Implications of inhibition of Rev1 interaction with Y family DNA polymerases for cisplatin chemotherapy.

Chemotherapy with cisplatin becomes limiting due to toxicity and secondary malignancies. In principle, therapeutics could be improved by targeting translesion synthesis (TLS) polymerases (Pols) that promote replication through intrastrand cross-links, the major cisplatin-induced DNA adduct. However, to specifically target malignancies with minimal adverse effects on normal cells, a good understanding of TLS mechanisms in normal versus cancer cells is paramount. We show that in normal cells, TLS through cisplatin intrastrand cross-links is promoted by Polη- or Polι-dependent pathways, both of which require Rev1 as a scaffolding component. In contrast, cancer cells require Rev1-Polζ. Our findings that a recently identified Rev1 inhibitor, JH-RE-06, purported to specifically disrupt Rev1 interaction with Polζ to block TLS through cisplatin adducts in cancer cells, abrogates Rev1's ability to function with Y family Pols as well, implying that by inactivating Rev1-dependent TLS in normal cells, this inhibitor will exacerbate the toxicity and tumorigenicity of chemotherapeutics with cisplatin.

DNA polymerase θ accomplishes translesion synthesis opposite 1,N6-ethenodeoxyadenosine with a remarkably high fidelity in human cells.

Here we show that translesion synthesis (TLS) opposite 1,N6-ethenodeoxyadenosine (εdA), which disrupts Watson-Crick base pairing, occurs via Polι/Polζ-, Rev1-, and Polθ-dependent pathways. The requirement of Polι/Polζ is consistent with the ability of Polι to incorporate nucleotide opposite εdA by Hoogsteen base pairing and of Polζ to extend synthesis. Rev1 polymerase and Polθ conduct TLS opposite εdA via alternative error-prone pathways. Strikingly, in contrast to extremely error-prone TLS opposite εdA by purified Polθ, it performs predominantly error-free TLS in human cells. Reconfiguration of the active site opposite εdA would provide Polθ the proficiency for error-free TLS in human cells.

DNA polymerase ε leading strand signature mutations result from defects in its proofreading activity.

The evidence that purified pol2-M644G DNA polymerase (Pol)ε exhibits a highly elevated bias for forming T:dTTP mispairs over A:dATP mispairs and that yeast cells harboring this Polε mutation accumulate A > T signature mutations in the leading strand have been used to assign a role for Polε in replicating the leading strand. Here, we determine whether A > T signature mutations result from defects in Polε proofreading activity by analyzing their rate in Polε proofreading defective pol2-4 and pol2-M644G cells. Since purified pol2-4 Polε exhibits no bias for T:dTTP mispair formation, A > T mutations are expected to occur at a much lower rate in pol2-4 than in pol2-M644G cells if Polε replicated the leading strand. Instead, we find that the rate of A > T signature mutations are as highly elevated in pol2-4 cells as in pol2-M644G cells; furthermore, the highly elevated rate of A > T signature mutations is severely curtailed in the absence of PCNA ubiquitination or Polζ in both the pol2-M644G and pol2-4 strains. Altogether, our evidence supports the conclusion that the leading strand A > T signature mutations derive from defects in Polε proofreading activity and not from the role of Polε as a leading strand replicase, and it conforms with the genetic evidence for a major role of Polδ in replication of both the DNA strands.

Mismatch repair operates at the replication fork in direct competition with mismatch extension by DNA polymerase δ.

DNA mismatch repair (MMR) in eukaryotes is believed to occur post-replicatively, wherein nicks or gaps in the nascent DNA strand are suggested to serve as strand discrimination signals. However, how such signals are generated in the nascent leading strand has remained unclear. Here we examine the alternative possibility that MMR occurs in conjunction with the replication fork. To this end, we utilize mutations in the PCNA interacting peptide (PIP) domain of the Pol3 or Pol32 subunit of DNA polymerase δ (Polδ) and show that these pip mutations suppress the greatly elevated mutagenesis in yeast strains harboring the pol3-01 mutation defective in Polδ proofreading activity. And strikingly, they suppress the synthetic lethality of pol3-01 pol2-4 double mutant strains, which arises from the vastly enhanced mutability due to defects in the proofreading functions of both Polδ and Polε. Our finding that suppression of elevated mutagenesis in pol3-01 by the Polδ pip mutations requires intact MMR supports the conclusion that MMR operates at the replication fork in direct competition with other mismatch removal processes and with extension of synthesis from the mispair by Polδ. Furthermore, the evidence that Polδ pip mutations eliminate almost all the mutability of pol2-4 msh2Δ or pol3-01 pol2-4 adds strong support for a major role of Polδ in replication of both the leading and lagging DNA strands.

