Collagenase Clostridium Histolyticum for the Treatment of Dupuytren Disease: A Delphi-Based Consensus Study.

Purpose: The aim of this study was to establish the consensus recommendations among hand surgeons who were experts in the use of collagenase clostridium histolyticum (CCH) on the appropriate treatment of Dupuytren disease in well-defined patient populations with varying degrees of disease severity and functional impairment. Methods: A three-round, blinded, modified Delphi process examined panelists' approaches to CCH treatment of metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures involving one or two fingers with varying degrees of severity. Clinical scenarios related to poor-quality skin, postfasciectomy scarring, boutonnière deformity, closed capsulotomy, and blood thinner use were also presented for panelist consideration. Panelists provided responses to clinical scenarios using a 5-point Likert scale or a yes/no response. Consensus was defined as ≥66.7% panelist agreement or disagreement. Results: Twenty panelists completed round 1; 19 of the 20 panelists completed rounds 2 and 3. Panelists achieved a high level of consensus for using CCH for the treatment of patients with palpable cords and varying severity contractures representing one- or two-finger MP joint contractures, most one- or two-finger PIP joint contractures, and most combined MP and PIP joint contractures. Consensus for the treatment of PIP joint contractures was mostly achieved, but clinical scenarios related to recurrent PIP contracture with poor-quality skin and/or significant postfasciectomy scarring, boutonnière deformity, PIP contractures >70°, closed capsulotomy, and blood thinner use were modified, and then most (95.3%) statements reached consensus for agreement in round 2. In round 3, open-ended responses indicated that panelists considered CCH appropriate for most patients with Dupuytren disease. Conclusions: Consensus-based findings among expert hand surgeons with substantial CCH experience indicated that CCH has a wide-ranging application for the treatment of Dupuytren disease in patients with varying degrees of disease severity and functional impairment. Type of study/level of evidence: Therapeutic V.

A large-scale and PCR-referenced vocal audio dataset for COVID-19.

The UK COVID-19 Vocal Audio Dataset is designed for the training and evaluation of machine learning models that classify SARS-CoV-2 infection status or associated respiratory symptoms using vocal audio. The UK Health Security Agency recruited voluntary participants through the national Test and Trace programme and the REACT-1 survey in England from March 2021 to March 2022, during dominant transmission of the Alpha and Delta SARS-CoV-2 variants and some Omicron variant sublineages. Audio recordings of volitional coughs, exhalations, and speech were collected in the 'Speak up and help beat coronavirus' digital survey alongside demographic, symptom and self-reported respiratory condition data. Digital survey submissions were linked to SARS-CoV-2 test results. The UK COVID-19 Vocal Audio Dataset represents the largest collection of SARS-CoV-2 PCR-referenced audio recordings to date. PCR results were linked to 70,565 of 72,999 participants and 24,105 of 25,706 positive cases. Respiratory symptoms were reported by 45.6% of participants. This dataset has additional potential uses for bioacoustics research, with 11.3% participants self-reporting asthma, and 27.2% with linked influenza PCR test results.

Phonon Thermal Transport in UO_{2} via Self-Consistent Perturbation Theory.

Computing thermal transport from first-principles in UO_{2} is complicated due to the challenges associated with Mott physics. Here, we use irreducible derivative approaches to compute the cubic and quartic phonon interactions in UO_{2} from first principles, and we perform enhanced thermal transport computations by evaluating the phonon Green's function via self-consistent diagrammatic perturbation theory. Our predicted phonon lifetimes at T=600 K agree well with our inelastic neutron scattering measurements across the entire Brillouin zone, and our thermal conductivity predictions agree well with previous measurements. Both the changes due to thermal expansion and self-consistent contributions are nontrivial at high temperatures, though the effects tend to cancel, and interband transitions yield a substantial contribution.

Impact of apitherapy on canine, equine, and chicken lymphocytes, in vitro.

