@article{didomenico_jacob_stowe_gruber_2024, title={Diagnostic utility of the total nucleated cell count for differentiation of septic and sterile peritoneal effusions in dogs}, volume={2}, ISSN={["1939-165X"]}, url={https://doi.org/10.1111/vcp.13315}, DOI={10.1111/vcp.13315}, abstractNote={Abstract}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Didomenico, Amy E. and Jacob, Megan E. and Stowe, Devorah M. and Gruber, Erika J.}, year={2024}, month={Feb} } @article{schlake_cassady_gruber_minter_2023, title={Effect of Prolonged Serum Storage Time and Varied Temperatures on Biochemical Values in African Savanna Elephants (Loxodonta africana)}, volume={4}, ISSN={["2673-5636"]}, DOI={10.3390/jzbg4010002}, abstractNote={Blood samples are routinely collected from wild populations in remote locations with limited electricity, minimal diagnostic capabilities, and extreme environmental conditions. Under these conditions, serum samples may be stored for prolonged time under varied temperatures prior to processing, which could affect the ability to interpretation the results. This study’s objective was to evaluate the effects of delayed processing of serum samples and varied storage temperatures on biochemical values in African savanna elephants (Loxodonta africana). Blood samples were collected from six elephants managed by the North Carolina Zoo. For each elephant, seven red top tubes were collected. One serum sample for each elephant was analyzed on Day 0 (control group). The remaining samples were stored under different temperatures including room temperature (23 °C), refrigeration (2.2 °C), and incubation (32.2 °C), with samples from each temperature group being analyzed on Day 5 and Day 10. Many of analytes (10 out of 18) did not change significantly regardless of storage temperature or time. Refrigeration improved stability in an additional four analytes over prolonged storage. We conclude that if serum is properly separated shortly after collection, many serum biochemical analytes can be accurately measured even after suboptimal serum storage, but refrigeration and prompt evaluation are still required for some analytes.}, number={1}, journal={JOURNAL OF ZOOLOGICAL AND BOTANICAL GARDENS}, author={Schlake, Emily L. and Cassady, Katherine R. and Gruber, Erika J. and Minter, Larry J.}, year={2023}, month={Mar}, pages={12–20} } @article{ripplinger_gruber_correa_martin_crespo_2023, title={Evaluation and establishment of reference intervals using the i-STAT1 blood chemistry analyzer in turkeys}, volume={102}, ISSN={["1525-3171"]}, url={https://doi.org/10.1016/j.psj.2023.102806}, DOI={10.1016/j.psj.2023.102806}, abstractNote={In veterinary medicine, point-of-care testing techniques have become popular, since they provide immediate results and only small amounts of blood are needed. The handheld i-STAT1 blood analyzer is used by poultry researchers and veterinarians; however, no studies have evaluated the accuracy of this analyzer determined reference intervals in turkey blood. The objectives of this study were to 1) investigate the effect of storage time on turkey blood analytes, 2) compare the results obtained by the i-STAT1 analyzer to those obtained by the GEM Premier 3000, a conventional laboratory analyzer, and 3) establish reference intervals for blood gases and chemistry analytes in growing turkeys using the i-Stat. For the first and second objectives, we used the CG8+ i-STAT1 cartridges to test blood from 30 healthy turkeys in triplicate and once with the conventional analyzer. To establish the reference intervals, we tested a total 330 blood samples from healthy turkeys from 6 independent flocks during a 3-yr period. Blood samples were then divided into brooder (<1 wk) and growing (1-12 wk of age). Friedman's test demonstrated significant time-dependent changes in blood gas analytes, but not for electrolytes. Bland-Altman analysis revealed that there was agreement between the i-STAT1 and the GEM Premier 300 for most of the analytes. However, Passing-Bablok regression analysis identified constant and proportional biases in the measurement of multiple analytes. Tukey's test revealed significant differences in the whole blood analytes between the means of brooding and growing birds. The data presented in the present study provide a basis for measuring and interpreting blood analytes in the brooding and growing stages of the turkey lifecycle, offering a new approach to health monitoring in growing turkeys.