A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands.

Genetic studies with S. cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.

Genetic evidence for reconfiguration of DNA polymerase θ active site for error-free translesion synthesis in human cells.

The action mechanisms revealed by the biochemical and structural analyses of replicative and translesion synthesis (TLS) DNA polymerases (Pols) are retained in their cellular roles. In this regard, DNA polymerase θ differs from other Pols in that whereas purified Polθ misincorporates an A opposite 1,N6-ethenodeoxyadenosine (ϵdA) using an abasic-like mode, Polθ performs predominantly error-free TLS in human cells. To test the hypothesis that Polθ adopts a different mechanism for replicating through ϵdA in human cells than in the purified Pol, here we analyze the effects of mutations in the two highly conserved tyrosine residues, Tyr-2387 and Tyr-2391, in the Polθ active site. Our findings that these residues are indispensable for TLS by the purified Pol but are not required in human cells, as well as other findings, provide strong evidence that the Polθ active site is reconfigured in human cells to stabilize ϵdA in the syn conformation for Hoogsteen base pairing with the correct nucleotide. The evidence that a DNA polymerase can configure its active site entirely differently in human cells than in the purified Pol establishes a new paradigm for DNA polymerase function.

Odontogenic Infections: Disease Burden During COVID-19 at a Single Institution.

PURPOSE: The purpose of this study was to document the effect of coronavirus disease 2019 (COVID-19) on patients presenting to the University of Washington Oral and Maxillofacial Surgery (UW OMS) with an odontogenic infection. MATERIALS AND METHODS: The investigators designed a retrospective cohort study and enrolled a sample of 889 subjects who presented for an odontogenic infection from March 19 to June 18 in the years 2017, 2018, 2019, and 2020. The primary predictor variable was OMS consultation for an odontogenic infection during a non-COVID-19 (2017, 2018, and 2019) year (control) or during the COVID-19 pandemic in 2020 (experimental). The primary outcome variable was treatment rendered. Appropriate univariate and bivariate statistics were computed, and the level of significance was set at .05 for all tests. RESULTS: There was no significant difference in the incidence of OMS consults in the 2 cohorts (P > .05). The number of patients presenting to the UW emergency department (ED) for an odontogenic infection decreased from an average of 246 in non-COVID years to 151 in 2020. Patients in the experimental cohort were more likely (55 vs 30.0%; P = .04) to present primarily to UW than a dentist and were less likely to undergo an incision and drainage (70.0 vs 88.8%; P = .04), aerosol-generating procedure (70.0 vs 88.8%; P = .04), and incision and drainage in the ED (15.0 vs 41.3%; P = .03). CONCLUSIONS: The investigators did not find evidence of increased hospital or ED burden by odontogenic infections during the COVID-19 pandemic.

Surgical Safety Checklists Are Underutilized in Ambulatory Oral and Maxillofacial Surgery.

PURPOSE: The objective of this study was to determine attitudes toward and the prevalence of using a surgical safety checklist in ambulatory oral and maxillofacial surgery (OMS) practice. MATERIALS AND METHODS: The authors designed and implemented a cross-sectional study and enrolled a random sample of oral and maxillofacial surgeons. The predictor variable was years removed from residency. The primary outcome was the prevalence of surgical safety checklist usage in ambulatory OMS practice. The secondary outcome was to determine whether surgeons who do not currently use a checklist would be willing to do so if provided with one. Other demographic variables included age, gender, location of practice, type of practice, and number of ambulatory procedures performed per week. Appropriate uni- and bivariate statistics were computed and the level of significance set at .05; 95% confidence intervals also were calculated. RESULTS: The study sample was composed of 120 clinicians. Forty-two percent of respondents reported that they were not using a surgical safety checklist for ambulatory surgery. Ninety-three percent of those respondents not currently using a checklist reported they would consider implementing a surgical safety checklist in their practice if provided with one. In addition, 45.3% of surgeons performing more than 30 procedures a week reported not using a surgical safety checklist. Most respondents (67.9%) who had completed OMS training more than 20 years previously reported not using a checklist in their practice. CONCLUSION: According to this survey, most practicing oral and maxillofacial surgeons do not currently use surgical safety checklists. Although the response rate was only 12%, the survey does reflect a clear lack of use of checklists among practicing oral and maxillofacial surgeons despite its widespread acceptance in the medical community.