Apitherapy is a form of alternative medicine that utilizes products from the western honeybee (Apis mellifera), including honey, propolis, and honeybee venom, to improve the health status of human patients by altering host immunity. An added benefit of these products is that they are nutraceuticals and relatively inexpensive to aquire. Currently, little is known about the use of honeybee products in veterinary species, as well as their impact on host immunity. In the present in vitro study, honey, propolis, and honeybee venom were co-cultured with enriched canine, equine, and chicken peripheral blood lymphocytes (PBLs) with cell proliferation, cell viability/apoptosis, and cellular morphology evaluated. Concanavalin A (Con A) and dexamethasone were used as stimulatory and suppressive controls, respectively. Honeybee products' effects on the three veterinary species varied by product and the species. Honey stimulated the PBLs proliferation in all three species but also displayed some increased cytotoxicity. Propolis stimulated proliferation in canine and equine PBLs, however, it suppressed proliferation in the chicken PBLs. Honeybee venom was the strongest PBL stimulant for all three species and in the equine, surpassed the stimulant response of Con A and yet, enhanced PBL cell viability post culture. In summary, the results of this preliminary in vitro study show that these three honeybee products do impact lymphocyte proliferation and viability in dogs, horses, and chickens, and that more research both in vitro and in vivo will be necessary to draw conclusions regarding their future use as immune stimulants or inhibitors.

Validation of a commercially available photometric analytical system for assessment of plasma oxidative status in healthy horses.

Reactive oxygen species (ROS) are the end-products of physiologic functions in health. Oxidative stress occurs when endogenous antioxidants are insufficient to neutralize ROS in the system. As a result, ROS can damage DNA, RNA, proteins, lipids, and cell organelles. To obtain accurate measurements of plasma oxidative stress, levels of both oxidants and antioxidants must be measured. This study validates a commercially available, semi-quantitative, photometric analytical system that measures systemic determinants of reactive oxygen metabolites (dROM) and plasma antioxidant capacity (PAC) in stored equine plasma. The objectives of this work were: 1) to validate a photometric analytical system to quantify dROM and PAC in equine plasma; and 2) to determine expected results for these tests in healthy adult horses. We hypothesized that this system would reliably and reproducibly assess dROM and PAC in equine plasma. We observed expected, dose-dependent increases in dROM generated by adding increasing concentrations of H2O2 or ascorbic acid to equine plasma to provide samples containing a known quantity of oxidants or antioxidants respectively. Mean dROM value in healthy horses was 103.3 ±20.7 U. Carr and mean PAC was 2881.0 ± 313.9 U. Cor. This system reliably and reproducibly quantified dROM and PAC in equine plasma samples.

Time-domain Brillouin scattering theory for probe light and acoustic beams propagating at an angle and acousto-optic interaction at material interfaces.

A theory has been developed to interpret time-domain Brillouin scattering (TDBS) experiments involving coherent acoustic pulse (CAP) and light pulse beams propagating at an angle to each other. It predicts the influence of the directivity pattern of their acousto-optic interaction on TDBS signals when heterodyne detection of acoustically scattered light is in backward direction to incident light. The theory reveals relationships between the carrier frequency, amplitude and duration of acoustically induced "wave packets" in light transient reflectivity signals, and factors such as CAP duration, widths of light and sound beams, and their interaction angle. It describes the transient dynamics of these wave packets when the light and CAP encounter material interfaces, and how the light scattering by the incident CAP transforms into scattering by the reflected and transmitted CAPs. The theory suggests that single-point TDBS experiments can determine not only depth positions of buried interfaces but also their local inclinations/orientations.

Congenital hypogonadotrophic hypogonadism, induction of minipuberty, and future fertility.

Summary: A 33-year-old man with Kallmann syndrome had received pulsatile GnRH as an infant for the treatment of cryptorchidism. As an adult, his treatment for fertility with gonadotrophins was unusually rapid compared with expectations, with a total sperm count of 25 million after only 12 months of gonadotrophin therapy. We propose that pulsatile GnRH treatment as an infant induced minipuberty and facilitated his successful, rapid response to therapy. We also propose that identification of the absence of minipuberty in infants with clinical signs suggesting congenital hypogonadotrophic hypogonadism (CHH) is an opportunity for intervention with pulsatile GnRH yielding benefits for fertility decades later. Learning points: Absence of minipuberty in males with CHH results in low Sertoli cell numbers and delayed response to induction of spermatogenesis in adulthood. Presentation with 'red flags' for androgen deficiency including cryptorchidism at birth, with or without micropenis, should prompt screening for CHH and minipuberty by measurement of gonadotrophins and testosterone in the first 2 months after birth. Pulsatile GnRH therapy in patients with CHH, given prior to age of attainment of Sertoli cell maturation, can replicate the normal physiology of minipuberty, thereby priming the testis for future fertility.

Implications of phonon anisotropy on thermal conductivity of fluorite oxides.