}, number={8}, journal={POULTRY SCIENCE}, author={Ripplinger, Eliza N. and Gruber, Erika J. and Correa, Maria T. and Martin, Michael P. and Crespo, Rocio}, year={2023}, month={Aug} } @article{cassady_minter_gruber_2023, title={Performance of a manually operated salad spinner centrifuge for serum separation in the healthy domestic horse (Equus caballus) and southern white rhinoceros (Ceratotherium simum)}, volume={7}, ISSN={["1939-165X"]}, url={https://doi.org/10.1111/vcp.13290}, DOI={10.1111/vcp.13290}, abstractNote={Abstract}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Cassady, Katherine R. and Minter, Larry J. and Gruber, Erika J.}, year={2023}, month={Jul} } @article{marin_ferris_gruber_2023, title={What is your diagnosis? Perineal swelling in a dog}, volume={1}, ISSN={["1939-165X"]}, url={https://doi.org/10.1111/vcp.13172}, DOI={10.1111/vcp.13172}, abstractNote={A 2-year-old male intact Terrier mix presented to the North Carolina State Veterinary Teaching Hospital (NCSU-VTH) for evaluation of an ill-defined, soft, fluctuant mass in the right dorsal perineal area that had been present for approximately 1 week. The subcutaneous lesion was approximately 10 by 8 centimeters, fluid-filled, non-painful, and initially reported to be non-reducible. The owner reported no abnormalities in behavior, urination, or defecation, and there was no known physical trauma. Other relevant history included a prior diagnosis of congenital renal dysplasia with stable proteinuria and azotemia. Targeted ultrasonography confirmed that the mass was fluid-filled, but did not identify communication with the abdominal cavity. Approximately 20 ml of fluid was removed from the perineal swelling via fine-needle aspiration, and submitted for cytologic evaluation (Figures 1 and 2). Atypical epithelial cells, concerning for carcinoma. The direct smears were of moderate cellularity consisting of mixed leukocytes and large atypical cells present individually and in small clusters on a light pink background with a moderate amount of blood. Atypical cells were round to polygonal with distinct cellular borders, round to oval nuclei, fine chromatin, and a moderate amount of mid to deep blue cytoplasm. Occasionally, these cells contained variably-sized bright pink round to oval inclusions that displaced the nucleus (Figures 2A-C). Cells displayed moderate anisocytosis and anisokaryosis. Occasional bi- and multi-nucleated and rare karyorrhectic cells were observed. Rarely, cells displayed cannibalistic phagocytosis. Leukocytes consisted mostly of macrophages, which occasionally contained non-specific phagocytic debris and/or clear vacuoles, along with low numbers of non-degenerate neutrophils and small lymphocytes. The large atypical cohesive cells were consistent with either epithelial or mesothelial cells, although the large eosinophilic cytoplasmic inclusions were unusual for mesothelial cells. Given the location and initial description of a non-reducible lesion, the atypical cells were interpreted to be concerning for carcinoma. Differential diagnoses included a congenital cyst or perineal hernia, although the latter was considered unlikely given that communication with the abdominal cavity had not been identified. Full abdominal ultrasonography revealed chronic nephropathy and cystic prostatomegaly, but no connection between the abdomen and the fluid-filled mass. No cytologic abnormalities or BRAF mutation (CADET BRAF) were detected on the prostatic wash sample. Further discussion with the primary clinician revealed that the lesion was, in fact reducible, and the clinical diagnosis was a perineal hernia. The NCSU-VTH Soft Tissue Surgery Service explored the lesion and identified a defect in the abdominal wall that communicated with the perineal swelling. The defect was repaired with a classic herniorrhaphy supplemented with an internal obturator muscle transposition. Excised tissue was examined by histopathology, which revealed adipose tissue with marked fibroplasia, mild mesothelial hypertrophy, and multifocal de novo lymphoid follicle formation. Findings were consistent with entrapped peritoneal adipose tissue that had undergone fibrosis, and the final diagnosis was a perineal hernia (Figure 3). The intracytoplasmic inclusions, observed only in the cytologic specimens, were Periodic acid-Schiff (PAS) negative. Here, we report cytologic findings from entrapped fluid collected from a perineal hernia in a dog, which to our knowledge, have not been previously described. Reflecting its connection to the abdominal cavity, cytologic findings are similar to peritoneal transudative effusions: primarily mixed leukocytes with fewer reactive mesothelial cells. At the time of cytologic evaluation, the connection between the