Let's Chalk About It: Introducing the TinyTalks Curriculum, a Paradigm for Short, Virtual Chalk Talks.

ABSTRACT: In busy clinical environments, educational opportunities must be designed to accommodate learner-specific needs. Many adult learners prefer short, relevant, technology-enhanced learning. As such, electronic learning (e-learning) experiences have become a prominent part of medical education. Yet, there remain challenges to e-learning experiences in the current educational landscape. To address these challenges, the authors developed the TinyTalks paradigm, which serves as the educational foundation for the TinyTalks curriculum.The TinyTalks paradigm was developed using the existing e-learning literature and foundational principles of adult learning and related theories. The TinyTalks paradigm includes 3 ground rules: (1) all TinyTalks videos must identify a category (approach to, explanation of, or application of) to clarify the focus of the topic, (2) all TinyTalks videos must be less than 7 minutes with all material presented on one virtual chalkboard screen, and (3) all TinyTalks videos must use the hook, frame, and delivery model, which guides the creation of the video. The resulting TinyTalks curriculum is an online repository of short, chalk talk-style educational videos, developed by interdisciplinary health professionals and targeted to the level of trainees, that is available to be used flexibly by learners for just-in-time learning, flipped classroom sessions, and/or self-study.The authors used Kern's 6-step approach to curriculum development as the conceptual framework for the development and implementation of the TinyTalks curriculum at Mass General for Children (June 2021-January 2023). While developing and implementing the curriculum, the authors focused on topic selection, stakeholder recruitment, establishing a process flow, and creating a virtual home.The authors believe the TinyTalks paradigm outlines an effective educational strategy that accommodates the unique needs of both learners and teachers in the medical education setting. The next steps are to scale the TinyTalks curriculum up by expanding the content library and to evaluate its efficacy.

How health literacy is taught and evaluated in dentistry, medicine, nursing, law, pharmacy, public health, and social work: a narrative review.

BACKGROUND: This narrative review examined the published peer-reviewed literature on how health literacy is taught and evaluated in seven health professional and adjacent disciplines: dentistry, medicine, nursing, law, pharmacy, public health, and social work. The study objectives were to assess how students are educated about health literacy and how their health literacy education and skills are evaluated. METHODS: Study selection followed guidelines outlined in PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We searched PubMed, CINAHL, SocINDEX (EBSCOhost), Lexis Advance and Public Health (ProQuest) for English-language publications of health literacy education studies across seven disciplines at U.S.-based institutions. Inclusion criteria included: 1) methods describing a primary health literacy educational intervention, 2) professional education in one or more of the seven disciplines, 3) educational institutions in the United States, and 4) articles published in peer-reviewed journals between 2000 and 2020. RESULTS: The searches yielded 44 articles. Health literacy education is evident in six of the seven studied disciplines, and varies widely in the quality, quantity, timing and mode of education and evaluation. Despite the presence of health literacy accreditation requirements, none of the seven disciplines has developed and implemented a standard, rigorous health literacy education program for students. CONCLUSIONS: Graduating institutions and professional accreditation organizations that set the standards for education must lead the way by implementing upstream changes in health literacy professional education. Teaching health literacy to students in health professions is one strategy to help close gaps in patient/client professional communication for graduates and those they serve.

Using electronic health record data to link families: an illustrative example using intergenerational patterns of obesity.

OBJECTIVE: Electronic health record (EHR) data are a valuable resource for population health research but lack critical information such as relationships between individuals. Emergency contacts in EHRs can be used to link family members, creating a population that is more representative of a community than traditional family cohorts. MATERIALS AND METHODS: We revised a published algorithm: relationship inference from the electronic health record (RIFTEHR). Our version, Pythonic RIFTEHR (P-RIFTEHR), identifies a patient's emergency contacts, matches them to existing patients (when available) using network graphs, checks for conflicts, and infers new relationships. P-RIFTEHR was run on December 15, 2021 in the Northwestern Medicine Electronic Data Warehouse (NMEDW) on approximately 2.95 million individuals and was validated using the existing link between children born at NM hospitals and their mothers. As proof-of-concept, we modeled the association between parent and child obesity using logistic regression. RESULTS: The P-RIFTEHR algorithm matched 1 157 454 individuals in 448 278 families. The median family size was 2, the largest was 32 persons, and 247 families spanned 4 generations or more. Validation of the mother-child pairs resulted in 95.1% sensitivity. Children were 2 times more likely to be obese if a parent is obese (OR: 2.30; 95% CI, 2.23-2.37). CONCLUSION: P-RIFTEHR can identify familiar relationships in a large, diverse population in an integrated health system. Estimates of parent-child inheritability of obesity using family structures identified by the algorithm were consistent with previously published estimates from traditional cohort studies.