Fluorite oxides are attractive ionic compounds for a range of applications with critical thermal management requirements. In view of recent reports alluding to anisotropic thermal conductivity in this face-centered cubic crystalline systems, we perform a detailed analysis of the impact of direction-dependent phonon group velocities and lifetimes on the thermal transport of fluorite oxides. We demonstrate that the bulk thermal conductivity of this class of materials remains isotropic despite notable anisotropy in phonon lifetime and group velocity. However, breaking the symmetry of the phonon lifetime under external stimuli including boundary scattering present in nonequilibrium molecular dynamics simulations of finite size simulation cell gives rise to apparent thermal conductivity anisotropy. We observe that for accurate determination of thermal conductivity, it is important to consider phonon properties not only along high symmetry directions commonly measured in inelastic neutron or x-ray scattering experiments but also of those along lower symmetry. Our results suggests that certain low symmetry directions have a larger contribution to thermal conductivity compared to high symmetry ones.

Incidence of Tendon Rupture After Collagenase Clostridium Histolyticum Injection for Treatment of Dupuytren Contracture in Adults: A Postmarketing Safety Analysis.

Purpose: Based, in part, on the clinical study reports of tendon rupture events after collagenase clostridium histolyticum (CCH) (Xiaflex, Endo Pharmaceuticals Inc) treatment for Dupuytren contracture (DC), a Risk Evaluation and Mitigation Strategy program was instituted in 2010 by Auxilium Pharmaceuticals (now Endo Pharmaceuticals Inc) to ensure that the benefits of CCH injection outweighed the risks when treating DC. Using the postmarketing surveillance data collected in this program, a retrospective analysis was conducted to evaluate the incidence of flexor tendon rupture after CCH treatment for DC in the clinical practice setting. Methods: The Endo Pharmaceuticals Inc safety database was searched for cases of tendon rupture reported between February 2, 2010, and October 8, 2015. Total number of CCH treatments for DC and incidence of tendon rupture were estimated using CCH dosing derived from clinical trial experience (1.7 CCH vials/treatment) or clinical practice evidence (1.08 CCH vials/treatment). Results: Over the 5.8-year surveillance period, 97,609 vials of CCH were distributed for the treatment of DC, equivalent to an estimated total of 57,416 treatments (at 1.7 CCH vials/treatment) or 90,378 treatments (at 1.08 CCH vials/treatment). Although CCH distribution increased during the surveillance period, reports of tendon rupture were infrequent (approximately 13 cases/y; total cases: flexor tendon, n = 57; ligament/pulley, n = 2), corresponding to a 0.10% (1.7 CCH vials/treatment) or 0.06% (1.08 CCH vials/treatment) mean estimated incidence of tendon rupture in patients with DC after CCH treatment. Conclusions: This retrospective analysis showed that flexor tendon rupture occurred infrequently in patients with DC who were treated with CCH in real-world practice settings between 2010 and 2015. On the basis of these findings and other favorable safety evidence, the Risk Evaluation and Mitigation Strategy program requirement for CCH for the treatment of DC was ended by the US Food and Drug Administration in November 2016. Type of study/level of evidence: Therapeutic IV.

Analytical validation of five diagnostic tests for the detection of polymorphonuclear cells in stallion semen.

The objectives of this study were to evaluate the ability of five diagnostic tests to detect polymorphonuclear cells (PMNs) in stallion semen, and to determine the concentration of PMNs that affects sperm motility. We hypothesized that all tests have diagnostic value, and even low concentrations of PMNs affect motility. One ejaculate was obtained from six stallions. Aliquots of 50 × 106 purified sperm were incubated, in triplicate, with six concentrations of purified PMNs: 1) no PMNs, 2) 0.25 × 106 PMN/ml, 3) 0.5 × 106 PMN/ml, 4) 2.5 × 106 PMN/ml, 5) 5 × 106 PMN/ml, 6) 10 × 106 PMN/ml. The PMNs were quantified using a hemacytometer, cytology, a leucocyte esterase dipstick test (LEDT), a peroxidase test, and CD13 immunolabeling. Sperm motility was evaluated after 4 h at 38 °C. The number of leucocytes detected with the LEDT differed among treatments (P<0.0001), from negative results in control samples to moderate or large numbers in the samples with the highest PMN concentration. The hemacytometer count and CD13 immunostaining detected differences with the control treatment at the lowest PMN concentration (2.5 × 106 PMN/ml; P<0.001). Sperm motion was lower in samples with ≥5 × 106 PMN/ml (P<0.0001). Thus, a sample was considered leucospermic if it contained ≥5 × 106 PMN/ml. The LEDT had the best sensitivity (100%), followed by cytology (78%), peroxidase test (60%), CD13 immunostaining (56%) and hemacytometer count (47%). The LEDT had the lowest specificity (65%), which was 95% for all other tests. In conclusion, the LEDT was a simple, economic and sensitive stall-side test to screen semen for presence of PMNs. Because of the lower specificity, positive LEDT results should be confirmed with the identification of peroxidase-positive cells or CD13-positive cells.

