Heightened Epstein-Barr virus immunity and potential cross-reactivities in multiple sclerosis.

BACKGROUND: Epstein-Barr virus (EBV) is a likely prerequisite for multiple sclerosis (MS) but the underlying mechanisms are unknown. We investigated antibody and T cell responses to EBV in persons with MS (pwMS), healthy EBV-seropositive controls (HC) and post-infectious mononucleosis (POST-IM) individuals up to 6 months after disease resolution. The ability of EBV-specific T cell responses to target antigens from the central nervous system (CNS) was also investigated. METHODS: Untreated persons with relapsing-remitting MS, POST-IM individuals and HC were, as far as possible, matched for gender, age and HLA-DRB1*15:01. EBV load was determined by qPCR, and IgG responses to key EBV antigens were determined by ELISA, immunofluorescence and Western blot, and tetanus toxoid antibody responses by multiplex bead array. EBV-specific T cell responses were determined ex vivo by intracellular cytokine staining (ICS) and cross-reactivity of in vitro-expanded responses probed against 9 novel Modified Vaccinia Ankara (MVA) viruses expressing candidate CNS autoantigens. RESULTS: EBV load in peripheral blood mononuclear cells (PBMC) was unchanged in pwMS compared to HC. Serologically, while tetanus toxoid responses were unchanged between groups, IgG responses to EBNA1 and virus capsid antigen (VCA) were significantly elevated (EBNA1 p = 0.0079, VCA p = 0.0298) but, importantly, IgG responses to EBNA2 and the EBNA3 family antigens were also more frequently detected in pwMS (EBNA2 p = 0.042 and EBNA3 p = 0.005). In ex vivo assays, T cell responses to autologous EBV-transformed B cells and to EBNA1 were largely unchanged numerically, but significantly increased IL-2 production was observed in response to certain stimuli in pwMS. EBV-specific polyclonal T cell lines from both MS and HC showed high levels of autoantigen recognition by ICS, and several neuronal proteins emerged as common targets including MOG, MBP, PLP and MOBP. DISCUSSION: Elevated serum EBV-specific antibody responses in the MS group were found to extend beyond EBNA1, suggesting a larger dysregulation of EBV-specific antibody responses than previously recognised. Differences in T cell responses to EBV were more difficult to discern, however stimulating EBV-expanded polyclonal T cell lines with 9 candidate CNS autoantigens revealed a high level of autoreactivity and indicate a far-reaching ability of the virus-induced T cell compartment to damage the CNS.

There and Back Again: A Forty-Year Perspective on Physician Nutrition Education.

Medical education faces an urgent need for evidence-based physician nutrition education. Since the publication of the 1985 National Academies report "Nutrition Education in the United States Medical Schools," little has changed. Although several key efforts sought to increase nutrition content in undergraduate medical education over the past 40 y, most medical schools still fail to include the recommended minimum of 25 h of nutrition training. Without foundational concepts of nutrition in undergraduate medical education, graduate medical education unsurprisingly falls short of meeting patient needs for nutritional guidance in clinical practice. Meanwhile, diet-sensitive chronic diseases continue to escalate, although largely preventable and treatable by nutritional therapies and dietary lifestyle changes. Fortunately, recent recognition and adoption of Food is Medicine programs across the country increasingly connect patients with healthy food resources and nutrition education as core to their medical care, and physicians must be equipped to lead these efforts alongside their dietitian colleagues. Filling the gap in nutrition training will require an innovative and interprofessional approach that pairs nutrition with personal wellness, interprofessional practice, and community service learning. The intersectional benefits of connecting these domains will help prepare future physicians to address the social, behavioral, and lifestyle determinants of health in a way that recognizes nourishing food access as a core part of clinical practice. There are numerous strategies to integrate nutrition into education pathways, including didactic and experiential learning. Culinary medicine, an evidence-based field combining the culinary arts with nutritional science and medicine, is 1 promising educational framework with a hands-on, interprofessional approach that emphasizes community engagement. Advancing the critical need for widespread adoption of nutrition education for physicians will require support and engagement across societal stakeholders, including co-leadership from registered dietitian nutritionists, health system and payor reform, and opportunities for clinical innovation that bring this essential field to frontline patient care.

Culinary Medicine: Needs and Strategies for Incorporating Nutrition into Medical Education in the United States.

