PARALLELS BETWEEN BIODIVERSITY AND HUMAN DIVERSITY: A MANDATE TO IMPROVE ECOLOGICAL AND ORGANIZATIONAL HEALTH AND VITALITY.

The veterinary medical profession-including in marine biology and oceanography, ecology, conservation science, and zoo, wildlife, aquatic, and exotic animal medicine-suffers from a well-known lack of diversity. It is the author's view that in order to ensure that animals (and plants) have the environment they need to thrive, and to address urgent ecosystem health and conservation issues in our global interconnected communities, our wildlife, zoo, and conservation science organizations must embrace diversity, equity, inclusion, and belonging (DEIB). Just as biodiversity is critical for the health and vitality of our ecosystem, the diversity of the people who care for those ecosystems will protect the health and vibrancy of our professions and organizations. Though research may not yet have established a direct link between the diversification of such organizations and the advancement of biodiversity, that does not mean there is no such effect or impact. With myriad evidence that diverse organizations are better at solving complex problems, why would there be an expectation that these professions would fare differently? A call to action is for such organizations to conduct and publish research regarding the impact of increased human diversity on their missions of enhancing biodiversity. The challenges to biodiversity are great, and our organizations must use every tool in the toolkit to find solutions-including enhancing DEIB. This article elaborates on the many benefits that come with prioritizing DEIB in our organizations-similar to those benefits arising from healthy, biodiverse ecosystems. Potential action steps are shared that organizations and associations may consider in promoting DEIB and igniting progress.

Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function.

The in-depth understanding of skin resident memory CD8+ T lymphocytes (TRM ) may help to uncover strategies for their manipulation during disease. We investigated isolated TRM from healthy human skin, which expressed the residence marker CD69, and compared them to circulating CD8+ T cell populations from the same donors. There were significantly increased proportions of CD8+ CD45RA- CD27- T cells in the skin that expressed low levels of killer cell lectin-like receptor G1 (KLRG1), CD57, perforin and granzyme B. The CD8+ TRM in skin were therefore phenotypically distinct from circulating CD8+ CD45RA- CD27- T cells that expressed high levels of all these molecules. Nevertheless, the activation of CD8+ TRM with T cell receptor (TCR)/CD28 or interleukin (IL)-2 or IL-15 in vitro induced the expression of granzyme B. Blocking signalling through the inhibitory receptor programmed cell death 1 (PD)-1 further boosted granzyme B expression. A unique feature of some CD8+ TRM cells was their ability to secrete high levels of tumour necrosis factor (TNF)-α and IL-2, a cytokine combination that was not seen frequently in circulating CD8+ T cells. The cutaneous CD8+ TRM are therefore diverse, and appear to be phenotypically and functionally distinct from circulating cells. Indeed, the surface receptors used to distinguish differentiation stages of blood T cells cannot be applied to T cells in the skin. Furthermore, the function of cutaneous TRM appears to be stringently controlled by environmental signals in situ.

Rituximab as a treatment for severe atopic eczema: failure to improve in three consecutive patients.

Biological therapies may provide the breakthrough in treating moderate to severe atopic eczema (AE) that is unresponsive to standard therapy. Rituximab has been shown to benefit some patients in published case series, and so we treated three consecutive patients with severe AE with rituximab. Despite achieving low/absent peripheral blood CD19 +  B-cell numbers following rituximab administration, this was not associated with clinical benefit as there was no major change in pre- and post-treatment Eczema Area and Severity Index (34, 64.4 and 42.2 compared with 33.2, 66 and 56.4, respectively). We would therefore recommend that that there is a compelling need for a formal, double-blind, placebo-controlled study to demonstrate efficacy of rituximab as a treatment of moderate to severe AE.

Sustained improvement in urticaria pigmentosa and pruritus in a case of indolent systemic mastocytosis treated with cladribine.

Systemic mastocytosis (SM) is a myeloproliferative disorder, characterized by a clonal proliferation of abnormal mast cells accumulating in internal organs and sometimes in the skin, leading to cutaneous and systemic symptoms. Mutations within the gene KIT, which encodes the receptor tyrosine kinase (KIT) on mast cells, is found in most patients with SM. We report a case of a 62-year-old woman presenting with a pruritic rash on her limbs and trunk. Several years later she developed gastrointestinal symptoms, associated with raised serum tryptase. Skin and bone marrow biopsies confirmed a diagnosis of SM, initially presenting with urticaria pigmentosa. Responses to multiple therapies, including potent topical steroids, oral antihistamines, phototherapy and the tyrosine kinase inhibitor, nilotinib, were inadequate. Treatment with cladribine (2-chlorodeoxyadenosine) produced a marked and sustained reduction in her symptoms and serum tryptase level.