Advances in actinide thin films: synthesis, properties, and future directions.

Actinide-based compounds exhibit unique physics due to the presence of 5f electrons, and serve in many cases as important technological materials. Targeted thin film synthesis of actinide materials has been successful in generating high-purity specimens in which to study individual physical phenomena. These films have enabled the study of the unique electron configuration, strong mass renormalization, and nuclear decay in actinide metals and compounds. The growth of these films, as well as their thermophysical, magnetic, and topological properties, have been studied in a range of chemistries, albeit far fewer than most classes of thin film systems. This relative scarcity is the result of limited source material availability and safety constraints associated with the handling of radioactive materials. Here, we review recent work on the synthesis and characterization of actinide-based thin films in detail, describing both synthesis methods and modeling techniques for these materials. We review reports on pyrometallurgical, solution-based, and vapor deposition methods. We highlight the current state-of-the-art in order to construct a path forward to higher quality actinide thin films and heterostructure devices.

Hematologic profiles and development of innate immune function in healthy Holstein calves during the pre-weaning period.

BACKGROUND: The development and state of innate immune cell function during the first 90 days of life in dairy calves have not been fully described. OBJECTIVE: This transversal study attempted to examine the changes that occur in circulating blood cells and the innate immune response in healthy calves from birth to 89 days of age. METHODS: Healthy Holstein calves represent three windows of development, G1 from 1 to 7 days old (n = 26), G2 from 30 to 40 days old (n = 28), and G3 from 60 to 89 days old (n = 36) were sampled once each from a single herd. A few biomarkers of the general health and innate and inflammatory immune responses were measured. RESULTS: The youngest calves had the lowest red blood cell (RBC) counts, cell hemoglobin concentration means (CHCMs), red cell distribution widths (RDWs), and cell hemoglobin contents of mature red blood cells (CHm) compared with the other groups. They also had the lowest iron concentrations and highest intracellular myeloperoxidase indices. However, white blood cell (WBC) and lymphocyte concentrations gradually increased from G1 to G3. G2 calves had the lowest serum protein concentrations and highest number of innate immune cells compared with the other groups. Calves were able to mount phagocytic and ROS responses from birth. CONCLUSIONS: The physiologic responses of circulating blood cells and innate immune responses in dairy calves are shown according to age. Neonates had limitations in several RBC and WBC indices and immunologic responses that would likely impact overall vigor and health. Fortunately, these limitations resolve by 90 days of age.

Real-world Medicare Healthcare Costs of Patients with Dupuytren's Contracture Treated with Collagenase or Fasciectomy.

Background: Our study aimed to compare real-world healthcare resource utilization (HRU) and healthcare cost (HC) of Medicare-insured patients (≥65 years old) with Dupuytren's contracture (DC) treated with Clostridium histolyticum (collagenase) or fasciectomy. Methods: DC patients treated with collagenase or fasciectomy between July 2011 and June 2017 were identified using the IBM MarketScan Medicare Supplemental Database. The index date was the date of the first procedure. Demographic characteristics were captured on the index date, and comorbidities were assessed during the 24-month preindex period. HRU and HC were analyzed throughout the 12-month postindex period. Patients were matched using propensity score weights. Gamma log-linked generalized linear models were used to evaluate HC drivers. Results: Out of 37,374 DC patients, 2911 received collagenase, while 6258 underwent fasciectomy. Postmatching, the total average annual HC was similar between collagenase and fasciectomy ($7271 versus $6220, P = 0.357). When HCs were stratified by the service provider, outpatient facility and physician office costs were lower in the collagenase cohort ($850 versus $1284, P = 0.047 and $546 versus $1001, P < 0.001). The costs of professional services were significantly higher than in the fasciectomy cohort due to the cost of collagenase injection ($1682 versus $629, P < 0.001). The HRU was similar between cohorts, except for more frequent outpatient facility visits in fasciectomy patients (12.3 versus 22.9, P < 0.001). Generalized linear model revealed Charlson comorbidity index, plan type, patients' residence region, sleep disorder, and hyperlipidemia as significant predictors of total HC. Conclusion: This study found comparable total annual HC and HRU between collagenase- and fasciectomy-treated Medicare patients.