In the past decade, medical education has increasingly incorporated evidence-based lifestyle interventions as primary strategies for preventing and managing noncommunicable diseases. This shift embraces the growing recognition of the significant impact of lifestyle on health outcomes, driving diseases including obesity, diabetes, heart disease, and cancer. Now deemed "food is medicine" (FIM), diet-related interventions witnessed integration into healthcare systems and recognition in the United States' White House Conference on Hunger, Nutrition, and Health in 2023. As FIM gains traction, investigating optimal strategies for team-based education becomes essential. Healthcare teams need the necessary knowledge and tools to effectively administer FIM services and collaborate across disciplines, ultimately enhancing disease prevention, chronic disease management, health quality, value, and overall wellness. Culinary medicine (CM), a vital component of FIM, bridges nutrition education, pragmatic culinary skills, and conventional strategies to improve chronic disease management. CM involves experiential learning, imparts practical skills, and encourages behavior change by addressing food-related determinants of health and promoting equitable access. Teaching kitchens serve as physical or virtual learning spaces and as a didactic and experiential method (skills lab), playing a crucial role by integrating culinary, lifestyle, integrative, and conventional medicine. A growing number of medical schools in the United States and globally offer CM education via diverse methods including interest groups, electives, and specialty tracks, encompassing didactic sessions, hands-on kitchen education, and virtual teaching methods. Given the rising demand for CM programs, this article aims to describe, map, and compare existing CM education types in medical education. It provides actionable recommendations for medical schools to establish and expand CM programs by fostering service-learning partnerships, clinical innovation, and interdisciplinary research. As FIM gains prominence, cultivating a robust foundation of educational strategies is vital to ensure seamless integration into both medical education and collaborative medical practice.

Culinary Medicine or Culinary Nutrition? Defining Terms for Use in Education and Practice.

Examination of how terms such as culinary nutrition, culinary nutrition science, culinary medicine, culinary nutrition professional, culinary nutrition intervention, culinary nutrition activity, and culinary nutrition competency are used in practice, and the creation of consensus definitions will promote the consistent use of these terms across work areas and disciplines. Thirty leading practitioners, academics, and researchers in the fields of food and nutrition across Australia, the United States, Canada, United Kingdom, Europe, and Asia were approached by investigators via email to submit definitions of key terms using a Qualtrics survey link. Further participants were reached through snowball recruitment. Initial emails were sent in October and November 2021 with subsequent reminders between November 2021 and March 2022. Two researchers undertook content analysis of the text answers for each of the terms and generated definitions for discussion and consensus. Thirty-seven participants commenced the survey and twenty-three submitted one or more definitions. Agreed definitions fell into two categories: practice concepts and practitioners. Further discussion amongst investigators led to the creation of a visual map to demonstrate the interrelationship of terms. Culinary nutrition science underpins, and interprofessional collaboration characterizes practice in this area, however, further work is needed to define competencies and model best practice.

Eat to Treat: The Methods and Assessments of a Culinary Medicine Seminar for Future Physicians and Practicing Clinicians.

Nutrition-associated chronic disease is an epidemic in the United States (US), yet most medical schools lack adequate nutrition education. We developed a six-session culinary medicine (CM) seminar entitled "Eat to Treat: A Nutrition Course for Future Clinicians" that teaches culinary skills, nutrition science, and counseling techniques to improve clinical nutrition management. The seminar was offered in-person to first-year medical students in a medical school-based teaching kitchen from 2017 to 2019. A virtual three-session course was also offered to practicing clinicians in 2020. Voluntary self-efficacy questionnaires were collected at the beginning of the first and last sessions of the student seminar, and paired t-tests determined the course's effect on survey items. A total of 53 first-year medical students attended the program over five semesters, and 39 students (73.6%) completed both surveys. All except one measure of self-efficacy were significantly higher at session 6 than session 1 (p < 0.05). A post-course survey was utilized for the clinician seminar and of the 31 participants, 14 completed the surveys; 93% and 86% of respondents agreed the course was clinically relevant and improved their confidence, respectively. We developed a CM curriculum that improved nutrition knowledge and confidence among a professionally diverse cohort and may represent a scalable education model to improve nutrition education in US medical schools.

Mimicking the brain: Epstein-Barr virus and foreign agents as drivers of neuroimmune attack in multiple sclerosis.