Investigation of the cutaneous response to recall antigen in humans in vivo.

In this paper we provide a detailed description of an experimental method for investigating the induction and resolution of recall immune response to antigen in humans in vivo. This involves the injection of tuberculin purified protein derivative (PPD) into the skin, followed by inducing suction blisters at the site of injection, from which leucocytes and cytokines that are involved in the response can be isolated and characterized. Using this technique we found that although the majority of CD4(+) T cells in the skin that are present early in the response express cutaneous lymphocyte antigen (CLA), the expression of this marker is reduced significantly in later phases. This may enable these cells to leave the skin during immune resolution. Furthermore, interleukin (IL)-2 production can be detected both in CD4(+) T cells and also in the blister fluid at the peak of the response at day 7, indicating that mediators found in the blister fluid are representative of the cytokine microenvironment in vivo. Finally, we found that older humans have defective ability to respond to cutaneous PPD challenge, but this does not reflect a global immune deficit as they have similar numbers of circulating functional PPD-specific CD4(+) T cells as young subjects. The use of the blister technology enables further characterization of the skin specific defect in older humans and also general mechanisms that govern immune regulation in vivo.

Late-onset pretibial recessive dystrophic epidermolysis bullosa.

Pretibial epidermolysis bullosa (EB) is a rare form of localized dystrophic EB, characterized by recurrent blistering and scarring plaques occurring predominantly in the pretibial area. In most cases, nail dystrophy, especially of the toenails, is also present. Often there are no clinical abnormalities at birth, and the disorder may only appear after several years. We report a patient who developed symptoms in his fifth decade. Genetic testing identified compound heterozygosity for two pathogenic mutations in the COL7A1 gene. This case highlights a rare variant of mechanobullous disease, and stresses the importance of molecular screening in establishing a correct diagnosis. Precisely why the disorder specifically localizes to the shins or why it may only become apparent in later life is not known.

Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data.

Conventional non-biologic systemic agents are regarded as second-line therapy for the treatment of moderate-to-severe plaque psoriasis after topical treatments. However, long-term data have highlighted a number of safety concerns associated with their prolonged use. Biologic agents targeting specific immune mediators have emerged as an alternative treatment option for patients with moderate-to-severe plaque psoriasis who are unresponsive to, or intolerant of, non-biologic systemic agents. Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third-line therapies due to a relative lack of long-term safety data. Here, we have reviewed the long-term (≥ 1 year) safety data from randomized controlled trials, open-label extension studies and meta-analyses of etanercept, infliximab, efalizumab, adalimumab, alefacept and ustekinumab in the treatment of adults with moderate-to-severe plaque psoriasis. With the exception of efalizumab, which has been withdrawn from both the European and U.S. markets due to long-term safety concerns, these biologics are generally well tolerated in long-term studies, and offer a viable alternative to conventional non-biologic agents in patients with moderate-to-severe plaque psoriasis.

Effects of a cognitive-behavioral skills building program on the mental health outcomes and healthy lifestyle behaviors of veterinary medicine students.

OBJECTIVE: To evaluate the effects of a cognitive-behavioral skills building program (ie, MINDSTRONG; The Ohio State University) on the mental health outcomes and healthy lifestyle beliefs and behaviors of Doctor of Veterinary Medicine (DVM) students. Sample: DVM students (n = 62) before beginning their program at a large public Midwest land-grant university. Procedures: All 171 incoming DVM students (class of 2024) were required to take the cognitive-behavioral skills building program (7 weeks in length) before starting their 2020 school year. Students were given the option to consent to the study portion of the program. Consenting participants completed a pre- and postsurvey containing demographic questions and 5 valid and reliable scales, including the Patient Health Questionnaire-9 that assesses depressive symptoms, the Generalized Anxiety Disorder-7 that evaluates anxiety, the Brief Inventory of Perceived Stress that measures stress, and the Healthy Lifestyle Beliefs and Healthy Lifestyle Behaviors scales. Descriptive statistics described sample characteristics, paired t tests assessed changes over time in the outcomes Personal Wellness Assessment, and Cohen's d determined effect sizes. Results: 62 DVM students completed both surveys. Postintervention, students had significant improvements in depressive symptoms, anxiety, and healthy lifestyle beliefs and behaviors. Clinical Relevance: Although this study used a small convenience sample of DVM students from a single university, a cognitive-behavioral skills building program demonstrated the ability to decrease rates of depression, anxiety, and suicidal ideation and improve healthy lifestyle beliefs and behaviors. Requiring DVM students to participate in such programming could provide benefit during their professional education and throughout their careers.

