Homeostatic functions of monocytes and interstitial lung macrophages are regulated via collagen domain-binding receptor LAIR1.

Myeloid cells encounter stromal cells and their matrix determinants on a continual basis during their residence in any given organ. Here, we examined the impact of the collagen receptor LAIR1 on myeloid cell homeostasis and function. LAIR1 was highly expressed in the myeloid lineage and enriched in non-classical monocytes. Proteomic definition of the LAIR1 interactome identified stromal factor Colec12 as a high-affinity LAIR1 ligand. Proteomic profiling of LAIR1 signaling triggered by Collagen1 and Colec12 highlighted pathways associated with survival, proliferation, and differentiation. Lair1-/- mice had reduced frequencies of Ly6C- monocytes, which were associated with altered proliferation and apoptosis of non-classical monocytes from bone marrow and altered heterogeneity of interstitial macrophages in lung. Myeloid-specific LAIR1 deficiency promoted metastatic growth in a melanoma model and LAIR1 expression associated with improved clinical outcomes in human metastatic melanoma. Thus, monocytes and macrophages rely on LAIR1 sensing of stromal determinants for fitness and function, with relevance in homeostasis and disease.

Mechanisms of reduced myocardial energetics of the dystrophic heart.

Heart disease is a leading cause of death in patients with Duchenne muscular dystrophy (DMD), characterized by the progressive replacement of contractile tissue with scar tissue. Effective therapies for dystrophic cardiomyopathy will require addressing the disease before the onset of fibrosis, however, the mechanisms of the early disease are poorly understood. To understand the pathophysiology of DMD, we perform a detailed functional assessment of cardiac function of the mdx mouse, a model of DMD. These studies use a combination of functional, metabolomic, and spectroscopic approaches to fully characterize the contractile, energetic, and mitochondrial function of beating hearts. Through these innovative approaches, we demonstrate that the dystrophic heart has reduced cardiac reserve and is energetically limited. We show that this limitation does not result from poor delivery of oxygen. Using spectroscopic approaches, we provide evidence that mitochondria in the dystrophic heart have attenuated mitochondrial membrane potential and deficits in the flow of electrons in complex IV of the electron transport chain. These studies provide evidence that poor myocardial energetics precede the onset of significant cardiac fibrosis and likely results from mitochondrial dysfunction centered around complex IV and reduced membrane potential. The multimodal approach used here implicates specific molecular components in the etiology of reduced energetics. Future studies focused on these targets may provide therapies that improve the energetics of the dystrophic heart leading to improved resiliency against damage and preservation of myocardial contractile tissue.NEW & NOTEWORTHY Dystrophic hearts have poor contractile reserve that is associated with a reduction in myocardial energetics. We demonstrate that oxygen delivery does not contribute to the limited energy production of the dystrophic heart even with increased workloads. Cytochrome optical spectroscopy of the contracting heart reveals alterations in complex IV and evidence of depolarized mitochondrial membranes. We show specific alterations in the electron transport chain of the dystrophic heart that may contribute to poor myocardial energetics.

Characteristics of good clinical teachers in anesthesiology from medical students' perspective: a qualitative descriptive study.

PURPOSE: Learning needs are influenced by the stage of learning and medical specialty. We sought to investigate the characteristics of a good clinical teacher in anesthesiology from the medical students' perspective. METHODS: We conducted a qualitative descriptive study to analyze written comments of medical students about their clinical teachers' performances. Our analysis strategy was the inductive content analysis method. The results are reported as a descriptive summary with major themes as the final product. RESULTS: Our study identified four themes. The first theme, teachers' individual characteristics, includes characteristics that are usually more related to students' subjective experiences and feelings. The second theme, teachers' characteristics that advance student learning, seems to be one of the most important contributions to learning because it increases the practice of procedural skills. The third theme, teachers' characteristics that prepare students for success, shows characteristics that facilitate students' learning by promoting a healthy and safe environment. Lastly, the fourth theme, characteristics related to teaching approaches, includes characteristics that can guide clinical teachers more objectively. CONCLUSION: Our analysis of the written comments of medical students identified many characteristics of a good clinical teacher that were organized in four different themes. These themes contribute to expand on existing understandings of clinical teaching in the anesthesiology clerkship environment, and add new interpretations that can be reflected upon and explored by other clinical educators.