T cells have an essential role in adaptive immunity against pathogens and cancer, but failure of thymic tolerance mechanisms can instead lead to escape of T cells with the ability to attack host tissues. Multiple sclerosis (MS) occurs when structures such as myelin and neurons in the central nervous system (CNS) are the target of autoreactive immune responses, resulting in lesions in the brain and spinal cord which cause varied and episodic neurological deficits. A role for autoreactive T cell and antibody responses in MS is likely, and mounting evidence implicates Epstein-Barr virus (EBV) in disease mechanisms. In this review we discuss antigen specificity of T cells involved in development and progression of MS. We examine the current evidence that these T cells can target multiple antigens such as those from pathogens including EBV and briefly describe other mechanisms through which viruses could affect disease. Unravelling the complexity of the autoantigen T cell repertoire is essential for understanding key events in the development and progression of MS, with wider implications for development of future therapies.

Characteristics of Current Teaching Kitchens: Findings from Recent Surveys of the Teaching Kitchen Collaborative.

Teaching kitchens are physical and virtual forums that foster practical life skills through participation in experiential education. Given the well-supported connection between healthy eating patterns and the prevention and management of chronic diseases, both private and public organizations are building teaching kitchens (TKs) to enhance the health and wellness of patients, staff, youth, and the general community. Although implementation of TKs is becoming more common, best practices for starting and operating programs are limited. The present study aims to describe key components and professionals required for TK operations. Surveys were administered to Teaching Kitchen Collaborative (TKC) members and questions reflected seven primary areas of inquiry: (1) TK setting(s), (2) audiences served, (3) TK model(s), (4) key lines of operations, (5) team member who manages or directs the TK, (6) team member(s) who performs key operations and other professionals or partnerships that may be needed, and (7) the primary funding source(s) to build and operate the TK (among various other topics). Findings were used to articulate recommendations for organizations seeking to establish a successful TK as well as for TKs to expand their collective reach, research capacity, and impact.

Neuronal Ndst1 depletion accelerates prion protein clearance and slows neurodegeneration in prion infection.

Select prion diseases are characterized by widespread cerebral plaque-like deposits of amyloid fibrils enriched in heparan sulfate (HS), a abundant extracellular matrix component. HS facilitates fibril formation in vitro, yet how HS impacts fibrillar plaque growth within the brain is unclear. Here we found that prion-bound HS chains are highly sulfated, and that the sulfation is essential for accelerating prion conversion in vitro. Using conditional knockout mice to deplete the HS sulfation enzyme, Ndst1 (N-deacetylase / N-sulfotransferase) from neurons or astrocytes, we investigated how reducing HS sulfation impacts survival and prion aggregate distribution during a prion infection. Neuronal Ndst1-depleted mice survived longer and showed fewer and smaller parenchymal plaques, shorter fibrils, and increased vascular amyloid, consistent with enhanced aggregate transit toward perivascular drainage channels. The prolonged survival was strain-dependent, affecting mice infected with extracellular, plaque-forming, but not membrane bound, prions. Live PET imaging revealed rapid clearance of recombinant prion protein monomers into the CSF of neuronal Ndst1- deficient mice, neuronal, further suggesting that HS sulfate groups hinder transit of extracellular prion protein monomers. Our results directly show how a host cofactor slows the spread of prion protein through the extracellular space and identify an enzyme to target to facilitate aggregate clearance.

The impact of hybrid immunity on immune responses after SARS-CoV-2 vaccination in persons with multiple sclerosis treated with disease-modifying therapies.

