Review of current and potential applications of mesenchymal stem cells in exotic animal species.

The discovery that a population of cells derived from adult tissues had regenerative properties and could be expanded and utilized therapeutically led to an abundance of research into the safety and efficacy of these cells for a variety of disease processes. Derived from tissues of mesenchymal origin, these cells were called mesenchymal stem cells or mesenchymal stromal cells (MSCs). MSCs were subsequently found to have a variety of anti-inflammatory, antimicrobial, and regenerative properties both in vitro and in vivo. These cells have been extensively studied and demonstrated to be effective in the treatment of autoimmune diseases, inflammatory diseases, infectious diseases, and other pathologic conditions. Multiple veterinary clinical trials have been performed for diseases such as osteoarthritis, soft tissue, and tendon injuries in addition to other inflammatory and infectious conditions. Exotic animal species can pose additional challenges to the treatment of common medical conditions such as osteoarthritis due to varying metabolism and tolerance to medications as well as potential difficulty to medicate or utilize other common forms of therapy such as physical therapy, laser, massage, and acupuncture. Current knowledge of MSC use in exotic species is limited, but there is a large potential for benefit to a variety of species utilizing this novel therapeutic tool. This review includes a brief overview of mechanisms and known applications of this therapy as well as current and potential applications of MSCs in exotic animal species.

Chiropractic Day 2023: A Report and Qualitative Analysis of How Thought Leaders Celebrate the Present and Envision the Future of Chiropractic.

Objective: This study aimed to (1) collect and analyze statements about how to celebrate chiropractic in the present and roles that chiropractors may fulfill in the future, (2) identify if there was congruence among the themes between present and future statements, and (3) offer a model about the chiropractic profession that captures its complex relationships that encompass its interactions within microsystem, mesosystem, exosystem, and macrosystem levels. Methods: For this qualitative analysis, we used pattern and grounded theory approaches. A purposive sample of thought leaders in the chiropractic profession were invited to answer the following 2 open-ended questions: (1) envision the chiropractor of the future, and (2) recommendations on how to celebrate chiropractic. Information was collected during April 2023 using Survey Monkey. The information was entered into a spreadsheet and analyzed for topic clusters, which resulted in matching concepts with social-ecological themes. The themes between the responses to the 2 questions were analyzed for congruence. We used the Standards for Reporting Qualitative Research to report our findings. Results: Of the 54 experts invited, 32 (59%) participated. Authors represented 7 countries and have a median of 32 years of chiropractic experience, with a range of 5 to 51 years. Nineteen major topics in the future statements and 23 major topics in statements about celebrating chiropractic were combined in a model. The topics were presented using the 4 levels of the social-ecological framework. Individual (microsystem): chiropractors are competent, well-educated experts in spine and musculoskeletal care who apply evidence-based practices, which is a combination of the best available evidence, clinical expertise, and patient values. Interpersonal relationships (mesosystem): chiropractors serve the best interests of their patients, provide person-centered care, embrace diversity, equity, and inclusion, consider specific health needs and the health of the whole person. Community (exosystem): chiropractors provide care within integrated health care environments and in private practices, serve the best interests of the public through participation in their communities, participate through multidisciplinary collaboration with and within the health care system, and work together as a profession with a strong professional identity. Societal (macrosystem): chiropractors contribute to the greater good of society and participate on a global level in policy, leadership, and research. There was concordance between both the future envisioning statements and the present celebration recommendations, which suggest logical validity based on the congruence of these concepts. Conclusion: A sample of independent views, including the perceptions from a broad range of chiropractic thought leaders from various backgrounds, philosophies, diversity characteristics, and world regions, were assembled to create a comprehensive model of the chiropractic profession. The resulting model shows an array of intrinsic values and provides the roles that chiropractors may provide to serve patients and the public. This study offers insights into the roles that future chiropractors may fulfill and how these are congruent with present-day values. These core concepts and this novel model may have utility during dialogs about identity, applications regarding chiropractic in policy, practice, education, and research, and building positive relationships and collaborations.

Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry.

Given the rapid potential spread of agricultural pathogens, and the lack of vaccines for many, there is an important unmet need for strategies to induce rapid and non-specific immunity against these viral and bacterial threats. One approach to the problem is to generate non-specific immune responses at mucosal surfaces to rapidly protect from entry and replication of both viral and bacterial pathogens. Using complexes of charged nanoparticle liposomes with both antiviral and antibacterial toll-like receptor (TLR) nucleic acid ligands (termed liposome-TLR complexes or LTC), we have previously demonstrated considerable induction of innate immune responses in nasal and oropharyngeal tissues and protection from viral and bacterial pathogens in mixed challenge studies in rodents, cattle, and companion animals. Therefore, in the present study, we used in vitro assays to evaluate the ability of the LTC immune stimulant to activate key innate immune pathways, particularly interferon pathways, in cattle, swine, and poultry. We found that LTC complexes induced strong production of type I interferons (IFNα and IFNß) in both macrophages and leukocyte cultures from all three species. In addition, the LTC complexes induced the production of additional key protective cytokines (IL-6, IFNγ, and TNFα) in macrophages and leukocytes in cattle and poultry. These findings indicate that the LTC mucosal immunotherapeutic has the capability to activate key innate immune defenses in three major agricultural species and potentially induce broad protective immunity against both viral and bacterial pathogens. Additional animal challenge studies are warranted to evaluate the protective potential of LTC immunotherapy in cattle, swine, and poultry.

Intravenous injection of adipose-derived mesenchymal stromal cells benefits gait and inflammation in a spontaneous osteoarthritis model.

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published. Therefore, the aim of this study was to evaluate the short-term impact of intravenous (IV) delivery of allogeneic adMSCs in an established model of spontaneous OA, the Hartley guinea pig. Animals with moderate OA received once weekly injections of 2 × 106 adMSCs or vehicle control for 4 weeks in peripheral veins; harvest occurred 2 weeks after the final injection. Systemic administration of adMSCs resulted in no adverse effects and was efficacious in reducing clinical signs of OA (as assessed by computer-aided gait analysis) compared to control injected animals. Further, there were significant decreases in key inflammatory mediators (including monocyte chemoattractant protein-1, tumor necrosis factor, and prostaglandin E2 ) both systemically (liver, kidney, and serum) and locally in the knee (joint tissues and synovial fluid) in animals treated with IV adMSCs relative to controls (as per enzyme-linked immunosorbent assay and/or immunohistochemistry, dictated by tissue sample). Thus, systemic administration of adMSCs by IV injection significantly improved gait parameters and reduced both systemic and intra-articular inflammatory mediators in animals with OA. These findings demonstrate the potential utility of alternative delivery approaches for cellular therapy of OA, particularly for patients with multiple affected joints.

Immune Activated Cellular Therapy for Drug Resistant Infections: Rationale, Mechanisms, and Implications for Veterinary Medicine.

Antimicrobial resistance and biofilm formation both present challenges to treatment of bacterial infections with conventional antibiotic therapy and serve as the impetus for development of improved therapeutic approaches. Mesenchymal stromal cell (MSC) therapy exerts an antimicrobial effect as demonstrated in multiple acute bacterial infection models. This effect can be enhanced by pre-conditioning the MSC with Toll or Nod-like receptor stimulation, termed activated cellular therapy (ACT). The purpose of this review is to summarize the current literature on mechanisms of antimicrobial activity of MSC with emphasis on enhanced effects through receptor agonism, and data supporting use of ACT in treatment of bacterial infections in veterinary species including dogs, cats, and horses with implications for further treatment applications. This review will advance the field's understanding of the use of activated antimicrobial cellular therapy to treat infection, including mechanisms of action and potential therapeutic applications.

Activated Mesenchymal Stromal Cell Therapy for Treatment of Multi-Drug Resistant Bacterial Infections in Dogs.