perineal swelling and abdominal cavity had not been identified; thus, the large atypical cells with cytoplasmic inclusions were concerning for carcinoma. After further discussion with the primary veterinarian, the lesion was described as reducible, and the perineal hernia was prioritized. The diagnosis was confirmed by surgery and histopathology. Two years post-surgery the patient has no evidence of recurrence or development of urothelial, prostatic, or other epithelial neoplasia, further supporting a non-neoplastic etiology. In this context, the atypical cells were re-assessed to be reactive mesothelial cells, which are notorious for being difficult to distinguish from carcinoma and mesothelioma cells. Reactive mesothelial cells may display increased nuclear to cytoplasmic ratio, large nuclei, prominent nucleoli, increased cytoplasmic basophilia, moderate to marked anisokaryosis and anisocytosis, and/or mitotic figures.1 Although not performed in this case, mesothelial cells are expected to be immunopositive for pan-cytokeratin, vimentin, and desmin.1, 2 The eosinophilic cytoplasmic inclusions in the mesothelial cells resembled Melamed-Wolinska bodies (MWB). MWB are a non-specific degenerative change, most likely composed of mucopolysaccharides or enlarged lysosomes, but unlike the inclusions observed in this case, are PAS-positive.3 MWB are most often associated with cells of urothelial origin, although similar inclusions have been reported in other cell types (eg, mammary, pulmonary carcinoma).3, 4 Cytoplasmic inclusions with a similar appearance to MWB may be observed in normal, degenerating, virus-infected, and neoplastic epithelial cell populations.3, 4 Intracytoplasmic targetoid mucin vacuoles observed in human urothelial cells appear very similar to MWB but differ with mucicarmine staining.5 Anecdotally, cytoplasmic inclusions resembling MWB have been observed in mesothelial cells, but to our knowledge, have not been documented. Here, the PAS-negative staining suggests a non-polysaccharide composition of the inclusions, not consistent with MWB. The origin and composition of these inclusions remain unknown. This case demonstrates the cytologic and histopathologic findings from entrapped fluid and tissue collected from a perineal hernia and documents PAS-negative eosinophilic cytoplasmic inclusions in mesothelial cells. This case also serves as a reminder of the importance of clinical context in the interpretation of atypical cells, which may require additional communication between the cytopathologist and the primary veterinarian. The authors have no affiliations or financial involvement with any organization or entity with a financial interest in, or in financial competition with, the subject matter or materials discussed in this article.}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Marin, Jessica and Ferris, Kelli and Gruber, Erika}, year={2023}, month={Jan} } @article{hastain_buchy_dombrowski_womble_armwood_gruber_2023, title={What is your diagnosis? Ulcerative shell lesions from a diamond-backed terrapin (Malaclemys terrapin)}, volume={7}, ISSN={["1939-165X"]}, url={https://doi.org/10.1111/vcp.13291}, DOI={10.1111/vcp.13291}, abstractNote={An adult female intact diamond-backed terrapin (Malaclemys terrapin) at the North Carolina Museum of Natural Sciences presented for an episode of scute sloughing and cystic ulcerative pitting lesions on the carapace and plastron. The patient was wild-caught as a hatchling or juvenile by another institution in 2004 and obtained by the museum in 2007. Since acquisition, this turtle has had a chronic history of pitting shell lesions, keratin scute flaking, and excessive keratin scute buildup. This turtle had two notable episodes with deep shell lesions and scute sloughing, the first of which completely resolved with topical antibiotics. During the second episode, the multifocal deep ulcerative lesions cultured positive for multiple aerobic bacteria that were initially susceptible to topical and injectable antibiotics. Healing was prolonged due to the development of antibiotic resistance, and antibiotic therapy was altered according to sensitivity results. Complete gross resolution occurred after 4 months of treatment. On presentation, multiple ulcerated and hemorrhagic lesions were present on the carapace after acute sloughing of the scutes, most notably between the right first and second costal scutes. The deep ulcers were associated with tan to yellow dry caseous granuloma-like exudative lesions that penetrated into the bone. Swabs from these lesions were submitted for cytology (Figure 1). The