Sanaa Zaki

Osteoarthritis (OA) is one of the most common health conditions worldwide leading to immense individual and societal burden. Current treatments for OA are inadequate with no approved structural disease modifying therapies, and existing options for chronic pain only moderately successful long-term. Improving this bleak picture requires a better understanding of OA molecular pathophysiology, how this differs between individuals and over time. Critical in this goal are animal models. There have been four key advancements in this field that have dramatically improved OA pathophysiology discovery research: (1) initial studies showing mouse OA-risk is modified by the same factors as humans-age, sex/sex-hormones, diet and genetics (1952-65); (2) first studies of naturally-occurring OA in mice with spontaneous (1972-81) and induced (1993) genetic mutations (GMs); (3) developing reproducible inducible models with good structural and symptomatic fidelity to human OA (1990-2005); and (4) using inducible and spontaneous OA-models in GM-mice to show disease and symptom modification and define molecular causality (1999-present). These milestones revolutionized OA pathophysiology research, such that there are now >500 unique genes/gene-products identified as having significant effects on OA (beneficial or detrimental). Studies in different mouse OA-models have underpinned the concept of OA-phenotypes, and more particularly endotypes and theratypes, with ~35% of tested molecular targets having different effects on post-traumatic (pt)OA versus spontaneous/age-associated-OA. Deciphering and translating the enormous and growing data from animal-models into effective therapeutics for people remains challenging. This will require better identification and stratification of patients with different OA pheno/endotypes, and improved collaboration between clinical and pre-clinical researchers.

PICO question In rabbits, undergoing general anaesthesia, does the placement of a v-gel® device result in less airway trauma compared to the use of other airway management devices? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Three papers were critically appraised, two blinded randomised experimental trial studies and one randomised crossover experimental trial study Strength of evidence Weak Outcomes reported One blinded randomised trial study demonstrated that the trauma to the upper airways of rabbits during anaesthesia is not significantly different between the use of v-gel® and an endotracheal tube. The other blinded randomised trial study demonstrated that the trauma to the upper airway caused by endotracheal intubation is significantly more than that caused by v-gel® placement. The randomised crossover trial study demonstrated that v-gel® placement causes more significant compression to the larynx compared to a laryngeal mask or face mask Conclusion The current evidence suggests that use of the v-gel® in rabbits causes less trauma / injury to the airways compared to placement of an endotracheal tube but not compared to the use of a laryngeal or face mask. However, based on the low number and quality of published studies, this evidence is weak, and better-quality studies are required to support the routine use of v-gel® over other airway devices in rabbits. While v-gel® may be a safer alternative for securing airways in rabbits compared to endotracheal intubation, knowing the injuries this device can cause to the upper airways is useful for managing rabbits during post anaesthesia recovery How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Cite this article: Bone Joint Res 2022;11(8):514–517.

This paper presents a mini-review of employability as a guiding outcome in veterinary education—its conceptualisation, utility, core elements and dimensions, and pedagogical approaches—through a summary of the findings of a major international project with the same aims (the VetSet2Go project). Guided by a conception of the successful veterinary professional as one capable of navigating and sustainably balancing the (sometimes competing) needs and expectations of multiple stakeholders, the project integrated multiple sources of evidence to derive an employability framework representing the dimensions and capabilities most important to veterinary professional success. This framework provides a useful complement to those based in narrower views of competency and professionalism. One notable difference is its added emphasis on broad success outcomes of satisfaction and sustainability as well as task-oriented efficacy, thus inserting “the self” as a major stakeholder and bringing attention to resilience and sustainable well-being. The framework contains 18 key capabilities consistently identified as important to employability in the veterinary context, aligned to five broad, overlapping domains: veterinary capabilities (task-oriented work performance), effective relationships (approaches to others), professional commitment (approaches to work and the broader professional “mission”), psychological resources (approaches to self), plus a central process of reflective self-awareness and identity formation. A summary of evidence supporting these is presented, as well as recommendations for situating, developing, and accessing these as learning outcomes within veterinary curricula. Though developed within the specific context of veterinarian transition-to-practise, this framework would be readily adaptable to other professions, particularly in other health disciplines.

