Nanoceria: an innovative strategy for cancer treatment.

Nanoceria or cerium oxide nanoparticles characterised by the co-existing of Ce3+ and Ce4+ that allows self-regenerative, redox-responsive dual-catalytic activities, have attracted interest as an innovative approach to treating cancer. Depending on surface characteristics and immediate environment, nanoceria exerts either anti- or pro-oxidative effects which regulate reactive oxygen species (ROS) levels in biological systems. Nanoceria mimics ROS-related enzymes that protect normal cells at physiological pH from oxidative stress and induce ROS production in the slightly acidic tumour microenvironment to trigger cancer cell death. Nanoceria as nanozymes also generates molecular oxygen that relieves tumour hypoxia, leading to tumour cell sensitisation to improve therapeutic outcomes of photodynamic (PDT), photothermal (PTT) and radiation (RT), targeted and chemotherapies. Nanoceria has been engineered as a nanocarrier to improve drug delivery or in combination with other drugs to produce synergistic anti-cancer effects. Despite reported preclinical successes, there are still knowledge gaps arising from the inadequate number of studies reporting findings based on physiologically relevant disease models that accurately represent the complexities of cancer. This review discusses the dual-catalytic activities of nanoceria responding to pH and oxygen tension gradient in tumour microenvironment, highlights the recent nanoceria-based platforms reported to be feasible direct and indirect anti-cancer agents with protective effects on healthy tissues, and finally addresses the challenges in clinical translation of nanoceria based therapeutics.

Large thyroid nodules: should size alone matter?

BACKGROUND: The management of thyroid nodules ≥ 4 cm is controversial due to conflicting evidence on the prevalence of malignancy and diagnostic accuracy of fine-needle aspiration cytology (FNAC). Some literature recommends routine excision of large thyroid nodules due to high cytology false negative rates (FNR). We aim to investigate the diagnostic accuracy of FNAC, prevalence of malignancy in large (≥ 4 cm) thyroid nodules compared to nodules < 4 cm, and the clinical and ultrasound characteristics of those large nodules with false negative cytology. METHODS: This was a retrospective case-log review in a tertiary referral hospital. All thyroid nodules subjected to Ultrasound (US)-guided FNAC by the Interventional Radiology department between December 2011 and November 2017 were included. Data on patient demographics, thyroid US features, cytology findings, and surgical histology were collected and analyzed. Sensitivity, specificity, and FNR were calculated based on FNAC results and final post-operative histology. Factors associated with a false negative result were analyzed using univariate and multivariate analyses. RESULTS: A total of 4982 nodules were studied, including 4419 < 4 cm and 563 ≥ 4 cm. Malignancy rates were similar in both groups. For nodules ≥ 4 cm, FNAC sensitivity was 40%, specificity 100%, and FNR 6.6% compared to 4.2% in nodules < 4 cm. Within malignant nodules, there was a significantly higher proportion of follicular and Hurthle cell carcinomas in nodules ≥ 4 cm. Amongst nodules ≥ 4 cm, multivariate analysis revealed male gender to be an independent predictor of FNR (OR 3.32; 95% CI 1.29-8.59). CONCLUSION: Larger nodules ≥ 4 cm have a similar malignancy rate as nodules < 4 cm, and FNAC FNR is low at 6.6%. Management of large thyroid nodules should be individualized based on their clinical, sonographic and cytological features rather than routine surgery.

Fluorinated Glycopolymers as Reduction-responsive 19F MRI Agents for Targeted Imaging of Cancer.