Population-attributable fraction of tubal factor infertility associated with chlamydia.

BACKGROUND: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. OBJECTIVES: The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates. STUDY DESIGN: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds ratios and population-attributable fraction, stratified by race. RESULTS: We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73-89%) among Black and 31% (95% confidence interval, 28-35%) among non-Black participants (P < .001). Using the primary Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45-3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95-2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, -97% to 68%) among Blacks and 11% (95% confidence interval, -3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia-tubal factor infertility association and resulted in a significant association among non-Blacks. CONCLUSION: Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates.

Effectiveness of neuromuscular electrical stimulation for management of shoulder subluxation post-stroke: a systematic review with meta-analysis.

OBJECTIVES: To examine the effectiveness of neuromuscular electrical stimulation (NMES) for the management of shoulder subluxation after stroke including assessment of short (1 hour or less) and long (more than one hour) daily treatment duration. DATA SOURCES: MEDLINE, CENTRAL, CINAHL, WOS, KoreaMed, RISS and reference lists from inception to January 2017 Review methods: We considered randomized controlled trials that reported neuromuscular electrical stimulation for the treatment of shoulder subluxation post-stroke. Two reviewers independently selected trials for inclusion, assessed trial quality, and extracted data. RESULTS: Eleven studies were included (432 participants); seven studies were good quality, four were fair. There was a significant treatment effect of neuromuscular electrical stimulation for reduction of subluxation for persons with acute and subacute stroke (SMD:-1.11; 95% CI:-1.53, -0.68) with either short (SMD:-0.91; 95% CI:-1.43, -0.40) or long (SMD:-1.49; 95% CI:-2.31, -0.67) daily treatment duration. The effect for patients with chronic stroke was not significant (SMD:-1.25; 95% CI:-2.60, 0.11). There was no significant effect of neuromuscular electrical stimulation on arm function or shoulder pain. CONCLUSION: This meta-analysis suggests a beneficial effect of neuromuscular electrical stimulation, with either short or long daily treatment duration, for reducing shoulder subluxation in persons with acute and subacute stroke. No significant benefits were observed for persons with chronic stroke or for improving arm function or reducing shoulder pain.

Structural basis for the suppression of skin cancers by DNA polymerase eta.

DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.

Most American Association of Oral and Maxillofacial Surgeons Members Have Not Adopted the American Society of Anesthesiologists-Recommended Nil Per Os Guidelines.

PURPOSE: The purpose of this study was to determine if American Association of Oral and Maxillofacial Surgeons members have integrated the current American Society of Anesthesiologists (ASA) nil per os (NPO) guidelines into their preoperative instructions. MATERIALS AND METHODS: We designed and implemented a cross-sectional study and enrolled a random sample of private-practice American Association of Oral and Maxillofacial Surgeons members who practice in the United States. The predictor variables were year of graduation from residency, dual degree (MD and DDS or DMD) or single degree, and region. The primary outcome variable was adoption of the ASA NPO guidelines, defined as recommending fasting times of 2 hours for clear liquids and 6 hours for solid foods. To collect data, a systematic online search was implemented. Appropriate univariate and bivariate statistics were computed, and the level of significance was set at .05; in addition, 95% confidence intervals were calculated. RESULTS: The study sample was composed of 431 oral and maxillofacial surgeons (OMSs). Almost all of the study sample (99.1%) did not adopt the ASA guidelines. The fasting recommendations were different from 2 hours for clear liquids and 6 hours for solid foods. However, recommendations of 2 hours or greater for clear liquids were made by 99.8% of OMSs, and recommendations of 6 hours or greater for solid foods were made by 99.3%. Only 4.4% of OMSs made different recommendations for clear liquids and solid foods. No substantial association was found between whether OMSs adopted the most current ASA guidelines and the year they graduated from residency or the obtainment of dual degrees. CONCLUSIONS: OMSs in private practice are overwhelmingly recommending longer fasting times for clear liquids and solid foods on their Web sites when compared with the current ASA guidelines before ambulatory anesthesia. The ASA guidelines are based on meta-analysis; therefore, deviations in practice, although not incorrect, may call for discussion.