New and creative approaches are required to treat chronic infections caused by increasingly drug-resistant strains of bacteria. One strategy is the use of cellular therapy employing mesenchymal stromal cells (MSC) to kill bacteria directly and to also activate effective host immunity to infection. We demonstrated previously that activated MSC delivered systemically could be used effectively together with antibiotic therapy to clear chronic biofilm infections in rodent models. Therefore, we sought in the current studies to gain new insights into the antimicrobial properties of activated canine MSC and to evaluate their effectiveness as a novel cellular therapy for treatment of naturally-occurring drug resistant infections in dogs. These studies revealed that canine MSC produce and secrete antimicrobial peptides that synergize with most classes of common antibiotics to trigger rapid bactericidal activity. In addition, activated canine MSC migrated more efficiently to inflammatory stimuli, and secreted factors associated with wound healing and fibroblast proliferation and recruitment of activated neutrophils. Macrophages incubated with conditioned medium from activated MSC developed significantly enhanced bactericidal activity. Clinical studies in dogs with chronic multidrug resistant infections treated by repeated i.v. delivery of activated, allogeneic MSC demonstrated significant clinical benefit, including infection clearance and healing of infected tissues. Taken together, the results of these studies provide new insights into antimicrobial activity of canine MSC, and their potential clinical utility for management of chronic, drug-resistant infections.

Intra-Articular Injections of Allogeneic Mesenchymal Stromal Cells vs. High Molecular Weight Hyaluronic Acid in Dogs With Osteoarthritis: Exploratory Data From a Double-Blind, Randomized, Prospective Clinical Trial.

This double-blind, randomized, prospective clinical trial was conducted to obtain exploratory data comparing the efficacy of intra-articular allogeneic mesenchymal stem/stromal cells (MSC) to high molecular weight hyaluronic acid (HA) for the treatment of pain associated with canine osteoarthritis (OA). Objective gait analysis (%Body Weight Distribution, %BWD), accelerometry, clinical metrology instruments and veterinary exams were used as outcome measures during various time points throughout the 48-week study period. Fourteen dogs with elbow or coxofemoral OA were enrolled and assigned in a 2:1 ratio to the treatment groups. Each patient received a set of two injections 4 weeks apart. Self-limiting joint flare was observed in seven patients, with six of these in the MSC group. Ten patients completed all follow-up appointments. Both treatment groups showed evidence of mild improvement following the treatment, but the results were inconsistent among the various outcome measures assessed. Overall, dogs enrolled in the HA group showed greater improvement compared to the MSC group. The primary outcome measure, %BWD, showed evidence of improvement, when compared to baseline values, at 36 weeks after injection for the HA group only (p = 0.048, estimated difference: 4.7). Similarly, when treatment groups were compared, evidence of a difference between treatment groups (with the HA-group showing greater improvement) were identified for weeks 24 and 36 (p = 0.02 and 0.01, respectively). The small sample size of this exploratory study does not allow firm conclusions. However, until studies with larger sample sizes are available, the current literature combined with our data do not support the clinical use of intra-articular MSC therapy over high molecular weight HA for the treatment of canine OA at this time.

Making Race Visible in the Speech, Language, and Hearing Sciences: A Critical Discourse Analysis.

PURPOSE: The purpose of this critical discourse analytic study is to identify how two key professional standards documents in the Speech, Language and Hearing Sciences field-the Standards for Certification document and the Essential Functions rubric-contribute to the discursive construction of the ideal speech-language pathologist and audiologist, and to examine whether the experiences and needs of people of color are taken into consideration in these documents. METHOD: Critical discourse analysis was used as both a conceptual and methodological lens for the systematic analysis of the targeted text. RESULTS: The findings show that considerations of race and racism were almost entirely absent from both documents and thus reflected a discourse of race neutrality that is ideologically consistent with color-blind racism. The enactment of racially coded expectations within a construct of race-neutral discourse maintains racial inequities in the speech, language, and hearing sciences professions. CONCLUSIONS: The findings highlight the need for the open acknowledgment of racism in our institutional policies and discourses and official and ongoing commitments to concrete and measurable antiracist actions to counteract systemic racism. Recommendations for and examples of antiracist measures are offered.