Imaging agents that can be targeted to specific diseases and respond to the microenvironment of the diseased tissue are of considerable interest due to their potential in diagnosing and managing diseases. Here we report a new class of branched fluorinated glycopolymers as 19F MRI contrast agents that respond to a reductive environment, for targeted imaging of cancer. The fluorinated glycopolymers can be readily prepared by a one-pot RAFT polymerization of glucose- and fluorine-containing monomers in the presence of a disulfide-containing cross-linking monomer. The incorporation of glucose units along the polymer chain enables these fluorinated glycopolymers to effectively target cancer cells due to interactions with the overexpressed sugar transporters present on the cell surface. In addition, the polymers exhibit an enhanced 19F MRI signal in response to a reductive environment, one of the unique hallmarks of many cancer cells, demonstrating their potential as promising candidates for targeted imaging of cancer.

Elevated fetal haemoglobin levels are associated with decreased incidence of retinopathy in adults with sickle cell disease.

Among the many vascular complications of sickle cell disease (SCD), retinopathy is the most prevalent and represents a leading cause of blindness. Hydroxycarbamide therapy ameliorates many symptoms of SCD, and high fetal haemoglobin (HbF) levels have been shown to protect against the development of retinopathy in children with HbSS. Its effect on adults with SCD, who are at a much higher risk of developing retinopathy, has not been studied. We aimed to investigate the effect of hydroxycarbamide use and HbF level on sickle cell retinopathy development in adults. We performed a retrospective cross-sectional study and collected demographics, comorbidities, and ocular and haematological data from 300 adult sickle cell subjects examined at the Henkind Eye Institute at Montefiore Medical Center during a 5-year period, from October 2012 to November 2017. The cohort was comprised mainly of Black and Hispanic subjects with all SCD genotypes, aged 18-71 years. Results show that in HbSS patients treated with hydroxycarbamide, those with retinopathy had significantly lower HbF levels compared to patients without retinopathy (P = 0·018). Our study identified the optimal HbF cut-off point for retinopathy protection to be 14·87%. Thus, a HbF level of 15% appears to be the threshold above which the odds for developing retinopathy in SS patients are reduced by 50%.

Postnatal Exposure to Ethanol Increases Its Oral Acceptability to Adolescent Rats.

The aversive flavor of ethanol limits intake by many consumers. We asked whether intermittent consumption of ethanol increases its oral acceptability, using rats as a model system. We focused on adolescent rats because they (like their human counterparts) have a higher risk for alcohol overconsumption than do adult rats following experience with the drug. We measured the impact of ethanol exposure on 1) the oral acceptability of ethanol and surrogates for its bitter (quinine) and sweet (sucrose) flavor components in brief-access lick tests and 2) responses of the glossopharyngeal (GL) taste nerve to oral stimulation with the same chemical stimuli. During the exposure period, the experimental rats had access to chow, water and 10% ethanol every other day for 16 days; the control rats had access to chow and water over the same time period. The experimental rats consumed 7-14 g/day of 10% ethanol across the exposure period. This ethanol consumption significantly increased the oral acceptability of 3%, 6% and 10% ethanol, but had no impact on the oral acceptability of quinine, sucrose or NaCl. The ethanol exposure also diminished responses of the GL nerve to oral stimulation with ethanol, but not quinine, sucrose or NaCl. Taken together, these findings indicate that ethanol consumption increases the oral acceptability of ethanol in adolescent rats and that this increased oral acceptability is mediated, at least in part, by an exposure-induced reduction in responsiveness of the peripheral taste system to ethanol per se, rather than its bitter and sweet flavor components.

Preventing Diabetes in Primary Care: Providers' Perspectives About Diagnosing and Treating Prediabetes.

IN BRIEF Offering patient-centered care to prevent diabetes will require collaborative decision-making between patients with prediabetes and their health care providers. From the perspective of primary care providers, prediabetes detection should be targeted to patients who are most likely to benefit from diagnosis and treatment. Improving access to lifestyle intervention programs and educating providers about evidence-based treatments for prediabetes and how to effectively discuss treatment options with patients may improve both providers' and patients' engagement in diabetes prevention.

Discovery of large genomic inversions using long range information.