No sodium in the vapour plumes of Enceladus.

The discovery of water vapour and ice particles erupting from Saturn's moon Enceladus fuelled speculation that an internal ocean was the source. Alternatively, the source might be ice warmed, melted or crushed by tectonic motions. Sodium chloride (that is, salt) is expected to be present in a long-lived ocean in contact with a rocky core. Here we report a ground-based spectroscopic search for atomic sodium near Enceladus that places an upper limit on the mixing ratio in the vapour plumes orders of magnitude below the expected ocean salinity. The low sodium content of escaping vapour, together with the small fraction of salt-bearing particles, argues against a situation in which a near-surface geyser is fuelled by a salty ocean through cracks in the crust. The lack of observable sodium in the vapour is consistent with a wide variety of alternative eruption sources, including a deep ocean, a freshwater reservoir, or ice. The existing data may be insufficient to distinguish between these hypotheses.

Pol31 and Pol32 subunits of yeast DNA polymerase δ are also essential subunits of DNA polymerase ζ.

Replication through a diverse array of DNA lesions occurs by the sequential action of two translesion synthesis (TLS) DNA polymerases (Pols), in which one inserts the nucleotide opposite the lesion and the other carries out the subsequent extension. By extending from the nucleotide inserted by another Pol, Polζ plays an indispensable role in mediating lesion bypass. Polζ comprises the Rev3 catalytic and Rev7 accessory subunits. Pol32, a subunit of the replicative polymerase Polδ, is also required for Polζ-dependent TLS, but how this Polδ subunit contributes to Polζ function in TLS has remained unknown. Here we show that yeast Polζ is a four-subunit enzyme containing Rev3, Rev7, Pol31, and Pol32; in this complex, association with Pol31/Pol32 is mediated via binding of the Rev3 C terminus to Pol31. The functional requirement of this complex is supported by evidence that mutational inactivation of Rev3's ability to bind Pol31 abrogates Polζ's role in TLS in yeast cells. These findings identify an unexpected role of Pol31 and Pol32 as two essential subunits of Polζ, and clarify why these proteins are required for Polζ-dependent TLS, but not for TLS mediated by Polη in yeast cells. To distinguish the four-subunit complex from the two-subunit Polζ, we designate the four-subunit enzyme "Polζ-d," where "-d" denotes the Pol31/Pol32 subunits of Polδ.

NGL-2 regulates pathway-specific neurite growth and lamination, synapse formation, and signal transmission in the retina.

Parallel processing is an organizing principle of many neural circuits. In the retina, parallel neuronal pathways process signals from rod and cone photoreceptors and support vision over a wide range of light levels. Toward this end, rods and cones form triad synapses with dendrites of distinct bipolar cell types, and the axons or dendrites, respectively, of horizontal cells (HCs). The molecular cues that promote the formation of specific neuronal pathways remain largely unknown. Here, we discover that developing and mature HCs express the leucine-rich repeat (LRR)-containing protein netrin-G ligand 2 (NGL-2). NGL-2 localizes selectively to the tips of HC axons, which form reciprocal connections with rods. In mice with null mutations in Ngl-2 (Ngl-2⁻/⁻), many branches of HC axons fail to stratify in the outer plexiform layer (OPL) and invade the outer nuclear layer. In addition, HC axons expand lateral territories and increase coverage of the OPL, but establish fewer synapses with rods. NGL-2 can form transsynaptic adhesion complexes with netrin-G2, which we show to be expressed by photoreceptors. In Ngl-2⁻/⁻ mice, we find specific defects in the assembly of presynaptic ribbons in rods, indicating that reverse signaling of complexes involving NGL-2 regulates presynaptic maturation. The development of HC dendrites and triad synapses of cone photoreceptors proceeds normally in the absence of NGL-2 and in vivo electrophysiology reveals selective defects in rod-mediated signal transmission in Ngl-2⁻/⁻ mice. Thus, our results identify NGL-2 as a central component of pathway-specific development in the outer retina.

