Shaping the Future of Infectious Diseases: The Journey to Promote Value, Opportunity, and Positive Messaging.

The field of infectious diseases (ID) offers a rewarding career path and is widely viewed as an essential subspecialty in medicine. However, in recent years, these positive aspects have been overshadowed by concerns surrounding low fellowship match rates, undercompensation, and burnout. The Infectious Diseases Society of America Fellowship Training Program Directors Committee met in 2023, discussed the future of ID as a specialty, and sought to develop strategies to highlight the value and opportunities of ID for future generations, as well as underscore the importance of and provide tools for positive messaging to trainees about the subspecialty.

Single-Cell Transcriptomics of Human Tonsils Reveals Nicotine Enhances HIV-1-Induced NLRP3 Inflammasome and Mitochondrial Activation.

Background: HIV-1 infection, even with effective antiretroviral therapy (ART), is associated with chronic inflammation and immune dysfunction, contributing to long-term health complications. Nicotine use, prevalent among people with HIV (PWH), is known to exacerbate immune activation and disease progression, but the precise biological mechanisms remain to be fully understood. This study sought to uncover the synergistic effects of HIV-1 infection and nicotine on immune cell function, focusing on beneficial insights into NLRP3 inflammasome activation, oxidative stress, and mitochondrial pathways.

The impacts of tobacco and nicotine on HIV-1 infection, inflammation, and the blood-brain barrier in the central nervous system.

Human immunodeficiency virus (HIV-1) remains a persistent global health crisis. Even while successfully virologically suppressed, people with HIV (PWH) experience a higher risk for inflammatory disorders such as HIV-associated neurocognitive disorder (HAND). Tobacco use puts PWH at higher risk for neurocognitive symptoms resulting from HIV-associated neuroinflammation.

An Analysis of Curricular Structures in MD-PhD Programs in the United States.

Purpose: This study describes the structure and timing of the clinical education components of MD-PhD programs to illustrate how variations in preclerkship curriculum correlate with the opportunity for early clinical exposure and other key program characteristics.

Method: A survey was disseminated to U.S.

An Evidence-Based Framework for Medical Student Research Training.

Background: As research becomes an increasingly important component of medical education, there is greater emphasis on incorporating programmatic enhancements to the research experience. This study builds a logic model to summarize research program inputs, outputs, and outcomes from research-oriented medical schools across the country, providing a framework that institutions can use to design and improve their medical student research training programs.

Methods: Between November 2021 and February 2022, we administered a survey assessing institutional characteristics, research offerings, curriculum, funding, and student scholarly products to the medical schools ranked 1-50 in research in 2021 by US News and World Report.

Oxidative phosphorylation in HIV-1 infection: impacts on cellular metabolism and immune function.

Human Immunodeficiency Virus Type 1 (HIV-1) presents significant challenges to the immune system, predominantly characterized by CD4 T cell depletion, leading to Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) effectively suppresses the viral load in people with HIV (PWH), leading to a state of chronic infection that is associated with inflammation. This review explores the complex relationship between oxidative phosphorylation, a crucial metabolic pathway for cellular energy production, and HIV-1, emphasizing the dual impact of HIV-1 infection and the metabolic and mitochondrial effects of ART.

A Call to Action: Urgently Strengthening the Future Physician-Scientist Workforce in Infectious Diseases.

Infectious diseases (ID) research is vital for global public health, typically led by physician-scientists. This Perspective addresses challenges in the ID workforce and suggests solutions. Physician-scientists have made key discoveries that have significantly impacted human health.

HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model.

Our mouse model is a powerful tool for investigating the genetic mechanisms governing central nervous system (CNS) human immunodeficiency virus type-1 (HIV-1) infection and latency in the CNS at a single-cell level. A major advantage of our model is that it uses induced pluripotent stem cell-derived microglia, which enables human genetics, including gene function and therapeutic gene manipulation, to be explored , which is more challenging to study with current hematopoietic stem cell-based models for neuroHIV. Our transgenic tracing of xenografted human cells will provide a quantitative medium to develop new molecular and epigenetic strategies for reducing the HIV-1 latent reservoir and to test the impact of therapeutic inflammation-targeting drug interventions on CNS HIV-1 latency.

Striving for equity in academia: embracing the power of no in decision-making.

In academia, saying "yes" to opportunities and "no" to distractions is crucial for effective decision-making. Here, we emphasize the importance of carefully considering commitments and courageously declining those that may lead to overextension. We highlight that discernment is vital, particularly for junior faculty/scientists and those with marginalized identities, as overcommitment can hinder career advancement.

Physician-scientist trainees with parenting responsibilities need financial and childcare support.

Physician–scientists who become parents during their long period of training need additional funding and support for lactation, childcare and healthcare, to ensure an equitable workforce.