Objectives: Identification of osteoarthritis(OA)-specific synovial inflammatory pathways, and when in the clinical course they are active, is critical for their utility as therapeutic targets. We directly compared the mononuclear inflammatory/immune-cell responses following joint injury that does and does-not lead to OA, to define bona-fide OA-associated cellular events. Methods: We undertook detailed temporal flow-cytometric and mRNA expression analysis in mice after sham or medial-meniscal-destiblization (DMM) surgery. We compared this with patients with meniscal injury and OA, and evaluated the role of synovial monocytes/macrophages versus lymphocytes in catabolic metalloproteinase secrection in vitro . We determined the effect of transient acute or delayed systemic T-cell depletion on DMM-induced OA pathology. Results: OA-inducing/DMM and non-OA-inducing/Sham surgery had identical synovial monocyte/macrophage number, activation and polarization. The number and activation of synovial (not splenic or peripheral-blood) CD4 and CD8 lymphocytes was increased from 1-day after DMM versus Sham, and showed a persistent cyclical elevation throughout OA onset and progression. There was a temporal imbalance in synovial Th17/Treg and Th1/Th2 lymphocytes during DMM-induced OA initiation and progression. We confirmed early post-injury and late-OA CD3/CD8 T-cell responses in synovial tissues from patients, identified an association between CD8 and early post-injury symptoms, and defined a significant role for CD3 ⁺ T-cells in synovial metalloproteinase secretion. Anti-CD3 cell-depletion studies in mice confirmed a key role for the earliest post-injury T-cell response in long-term OA pathology. Conclusions: We identify a hitherto unappreciated pathophysiological role of acute T-cell activation after joint injury in long-term post-traumatic OA risk, providing a novel diagnostic and therapeutic target. Key Messages: What is already known about this subject?: The presence of synovitis/joint-inflammation increases the risk not only of osteoarthritis (OA) progression but incident disease. While numerous inflammatory effectors including macrophages and lymphocytes have been identified in OA, their disease-specificity, temporal regulation, and association with risk of pathology onset and progression is lacking. How does this study add?: By directly comparing the mononuclear inflammatory/immune-cell responses following significant joint injury that does (medial-meniscal-destabilization; DMM) and does-not (Sham-surgery) lead to OA in mice, we have defined bona-fide OA-associated cellular events. There was no difference in synovial or systemic monocyte/macrophage cell number, activation or polarization between DMM and Sham, both showing a successful wound-healing response. In contrast, increases in number and activation of synovial Th1- and Th17-CD4, and CD8 T-cells in DMM compared with Sham occurred within the first 3 days, and while recurring cyclically through subsequent disease onset, depletion studies indicated this initial influx was key to long-term ptOA risk. How might this impact on clinical practice of future developments?: Acute increases in synovial T-cells following jont injury may be both a novel marker of OA risk, and a target to reduce long term structural damage.

Despite the critical influence of motivation on education and work outcomes, little is known about the motivations driving people to become and remain veterinarians. This qualitative study explored the career motivations stated by Australian veterinary graduates (n = 43) using a free-response Ten Statements Test (TST) at graduation, with follow-up interviews 6–8 months later (n = 10). TST responses were coded using an alternate inductive-deductive approach that tested their fit against existing theories of motivation. Results showed that the stated motivations were predominantly oriented to perceived value, rather than self-beliefs such as expectancy of success. About a quarter of the statements were animal-related, principally themed around intrinsic animal orientation (e.g., I like animals) or extrinsic animal-related purpose (e.g., I want to help animals). However, many non-animal themes also emerged, including both intrinsic (e.g., love of learning, challenge/problem solving, variety, social relatedness) and extrinsic (e.g., helping people, social contribution, career opportunity) motivations. Interview data revealed a motivational narrative of early formative influences, with some interviewees describing a later transition toward more people- or goal-oriented motivations. This exploratory study, outlining a broad taxonomy of veterinary career motivations and their alignment to self-determination theory in particular, may provide a useful framework for exploring career motivations in veterinary education.