Collagenase Clostridium Histolyticum-aaes for Treatment of Cellulite: A Pooled Analysis of Two Phase-3 Trials.

Background: Collagen-rich fibrous septae and subcutaneous adipose protrusions play a role in cellulite pathophysiology. Collagenase clostridium histolyticum-aaes (CCH-aaes) injection causes enzymatic release of septae to resolve cellulite depressions and create a skin smoothing effect. This analysis pooled data from two identically designed, phase-3, randomized, double-blind, placebo-controlled studies to examine the efficacy and safety of CCH-aaes. Methods: Adult women with moderate/severe cellulite (3-4 on Clinician Reported Photonumeric Cellulite Severity Scale and Patient Reported Photonumeric Cellulite Severity Scale) on the buttocks received up to three treatment sessions (Days 1, 22, and 43) of subcutaneous CCH-aaes 0.84 mg or placebo per treatment area. Composite and individual component response (≥2-level or ≥1-level improvement from baseline in Patient Reported Photonumeric Cellulite Severity Scale and/or Clinician Reported Photonumeric Cellulite Severity Scale) and additional patient-reported outcomes were determined at Day 71. Results: Analysis included 424 CCH-aaes-treated and 419 placebo-treated women. CCH-aaes-treated women were 5.9 times more likely than placebo-treated women to be ≥2-level composite responders at Day 71 (odds ratio [95% confidence interval], 5.9 [2.2-15.4]; P < 0.001). A significantly greater percentage of CCH-aaes-treated women versus placebo-treated women were ≥1-level composite responders at Day 71 (39.4% versus 14.6%; P < 0.001). Subgroup analyses indicated no apparent impact of Fitzpatrick skin type category and baseline cellulite severity (moderate/severe) on CCH-aaes efficacy. An inverse relationship between age and CCH-aaes response was observed in those with a body mass index less than 32 kg per m2. The most common adverse events with CCH-aaes were injection-site bruising and injection-site pain. Conclusion: CCH-aaes treatment significantly improved moderate-to-severe buttock cellulite appearance and was generally well tolerated.

Type 2 diabetes: an exploratory genetic association analysis of selected metabolizing enzymes and transporters and effects on cardiovascular and renal biomarkers.

OBJECTIVES: This study sought to identify potential pharmacogenetic associations of selected enzymes and transporters with type 2 diabetes (T2D). In addition, pharmacogenomic profiles, concentrations of asymmetric dimethylarginine (ADMA) or kidney injury molecule-1 (KIM-1), and several covariates were investigated. METHODS: Whole blood was collected from 63 patients, with 32 individuals with T2D. A pharmacogenomic panel was used to assay genetic profiles, and biomarker ELISAs were run to determine subject concentrations of ADMA and KIM-1. Additive genetic modeling with multiple linear and logistic regressions were performed to discover potential SNPs-outcome associations using PLINK. RESULTS: Ten SNPs were found to be significant (p<0.05) depending on the inclusion or exclusion of covariates. Of these, four were found in association with the presence of T2D, rs2231142, rs1801280, rs1799929, and rs1801265 depending on covariate inclusion or exclusion. Regarding ADMA, one SNP was found to be significant without covariates, rs1048943. Five SNPs were identified in association with KIM-1 and T2D in the presence of covariates, rs12208357, rs34059508, rs1058930, rs1902023, and rs3745274. Biomarker concentrations were not significantly different in the presence of T2D. CONCLUSIONS: This exploratory study found several SNPs related to T2D; further research is required to validate and understand these relationships.

Evaluation of equine xenogeneic mixed lymphocyte reactions using 5-ethynyl-2'-deoxyuridine (EdU).

Allogeneic solid organ transplantation is currently the only treatment option for end stage organ disease. The shortage of available donor organs has driven efforts to utilize xenogeneic organs for transplantation. In vitro methods for evaluating immune-compatibility are a quick and low cost means of screening novel tissue products prior to more involved, expensive, and invasive live animal studies. Recently, a new analog of the DNA base thymidine, 5-ethynyl-2'-deoxyuridine (EdU), was developed. It may be used in a fast, efficient and specific means of evaluating cell proliferation via flow cytometry. This study was designed to test and optimize this platform for assessing equine xenogeneic one-way mixed lymphocyte reaction (MLR) to porcine stimulator cells. Furthermore, it was hypothesized that an enriched T-lymphocyte (T-cell) population would generate a stronger proliferative response to stimulation, and higher levels of cytokine production when compared to unfractionated peripheral blood mononuclear cells (PBMCs). PBMCs and T-cells were isolated from 3 horses and 4 pigs. Equine xenogeneic MLRs were set up using porcine allogeneic MLRs as a reference for clinically acceptable levels of cell proliferation. Equine T-cells showed significantly greater EdU incorporation in one-way xenogeneic MLRs than equine PBMCs. However, there was no significant difference in cell proliferation between porcine T-cell and PBMC as responders in allogenic one-way MLRs. Given the results of this study, we consider that enriched equine T-cells should be used in preference to unfractionated PBMCs when attempting to evaluate the equine xenogeneic response using the EdU assay as an indicator of suitability for transplant in vivo.

