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.

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.

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.

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.

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.

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.

Maintenance of certification for practicing physicians: a review of current challenges and considerations.

Maintenance of certification (MOC) has become increasingly important in medicine to ensure maintenance of competence throughout a physician's career. This paper reviews current issues and challenges associated with MOC in medicine, including how to define medical competencies for practicing physicians, assessment, and how best to support physicians' lifelong learning in a continuous and self-motivated way. We explore how the combination of self-monitoring, regular feedback, and peer support could improve self-assessment. Effective MOC programs are learner-driven, focused on every day practice, and incorporate educational principles. We discuss the importance of MOC to the physicians' actual practice to improve acceptability. We review the benefits of tailored programs as well as decentralization of MOC programs to better characterize the physician's practice. Lastly, we discuss the value of simulation-based medical education in MOC programs. Simulation-based education could be used to practice uncommon complications, life-threatening scenarios, non-technical skills improvement, and become proficient with new technology. As learners find simulation experiences educationally valuable, clinically relevant, and positive, simulation could be a way of increasing physicians' participation in MOC programs.

Le maintien de la certification (MDC) revêt de plus en plus d'importance en médecine pour assurer le maintien des compétences tout au long de la carrière d'un médecin. Cet article examine les problèmes et les défis liés au MDC en médecine, notamment au chapitre de la définition descompétences médicales nécessaires aux médecins en pratique, de l'évaluation, et des meilleurs moyens d'appuyer la démarche d'apprenant à vie de façon continue et avec motivation intrinsèque. Nous explorons comment l'effet conjugué de l'autosurveillance, de la rétroaction régulière, et du soutien des pairs peut améliorer l'autoévaluation. Les programmes de MDC efficaces rendent l'apprenant actif, ciblés sur la pratique quotidienne, et ils intègrent également des principes d'enseignements. Afin d'améliorer l'acceptabilité, nous discutons de l'importance du MDC dans la pratique actuelle des médecins. Nous examinons les avantages liés aux programmes personnaliséset à la décentralisation des programmes MDC pour mieux caractériser la pratique du médecin. En dernier lieu, nous discutons de la valeur de l'enseignement par simulation dans les programmes de MDC. L'enseignement par simulation pourrait être utilisé pour pratiquer dans des contextes de complications rares ou de scénariosoù la vie du patient est menacée, à l'amélioration des compétences non techniques et à la maîtrise des nouvelles technologies. Avecles apprenants qui constatent que les expériences de simulations sont éducatives, cliniquement pertinentes et positives, celles-ci pourraient inciter les médecins à participer davantage aux programmes de MDC.

What's the fuss? Gender and academic leadership.

PURPOSE: Women continue to be disproportionately represented in top leadership positions. Leadership development programs typically focus on skills attainment. The purpose of this paper is to explore the perceptions and experiences of academic leaders in order to inform how leadership development programs may more effectively address the gender gap in leadership. DESIGN/METHODOLOGY/APPROACH: A sequential mixed methods study design was used. Participants completed the Leadership Practice Inventory ®(LPI) survey followed by individual interviews of a subset of participants. The survey results were analyzed and compared by gender using the t-test. Thematic analysis was used to compare themes across and between genders. Quantitative and qualitative findings were integrated in the final analysis. FINDINGS: In total, 65 leaders (38 women; 27 men) (37.7 percent response rate) participated in the survey. There were no significant demographic or statistical differences between women and men on any of the LPI® components. Five women and five men were interviewed. Thematic analysis revealed common leadership aspirations and values. Gender differences were noted in leadership attainment, mentorship and the influence of gender on leadership. While the male narratives reflected cognitive awareness of gender inequities, the female narratives also included lived experiences. Male participants focused on the importance of meritocracy whereas the female participants emphasized the gendered social and structural influences on leadership attainment. PRACTICAL IMPLICATIONS: Leadership development programs need go beyond generic "skills-building" in order to conceptualize leadership within a gendered social context. This framework will enable critical awareness and tools for developing both women and men's fullest leadership potential. ORIGINALITY/VALUE: This study was conducted in order to better understand how academic health leaders experience the intersection of gender and leadership. The findings contribute to the current literature by providing insight into perceptual gaps that exist at the level of practice between women and men leaders. In doing so, the authors discuss how leadership development programs may play a more effective role in addressing gender equity in leadership.

Exploring Faculty Developers' Experiences to Inform Our Understanding of Competence in Faculty Development.