patient was otherwise active and eating well. Fungal hyphae with mild heterophilic inflammation The sample is of low cellularity consisting mostly of keratinized squamous epithelial cells. Focal areas of the slides contain low numbers of poorly preserved heterophils (not pictured). Numerous variably staining fungal hyphae are associated with many of the keratin aggregates. The hyphae are found individually and in mats. Hyphae are approximately 2–4 μm in diameter and septate, with thin nonstaining walls that are mostly parallel but occasionally nonparallel. They display internal complexity, often containing variably sized clear, distinct vacuoles. Rare acute and right-angled lateral branching is observed. Gross examination of the dermal fragments and multiple fragments of surrounding tissue reveals multifocal to coalescing pale tan plaques, nodules, and pitting lesions (Figure 2). On histopathologic examination, the superficial dermis is expanded by epithelial inclusion cysts. Cyst structures are lined by well-differentiated stratified squamous epithelium with central keratinization and the accumulation of lamellated layers of keratin debris (Figure 3A). Embedded within the central layers of keratin are numerous fungal hyphae highlighted by Grocott's methenamine silver stain (Figure 3B). Hyphae are approximately 4 μm in diameter with nonparallel cell walls and display acute and right-angle branching and septation. The dermal fragments display marked orthokeratotic to parakeratotic hyperkeratosis, with conglomerates of keratin debris, degenerative leukocytes, and eosinophilic fluid also containing the fungal hyphae (not pictured). A pooled swab prepared from the oral cavity, cloaca, and shell submitted to the University of Illinois College of Veterinary Medicine Zoological Pathology Program Molecular Diagnostic Laboratory tested positive for Emydomyces testavorans by quantitative PCR. Ulcerative shell disease is a common cause of morbidity and mortality in captive and free-ranging populations of turtles,1, 2 and clinical signs include shell erosions, lethargy, and emaciation.3 Reported causes of ulcerative shell disease include trauma, malnutrition (eg, calcium and vitamin D3 deficiencies), and various bacterial and fungal etiologies, though the cause is often unknown.1, 4 In captive individuals, poor husbandry practices such as inappropriate temperature, humidity, lighting, and/or nutrition are considered predisposing factors.4 Infectious causes are most often identified as gram-negative commensals within the Enterobacteriae order, including Escherichia, Klebsiella, and Enterobacter spp.4 Bacterial ulcerative shell disease has the potential to progress to septicemic cutaneous ulcerative disease (SCUD), in which bacterial dermatitis and osteomyelitis may be identified.1 Fungal causes of ulcerative shell disease are rarely reported, and the majority of published reports are from nonaquatic turtle species.2 Emydomyces testavorans is a keratinophilic fungal organism in the Onygenales order.5 Onygenalean fungi have been identified as primary pathogens for ulcerative dermatitis in captive and free-ranging reptilian species, including crocodilians, lizards, and snakes.1 E. testavorans has only been recently described and has been isolated from ulcerative shell lesions in aquatic turtles, causing keratin discoloration, flaking and textural change, erosion, ulceration, and osteonecrosis.2, 5 The most consistent and striking histopathologic lesion with E. testavorans infection is the presence of epithelial inclusion cysts, identified in more than 90% of cases.2 Epithelial inclusion cysts are cystic spaces lined by stratified squamous epithelium with central keratinization. E. testavorans hyphae are typically embedded in keratin debris.5 Although the underlying mechanism of epithelial inclusion cyst formation with E. testavorans infection is unclear, it is presumed that the excessive keratinization occurs secondary to the fungal infection rather than fungal infection with tropism for previously established epithelial inclusion cysts. Since epithelial inclusion cysts in other species are not often associated with fungal infections, it is possible that immunosuppression is contributing to the pathogenesis in aquatic turtles. Definitive diagnosis of E. testavorans typically requires PCR with or without DNA sequencing. Although culture can be performed, it may be complicated by sample contamination with other common environmental bacterial and fungal organisms and by the requirement for reptile keratin-enriched media. Preferred samples are lesion swabs and biopsy