Supporting diversity, equity, inclusion, and belonging to strengthen and position the veterinary profession for service, sustainability, excellence, and impact.

Advancing equality and equity in society is creating positive change, and the time has come to critically evaluate veterinary medicine, which, by all metrics, lacks diversity. To keep pace with increasingly diverse demographics and recent surges in pet ownership among all racial/ethnic groups, significant efforts to enhance diversity, equity, inclusion, and belonging (DEIB) must occur in veterinary colleges and the profession. Recruiting more underrepresented students, building pipelines for diverse faculty/staff, and creating inclusive, welcoming environments where all can thrive are critical steps toward enhancing DEIB within our organizations and profession. Our goal is to share experiences and lessons learned from our intentional commitment to strengthen DEIB, with the hope that our journey will be helpful to others. Increasing diversity in the veterinary profession will be facilitated through removing barriers, creating inclusive work environments where all people feel they belong, and ensuring fair and equitable hiring and personnel management practices. These steps should in turn improve access and quality of veterinary care, ensure we are more representative of the communities we serve, increase revenue, and preserve the human-animal bond. "You cannot change any society unless you take responsibility for it, unless you see yourself belonging to it, and responsible for changing it." - Grace Lee Boggs.

Transcriptional changes associated with recurrent airway obstruction in affected and unaffected horses.

OBJECTIVE: To identify differentially expressed genes in pulmonary tissues of horses affected with summer pasture-associated obstructive pulmonary disease (SPAOPD), which is a form of recurrent airway obstruction (RAO), compared with those of unaffected horses. ANIMALS: 6 horses with SPAOPD-RAO and 6 unaffected (healthy) horses. PROCEDURES: Horses were assigned to 2 groups on the basis of medical history, clinical score, and transpleural pressure. Total RNA from each of the 5 lung lobes of each of the 6 SPAOPD-RAO-affected horses was extracted and pooled. Similarly, total RNA from unaffected horses was pooled. Differential display (DD) PCR assay was performed, and differentially expressed bands were purified and cloned into a plasmid vector. Plasmids were extracted from recombinant colonies, and purified DNA was sequenced. Genes of interest for RAO pathogenesis were identified. Real-time PCR assay was performed to confirm findings for the DD PCR assay. RESULTS: 18 differentially expressed genes (17 upregulated and 1 downregulated) were identified. Three genes of particular interest were found to be altered (2 upregulated and 1 downregulated) in horses with SPAOPD-RAO by use of real-time PCR assay, and these findings matched the differential expression found by use of the DD PCR assay. CONCLUSIONS AND CLINICAL RELEVANCE: SPAOPD-RAO in horses is a multifactorial, complex disease involving several genes. Upregulated genes, particularly beta2-microglobulin, and the downregulated secretoglobin gene can serve as marker genes that may help to identify SPAOPD-RAO at an early age.

Effects of energy dissipation rate on islets of Langerhans: implications for isolation and transplantation.

Acute physical stresses can occur in the procurement and isolation process and potentially can contribute to islet death or malfunction upon transplantation. A contractional flow device, previously used to subject suspended cells to well-defined hydrodynamic forces, has been modified and used to assess the vulnerability of porcine islets of Langerhans to hydrodynamic forces. The flow profiles and velocity gradients in this modified device were modeled using commercial CFD software and characterized, as in previous studies, with the scalar parameter, energy dissipation rate (EDR). Porcine islets were stressed in a single pass at various stress levels (i.e., values of EDR). Membrane integrity, oxygen uptake rate, caspase 3/7 activity, and insulin release were not affected by the levels of fluid stress tested up to an EDR of 2 x 10(3) W/m(3). Visual observation of the stressed islets suggested that cells at the islet exterior were peeled away at EDR greater than 10,000 W/m(3), however, this observation could not be confirmed using image analysis software, which determined the ratio of surface perimeter to total area. The result of this study suggests an upper limit in fluid stress to which islets can be subjected. Such upper limits assist in the design and operation of future islet processing equipment and processes.

Use of serial laminar tissue collection via biopsy in conscious healthy horses.