PURPOSE: Now a mainstay in medical education, faculty development has created the role of the faculty developer. However, faculty development research tends to overlook faculty developers' roles and experiences. This study aimed to develop an empirical understanding of faculty developer competence by digging deeper into the actions, experiences, and perceptions of faculty developers as they perform their facilitator role. METHOD: A constructivist grounded theory approach guided observations of faculty development activities, field interviews, and formal interviews with 31 faculty developers across two academic institutions from 2013 to 2014. Analysis occurred alongside and informed data collection. Themes were identified using a constant comparison process. RESULTS: Consistent with the literature, findings highlighted the knowledge and skills of the faculty developer and the importance of context in the design and delivery of faculty development activities. Three novel processes (negotiating, constructing, and attuning) were identified that integrate the individual faculty developer, her context, and the evolution of her competence. CONCLUSIONS: These findings suggest that faculty developer competence is best understood as a situated construct. A faculty developer's ability to attune to, construct, and negotiate her environment can both enhance and minimize the impact of contextual variables as needed. Thus, faculty developers do not passively experience context; rather, they actively interact with their environment in ways that maximize their performance. Faculty developers should be trained for the adaptive, situated use of knowledge.

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.

Why Do Parents Bring Their Children to the Emergency Department? A Systematic Inventory of Motives.

Parents frequently bring their children to general or pediatric emergency departments (EDs), even though many of these visits are judged by others to be "nonurgent" and inappropriate. This study examined the motives behind parents' decisions to take their children to a pediatric emergency department (PED). At a PED in Toulouse, France, 497 parents rated their level of agreement with each of 69 possible motives-representing all categories of human motivation-for coming to the PED that day. Exploratory and confirmatory factor analyses found evidence for six separable motives, called (in order of importance) (a) Seeking Quick Diagnosis, Treatment, and Reassurance; (b) PED as the Best Place to Go; (c) Empathic Concern for Child's Suffering; (d) Being Considered by Others as Responsible Parents; (e) External Factors; and (f) Dissatisfaction with Previous Consultation. Conclusions. Parents' motives in bringing their children to the PED are primarily serious and goal-oriented. They are also often emotion based, as would be expected in parents of ill children. The parents would be unlikely to agree that these visits were inappropriate.

Web-Based Learning for Emergency Airway Management in Anesthesia Residency Training.

Introduction. Web-based learning (WBL) is increasingly used in medical education; however, residency training programs often lack guidance on its implementation. We describe how the use of feasibility studies can guide the use of WBL in anesthesia residency training. Methods. Two case-based WBL emergency airway management modules were developed for self-directed use by anesthesia residents. The feasibility of using this educational modality was assessed using a single cohort pretest/posttest design. Outcome measures included user recruitment and retention rate, perceptions of educational value, and knowledge improvement. The differences between pre- and postmodule test scores and survey Likert scores were analysed using the paired t test. Results. Recruitment and retention rates were 90% and 65%, respectively. User-friendliness of the modules was rated highly. There was a significant improvement in perceptions of the value of WBL in the postsurvey. There was a significant knowledge improvement of 29% in the postmodule test. Conclusions. Feasibility studies can help guide appropriate use of WBL in curricula. While our study supported the potential feasibility of emergency airway management modules for training, collaboration with other anesthesia residency programs may enable more efficient development, implementation, and evaluation of this resource-intensive modality in anesthesia education and practice.

Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge.

Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.9 mL/day/kg). This antibody binds to the rat recycling receptor FcRn as expected for a human IgG1 antibody and does not display non-specific binding to baculovirus particles in an assay that is correlated with fast clearance in cynomolgus monkey. The antigen is not expressed in rat so target-dependent clearance does not contribute to PK. Removal of the affinity maturation changes (hu5B3.κ1VH3.v1) did not restore normal clearance. The antibody was re-humanized on a κ4, VH1 framework and the non-affinity matured version (hu5B3.κ4VH1.v1) was shown to have normal clearance (8.5 mL/day/kg). Since the change in framework results in a lower pI, primarily due to more negative charge on the κ4 template, the effect of additional charge variation on antibody PK was tested by incorporating substitutions obtained through phage display affinity maturation of hu5B3.κ1VH3.v1. A variant having a pI of 8.61 gave very fast clearance (140 mL/day/kg) whereas a molecule with pI of 6.10 gave slow clearance (5.8 mL/kg/day). Both antibodies exhibited comparable binding to rat FcRn, but biodistribution experiments showed that the high pI variant was catabolized in liver and spleen. These results suggest antibody charge can have an effect on PK through alterations in antibody catabolism independent of FcRn-mediated recycling. Furthermore, introduction of affinity maturation changes into the lower pI framework yielded a candidate with PK and virus neutralization properties suitable for clinical development.

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.