BACKGROUND: Although many algorithms are now available that aim to characterize different classes of structural variation, discovery of balanced rearrangements such as inversions remains an open problem. This is mainly due to the fact that breakpoints of such events typically lie within segmental duplications or common repeats, which reduces the mappability of short reads. The algorithms developed within the 1000 Genomes Project to identify inversions are limited to relatively short inversions, and there are currently no available algorithms to discover large inversions using high throughput sequencing technologies. RESULTS: Here we propose a novel algorithm, VALOR, to discover large inversions using new sequencing methods that provide long range information such as 10X Genomics linked-read sequencing, pooled clone sequencing, or other similar technologies that we commonly refer to as long range sequencing. We demonstrate the utility of VALOR using both pooled clone sequencing and 10X Genomics linked-read sequencing generated from the genome of an individual from the HapMap project (NA12878). We also provide a comprehensive comparison of VALOR against several state-of-the-art structural variation discovery algorithms that use whole genome shotgun sequencing data. CONCLUSIONS: In this paper, we show that VALOR is able to accurately discover all previously identified and experimentally validated large inversions in the same genome with a low false discovery rate. Using VALOR, we also predicted a novel inversion, which we validated using fluorescent in situ hybridization. VALOR is available at https://github.com/BilkentCompGen/VALOR.

Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes.NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal chemosensory neurons. We found that FAE substantially reduced taste and trigeminal responsiveness to ethanol and its flavor components.

The Impact of Residual Subgingival Cement on Biological Complications Around Dental Implants: A Systematic Review.

OBJECTIVES: To perform a systematic review on the impact of residual subgingival cement on peri-implant diseases and crestal bone loss. MATERIAL AND METHODS: MEDLINE, SCOPUS, ISI Web of Knowledge and Cochrane Central Register of Controlled Trials (CENTRAL) databases were used to identify articles published without time limits. RESULTS: A total of 6 articles were selected for a total of 389 patients (687 implants). The studies were heterogeneous and had a moderate-to-high risk of bias, but met the inclusion criteria. Four of 6 studies were published by the same research group and assessed similar populations over time. A positive relationship between residual cement and peri-implant inflammation was observed. Data on peri-implant probing depths and crestal bone loss were reported in 1 study. CONCLUSION: Residual subgingival cement seems to be strongly associated with peri-implant mucositis which is a risk factor for increased probing depths crestal bone loss and peri-implantitis. Zinc oxide eugenol cements should be preferred to resin cements especially in patients with a history of periodontitis.

Perspectives on prevention of type 2 diabetes after gestational diabetes: a qualitative study of Hispanic, African-American and White women.

Women with gestational diabetes (GDM) have a fivefold higher risk of developing type 2 diabetes (T2DM). Furthermore, Hispanic and African-American women are disproportionately affected by GDM, but their views on prevention of T2DM after gestational diabetes are largely unknown. We conducted semi-structured interviews with 23 women (8 Hispanic, 8 African-American, 7 non-Hispanic White) from two academic clinics in Chicago, IL. Interview questions elicited perspectives on prevention of T2DM; the interview protocol was developed based on the Health Belief Model. Two investigators applied template analysis to identify emergent themes. Women conceptualized risk for T2DM based on family history, health behaviors, and personal history of GDM. A subgroup of women expressed uncertainty about how GDM influences risk for T2DM. Women who described a strong link between GDM and T2DM often viewed the diagnosis as a cue to action for behavior change. T2DM was widely viewed as a severe condition, and desire to avoid T2DM was an important motivator for behavior change. Children represented both a key motivator and critical barrier to behavior change. Women viewed preventive care as important to alert them to potential health concerns. Identified themes were congruent across racial/ethnic groups. Diagnosis with GDM presents a potent opportunity for engaging women in behavior change. To fully harness the potential influence of this diagnosis, healthcare providers should more clearly link the diagnosis of GDM with risk for future T2DM, leverage women's focus on their children to motivate behavior change, and provide support with behavior change during healthcare visits in the postpartum period and beyond.