RéSUMé: OBJECTIF: Les besoins d'apprentissage sont influencés par le stade d'apprentissage et la spécialité médicale. Nous avons cherché à étudier les caractéristiques d'un bon enseignant clinique en anesthésiologie selon la perspective des étudiants en médecine. MéTHODE: Nous avons mené une étude descriptive qualitative pour analyser les commentaires écrits des étudiants en médecine sur les performances de leurs enseignants cliniques. Notre stratégie d'analyse était la méthode inductive d'analyse de contenu. Les résultats sont présentés sous forme de résumé descriptif avec les principaux thèmes comme produit final. RéSULTATS: Notre étude a identifié quatre thèmes. Le premier thème, les caractéristiques individuelles des enseignants, comprend des caractéristiques qui sont habituellement davantage liées aux expériences subjectives et aux sentiments des étudiants. Le deuxième thème, les caractéristiques de l'enseignant qui font progresser l'apprentissage des étudiants, semble être l'une des contributions les plus importantes à l'apprentissage parce qu'elle augmente la pratique des compétences procédurales. Le troisième thème, les caractéristiques de l'enseignant qui préparent les étudiants à la réussite, présente des caractéristiques qui facilitent l'apprentissage des étudiants en favorisant un environnement sain et sécuritaire. Enfin, le quatrième thème, les caractéristiques liées aux approches pédagogiques, comprend des caractéristiques qui peuvent guider les enseignants cliniques de manière plus objective. CONCLUSION: Notre analyse des commentaires écrits des étudiants en médecine a identifié de nombreuses caractéristiques d'un bon enseignant clinique qui étaient organisées en quatre thèmes différents. Ces thèmes contribuent à élargir les connaissances existantes de l'enseignement clinique dans l'environnement de stage clinique en anesthésiologie et ajoutent de nouvelles interprétations qui peuvent inciter d'autres éducateurs cliniques à y réfléchir et à les explorer.

Mentorship in anesthesia: a survey of perspectives among Canadian anesthesia residents.

PURPOSE: Mentorship is important for professional and academic growth; however, the role of mentorship in anesthesia is still being defined. We surveyed Canadian anesthesia residents to explore their perceptions of mentorship relationships. METHODS: We administered a 20-item cross-sectional survey to program directors and anesthesia residents in all Canadian departments of anesthesia. Program directors were asked about their mentorship programs, and residents were asked about their perceptions of benefits and barriers to effective mentoring. RESULTS: Sixteen of 17 (94%) program directors and 189 of 585 (32%) anesthesia residents responded to our survey. While 143 of 180 (79%) residents agreed that mentorship was beneficial to overall success as an anesthesiologist, only 11 of 16 (69%) program directors reported formal mentorship as part of their residency program, and only 119 of 189 (63%) residents reported access to a mentor. Barriers reported by residents included insufficient time with mentors, lack of formalized meeting times and objectives, mentor-mentee incompatibility (personal or professional), and lack of resident choice in mentor selection. CONCLUSION: Our study confirms that, despite positive perceptions among residents, mentorship remains underutilized in anesthesia programs. We identify barriers to effective mentorship, including the need to consider resident choice as a means to improve formal anesthesia mentorship programs.

Real-time immuno-polymerase chain reaction in a 384-well format: detection of vascular endothelial growth factor and epidermal growth factor-like domain 7.

Immuno-polymerase chain reaction (immuno-PCR) combines the specificity of antibodies with the amplification power of PCR to detect low levels of proteins. Here, we describe the development of a 384-well immuno-PCR method that uses streptavidin coated on a PCR plate to capture complexes of biotinylated capture antibody, antigen, and DNA-labeled detection antibody. Unbound molecules are removed by a wash step using a standard plate washer. Antibody-DNA molecules in bound complexes are then detected directly on the plate using real-time PCR. Circulating human vascular endothelial growth factor concentrations measured by this method correlated with measurements obtained from enzyme-linked immunosorbent assay (ELISA). Using this method, we developed an assay for human epidermal growth factor-like domain 7 (EGFL7), an extracellular matrix-bound angiogenic factor. EGFL7 is expressed at a higher level in certain cancers, although endogenous EGFL7 concentrations have not been reported. Our 384-well EGFL7 immuno-PCR assay can detect 0.51pM EGFL7 in plasma, approximately 16-fold more sensitive than the ELISA, utilizing the same antibodies. This assay detected EGFL7 in lysates of non-small-cell lung cancer and hepatocellular carcinoma cell lines and also hepatocellular carcinoma, breast cancer, and ovarian cancer tissues. This 384-well immuno-PCR method can be used to develop high-throughput biomarker assays.