Establishing a reference interval for acute phase proteins, cytokines, antioxidants and commonly measured biochemical and hematologic parameters in the northern fur seal (Callorhinus ursinus).

Over the past several decades there has been a precipitous decline of northern fur seals (Callorhinus ursinus; NFS) at their breeding grounds on the Pribilof Islands in the Bering Sea. The cause of this decline is likely multifactorial and could include changes in environmental parameters, prey abundance and distribution as well as exposure to pathogens and pollutants. Evaluation of inflammatory markers and antioxidant levels of the current population of fur seals in addition to hematologic and biochemical profiles could provide important information regarding health and subclinical or clinical disease in this population. Serum and plasma samples were obtained from clinically healthy adult female NFS and references intervals were determined for multiple parameters that can be altered in response to the presence of disease and environmental stressors. We established a reference interval for cytokines involved in acute inflammation and infection (TNFa, IL1, IL6, IL8, KC, IL10, C-reactive Protein) by utilizing commercially available canine cross-reactive antibodies. Reference intervals were also established for reactive oxygen species (hydrogen peroxide and malondialdehyde), as well as antioxidant levels (vitamin E and selenium) and acute phase proteins evaluated by serum electrophoresis. To improve the ability to compare and interpret indicators of health and disease in this species, we developed reference intervals for commonly utilized hematologic and biochemical tests in addition to the aforementioned markers of oxidative stress and inflammatory biomarkers. There were several animals identified as outliers indicating that they may have had subclinical illness or inflammation. Further investigation utilizing these tests in clinically ill animals and comparison to animals that exhibit normal behavior and no overt signs of illness could increase our understanding of the utility of measuring these parameters in this species.

Toll-like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion.

OBJECTIVE: To evaluate effects of Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor (TLR, NLR) ligand stimulation of equine mesenchymal stromal cells (MSCs) on antibacterial and immunomodulatory properties in vitro. STUDY DESIGN: Controlled laboratory study. SAMPLE POPULATION: Equine bone-marrow-derived MSCs (three horses). METHODS: MSCs were stimulated with TLR (polyinosinic:polycytidylic acid [pIC] and lipopolysaccharide [LPS]) and NLR agonists (γ-d-Glu-mDAP [IE-DAP]) for 2 h, and plated at 1 × 105 cells/well 24 h. MSC-conditioned media (MSC-CM) were collected and assessed for antimicrobial peptide cathelicidin/LL-37 production, bactericidal action against multidrug-resistant planktonic and biofilm Staphylococcus aureus and neutrophil phagocytosis. Bacterial growth was measured by plating bacteria and counting viable colonies, reading culture absorbance, and live-dead staining with confocal microscopy imaging. Following initial comparison of activating stimuli, TLR3-agonist pIC protocols (cell density during activation and plating, culture time, %serum) were further optimized for bactericidal activity and secretion of interleukin-8 (IL-8), monocyte-chemoattractant-protein (MCP-1), and cathelicidin/LL37. RESULTS: MSCs stimulation with pIC (p = .004) and IE-DAP (p = .03) promoted increased bactericidal activity, evidenced by reduced viable planktonic colony counts. PIC stimulation (2 × 106 cells/ml, 2 h, 10 µg/ml) further suppressed biofilm formation (p = .001), enhanced neutrophil bacterial phagocytosis (p = .009), increased MCP-1 secretion (p < .0001), and enhanced cathelicidin/LL-37 production, which was apparent when serum concentration in media was reduced to 1% (p = .01) and 2.5% (p = .05). CONCLUSION: TLR-3 pIC MSCs activation was most effective to enhance antibacterial and cytokine responses, which were affected by serum reduction. CLINICAL SIGNIFICANCE: In vitro TLR-3 activation of equine MSCs tested here may be a strategy to improve antibacterial properties of MSCs to treat antibiotic-resistant infections.