Clinical Outcomes in Patients With Benign Paroxysmal Positional Vertigo and Vitamin D Deficiency: A Singaporean Perspective.

INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) is the primary vestibular disorder causing peripheral vertigo. Given the role of vitamin D in maintaining otoconia homeostasis, its deficiency may elevate the risk of BPPV. Our study seeks to evaluate the correlation between vitamin D deficiency and clinical outcomes of patients with BPPV in the local Asian population. METHODOLOGY: We performed a retrospective analysis of 149 consecutive adult patients referred to a tertiary center's Otolaryngology dizziness clinic between 2018 and 2021. All of these patients had both BPPV and vitamin D deficiency. RESULTS: The mean serum vitamin D level was 19.4 ± 5.5 ng/mol. Approximately 51.7% (77/149) of patients experienced recurrent episodes of BPPV. Univariate Chi-square analyses demonstrated vitamin D levels (P < 0.001) and history of migraine (P = 0.04) were related to BPPV recurrence. On multivariate analyses, patients with higher serum vitamin D levels were 16.7% less likely to develop recurrent BPPV (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.76-0.90, P < 0.001). However, migraine history was not significantly related to BPPV recurrence (OR 0.38, 95% CI 0.14-1.00, P = 0.050). There was no statistically significant difference in the duration of BPPV episodes based on vitamin D levels (P = 0.327). CONCLUSIONS: Patients with vitamin D deficiency are at higher risk of recurrent BPPV. Future research directions that would be beneficial include conducting a randomized controlled trial to evaluate both the effectiveness of vitamin D supplementation and its optimal dosage.

Using Pupillometry to Evaluate Balance in Patients Implanted with a Cochleo-Vestibular Implant.

Maintaining balance comes naturally to healthy people. In subjects with vestibulopathy, even when compensated, and especially if it is bilateral, maintaining balance requires cognitive effort. Pupillometry is an established method of quantifying cognitive effort. Background/Objectives: We hypothesized that pupillometry would be able to capture the increased effort required to maintain posture in subjects with bilateral vestibulopathy in increasingly difficult conditions. Additionally, we hypothesized that the cognitive workload during balance tasks, indexed by pupil size, would decrease with the activation of the BionicVEST cochleo-vestibular implants. Methods: Subjects with a cochleo-vestibular implant as of March 2023 were recruited, excluding those with ophthalmological issues that precluded pupillometry. Pupillometry was performed using a validated modified videonystagmography system. Computed dynamic posturography and a Modified Clinical Test of Sensory Integration on Balance were performed while the pupil was recorded. Tests were first performed after 24 h of deactivating the vestibular component of the implant. Thereafter, it was reactivated, and after 1 h of rest, the tests were repeated. The pupil recording was processed using custom software and the mean relative pupil diameter (MRPD) was calculated. Results: There was an average of 10.7% to 24.2% reduction in MRPD when the vestibular implant was active, with a greater effect seen in tasks of moderate difficulty, and lesser effect when the task was easy or of great difficulty. Conclusions: Despite technical challenges, pupillometry appears to be a promising method of quantifying the cognitive effort required for maintaining posture in subjects with bilateral vestibulopathy before and after vestibular implantation.

Development and Implementation of an Experiential Longitudinal Health Systems Science Thread Into an Existing Medical School Curriculum.