Reflections: an inquiry into medical students' professional identity formation.

CONTEXT: Professional identity formation plays a crucial role in the transition from medical student to doctor. At McMaster University, medical students maintain a portfolio of narrative reflections of their experiences, which provides for a rich source of data into their professional development. The purpose of this study was to understand the major influences on medical students' professional identity formation. METHODS: Sixty-five medical students (46 women; 19 men) from a class of 194 consented to the study of their portfolios. In total, 604 reflections were analysed and coded using thematic narrative analysis. The codes were merged under subthemes and themes. Common or recurrent themes were identified in order to develop a descriptive framework of professional identity formation. Reflections were then analysed longitudinally within and across individual portfolios to examine the professional identity formation over time with respect to these themes. RESULTS: Five major themes were associated with professional identity formation in medical students: prior experiences, role models, patient encounters, curriculum (formal and hidden) and societal expectations. Our longitudinal analysis shows how these themes interact and shape pivotal moments, as well as the iterative nature of professional identity from the multiple ways in which individuals construct meaning from interactions with their environments. CONCLUSIONS: Our study provides a window on the dynamic, discursive and constructed nature of professional identity formation. The five key themes associated with professional identity formation provide strategic opportunities to enable positive development. This study also illustrates the power of reflective writing for students and tutors in the professional identity formation process.

The Evolving Landscape of Male Varicocele Pathophysiology in the Era of Multi-Omics: A Narrative Review of the Current Literature.

Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition.

Engineering upper hinge improves stability and effector function of a human IgG1.

Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys(231) directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His(229)-mediated hinge cleavage. On the other hand, the substitution of His(229) with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2-3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed.

Undergraduate Learners' Receptiveness to Feedback in Medical Schools: A Scoping Review.

Feedback from educators to learners is considered an important element of effective learning in medical school. While early studies were focused on the processes of providing feedback, recent work has showed that factors related to how learners receive feedback seems to be equally important. Considering that the literature on this topic is new in medical education, and studies are diverse and methodologically variable, we sought to conduct a scoping review to map the articles on receptiveness to feedback, to provide an overview of its related factors, to identify the types of research conducted in this area, and to document knowledge gaps in the existing literature. Using the Joanna Briggs Institute scoping review methodology, we searched four databases (CINAHL, Ovid, PubMed, and Web of Science) and screened 9120 abstracts, resulting in 98 articles for our final analysis. In this sample, 80% of studies on the feedback receiver were published in the last 10 years, and there is a vast variation in the studies' methodologies. The main factors that affect medical students' receptiveness to feedback are students' characteristics, feedback content, educators' credibility, and the learning environment. Feedback literacy is a very recent and rarely used term in medical education; therefore, an important area for further investigation. Lastly, we identified some gaps in the literature that might guide future research, such as studying receptiveness to feedback based on academic seniority and feedback literacy's long-term impacts on learning. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01858-0.

Effects of the COVID-19 pandemic on sales of sexual and reproductive health products: an ecological study of pharmacies in Kenya.

OBJECTIVES: To examine how sales of sexual and reproductive health (SRH) products varied among pharmacies in Kenya using administrative data, leveraging natural variation in the COVID-19 pandemic and accompanying policy restrictions between 2019 and 2021. DESIGN AND SETTING: Ecological study of pharmacies in Kenya. PARTICIPANTS: 761 pharmacies using the Maisha Meds product inventory management system (capturing 572 916 products sold). OUTCOMES: Sales quantity, price and revenue of SRH products sold per pharmacy per week. RESULTS: COVID-19 deaths were associated with a -2.97% (95% CI -3.82%, -2.11%) decrease in sales quantity, a 1.09% (95% CI 0.44%, 1.72%) increase in sales price and a -1.89% (-1.00%, -2.79%) decrease in revenues per pharmacy per week. Results were similar when considering new COVID-19 cases (per 1000) and the Average Policy Stringency Index. Results differed substantially between individual SRH products-a large decrease in sales quantity in pregnancy tests, injectables and emergency contraception, a modest decrease in condoms and no change in oral contraception. Sales price increases were similarly varied; four of the five most sold products were revenue neutral. CONCLUSIONS: We found a robust negative association between SRH sales at pharmacies in Kenya and COVID-19 reported cases, deaths and policy restriction. Although our data cannot definitively point to reduced access, existing evidence from Kenya regarding unchanged fertility intentions, increases in unintended pregnancies and reported reasons for non-use of contraceptives during COVID-19 suggests a prominent role of reduced access. While policymakers may have a role in sustaining access, their role may be limited by broader macroeconomic problems, such as global supply chain disruptions and inflation, during supply shocks.