material that should be refrigerated for culture and frozen for molecular diagnostics.5 In summary, this case described the cytologic features of the onygenalean fungus E. testavorans, a newly described cause of ulcerative shell lesions in aquatic turtles. The frequent association of fungal hyphae with keratin and concurrent inflammation is consistent with histologic findings of epithelial inclusion cysts associated with E. testavorans.2 The heterophilic inflammation, in this case, could be in response to the fungus, keratin, and/or concurrent bacterial infection. Although bacteria were not identified cytologically, bacterial culture was not performed to exclude this possibility. A thorough examination of keratin aggregates for fungal hyphae elements is warranted in samples from ulcerative shell lesions in aquatic turtles. The authors have no affiliations or financial involvement with any organization or entity with a financial interest in, or in financial compensation with, the subject matter or materials discussed in this article.}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Hastain, Sydney A. A. and Buchy, Jessica M. M. and Dombrowski, Daniel S. S. and Womble, Mandy A. A. and Armwood, Abigail R. R. and Gruber, Erika J. J.}, year={2023}, month={Jul} } @article{parsley_schnelle_gruber_sander_barger_2022, title={Total protein concentration as a predictor of in neoplastic peritoneal and pleural effusions of dogs}, volume={5}, ISSN={["1939-165X"]}, url={https://doi.org/10.1111/vcp.13122}, DOI={10.1111/vcp.13122}, abstractNote={Abstract}, journal={VETERINARY CLINICAL PATHOLOGY}, publisher={Wiley}, author={Parsley, Ashley L. and Schnelle, Amy N. and Gruber, Erika J. and Sander, William E. and Barger, Anne M.}, year={2022}, month={May} } @article{parsley_rasche_yang_gruber_2022, title={What is your diagnosis? Ovarian mass in a mare}, volume={9}, ISSN={["1939-165X"]}, url={https://doi.org/10.1111/vcp.13161}, DOI={10.1111/vcp.13161}, abstractNote={An 18-year-old Hanoverian mare was referred to the North Carolina State University Veterinary Hospital for removal of an intra-abdominal mass after an initial assessment for a 6-month history of stallion-like behavior, including increased kicking, striking, biting, and bucking when riding. Rectal palpation and ultrasound revealed a large multicystic mass in the region of the right ovary. Physical exam and CBC were unremarkable, and the mass was removed by standing laparoscopic surgery. The mass was 25 × 20 × 17 cm, had a smooth surface, and on cross-section contained many variably sized cystic structures containing watery, translucent, yellow fluid, or occasionally red-tinged fluid. Fine-needle aspiration of tissue with cytocentrifuged fluid from adjacent cystic structures was obtained (Figure 1). The sample is of moderate cellularity consisting of frequent loosely cohesive clusters of cells that are disorganized or occasionally forming rosette-like arrangements and associated with the wispy magenta matrix, scattered individualized leukocytes, and a moderate amount of blood on a bright pink stippled proteinaceous background. Cells in clusters are oval to polygonal, with a moderate nuclear to cytoplasmic ratio, and variably distinct borders. They contain a single uniform round nucleus with coarse chromatin and have a moderate amount of pale blue cytoplasm with fine, clear vacuoles or occasionally several larger clear, distinct vacuoles. Cells display mild anisokaryosis and mild anisocytosis. Also present are low numbers of macrophages. Histologic examination reveals a poorly demarcated neoplasm expanding and almost completely effacing the ovarian parenchyma. The neoplasm consists of polyhedral cells arranged in variably-sized cystic structures (macrofollicular pattern) and smaller round to irregular solid islands supported by a moderate amount of fibrovascular stroma (Figure 2). The cystic structures are lined by multiple layers of neoplastic cells with peripheral palisading. Neoplastic cells have a small to moderate amount of finely vacuolated pale eosinophilic cytoplasm and round nuclei with stippled chromatin and 0–1 small nucleoli (granulosa cells). Neoplastic granulosa cells exhibit mild anisocytosis and anisokaryosis with 2 mitotic figures in 10 high magnification fields (2.37 mm2). Occasionally surrounding neoplastic islands and cystic structures is a layer of moderately cellular streaming spindle cells with scant wispy eosinophilic cytoplasm (presumed theca cells). These cells occasionally have a moderate amount of hypereosinophilic cytoplasm with small discrete lipid vacuoles (presumed luteinized