OBJECTIVE: To determine the feasibility of performing serial laminar and skin biopsies on sedated horses and whether sampling affected adjacent tissues. ANIMALS: 6 horses. PROCEDURES: Laminar tissues were harvested via biopsy through the hoof wall from healthy conscious horses via sedation and regional anesthesia. Eight specimens were collected at 4 time points during 24 hours from a single foot. Laminar biopsy specimens were harvested with a 6-mm-diameter biopsy punch after burring through the horny corium to the stratum medium. Skin biopsy specimens were collected from an area proximal to the coronary band. All tissues were examined via light microscopy. Total RNA was extracted and quantified, and gene expression analysis was completed for 2 housekeeping genes and the inflammatory mediator cyclooxygenase-2. RESULTS: Laminar and skin biopsies yielded adequate specimens for histologic and gene expression evaluation. There was no extension of inflammation or detectable damage to adjacent tissues during the 24-hour period in either laminar or skin specimens as judged via histologic findings and cyclooxygenase-2 expression. Lameness and discomfort induced by the procedure were minimal. CONCLUSIONS AND CLINICAL RELEVANCE: Laminar biopsy provided a satisfactory method of collecting laminar specimens and allowed serial sampling of individual horses.

Multi-trait animal model estimation of genetic parameters for linear type and gait traits in the Belgian warmblood horse.

Genetic parameters for the height at withers, 27 linear type and six linear gait traits were estimated for the Belgian warmblood horse. Observations on 987 mares, mostly 3 years old, were analysed using a multi-trait animal model. The statistical model included appraiser, age and location (date x place of appraisal) as fixed effects. Genetic parameters were estimated using a canonical transformation and an expectation-maximization restricted maximum likelihood algorithm with an additional deceleration step. Estimates of heritability for the 33 linear traits were between 0.15 and 0.55. Heritability of the height at withers was 0.34 +/- 0.06. Estimated genetic correlations ranged from -0.60 to 0.98 with an average SE of 0.10. The highest positive correlations were found among traits of walk and among traits of trot. Volume and the quality of legs were the most negatively correlated. Estimated genetic parameters indicated that the linear scoring system is a valuable tool to assess conformation. The full (co)variance matrix is now available for breeding value estimation to support selection for conformation and gaits.

The need for veterinarians in biomedical research.

The number of veterinarians in the United States is inadequate to meet societal needs in biomedical research and public health. Areas of greatest need include translational medical research, veterinary pathology, laboratory-animal medicine, emerging infectious diseases, public health, academic medicine, and production-animal medicine. Veterinarians have unique skill sets that enable them to serve as leaders or members of interdisciplinary research teams involved in basic science and biomedical research with applications to animal or human health. There are too few graduate veterinarians to serve broad national needs in private practice; academia; local, state, and federal government agencies; and private industry. There are no easy solutions to the problem of increasing the number of veterinarians in biomedical research. Progress will require creativity, modification of priorities, broad-based communication, support from faculty and professional organizations, effective mentoring, education in research and alternative careers as part of the veterinary professional curriculum, and recognition of the value of research experience among professional schools' admissions committees. New resources should be identified to improve communication and education, professional and graduate student programs in biomedical research, and support to junior faculty. These actions are necessary for the profession to sustain its viability as an integral part of biomedical research.

Treatment of rosacea with intense pulsed light: significant improvement and long-lasting results.

BACKGROUND: Rosacea is a common skin condition but the treatments currently available are not satisfactory. OBJECTIVES: To assess the efficacy of intense pulsed light (IPL) for treatment of stage I rosacea (flushing, erythema and telangiectasia). METHODS: Thirty-four patients were treated, 25 women and nine men, mean age 47 years. The treatment employed was IPL 515-1200 nm, with a 560 nm cut-off filter. The fluence range was 24-32 J cm(-2). Four treatments were administered on the face at 3-week intervals. Erythema values were measured at baseline and at the end of the treatment period on the cheeks and chin. Digital photographs were assessed by a consultant dermatologist on a 10-point visual analogue scale (VAS). Patients' assessments were also made using a 10-point VAS. Outcome measures were repeated 6 months after treatment. RESULTS: After four treatments the mean reduction of the erythema values was 39% on the cheeks (P < 0.001) and 22% on the chin (P < 0.001). This was confirmed by photographic assessment where erythema improved by 46% and telangiectasia by 55% (P < 0.001). The severity of rosacea was reduced on average by 3.5 points on the 10-point VAS. Patients' and physicians' assessments of the overall improvement of rosacea were similar: more than 50% improvement was noticed in 73% and 83% of patients, respectively (P < 0.001). The results were sustained at 6 months. Side-effects were minimal and self-limiting. CONCLUSIONS: IPL significantly reduces erythema and telangiectasia of rosacea and this is sustained for at least 6 months.