PROBLEM: Medical school graduates enter a complex health care delivery system involving interprofessional teamwork and multifaceted value-based patient care decisions. However, current curricula on health systems science (HSS) are piecemeal, lecture based, and confined to preclinical training. APPROACH: The VISTA program is a longitudinal, immersive learning curriculum integrated into the University of Chicago Pritzker School of Medicine curriculum between 2016 and 2018. Key components include a unit-based nursing interprofessional team experience, a discharge objective structured clinical examination (OSCE), a patient safety simulation, and the implementation of a Choosing Wisely SmartPhrase. Graduates before (2016-2017) and after (2018-2020) VISTA implementation completed a Likert-style survey assessing attitudes, knowledge, and behaviors on HSS topics. A free response question solicited improvement areas. The Association of American Medical Colleges (AAMC) Graduation Questionnaire (GQ) was also examined. OUTCOMES: The overall VISTA survey response rate was 59%, with 126 fourth-year medical student respondents before VISTA and 120 after VISTA. Compared with pre-VISTA graduates, post-VISTA graduates reported a significantly higher rate of competence on the HSS questions, with the greatest increases seen in effective communication at discharge (n = 73/126 [57.9%] to 116/120 [96.7%], P < .001), knowledge on safety event reporting (n = 53/126 [42.1%] to 96/120 [79.8%], P < .001), and considering costs in making health care decisions (n = 76/126 [60.3%] to 117/120 [97.5%], P < .001). All were directly addressed through experiential learning interventions, and 2 were intended practice behaviors. VISTA graduate responses to free-text questions demonstrated a more nuanced understanding of HSS compared with pre-VISTA responses. The AAMC GQ data showed increased agreement with an item that mapped to HSS understanding. NEXT STEPS: The VISTA program provides a model for institutions to enhance HSS education between curricular overhauls. Next steps include implementing value-added roles and additional immersive learning exercises.

Developing a production workflow for 3D-printed temporal bone surgical simulators.

INTRODUCTION: 3D-printed temporal bone models enable the training and rehearsal of complex otological procedures. To date, there has been no consolidation of the literature regarding the developmental process of 3D-printed temporal bone models. A brief review of the current literature shows that many of the key surgical landmarks of the temporal bone are poorly represented in models. This study aims to propose a novel design and production workflow to produce high-fidelity 3D-printed temporal bone models for surgical simulation. METHODS: Developmental phases for data extraction, 3D segmentation and Computer Aided Design (CAD), and fabrication are outlined. The design and fabrication considerations for key anatomical regions, such as the mastoid air cells and course of the facial nerve, are expounded on with the associated strategy and design methods employed. To validate the model, radiological measurements were compared and a senior otolaryngologist performed various surgical procedures on the model. RESULTS: Measurements between the original scans and scans of the model demonstrate sub-millimetre accuracy of the model. Assessment by the senior otologist found that the model was satisfactory in simulating multiple surgical procedures. CONCLUSION: This study offers a systematic method for creating accurate 3D-printed temporal bone models for surgical training. Results show high accuracy and effectiveness in simulating surgical procedures, promising improved training and patient outcomes.

Health-care access and weight change among young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

OBJECTIVE: Health-care access is associated with improved control of multiple chronic diseases, but the association between health-care access and weight change is unclear. The present study aims to test the association between health-care access and weight change. DESIGN: The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a multicentre population-based prospective study. Weight change was calculated at 3 and 13 years after CARDIA year 7 (1992-1993). Health-care access was defined as no barriers or one or more barriers to access (health insurance gap, no usual source of care, not seeking care due to expense). Intermediary variables evaluated included history of dieting and use of diet pills, meal replacements or weight-control programmes. SETTING: Four cities in the USA. SUBJECTS: Participants were aged 18-30 years at baseline (1985-1986). Analyses include 3922 black and white men and women with relevant data from CARDIA years 7, 10 and 20 (1992-1993, 1995-1996 and 2005-2006, respectively). RESULTS: Mean weight change was +2.22 kg (+4.9 lb) by 3 years and +8.48 kg (+18.7 lb) by 13 years, with no differences by health-care access. Being on a weight-reducing diet was not consistently associated with health-care access across examinations. Use of diet pills, meal replacements or organized weight-control programmes was low, and did not vary by health-care access. CONCLUSIONS: Weight gain was high irrespective of health-care access. Public health and clinical approaches are needed to address weight gain.

Relapsing Aspergillus otomycosis despite prolonged systemic antifungal therapy and resolution after topical voriconazole administration: A case report.