Liver Lobe Torsion in a Guinea Pig (Cavia porcellus).

A 5-year-old, female intact guinea pig (Cavia porcellus) presented for acute inappetence. The abdomen was severely distended and tympanic with moderate discomfort. Radiographs showed gastric distension and displacement. Gastric dilatation and volvulus were suspected. At necropsy, the left lateral liver lobe was torsed at the hilus and infarcted. Histopathology showed regionally extensive coagulative necrosis and markedly congested sinusoids, causing marked hepatic cord atrophy and dissociation. Final diagnoses were severe gastric dilatation with left lateral liver lobe torsion (LLT) and regionally extensive liver infarction, and hemoabdomen. Reports of LLT in guinea pigs are likely underrepresented in the literature. LLTs should be considered in guinea pigs presenting for acute inappetence and abdominal distension. Laboratory tests and abdominal ultrasound can help differentiate LLT from other gastrointestinal pathologies seen in guinea pigs, such as gastric dilatation and volvulus. Early recognition of LLT in guinea pigs could potentially improve patient outcomes. This is the first published report of LLT in a guinea pig.

Exploring Diverse Career Paths and Recommendations for Celebrating Chiropractic Day 2021: A Narrative Inquiry.

OBJECTIVE: The purpose of this report was to explore the views of chiropractors about their career paths and recommendations for Chiropractic Day. METHODS: For this narrative inquiry, selected individuals from diverse backgrounds were invited to share their experiences about becoming chiropractors and their recommendations for Chiropractic Day. Each doctor of chiropractic was asked to provide a response to a set of structured questions. The responses were collated into a descriptive narrative, and themes were identified from these narratives. RESULTS: Five chiropractors from diverse backgrounds, who graduated from chiropractic programs in the United States, participated in this project. Each reported a different path to becoming a chiropractor. From these different career paths, common themes emerged, which included (1) a drive to serve others, (2) a personal experience or quest, (3) and a propensity to be problem solvers and inquisitive learners. Their recommendations for celebrating Chiropractic Day paralleled their individual qualities and values, which included providing educational seminars to patients and other health care providers, mentoring students, reading scientific papers about health issues related to diversity, providing chiropractic services to underserved populations, appreciating our predecessors and mentors, and performing community outreach. CONCLUSION: This narrative provides insight into the thoughts of people from diverse backgrounds about why they may choose chiropractic as a profession and their paths to a career in chiropractic. This article demonstrates that chiropractors come to the profession for a variety of reasons but may have similar themes such as that the choice may generate from a personal experience, a quest for knowledge, an interest in helping others, and a joy for service. This narrative provides unique insights about the authors' values for chiropractic, which were congruent with their recommendations for celebrating Chiropractic Day.

Clinical evaluation of hyperimmune plasma for treatment of dogs with naturally occurring parvoviral enteritis.