BACKGROUND AND PURPOSE: Hybrid immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops from a combination of natural infection and vaccine-generated immunity. Multiple sclerosis (MS) disease-modifying therapies (DMTs) have the potential to impact humoral and cellular immunity induced by SARS-CoV-2 vaccination and infection. The aims were to compare antibody and T-cell responses after SARS-CoV-2 mRNA vaccination in persons with MS (pwMS) treated with different DMTs and to assess differences between naïvely vaccinated pwMS and pwMS with hybrid immunity vaccinated following a previous SARS-CoV-2 infection. METHODS: Antibody and T-cell responses were determined in pwMS at baseline and 4 and 12 weeks after the second dose of SARS-CoV-2 vaccination in 143 pwMS with or without previous SARS-CoV-2 infection and 40 healthy controls (HCs). The MS cohort comprised natalizumab (n = 22), dimethylfumarate (n = 23), fingolimod (n = 38), cladribine (n = 30), alemtuzumab (n = 17) and teriflunomide (n = 13) treated pwMS. Immunoglobulin G antibody responses to SARS-CoV-2 antigens were measured using a multiplex bead assay and FluoroSpot was used to assess T-cell responses (interferon γ and interleukin 13). RESULTS: Humoral and T-cell responses to vaccination were comparable between naïvely vaccinated HCs and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but were suppressed in fingolimod-treated pwMS. Both fingolimod-treated pwMS and HCs vaccinated following a previous SARS-CoV-2 infection had higher antibody levels 4 weeks after vaccination compared to naïvely vaccinated individuals. Antibody and interferon γ levels 12 weeks after vaccination were positively correlated with time from last treatment course of cladribine. CONCLUSION: These findings are of relevance for infection risk mitigation and for vaccination strategies amongst pwMS undergoing DMT.

Epstein-Barr virus and multiple sclerosis: moving from questions of association to questions of mechanism.

The link between Epstein-Barr virus (EBV) and multiple sclerosis (MS) has puzzled researchers since it was first discovered over 40 years ago. Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS. Early MS disease is characterised by episodic neuroinflammation and focal lesions in the central nervous system (CNS) that over time develop into progressive neurodegeneration and disability. Risk of MS is vanishingly low in EBV seronegative individuals, history of infectious mononucleosis (acute symptomatic primary infection with EBV) significantly increases risk and elevated antibody titres directed against EBV antigens are well-characterised in patients. However, the underlying mechanism - or mechanisms - responsible for this interplay remains to be fully elucidated; how does EBV-induced immune dysregulation either trigger or drive MS in susceptible individuals? Furthermore, deep understanding of virological and immunological events during primary infection and long-term persistence in B cells will help to answer the many questions that remain regarding MS pathogenesis. This review discusses the current evidence and mechanisms surrounding EBV and MS, which have important implications for the future of MS therapies and prevention.

Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4+ T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development.

Tau seeds occur before earliest Alzheimer's changes and are prevalent across neurodegenerative diseases.

Tau neurofibrillary tangles are a hallmark of Alzheimer's disease neuropathological change. However, it remains largely unclear how distinctive Alzheimer's disease tau seeds (i.e. 3R/4R) correlate with histological indicators of tau accumulation. Furthermore, AD tau co-pathology is thought to influence features and progression of other neurodegenerative diseases including Lewy body disease; yet measurements of different types of tau seeds in the setting of such diseases is an unmet need. Here, we use tau real-time quaking-induced conversion (RT-QuIC) assays to selectively quantitate 3R/4R tau seeds in the frontal lobe which accumulates histologically identifiable tau pathology at late disease stages of AD neuropathologic change. Seed quantitation across a spectrum of neurodegenerative disease cases and controls indicated tau seeding activity can be detected well before accompanying histopathological indication of tau deposits, and even prior to the earliest evidence of Alzheimer's-related tau accumulation anywhere in the brain. In later stages of AD, 3R/4R tau RT-QuIC measures correlated with immunohistochemical tau burden. In addition, Alzheimer's tau seeds occur in the vast majority of cases evaluated here inclusive of primary synucleinopathies, frontotemporal lobar degeneration and even controls albeit at multi-log lower levels than Alzheimer's cases. α-synuclein seeding activity confirmed synucleinopathy cases and further indicated the co-occurrence of α-synuclein seeds in some Alzheimer's disease and primary tauopathy cases. Our analysis indicates that 3R/4R tau seeds in the mid-frontal lobe correlate with the overall Braak stage and Alzheimer's disease neuropathologic change, supporting the quantitative predictive value of tau RT-QuIC assays. Our data also indicate 3R/4R tau seeds are elevated in females compared to males at high (≥ IV) Braak stages. This study suggests 3R/4R tau seeds are widespread even prior to the earliest stages of Alzheimer's disease changes, including in normal, and even young individuals, with prevalence across multiple neurodegenerative diseases to further define disease subtypes.

How Does Orthopaedic Surgeon Gender Representation Vary by Career Stage, Regional Distribution, and Practice Size? A Large-Database Medicare Study.