We report a case of intractable Aspergillus otomycosis with multiple relapses despite conventional topical and systemic antifungal treatment, and adjunctive usage of hyperbaric oxygen therapy. Of note, otomycosis relapsed even after six months of continuous systemic antifungal treatment with therapeutic drug levels and without treatment interruption; and only resolved after application of topical voriconazole. (max. 75 words).

Implementation of a Biopsychosocial History and Physical Exam Template in the Electronic Health Record: Mixed Methods Study.

BACKGROUND: Patients' perspectives and social contexts are critical for prevention of hospital readmissions; however, neither is routinely assessed using the traditional history and physical (H&P) examination nor commonly documented in the electronic health record (EHR). The H&P 360 is a revised H&P template that integrates routine assessment of patient perspectives and goals, mental health, and an expanded social history (behavioral health, social support, living environment and resources, function). Although the H&P 360 has shown promise in increasing psychosocial documentation in focused teaching contexts, its uptake and impact in routine clinical settings are unknown. OBJECTIVE: The aim of this study was to assess the feasibility, acceptability, and impact on care planning of implementing an inpatient H&P 360 template in the EHR for use by fourth-year medical students. METHODS: A mixed methods study design was used. Fourth-year medical students on internal medicine subinternship (subI) services were given a brief training on the H&P 360 and access to EHR-based H&P 360 templates. Students not working in the intensive care unit (ICU) were asked to use the templates at least once per call cycle, whereas use by ICU students was elective. An EHR query was used to identify all H&P 360 and traditional H&P admission notes authored by non-ICU students at University of Chicago (UC) Medicine. Of these notes, all H&P 360 notes and a sample of traditional H&P notes were reviewed by two researchers for the presence of H&P 360 domains and impact on patient care. A postcourse survey was administered to query all students for their perspectives on the H&P 360. RESULTS: Of the 13 non-ICU subIs at UC Medicine, 6 (46%) used the H&P 360 templates at least once, which accounted for 14%-92% of their authored admission notes (median 56%). Content analysis was performed with 45 H&P 360 notes and 54 traditional H&P notes. Psychosocial documentation across all H&P 360 domains (patient perspectives and goals, mental health, expanded social history elements) was more common in H&P 360 compared with traditional notes. Related to impact on patient care, H&P 360 notes more commonly identified needs (20% H&P 360; 9% H&P) and described interdisciplinary coordination (78% H&P 360; 41% H&P). Of the 11 subIs completing surveys, the vast majority (n=10, 91%) felt the H&P 360 helped them understand patient goals and improved the patient-provider relationship. Most students (n=8, 73%) felt the H&P 360 took an appropriate amount of time. CONCLUSIONS: Students who applied the H&P 360 using templated notes in the EHR found it feasible and helpful. These students wrote notes reflecting enhanced assessment of goals and perspectives for patient-engaged care and contextual factors important to preventing rehospitalization. Reasons some students did not use the templated H&P 360 should be examined in future studies. Uptake may be enhanced through earlier and repeated exposure and greater engagement by residents and attendings. Larger-scale implementation studies can help further elucidate the complexities of implementing nonbiomedical information within EHRs.

A 7-Domain Framework That Can Bridge Clinical Care, Health Systems Science, and Health Equity: Lessons From the H&P 360.