OBJECTIVE: To evaluate the clinical efficacy of a single infusion of hyperimmune plasma (HIP) in dogs with canine parvovirus (CPV). DESIGN: Prospective, randomized, placebo-controlled clinical trial. SETTING: University teaching hospital. ANIMALS: Client-owned dogs with naturally occurring CPV. INTERVENTIONS: Dogs presenting for CPV treatment (n = 31) underwent cardiovascular resuscitation and were randomized to receive a single dose of either HIP (10 mL/kg IV) or placebo (0.9% sodium chloride [10 mL/kg IV]) during the first 6 hours of hospitalization. All dogs were treated with a standardized treatment protocol (IV fluid therapy [120 mL/kg/d isotonic crystalloids], cefoxitin [30 mg/kg IV q 8 h], maropitant [1 mg/kg IV q 24 h], and buprenorphine [0.01-0.02 mg/kg IV q 8 h]) until hospital discharge. MEASUREMENTS AND MAIN RESULTS: Dogs treated with HIP (n = 16) demonstrated a lower shock index at 24 hours (median = 0.77, range: 0.5-1.5) than those treated with placebo (n = 15, median = 1.34, range: 0.5-1.7; P = 0.02). Plasma lactate concentration was lower at 24 hours in HIP-treated dogs (median = 1.3 mmol/L, range: 0.9-3.4 mmol/L) than in placebo-treated dogs (median = 2.1 mmol/L, range: 1.1-3.4 mmol/L; P = 0.01). There was no difference in duration of hospitalization when comparing HIP-treated dogs (median = 3.2 days, range: 0.83-10 days) to placebo-treated dogs (median = 2.83 days, range: 1-8.38 days; P = 0.35). Survival was 16 of 16 (100%) for the HIP group and 14 of 15 (93.3%) for the placebo group (P = 0.32). CONCLUSIONS: HIP at 10 mL/kg IV administered to dogs with CPV within the first 6 hours of hospitalization improves markers of shock during the initial 24 hours of hospitalization. No effects were observed on duration of hospitalization or mortality; however, this study was underpowered to evaluate these effects. HIP was well tolerated in this population of critically ill dogs.

Pretreatment aerobic bacterial swab cultures to predict infection in acute open traumatic wounds: A prospective clinical study of 64 dogs.

OBJECTIVE: To determine the value of initial aerobic bacterial cultures of acute open traumatic wounds to predict bacterial species in wounds that become infected. STUDY DESIGN: Prospective clinical trial. ANIMALS: Sixty-four dogs with naturally occurring acute cutaneous traumatic wounds (2017-2018). METHODS: Initial swabs were taken from each wound prior to and after lavage and debridement for quantitative and qualitative aerobic bacterial culture. Cultures were repeated on wounds that displayed any clinical sign of infection within 14 days of presentation. RESULTS: Fewer bacteria were cultured from postlavage than from prelavage swabs in 43 of 50 (86%) acute wounds. All primary clinicians prescribed ß-lactam antibiotics to the dogs at initial presentation. All bacteria cultured from postlavage/debridement cultures at initial presentation were susceptible to the prophylactic antimicrobial prescribed. Postoperative infection was subsequently diagnosed in 14 of 64 (22%) dogs; 13 of these dogs had positive culture results. No correlation was detected between the results of initial wound cultures and the subsequent development of wound infection. Bacterial species present in the initial wound swab did not correlate with those subsequently cultured from infected tissues. CONCLUSION: Results of pretreatment wound cultures from open traumatic wounds in dogs were not predictive of bacterial species subsequently recovered from infected wounds. The bacterial burden present in pretreatment wounds was not predictive of whether wounds would ultimately become infected after surgical management. CLINICAL SIGNIFICANCE: Routine bacterial culturing of acute wounds is not likely to help predict subsequent wound infection, nor is it likely to accurately guide early selection of antimicrobials to treat wounds that become infected.

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells.

Mesenchymal stem cells (MSC) have been shown to improve wound healing and suppress inflammatory immune responses. Newer research also indicates that MSC exhibit antimicrobial activity, although the mechanisms underlying this activity have not been fully elucidated. Therefore, we conducted in vitro and in vivo studies to examine the ability of resting and activated MSC to kill bacteria, including multidrug resistant strains. We investigated direct bacterial killing mechanisms and the interaction of MSC with host innate immune responses to infection. In addition, the activity of MSC against chronic bacterial infections was investigated in a mouse biofilm infection model. We found that MSC exhibited high levels of spontaneous direct bactericidal activity in vitro. Moreover, soluble factors secreted by MSC inhibited Staphylococcus aureus biofilm formation in vitro and disrupted the growth of established biofilms. Secreted factors from MSC also elicited synergistic killing of drug-resistant bacteria when combined with several major classes of antibiotics. Other studies demonstrated interactions of activated MSC with host innate immune responses, including triggering of neutrophil extracellular trap formation and increased phagocytosis of bacteria. Finally, activated MSC administered systemically to mice with established S. aureus biofilm infections significantly reduced bacterial numbers at the wound site and improved wound healing when combined with antibiotic therapy. These results indicate that MSC generate multiple direct and indirect, immunologically mediated antimicrobial activities that combine to help eliminate chronic bacterial infections when the cells are administered therapeutically.