BACKGROUND: Orthopaedic surgery has the lowest proportion of women surgeons in practice of any specialty in the United States. Preliminary studies suggest that patients who are treated by physicians of the same race, ethnicity, cultural background, or gender feel more comfortable with their care and may have better outcomes. Therefore, understanding the discrepancies in the diversity of the orthopaedic surgeon workforce is crucial to addressing system-wide healthcare inequities. QUESTIONS/PURPOSES: (1) Does a difference exist in gender representation among practicing orthopaedic surgeons across geographic distributions and years in practice? (2) Does a difference exist in gender representation among practicing orthopaedic surgeons with regard to rural-urban setting, group practice size, and years in practice? METHODS: Orthopaedic surgeons serving Medicare patients in 2017 were identified in the Medicare Physician and Other Supplier Public Use File and Physician Compare national databases. This dataset encompasses more than 64% of practicing orthopaedic surgeons, providing a low proportion of missing data compared with other survey techniques. Group practice size, location, and Rural-urban Commuting Area scores were compared across physician gender and years in practice. Linear and logistic regressions modeled gender and outcomes relationships adjusted by years in practice. Least-square means estimates for outcomes were calculated by gender at the median years in practice (19 years) via regression models. RESULTS: According to the combined Medicare databases used, 5% (1019 of 19,221) of orthopaedic surgeons serving Medicare patients were women; this proportion increased with decreasing years in practice (R 2 0.97; p < 0.001). Compared by region, the West region demonstrated the highest proportion of women orthopaedic surgeons overall (7% [259 of 3811]). The Midwest and South regions were below the national mean for proportions of women orthopaedic surgeons, both overall (5% [305 of 6666] and 5% [209 of 4146], respectively) and in the first 5 years of practice (9% [54 of 574] and 9% [74 of 817], respectively). Women worked in larger group practices than men (median [interquartile range] 118 physicians [20 to 636] versus median 56 [12 to 338]; p < 0.001, respectively). Both genders were more likely to practice in an urban setting, and when controlling for years in practice, there was no difference between men and women orthopaedic surgeons practicing in rural or urban settings (respectively, R 2 = 0.0004 and 0.07; p = 0.89 and 0.09). CONCLUSION: Among orthopaedic surgeons, there is only one woman for every 20 men caring for Medicare patients in the United States. Although gender representation is increasing longitudinally for women, it trails behind other surgical subspecialties substantially. Longitudinal mentoring programs, among other evidenced initiatives, should focus on the more pronounced underrepresentation identified in Midwestern/Southern regions and smaller group practices. Gender-based equity, inclusion, and diversity efforts should focus on recruitment strategies, and further research is needed to study how inclusion and diversity efforts among orthopaedic surgeons improves patient-centered care. LEVEL OF EVIDENCE: Level III, therapeutic study.

Does the Number of Preoperative Corticosteroid Injections Affect Clinical and Radiographic Outcomes of Trapeziectomy and Suspensionplasty?

PURPOSE: This study aimed to determine whether an increasing number of preoperative corticosteroid injections is associated with greater radiographic subsidence of the thumb metacarpal at long-term follow-up after abductor pollicis longus suspensionplasty, secondary to steroid-induced pathologic weakening of capsuloligamentous restraints surrounding the thumb carpometacarpophalangeal joint and greater extension of the lunate, but neither affect patient-reported outcomes nor revision rates. METHODS: A retrospective chart review was performed of patients who underwent primary trapeziectomy and abductor pollicis longus suspensionplasty by a single surgeon over a 10-year period. The number of preoperative corticosteroid injections in the trapeziometacarpal joint was documented, and patients were separated into 4 subgroups: 0, 1, 2, or 3 or more injections. Preoperative and final radiographs were evaluated for a change in the distance between the base of the thumb metacarpal and the distal pole of the scaphoid as a measure of thumb metacarpal subsidence and radiolunate angle as a measure of nondissociative carpal instability, which has been reported as a complication after basal joint arthroplasty. Additionally, the final patient-reported outcomes (Quick Disabilities of the Arm, Shoulder, and Hand and Patient-Rated Wrist Evaluation) and revision rates were also assessed. RESULTS: Of a total of 60 patients with an average age of 64 years that were included in the study, 16 (26.7%) received 0, 19 (31.7%) received 1, 12 (20%) received 2, and 13 (21.7%) received 3+ preoperative injections. The median postoperative follow-up was 92 months. The mean distance between the base of the thumb metacarpal and the distal pole of the scaphoid decreased by 2 mm, and the mean radiolunate angle increased by 4° across the entire cohort. When comparing subgroups, no differences were observed in either parameter or the final Patient-Rated Wrist Evaluation and Quick Disabilities of the Arm, Shoulder, and Hand scores. CONCLUSIONS: This study demonstrates no apparent detrimental effect of an increased number of preoperative corticosteroid injections on radiographic thumb metacarpal subsidence, increase in extension of radiolunate angle (nondissociative carpal instability), patient-reported outcomes, or revision rates at an average of almost 8 years after trapeziectomy and abductor pollicis longus suspensionplasty. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains.