theca cells). The neoplastic granulosa cells show immunoreactivity for vimentin, pancytokeratin, inhibin-α, and anti-Müllerian hormone (AMH). Theca cells only show immunoreactivity for vimentin (Figure 3). The final diagnosis was granulosa-theca cell tumor. Primary ovarian neoplasms are classified into one of three histologic tumor types: epithelial, germ cell, and sex cord-stromal tumors.1-3 The granulosa cell tumor (GCT) is a sex cord-stromal tumor and is by far the most common tumor of the equine ovary.1, 3 GCTs are generally benign tumors that occur more frequently in older mares, although they can occur at any age.1, 3 When these tumors contain a significant theca cell component in addition to granulosa cells, they are referred to as granulosa-theca cell tumors (GTCTs), although some authors use GCT interchangeably with GTCT.2, 3 When present, increased numbers of theca cells may be associated with an increase in blood testosterone (often >100 pg/mL), which, in turn, is associated with stallion-like behavior.2 In this case, the histologic theca cell component and behavioral abnormalities are consistent with the more specific diagnosis of granulosa-theca cell tumor. Cytology of a GCT has been minimally described in the veterinary literature,4 and rarely described in horses.5 In dogs, cells from GCTs exfoliate individually or in loose clusters, with occasional rosette-like arrangements, and are oval to polygonal with round nuclei, coarsely stippled chromatin, and a small to moderate amount of lightly basophilic cytoplasm containing a few discrete vacuoles.4, 6 These features were seen in this case and supported the diagnosis of a granulosa cell tumor. Call-Exner bodies, eosinophilic proteinaceous material deposits surrounded by granulosa cells, are frequently observed in histologic samples but rarely reported in cytologic samples.3, 5 Call-Exner bodies were not observed in either cytologic or histologic samples in this case. Although Call-Exner bodies are a useful diagnostic feature, their absence does not rule out a GCT.3 The histology of GCTs is described as resembling disorganized follicle formation, consisting of irregular accumulations of granulosa cells in sheets, cords, trabeculae, or nests with supporting stromal cells. Granulosa cells are vimentin-positive and variably cytokeratin positive; theca cells are vimentin-positive with no cytokeratin positivity.3 Other useful IHC markers include inhibin–α and AMH (also called Müllerian-inhibiting substance), which both show cytoplasmic immunoreactivity in granulosa cells, as observed in this case.3, 7 Other differentials for equine ovarian tumors include teratoma (germ cell) or cystadenoma (epithelial). Rarely, adenocarcinomas (epithelial), dysgerminomas (germ cell), and others have been reported.1, 2 Cytologically, germ cell tumors may appear as large individual round to ovoid cells with a large round nucleus, which is inconsistent with the findings in this case. Cystadenomas and adenocarcinomas may be cystic to multicystic in nature; however, the morphology and indistinct borders of the cells, in this case, are not consistent with these lesions.2}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Parsley, Ashley L. and Rasche, Brittany L. and Yang, Tzushan S. and Gruber, Erika J.}, year={2022}, month={Sep} } @article{ruiz-jimenez_gruber_correa_crespo_2021, title={Comparison of portable and conventional laboratory analyzers for biochemical tests in chickens}, volume={100}, ISSN={["1525-3171"]}, url={https://doi.org/10.1016/j.psj.2020.11.060}, DOI={10.1016/j.psj.2020.11.060}, abstractNote={Antemortem blood biochemical and blood gas analyses are routinely used in health screening and diagnosis of disease in domestic veterinary species. These testing modalities are not routinely performed in poultry, in part, due to the distance from the diagnostic laboratory. Portable blood analyzers such as the i-STAT and VetScan (VS2) can be used to obtain results on the farm without delay, potentially offering a more practical option for poultry practitioners. We investigated the time effect on blood chemistry values and compared the results obtained using the i-STAT and VS2 with those obtained using conventional laboratory analyzers (GEM Premier 3000 and Cobas c501, respectively). We tested blood from 60 healthy chickens. Each sample was tested in triplicate using each of the portable analyzers and once using conventional analyzers. All samples were analyzed within 60 minutes of collection. The concentrations of some analytes were outside the limit of detection of the portable analyzers (i.e., bile