Preserving the Future of Infectious Diseases: Why We Must Address the Decline in Compensation for Clinicians and Researchers.

Infectious diseases (ID) physicians play a pivotal role in patient care and public health, yet concerns are mounting about their under-compensation compared with other medical specialties. This trend sees ID physicians, including new graduates, receiving lower remuneration than their general and hospital medicine peers, despite their significant contributions. The persistent disparity in compensation has been identified as a key factor behind the declining interest in the ID specialty among medical students and residents, potentially threatening patient care quality, research advancement, and diversity within the ID workforce.

HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model.

Introduction: Human immunodeficiency virus type 1 (HIV-1) causes a chronic, incurable infection leading to immune activation and chronic inflammation in people with HIV-1 (PWH), even with virologic suppression on antiretroviral therapy (ART). The role of lymphoid structures as reservoirs for viral latency and immune activation has been implicated in chronic inflammation mechanisms. Still, the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue remain unexplored.

HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model.

The central nervous system (CNS) is a major human immunodeficiency virus type 1 reservoir. Microglia are the primary target cell of HIV-1 infection in the CNS. Current models have not allowed the precise molecular pathways of acute and chronic CNS microglial infection to be tested with in vivo genetic methods.

The impact of cannabinoids on inflammasome signaling in HIV-1 infection.

Human immunodeficiency virus type 1 (HIV-1) is a chronic disease that afflicts over 38 million people worldwide without a known cure. The advent of effective antiretroviral therapies (ART) has significantly decreased the morbidity and mortality associated with HIV-1 infection in people living with HIV-1 (PWH), thanks to durable virologic suppression. Despite this, people with HIV-1 experience chronic inflammation associated with co-morbidities.

Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People With Treated Human Immunodeficiency Virus.

Background: Inflammasome activation is increased in people with human immunodeficiency virus (PWH), but its relationship with coronary plaque is poorly understood in this setting.

Methods: In a large human immunodeficiency virus cardiovascular prevention cohort, relationships between caspase-1, interleukin (IL)-1β, and IL-18 and coronary plaque indices were assessed by multivariate logistic regression.

Results: Higher IL-18 and IL-1β were associated with Leaman score, an integrative measure of plaque burden and composition.

The role of extracellular ATP and P2X receptors in the pathogenesis of HIV-1.

Human Immunodeficiency Virus Type 1 (HIV-1) causes a chronic, incurable infection associated with chronic inflammation despite virologic suppression on antiretroviral therapy (ART). This chronic inflammation underlies significant comorbidities, including cardiovascular disease, neurocognition decline, and malignancies. The mechanisms of chronic inflammation have been attributed, in part, to the role of extracellular ATP and P2X-type purinergic receptors that sense damaged or dying cells and undergo signaling responses to activate inflammation and immunomodulation.

"Time-In": A Tool for Interrupting Bias in Medical School Admissions Committee Meetings.

Problem: During high-stakes committee meetings, bias is often expressed but goes uninterrupted because there is no formal structure to interrupt it. Bias impacts decision making and can further disadvantage those from backgrounds that have been marginalized.

Approach: The MD and MD-PhD admissions committees at the Icahn School of Medicine at Mount Sinai in NY in the 2020-2021 admissions season introduced a "Time-In" tool to interrupt bias during committee meetings.

Inflammasomes as mediators of inflammation in HIV-1 infection.

Human immunodeficiency virus type 1 (HIV-1) infection is a chronic disease without a known cure. The advent of effective antiretroviral therapy (ART) has enabled people with HIV (PWH) to have significantly prolonged life expectancies. As a result, morbidity and mortality associated with HIV-1 infection have declined considerably.

Social Media: Flattening Hierarchies for Women and Black, Indigenous, People Of Color (BIPOC) to Enter the Room Where It Happens.

Social media platforms are widely used to connect people across multiple settings, including country of origin, profession, race/ethnicity, sexual orientation, gender identity, seniority, and training. Groups that have been marginalized or historically excluded from decision-making encounters may lack formal mentors/sponsors because of a lack of representation of women and Black, Indigenous, People Of Color (BIPOC) in senior leadership positions. This can serve as a barrier to professional advancement at all stages of career development.

Digital Strategy and Social Media for Infectious Diseases.

This supplement demonstrates the profound reach of social media across several domains: improved clinical care and advocacy, data analysis, broad reach to diverse patient populations, educational access, best practices in medical education, peer review, digital strategy for individuals and institutions, and combating misinformation.

The HIV Env Glycoprotein Conformational States on Cells and Viruses.

The HIV Env glycoprotein is the surface glycoprotein responsible for viral entry into CD4 immune cells. During infection, Env also serves as a primary target for antibody responses, which are robust but unable to control virus replication. Immune evasion by HIV-1 Env appears to employ complex mechanisms to regulate what antigenic states are presented to the immune system.