Little is known about the structural basis of prion strains. Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register ß-sheet-based core. Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three ß-arches. However, detailed comparisons reveal variations in these shared structural topologies and other features. Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. This work demonstrates both common and divergent structural features of prion strains at the near-atomic level.

Senior Care Pharmacists, Audiologists, and Otologists: Improving Hearing Health for Older Patients Through Interprofessional Collaboration.

The purpose of this manuscript is to provide pharmacists with education on hearing loss that colleagues in audiology believe is most critical for pharmacists. As well as highlighting insightful interventions pharmacists can make in collaboration with hearing professionals, such as audiologists, otolaryngologists, and otologists, to improve patient care. This project was initiated by professional students at the University of Maryland in both Baltimore and College Park campuses, after completing the interprofessional elective course IPE Care in Geriatrics. Upon completion of the course, the authors performed an extensive literature search and reviewed publications pertaining to pharmacy, audiology, and their integration.Hearing loss can have a significant impact on a patient's quality of life. Older people are at an increased risk for experiencing hearing impairment, but often do not seek help from health care providers. Collaboration between audiologists, otolaryngologists, and pharmacists has the potential to improve patients' access to hearing health and break barriers for patients. Important interventions that pharmacists can make to better serve their patients with hearing loss include screening, enhancing communication, and hearing aid assistance. This article also provides guidance on identifying patients who would be candidates for over-the-counter hearing aids and patients who should be referred to a hearing professional. This skill will become increasingly relevant with the emergence of over-the-counter hearing aids.

Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role. Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins. We identified four previously unreported autoantigens in MS: fatty acid-binding protein 7, prokineticin-2, reticulon-3, and synaptosomal-associated protein 91, which were verified to induce interferon-γ responses in MS in two cohorts. Autoreactive profiles were heterogeneous, and reactivity to several autoantigens was MS-selective. Autoreactive T cells were predominantly CD4+ and human leukocyte antigen-DR restricted. Mouse immunization induced antigen-specific responses and CNS leukocyte infiltration. This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS.

An Initiative to Increase Residency Program Diversity.

A physician workforce that reflects the patient population is associated with improved patient outcomes and promotes health equity. Notwithstanding, racial and ethnic disparities persist within US medical schools, making some individuals underrepresented in medicine (URM). We sought to increase the percentage of URM residents who matched into our pediatric residency programs from a baseline of 5% to 35% to achieve demographic parity with our patients. We developed a multifaceted approach using multiple iterative tests of change, with the primary strategy being increased visibility of URM trainees and faculty to residency applicants. Strategies included applicant interviews with URM faculty, interview dinners with URM residents, visibility at academic conferences for URM trainees, development of targeted marketing materials, and a visiting student program supported by networking with URM residents. The primary outcome measure was the percentage of matched residents in the categorical pediatrics, child neurology, and medical genetics training programs who identified as URM. The percentage of URM residents increased to 16% (6 of 37) in 2018, 26% (11 of 43) in 2019, 19% (8 of 43) in 2020, and 21% (9 of 43) in 2021 (a four-year average of 22% URM residents; P = .0002). This progress toward a more representative residency program was met by challenges, such as pipeline concerns, the minority tax, and recruitment during a pandemic. We were able to implement small, low-resource strategies that had a large cumulative impact and could be implemented in other residency programs. Specific tactics and challenges encountered are discussed in this special article.

Psychosis Biotypes: Replication and Validation from the B-SNIP Consortium.

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called "B-SNIP1" with 711 psychosis and 274 healthy persons, and the "replication sample" with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r's from .96-.99) and temporally stable (r's from .76-.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%-89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.