The H&P 360 is a reconceptualized history and physical (H&P), which clinical medical students have reported reveals clinically relevant information not elicited by the traditional H&P, informs care planning, promotes interprofessional team care, and enhances patient rapport. In addition to the traditional checklist focused on patients' medical conditions, the H&P 360 includes prompts for gathering limited but critical information in 6 other domains directly relevant to patients' overall health-patient values, goals, and priorities; mental health; behavioral health; social support; living environment and resources; and function. Clinicians are thus reminded to elicit relevant information from each domain appropriate to the context of each clinical encounter. As health systems explore ways to identify and address social drivers of health, medical schools are rapidly expanding curricula beyond biomedical conditions, as reflected in the multifaceted health systems science curriculum. Many of today's medical students struggle to find connections among the core tasks of mastering biomedical clinical medicine, their evolving professional identity and career trajectory, and addressing systemic and societal barriers to population health. The authors argue that the 7-domain framework can serve as a conceptual bridge that links the care of individual patients with topics in the health systems science curriculum to promote health equity. The authors provide illustrative examples of the 7 domains as an organizing lens that can promote curiosity and understanding of seemingly disparate topics, such as interpersonal violence, social drivers of health, and structural racism, as well as help students expand and define their professional identities as physicians beyond diagnosis and treatment of biomedical conditions. The authors invite discussion and experimentation around the use of the 7-domain framework in teaching, assessment, and curriculum development and point to resources for clinical educators for teaching and measuring the effects of the H&P 360 on learners, preceptors, and patients.

Does the Doctor-Patient Relationship Affect Enrollment in Clinical Research?

PURPOSE: Recruiting patients for clinical research is challenging, especially for underrepresented populations, and may be influenced by patients' relationships with their physicians, care experiences, and engagement with care. This study sought to understand predictors of enrollment in a research study among socioeconomically diverse participants in studies of care models that promote continuity in the doctor-patient relationship. METHOD: A study of the effects of vitamin D levels and supplementation on COVID-19 risk and outcomes was implemented from 2020 to 2022 within 2 studies of care models at the University of Chicago that promoted continuity of inpatient and outpatient care from the same physician. Hypothesized predictors of vitamin D study enrollment included patient-reported measures of the care experience (quality of relationship with the doctor and their staff, timely receipt of care), engagement in care (scheduling and completing outpatient visits), and engagement with these "parent" studies (follow-up survey completion). The authors used univariate tests and multivariable logistic regression to examine the association of these predictors with enrollment in the vitamin D study among participants in the parent study intervention arms. RESULTS: Among 773 eligible participants, 351/561 (63%) in the parent study intervention arms enrolled in the vitamin D study, versus 35/212 (17%) in the control arms. Among intervention arm participants, vitamin D study enrollment was not associated with reported quality of communication with or trust in the doctor, or helpful/respectful office staff, but was associated with report of receiving timely care, more completed clinic visits, and higher parent study follow-up survey completion. CONCLUSIONS: Study enrollment may be high in care models with high levels of continuity in the doctor-patient relationship. Rates of clinic involvement, parent study engagement, and experience of receiving timely access to care may better predict enrollment than quality of the doctor-patient relationship.

Spiky Silver-Iron Oxide Nanohybrid for Effective Dual-Imaging and Synergistic Thermo-Chemotherapy.

Nanophotothermal therapy based on nanoparticles (NPs) that convert near-infrared (NIR) light to generate heat to selectively kill cancer cells has attracted immense interest due to its high efficacy and being free of ionizing radiation damage. Here, for the first time, we have designed a novel nanohybrid, silver-iron oxide NP (AgIONP), which was successfully tuned for strong absorbance at NIR wavelengths to be effective in photothermal treatment and dual-imaging strategy using MRI and photoacoustic imaging (PAI) in a cancer model in vivo and in vitro, respectively. We strategically combine the inherent anticancer activity of silver and photothermal therapy to render excellent therapeutic capability of AgIONPs. In vitro phantoms and in vivo imaging studies displayed preferential uptake of folate-targeted NPs in a cancer mice model, indicating the selective targeting efficiency of NPs. Importantly, a single intravenous injection of NPs in a cancer mice model resulted in significant tumor reduction, and photothermal laser resulted in a further substantial synergistic decrease in tumor size. Additionally, biosafety and biochemical assessment performed in mice displayed no significant difference between NP treatment and control groups. Overall, our folic acid AgIONPs displayed excellent potential in the simultaneous application for safe and successful targeted synergistic photothermal treatment and imaging of a cancer model.