Humoral immune responses against gut bacteria in dogs with inflammatory bowel disease.

Inflammatory bowel disease (IBD) in dogs is associated with clinical signs of intestinal dysfunction, as well as abnormal lymphocytic and myeloid cell infiltrates in the small and/or large intestine. Thus, in many respects IBD in dogs resembles IBD in humans. However, the factors that trigger intestinal inflammation in dogs with IBD are not well understood and have been variously attributed to immune responses against dietary antigens or intestinal antigens. Previous studies in humans with IBD have documented increased production of IgG and IgA antibodies specific to intestinal bacteria, and this abnormal immune response has been linked to disease pathogenesis. Therefore, we investigated the humoral immune response against gut bacteria in dogs with IBD, using flow cytometry to quantitate IgG and IgA binding. Studies were also done to investigate the source of these antibodies (locally produced versus systemic production) and whether greater antibody binding to bacteria is associated with increased inflammatory responses. We found that dogs with IBD had significantly higher percentages and overall amounts of IgG bound to their intestinal bacteria compared to healthy dogs. Similarly, significantly higher percentages of bacteria were IgA+ bacteria were also found in dogs with IBD. Serum antibody recognition of gut bacteria was not different between healthy dogs and dogs with IBD, suggesting that anti-bacterial antibodies were primarily produced locally in the gut rather than systemically. Importantly, bacteria in the Actinobacteria phylum and in particular the genus Collinsella had significantly greater levels of antibody binding in dogs with IBD. Based on these findings, we concluded that antibody binding to commensal gut bacteria was significantly increased in dogs with IBD, that particular phyla were preferential targets for gut antibodies, and that anti-bacterial antibody responses may play an important role in regulating gut inflammation.

Evaluation of Intravenously Delivered Allogeneic Mesenchymal Stem Cells for Treatment of Elbow Osteoarthritis in Dogs: A Pilot Study.

OBJECTIVES: The aim of this study was to evaluate the safety and collect pilot data measuring clinical effects of intravenously administered, adipose-derived, culture-expanded, allogeneic mesenchymal stem cells in dogs with elbow osteoarthritis. MATERIALS AND METHODS: Dogs (n = 13) with naturally occurring elbow osteoarthritis received three intravenous doses of allogeneic canine mesenchymal stem cells via an open-label clinical trial. Primary outcome measures collected over a 6-month study period included objective gait analysis, accelerometry, owner questionnaires and joint fluid analysis. RESULTS: No acute adverse events were observed following repeated intravenous treatment with allogeneic mesenchymal stem cells. A significant improvement in mean client-specific outcome measure (CSOM) activity score and CSOM behaviour score was observed when pre-treatment values were compared with post-treatment values (day >28). In contrast, mean peak vertical force significantly decreased from baseline to post-treatment (>day 28). Weekly activity counts did not show a significant difference between baseline to post-treatment time points. Synovial fluid biomarkers did not change during treatment, and labelled mesenchymal stem cells were rarely detected in synovial fluid samples collected after mesenchymal stem cell administration. CLINICAL SIGNIFICANCE: For dogs with naturally occurring elbow osteoarthritis, intravenous administration of mesenchymal stem cells was clinically well tolerated. While some subjective outcome measures showed significant improvements, objective outcome measures did not confirm similar changes. Further research is needed before intravenous mesenchymal stem cells can be recommended as a treatment for elbow osteoarthritis in dogs.

Curriculum-Based Language Assessment With Culturally and Linguistically Diverse Students in the Context of Mathematics.