Local measurement of bulk thermal diffusivity using photothermal radiometry.

An experimental methodology using photothermal radiometry is developed for the accurate measurement of bulk thermal diffusivity of nuclear fuels and materials irradiated to high doses. Under these conditions, nuclear fuels, such as uranium oxide, and moderator materials, such as graphite, become friable, which requires characterization techniques that can accommodate irregularly shaped fragments. Photothermal radiometry, a good candidate for this application, involves locally heating a sample by using a laser and measuring the temperature field by monitoring blackbody radiation. The interaction volume for this study, less than a millimeter, is carefully chosen to sample a statistically significant number of large-scale structural features, such as pores and gas filled bubbles, and is small enough that the sample fragments can be treated as a thermal half-space. The thermal diffusivity standards considered in this study cover a range of thermal diffusivities representative of both fresh and spent nuclear fuels. We also consider a sample having a porous microstructure representative of large-scale structures found in materials irradiated to high doses. Our measurement methodology circumvents complex thermal wave models that address optical diffraction, nonlinear transfer function associated with blackbody radiation, and finite sample size effects. Consequently, the large measurement uncertainty associated with modeling these effects can be avoided. While the emphasis here is on nuclear fuels and materials, this measurement approach is well suited to measure thermal transport in a variety of technologically important materials associated with advanced synthesis techniques. Examples range from small, exotic single crystals grown using hydrothermal growth techniques to additively manufactured components having complex geometries.

Influence of exposure to microbial ligands, immunosuppressive drugs and chronic kidney disease on endogenous immunomodulatory gene expression in feline adipose-derived mesenchymal stem cells.

OBJECTIVES: Feline autologous mesenchymal stem cells (MSCs) show promise for immunomodulatory activity, but the functional impact of chronic kidney disease (CKD), concurrent immunosuppressive drug administration or infection is unknown. The study objectives compare endogenous cytokine gene expression (interleukin [IL]-6, IL-10, IL-12p40, IL-18 and transforming growth factor beta [TGF-ß]) in adipose-derived MSCs (aMSCs) from cats with and without CKD, following in vitro exposure to microbial ligands and treatment with common immunosuppressive drugs. METHODS: Previously obtained aMSCs, phenotype CD44+, CD90+, CD105+ and MHCII-, from cats with (n = 6) and without (n = 6) CKD were compared via real-time PCR (RT-PCR) for immunomodulatory gene expression. aMSCs were exposed in vitro to lipopolysaccharide (LPS), peptidoglycan or polyinosinic:polycytidylic acid (Poly I:C), simulating bacterial or viral exposure, respectively. aMSCs were also exposed to ciclosporin, dexamethasone or methotrexate. Gene expression was measured using RT-PCR, and Cq was utilized after each run to calculate the delta cycle threshold. RESULTS: aMSCs isolated from healthy and CKD cats showed no significant differences in gene expression in the five measured cytokines. No significant changes in measured gene expression after drug treatment or microbial ligand stimulation were observed between normal or CKD affected cats. Proinflammatory genes (IL-6, IL-12p40 and IL-18) showed altered expression in aMSCs from both groups when compared with the same cells in standard culture after exposure to methotrexate. Poly I:C altered IL-6 and TGF-ß gene expression in aMSCs from both healthy and CKD cats when compared with the same cells in standard culture. CONCLUSIONS AND RELEVANCE: The five genes tested showed no statistical differences between aMSCs from healthy or CKD cats. There was altered cytokine gene expression between the control and treatment groups of both healthy and CKD cats suggesting feline aMSCs have altered function with immunosuppressive treatment or microbial ligand exposure. Although the current clinical relevance of this pilot study comparing brief exposure to select agents in vitro in aMSCs from a small number of cats is unknown, the study highlights a need for continued investigation into the effects of disease and concurrent therapies on use of cell-based therapies in feline patients.