acids). Although statistically significant differences were found for some biochemical analytes over time, the actual mean or median differences were too small to be considered of clinical importance. As observed in mammals, significant time-dependent changes in blood gas analytes were observed in whole blood samples exposed to ambient air. Correlation coefficients between portable and conventional analyzers were moderate to high for most of the analytes. For the most part, there was an agreement between the portable and conventional analyzers. We identified constant and proportional biases in the measurement of multiple analytes by both the i-STAT and VS2. Future studies are warranted to establish analyzer-specific reference intervals for poultry.}, number={2}, journal={POULTRY SCIENCE}, publisher={Elsevier BV}, author={Ruiz-Jimenez, Fernando and Gruber, Erika and Correa, Maria and Crespo, Rocio}, year={2021}, month={Feb}, pages={746–754} } @article{mones_gruber_harms_lohmann_lohmann_lewbart_2021, title={LACTIC ACIDOSIS INDUCED BY MANUAL RESTRAINT FOR HEALTH EVALUATION AND COMPARISON OF TWO POINT-OF-CARE ANALYZERS IN HEALTHY LOGGERHEAD SEA TURTLES (CARETTA CARETTA)}, volume={52}, ISSN={["1937-2825"]}, DOI={10.1638/2021-0029}, abstractNote={Abstract: Sea turtles are often restrained manually for brief periods during veterinary evaluation and care in rescue, rehabilitation, research, and aquarium settings. Blood gas values and lactate are routinely evaluated during triage of sea turtles, and lactate clearance is of prognostic significance in cold-stunned individuals. Although increases in blood lactate have been associated with muscle exertion, experimental forced submergence, trawl and pound net capture, and general anesthesia, changes in blood lactate associated with short periods of manual restraint have not been evaluated. Venous blood gas and lactate values were tested in 16 juvenile loggerhead sea turtles (Caretta caretta) before and after manual restraint for a 15-min routine veterinary examination. The agreement of blood lactate values between two point-of care analyzers (i-STAT and Lactate Plus) was also compared. Blood pH and bicarbonate (HCO3–) decreased significantly (P < 0.001), and partial pressure of carbon dioxide (pCO2) increased significantly (P < 0.0001) after 15 min. Lactate increased significantly between time points for both analyzers (P < 0.0001). Linear regression analysis showed excellent correlation for lactate measurements obtained on both analyzers (r = 0.998). The mean difference in lactate concentrations between the analyzers was statistically significant, indicating that the methods cannot be used interchangeably (P < 0.0001). Deming regression and Bland-Altman plots identified a slight negative proportional bias for lactate measurement by the Lactate Plus compared with the i-STAT. These results suggest that clinicians should evaluate blood gas values and lactate at the beginning of health evaluations and interpret serial lactate values in sea turtles with caution, because even short periods of manual restraint can induce lactic acidosis and considerably influence these values.}, number={4}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Mones, Alissa B. and Gruber, Erika J. and Harms, Craig A. and Lohmann, Catherine M. F. and Lohmann, Kenneth J. and Lewbart, Gregory A.}, year={2021}, month={Dec}, pages={1195–1204} } @article{gruber_aygun_leifer_2021, title={Macrophage uptake of oxidized and acetylated low-density lipoproteins and generation of reactive oxygen species are regulated by linear stiffness of the growth surface}, url={https://doi.org/10.1371/journal.pone.0260756}, DOI={10.1371/journal.pone.0260756}, abstractNote={Macrophages are key players in the development of atherosclerosis: they scavenge lipid, transform into foam cells, and produce proinflammatory mediators. At the same time, the arterial wall undergoes profound changes in its mechanical properties. We recently showed that macrophage morphology and proinflammatory potential are regulated by the linear stiffness of the growth surface. Here we asked whether linear stiffness also regulates lipid uptake by macrophages. We cultured murine bone marrow-derived macrophages (BMMs) on polyacrylamide gels modeling stiffness of healthy (1kPa) and diseased (10-150kPa) blood vessels. In unprimed BMMs, increased linear stiffness increased uptake of oxidized (oxLDL) and acetylated (acLDL) low density lipoproteins and generation of reactive oxygen species, but did not alter phagocytosis of bacteria or silica particles. Macrophages adapted to stiff growth surfaces