PCNA binding domains in all three subunits of yeast DNA polymerase δ modulate its function in DNA replication.

DNA polymerase δ (Polδ) plays an essential role in replication from yeast to humans. Polδ in Saccharomyces cerevisiae is comprised of three subunits, the catalytic subunit Pol3 and the accessory subunits Pol31 and Pol32. Yeast Polδ exhibits a very high processivity in synthesizing DNA with the proliferating cell nuclear antigen (PCNA) sliding clamp; however, it has remained unclear how Polδ binds PCNA to achieve its high processivity. Here we show that PCNA interacting protein (PIP) motifs in all three subunits contribute to PCNA-stimulated DNA synthesis by Polδ, and mutational inactivation of all three PIP motifs abrogates its ability to synthesize DNA with PCNA. Genetic analyses of mutations in these PIPs have revealed that in the absence of functional Pol32 PIP domain, PCNA binding by both the Pol3 and Pol31 subunits becomes essential for cell viability. Based on our biochemical and genetic studies we infer that yeast Polδ can simultaneously utilize all three PIP motifs during PCNA-dependent DNA synthesis, and suggest that Polδ binds the PCNA homotrimer via its three subunits. We consider the implications of these observations for Polδ's role in DNA replication.

Cryo-EM structure of the Rev1-Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis.

Rev1-Polζ-dependent translesion synthesis (TLS) of DNA is crucial for maintaining genome integrity. To elucidate the mechanism by which the two polymerases cooperate in TLS, we determined the cryogenic electron microscopic structure of the Saccharomyces cerevisiae Rev1-Polζ holocomplex in the act of DNA synthesis (3.53 Å). We discovered that a composite N-helix-BRCT module in Rev1 is the keystone of Rev1-Polζ cooperativity, interacting directly with the DNA template-primer and with the Rev3 catalytic subunit of Polζ. The module is positioned akin to the polymerase-associated domain in Y-family TLS polymerases and is set ideally to interact with PCNA. We delineate the full extent of interactions that the carboxy-terminal domain of Rev1 makes with Polζ and identify potential new druggable sites to suppress chemoresistance from first-line chemotherapeutics. Collectively, our results provide fundamental new insights into the mechanism of cooperativity between Rev1 and Polζ in TLS.

How Do Curricula for Medical Students and Physician Learners Address the Social Determinants of Health? A Scoping Review.

PURPOSE: Curricula about social determinants (drivers) of health (SDOH) are becoming more common in medical education, reflecting increasing expectations from payers and accreditors that health care systems do more to address health-related social needs and close pervasive health equity gaps. Few previous reviews have addressed the content of SDOH-related curricula. This review examines the scope and focus of medical education on SDOH and adjacent concepts. METHOD: The authors screened 2,442 articles describing curricula delivered in undergraduate, graduate, and continuing medical education settings between 2010 and 2023 using PubMed and 2 field-specific databases, yielding 289 articles. Data on course duration, pedagogic approach, assessment methods, and curricular content were extracted and analyzed. Curricular content was categorized using the National Academies of Science, Engineering, and Medicine's (NASEM's) 5As framework, which recommends 5 key activities health care can undertake to mitigate social risk (awareness, adjustment, assistance, alignment, and advocacy). RESULTS: A total of 289 articles were included in this review. Curricula covering SDOH-related concepts have increased over time. Of the included articles, 190 (65.7%) referenced at least 1 of NASEM's 5 key activities. Training on social risk screening and other awareness activities were noted most frequently (123 [42.6%]), followed by curricula on helping patients get social care (assistance; 86 [29.8%]) and providing social risk-adjusted health care (adjustment; 81 [28.0%]). Curricula on system- and policy-level activities, including alignment of health care and social care organizations (alignment), and advocacy (advocacy) were described less frequently (43 [14.9%] and 49 [17.0%], respectively). Ninety-four articles (32.5%) referenced only general information about SDOH without describing specific actions to adjust care or reduce social adversity. CONCLUSIONS: NASEM's 5As framework provides a useful construct for characterizing SDOH-related curricula. Medical educators should teach not only the prevalence and pathophysiology of SDOH but also what physicians can do to address these factors.