Review article: teaching, learning, and the pursuit of excellence in anesthesia education.

PURPOSE: Excellence in anesthesia education has been advocated to meet the future needs and direction of the specialty. The purpose of this article is twofold: first, to review the current medical education literature and theory in order to inform teaching and learning in anesthesia; and second, to advocate for excellence in anesthesia education. SOURCE: This review considers the general education, educational psychology, and medical education literature based on a search of the MEDLINE and ERIC databases, educational Web sites, and library catalogues. PRINCIPAL FINDINGS: Excellent teaching is considered that which facilitates and maximizes learning. A conceptual framework of learning as a convergence of teacher, learner, assessment, and context is proposed. The contribution of each component to learning is examined in order to enable anesthesia teachers to choose and adapt the most appropriate educational approaches for their particular contexts. The relationship of excellent teaching, scholarly teaching, and the scholarship of teaching is explored. Strategies for promoting excellence in anesthesia education are suggested. CONCLUSIONS: The call for excellence in anesthesia has become an important theme, particularly with respect to education. While excellent teaching is a goal to which all anesthesia faculty should aspire, scholarly teaching and scholarship in teaching should also be promoted in order to advance anesthesia education for the benefit of the profession and ultimately for patient care.

Review article: leading the future: guiding two predominant paradigm shifts in medical education through scholarship.

PURPOSE: The purpose of this article is to consolidate some of the key concepts about scholarship in education related to the specialty of anesthesiology. We frame the discussion on two paradigm shifts in medical education, i.e., competency-based education and lifelong learning, and the scholarly approaches to lead these paradigm shifts in anesthesiology. PRINCIPAL FINDINGS: Conventional medical education is being challenged by a shift from time-based education to competency-based education. This potential shift will also create a continuous need to foster a culture of lifelong learning in contrast with the traditional compartmentalized model of undergraduate, postgraduate, and continuing medical education. The specialty of anesthesia has the capacity to lead these changes by enhancing scholarship in education locally and nationally. The promotion of scholarship in education necessitates the creation of infrastructure and accountability frameworks to show return on investment. High-quality scholarship in medical education requires a solid rationale and, ultimately, a demonstrable benefit to patient care. CONCLUSION: Accountability of lifelong learning to established competency frameworks seems inevitable. Anesthesiology is one of only a few specialties that can truly protect faculty from clinical responsibilities in favour of scholarship pursuits. With appropriate support for scholarship in education, anesthesiologists have an opportunity to lead these paradigm shifts.

Learning while leading: a realist evaluation of an academic leadership programme.

INTRODUCTION: Many academic health centres and universities have implemented leadership development programmes; however, their potential impact in different contexts in healthcare remains unknown. We assessed the impact of an academic leadership development programme on the self-reported leadership activities of faculty leaders in their respective work contexts. METHODS: Ten faculty leaders who participated in a 10-month leadership development programme between 2017 and 2020 were interviewed. The realist evaluation approach was used to guide deductive content analysis, allowing concepts related to what works for whom, why and when to emerge from the data. RESULTS: Faculty leaders benefited in different ways depending on the organisational context (eg, culture) in which they reside and their individual contexts (eg, personal aspirations as a leader). Faculty leaders who have minimal mentorship in their leadership role gained an increased sense of community and belongingness with peer leaders and received validation in their personal leadership approach from the programme. Faculty leaders with accessible mentors were more likely than their peers to apply the knowledge they learnt to their work settings. Prolonged engagement among faculty leaders in the 10-month programme fostered continuity of learning and peer support that extended beyond programme completion. CONCLUSIONS: This academic leadership programme included participation of faculty leaders in different contexts, resulted in varying impacts on participants' learning outcomes, leader self-efficacy and application of acquired knowledge. Faculty administrators should look for programmes with a multitude of learning interfaces to extract knowledge, hone leadership skills and build networks.

Culture in medical education: comparing a Thai and a Canadian residency programme.