had increased mRNA and protein expression of two key lipoprotein receptors: CD36 and scavenger receptor b1. Regulation of the lipoprotein receptor, lectin-like receptor for ox-LDL, was more complex: mRNA expression decreased but surface protein expression increased with increased stiffness. Focal adhesion kinase was required for maximal uptake of oxLDL, but not of acLDL. Uptake of oxLDL and acLDL was independent of rho-associated coiled coil kinase. Through pharmacologic inhibition and genetic deletion, we found that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, plays an inhibitory role in the uptake of acLDL, but not oxLDL. Together, these results implicate mechanical signaling in the uptake of acLDL and oxLDL, opening up the possibility of new pharmacologic targets to modulate lipid uptake by macrophages in vivo.}, journal={PLOS ONE}, author={Gruber, Erika J. and Aygun, Ali Y. and Leifer, Cynthia A.}, editor={Zirlik, AndreasEditor}, year={2021}, month={Dec} } @article{gruber_leifer_2020, title={Molecular regulation of TLR signaling in health and disease: mechano-regulation of macrophages and TLR signaling}, volume={26}, ISSN={1753-4259 1753-4267}, url={http://dx.doi.org/10.1177/1753425919838322}, DOI={10.1177/1753425919838322}, abstractNote={ Immune cells encounter tissues with vastly different biochemical and physical characteristics. Much of the research emphasis has focused on the role of cytokines and chemokines in regulating immune cell function, but the role of the physical microenvironment has received considerably less attention. The tissue mechanics, or stiffness, of healthy tissues varies dramatically from soft adipose tissue and brain to stiff cartilage and bone. Tissue mechanics also change due to fibrosis and with diseases such as atherosclerosis or cancer. The process by which cells sense and respond to their physical microenvironment is called mechanotransduction. Here we review mechanotransduction in immunologically important diseases and how physical characteristics of tissues regulate immune cell function, with a specific emphasis on mechanoregulation of macrophages and TLR signaling. }, number={1}, journal={Innate Immunity}, publisher={SAGE Publications}, author={Gruber, Erika J and Leifer, Cynthia A}, year={2020}, month={Jan}, pages={15–25} } @article{gruber_heyward_cameron_leifer_2018, title={Toll-like receptor signaling in macrophages is regulated by extracellular substrate stiffness and Rho-associated coiled-coil kinase (ROCK1/2)}, volume={30}, ISSN={0953-8178 1460-2377}, url={http://dx.doi.org/10.1093/intimm/dxy027}, DOI={10.1093/intimm/dxy027}, abstractNote={Abstract}, number={6}, journal={International Immunology}, publisher={Oxford University Press (OUP)}, author={Gruber, Erika and Heyward, Christa and Cameron, Jody and Leifer, Cynthia}, year={2018}, month={Apr}, pages={267–278} } @article{witter_gruber_lean_stokol_2017, title={Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines}, volume={78}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.78.1.69}, DOI={10.2460/ajvr.78.1.69}, abstractNote={Abstract}, number={1}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Witter, Lauren E. and Gruber, Erika J. and Lean, Fabian Z. X. and Stokol, Tracy}, year={2017}, month={Jan}, pages={69–79} } @article{gruber_catalfamo_stokol_2016, title={Role of tissue factor expression in thrombin generation by canine tumor cells}, volume={77}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.77.4.404}, DOI={10.2460/ajvr.77.4.404}, abstractNote={Abstract}, number={4}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Gruber, Erika J. and Catalfamo, James L. and Stokol, Tracy}, year={2016}, month={Apr}, pages={404–412} } @article{hasan_gruber_cameron_leifer_2016, title={TLR9 stability and signaling are regulated by phosphorylation and cell stress}, volume={100}, ISSN={0741-5400}, url={http://dx.doi.org/10.1189/jlb.2a0815-337r}, DOI={10.1189/jlb.2a0815-337r}, abstractNote={Abstract}, number={3}, journal={Journal of Leukocyte Biology}, publisher={Wiley}, author={Hasan, Maroof and Gruber, Erika and Cameron, Jody and Leifer, Cynthia A.}, year={2016}, month={Mar}, pages={525–533} } @article{sipe_gruber_saha_2004, title={Short upstream region drives dynamic expression of hypoxia-inducible factor 1α during Xenopus development}, volume={230}, ISSN={1058-8388 1097-0177}, url={http://dx.doi.org/10.1002/dvdy.20049}, DOI={10.1002/dvdy.20049}, abstractNote={Abstract}, number={2}, journal={Developmental Dynamics}, publisher={Wiley}, author={Sipe, Conor W. and Gruber, Erika J. and Saha, Margaret S.}, year={2004}, pages={229–238} }