacy of siRNAs as potential anticancer therapeutics can be increased by their targeted delivery into cancer cells via tumor-specific ligands. Phage display offers a unique approach to identify highly specific and selective ligands that can deliver nanocarriers to the site of disease. In this study, we proved a novel approach for intracellular delivery of siRNAs into breast cancer cells through their encapsulation into liposomes targeted to the tumor cells with preselected intact phage proteins. The targeted siRNA liposomes were obtained by a fusion of two parental liposomes containing spontaneously inserted siRNA and fusion phage proteins. The presence of pVIII coat protein fused to a MCF-7 cell-targeting peptide DMPGTVLP in the liposomes was confirmed by Western blotting. The novel phage-targeted siRNA-nanopharmaceuticals demonstrate significant down-regulation of PRDM14 gene expression and PRDM14 protein synthesis in the target MCF-7 cells. This approach offers the potential for development of new anticancer siRNA-based targeted nanomedicines., From the Clinical Editor: In this study, the authors report a novel approach for targeted intracellular delivery of siRNAs into breast cancer cells through encapsulation into liposomes targeted to the tumor cells with preselected intact phage proteins., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The neural-specific calmodulin-sensitive adenylyl cyclase (type I), which was first cloned from bovine brain, has been implicated in learning and memory. The objective of this study was to clone and determine the chromosomal localization of human fetal brain type I adenylyl cyclase. A 3.8-kb cDNA clone was isolated that contained sequence coinciding with the 3' end 2553 nucleotides of the bovine open reading frame. This clone shows 87% nucleotide and 92% translated amino acid sequence identity to the bovine clone. The most significant sequence differences were in the carboxy-terminal 100 amino acid residues. This region contains one of several possible calmodulin binding domains and the only putative cAMP-dependent protein kinase A phosphorylation site. A chimera was constructed that contained the 5' half of the bovine type I adenylyl cyclase and the 3' half of the human type I adenylyl cyclase. The activity of the chimeric gene product and its sensitivity to calmodulin and calcium were indistinguishable from those of the bovine type I adenylyl cyclase. In situ hybridization was used to localize the human type I adenylyl cyclase gene to the proximal portion of the short arm of chromosome 7.

Addition of [gamma -32P]ATP to a 2% Brij-78 40,000g supernatant of sea urchin sperm results in the cAMP-dependent phosphorylation of eight to ten proteins. One phosphoprotein of Mr 190 kD is sperm adenylate cyclase (AC). An antiserum to the AC immunoprecipitates the Mr 190 kD protein. Peptide maps of immunoprecipitates show that the AC is the only phosphoprotein present in the Mr 200 kD range. With respect to the in vitro phosphorylation of AC, the endogenous kinase has a Km for ATP of 5.2 microM and is maximally stimulated by 4-8 microM cAMP. The protein kinase inhibitors H8 (9 microM) and PKI (30 U/ml) inhibit the phosphorylation of the AC. The catalytic subunit of bovine cAMP-dependent protein kinase phosphorylates the AC on the same peptides as the endogenous protein kinase. Cyanogen bromide generated peptide maps of the phosphorylated AC show a minimum of five sites of phosphorylation. No change in the Km or Vmax of the sperm AC resulted from the additional phosphorylation by bovine kinase. Calcium ions at submicromolar concentrations completely block the in vitro phosphorylation of the AC, suggesting the presence in the preparation of a Ca2(+) -activated protein phosphatase. To our knowledge, this is the first report of the phosphorylation of an AC by cAMP-dependent protein kinase.