Purpose: The purpose of this tutorial is to discuss the use of curriculum-based language assessment (CBLA) with students who are English language learners and students who speak nonmainstream varieties of English, such as African American English. Method: The article begins with a discussion of the discourse of mathematics and the role of the speech-language pathologist (SLP), followed by a review of studies that includes those that examined the performance of English language learner and nonmainstream dialect-speaking students on word-based math items. Results: The literature review highlights the linguistic and content biases associated with word-based math problems. Useful strategies that SLPs and educators can incorporate in culturally and linguistically appropriate assessments are discussed. The tutorial ends with a discussion of CBLA as a viable assessment approach to use with culturally and linguistically diverse students. Conclusions: Tests used at national, state, and school levels to assess students' math abilities have associated linguistic bias and content bias often leading to an inaccurate depiction of culturally and linguistically diverse students' math skills. CBLA as an assessment method can be used by school-based SLPs to gather valid and useful information about culturally and linguistically diverse students' language for learning math. By using CBLA, SLPs can help modify curricular tasks in broader contexts in an effort to make math, including high-level math, "accessible and achievable for all" students (American Speech-Language-Hearing Association, 2017).

Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model.

Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has emerged as a promising new therapeutic strategy for managing inflammatory bowel disease (IBD). However, MSC therapy ideally requires a convenient and relatively homogenous cell source (typically bone marrow or adipose tissues) and the ability to generate cells with stable phenotype and function. An alternative means of generating allogeneic MSC is to derive them from induced pluripotent stem cells (iPSC), which could in theory provide an indefinite supply of MSC with well-defined phenotype and function. Therefore, we compared the effectiveness of iPSC-derived MSC (iMSC) and adipose-derived MSC (adMSC) in a mouse model of IBD (dextran sodium sulfate-induced colitis), and investigated mechanisms of intestinal protection. We found that iMSC were equivalent to adMSC in terms of significantly improving clinical abnormalities in treated mice and reducing lesion scores and inflammation in the gut. Administration of iMSC also stimulated significant intestinal epithelial cell proliferation, increased in the numbers of Lgr5+ intestinal stem cells, and increased intestinal angiogenesis. In addition, the microbiome alterations present in mice with colitis were partially restored to resemble those of healthy mice following treatment with iMSC or adMSC. Thus, iMSC administration improved overall intestinal health and healing with equivalent potency to treatment with adMSC. This therefore is the first report of the effectiveness of iMSC in the treatment of IBD, along with a description of unique mechanisms of action with respect to intestinal healing and microbiome restoration. Stem Cells Translational Medicine 2018;7:456-467.

Cationic Liposome-Oligonucleotide Complex as an Alternative Adjuvant for Polyclonal Antibody Production in New Zealand White Rabbits (Oryctolaguscuniculus).

Because of their ideal size and temperament, rabbits are commonly used in polyclonal antibody production. Immunostimulatory adjuvants-such as Freund complete and incomplete adjuvants as well as various proprietary products-trigger a robust immune response, which increases antibody concentrations. However, these adjuvants can cause excessive soft tissue reactions, prompting concerns regarding animal wellbeing. This study assessed the safety and efficacy of cationic liposome- oligonucleotide complexes (CLDC) as an alternative adjuvant to conventional adjuvants. On days 0 and 14, 15 female New Zealand white rabbits were vaccinated subcutaneously with 15 µg ovalbumin mixed with either CLDC, Freund adjuvant (day 0, complete; day 14, incomplete), or a proprietary adjuvant (n = 5 per group). Antibody titers were measured by direct ELISA on days 0, 14, and 28. Rabbits were palpated daily for lesion development, and all lesions were measured. Rabbits in all groups developed a significant antibody response to ovalbumin over 28 d. However, the differences between groups were not statistically significant. No rabbits in the CLDC group developed skin lesions, whereas 80% of rabbits that received Freund adjuvant and 100% of those that received the proprietary product developed skin lesions. This study demonstrates that CLDC may be a valuable and effective alternative adjuvant for polyclonal antibody production in rabbits-one that avoids the palpable injection-site lesions often seen with other adjuvants.