CONTEXT: Globalisation initiatives in medical education are premised on a universal model of medical education. This study was conducted to challenge this premise by empirically examining the impact of culture on the practice of medical education in anaesthesia residency training programmes in Thailand and Canada. METHODS: Using a mixed-methods comparative case study research approach, one Thai and one Canadian anaesthesia residency training programme were examined with respect to curriculum, educational practices and teacher beliefs. Data sources included observations of academic and clinical teaching, programme document analysis, surveys and faculty interviews. Recruitment resulted in a 76% survey response rate and 13 interview participants at the Thai site and a 61% survey response rate and 16 interview participants at the Canadian site. Multiple linear regression analysis was used to compare survey responses between the two programmes. The qualitative analysis consisted of primary coding, clustering into pattern codes, and identifying themes and sub-themes. The integration of quantitative and qualitative data for each case was followed by a cross-case analysis. RESULTS: The two programmes were similarly organised and had similar curricular content. However, important differences emerged in curricular emphasis, educational practices, and teacher beliefs and values. Thai faculty staff emphasised knowledge and scholarship, described the faculty-resident relationship as 'familial' and focused on 'teaching methods'. Canadian faculty members emphasised clinical abilities, described the faculty-resident relationship as 'collegial' and focused on 'learning environments'. These findings were related to broader cultural differences that influenced how the curriculum was interpreted and enacted at each site. CONCLUSIONS: This study shows that although the scientific and knowledge base of medical education is universal, its enactment may be influenced by culture and context. Globalisation initiatives in medical education must be tempered by recognition of these considerations.

From the front lines: a qualitative study of anesthesiologists' work and professional values.

PURPOSE: Despite significant contributions to medicine, anesthesiology is poorly recognized and faces the threat of "deprofessionalization". Clear articulation of its work and professional values plays an integral role in maintaining the viability of a profession. The purpose of this qualitative study is to explore anesthesiologists' perspectives in order to define the distinct elements of their work and their professional values. METHODS: A qualitative research approach was used for this study. Sixteen Canadian faculty anesthesiologists were interviewed regarding their choice of anesthesiology as a career, the characteristics of a good anesthesiologist and good anesthetic care, and the sources of work-related stress. The interviews were taped and transcribed. The qualitative analysis of the interviews included primary coding, which separated the data into units of meaning. Next, similar codes were clustered into pattern codes to identify common themes and subthemes. The relationships between the themes and subthemes were analyzed and interpreted to identify core values. RESULTS: The anesthesiologists were motivated to choose their career path by the academic, technical, and practice aspects of the profession, influential role models, and an interest in human consciousness. Five themes characterized a good anesthesiologist: clinical competence, personality traits, physician-patient relationship, approach to anesthetic care, and outcomes. The major sources of stress were: balancing clinical care and teaching, unexpected critical events, and administrative issues. Four core professional values were identified: goal-directed care, responsibility, control, and humility. CONCLUSIONS: Anesthesiology is characterized by its distinct work and core professional values. Under the threat of deprofessionalization, the practice of anesthesiology should be guided by its professional values in defining and envisioning its future.

Canadian and Australian licensing policies for international medical graduates: a web-based comparison.

CONTEXT: The increasing global mobility of physicians and severe physician shortages of many countries has led to an increasing reliance on International Medical Graduates (IMGs) by countries including Australia and Canada. OBJECTIVES: A web-based comparison of licensing policies for IMGs in Australia and Canada to inform and improve policies in each country. METHODS: The research involved identification of relevant government and medical regulatory bodies' official websites documenting information on the licensing process for IMGs from each respective country; in-depth examination and comparison of the licensing processes outlined on these sites; and compilation of a comprehensive list of similarities and differences. FINDINGS: While difficult entry requirements are imposed in Canada, once full registration is achieved IMGs have the same membership rights as Canadian medical graduates and their separate status (nominally) ends. In Australia, IMGs are allowed relatively easy access to temporary or conditional licenses, especially in designated underserviced areas or areas of need in order to fulfil resource demands. However IMGs are predominantly restricted to practise in limited and less prestigious positions within the medical hierarchy. DISCUSSION: The Canadian process for recertifying IMGs can be characterized as being based on the integration/assimilation of IMGs with domestically trained doctors. In contrast, Australia has pursued a different strategy of parallelism of its IMGs. CONCLUSIONS: The findings provide insights into how each country balances national licensing requirements with physician shortages in a globalized environment in order to provide healthcare for its citizens.