Hospital-Based Medical-Legal Partnerships for Complex Care Patients: Intersectionality and Ethics Considerations.

Health systems are integrating medical-legal partnerships (MLPs) into clinical care and increasingly center "complex care" patients. These patients have intersecting medical and social needs and often face systemic inequities that exacerbate their chronic health conditions. This paper describes a role for MLPs in hospital quality initiatives; examines the ethics of MLPs assisting with guardianship and institutionalization of hospital patients including marginalized groups; and advocates for MLP interventions designed to address intersectional and ethical concerns.

Asylum seeker trauma in a student-run clinic: reducing barriers to forensic medical evaluations.

Introduction This research, through the analysis of the case-law of the Inter-American Court of Human Rights (IACtHR), seeks to shed light on the nexus between families of the missing' claims, their agency and State compliance with reparations. The IACtHR has a unique follow-up system in the area of reparations, where victims can directly address the judges during hearings. This paper suggests that victims' participation - before and after the judgment- pervades the legal rigidity of international jurisdictions and contributes to a better understanding of reparations. INTRODUCTION: The number of forcibly displaced immigrants seeking asylum in the United States continues to rapidly increase. Movement from Latin America to the United States was the third-largest migration worldwide in 2017 (Leyva-Flores et al., 2019). As migration patterns change, understanding the background and trauma profile of newly displaced populations is essential to meet their health needs and aid successful resettlement. University-affiliated student-run asylum clinics conduct a growing number of forensic medical evaluations of asylum seekers and provide a vital lens to study changes in this population's profile over time. METHODS: A retrospective review was conducted of the first 102 asylum seekers receiving forensic medical evaluations between 2019 and 2021 at a university-affiliated student- run clinic, reporting demographics; trauma, medical, and mental health histories; referral patterns; and legal outcomes. Bivariate statistics were used to investigate the relationship between past trauma and mental health outcomes. RESULTS: Clients reported an average of 4.4 different types of physical, psychological, and sexual ill-treatment per person. The current mental health burden was extensive with 86.9 percent of clients reporting symptoms of PTSD and/or depression. Clinician-student teams evaluated clients within a clinic structure deploying a continuous improvement model to reduce common barriers to forensic evaluations and promote longitudinal follow- up and referrals. DISCUSSION: This study demonstrates the complexity of trauma exposure reported by asylum seekers, contributes to the evidence on how trauma results in mental health outcomes, and describes trauma-centred clinic adaptations that reduce barriers to forensic evaluations known to improve the rates of legal protection.

Discharge Navigator: Implementation and Cross-Sectional Evaluation of a Digital Decision Tool for Social Resources upon Emergency Department Discharge.

INTRODUCTION: Many patients have unaddressed social needs that significantly impact their health, yet navigating the landscape of available resources and eligibility requirements is complex for both patients and clinicians. METHODS: Using an iterative design-thinking approach, our multidisciplinary team built, tested, and deployed a digital decision tool called "Discharge Navigator" (edrive.ucsf.edu/dcnav) that helps emergency clinicians identify targeted social resources for patients upon discharge from the acute care setting. The tool uses each patient's clinical and demographic information to tailor recommended community resources, providing the clinician with action items, pandemic restrictions, and patient handouts for relevant resources in five languages. We implemented two modules at our urban, academic, Level I trauma center. RESULTS: Over the 10-week period following product launch, between 4-81 on-shift emergency clinicians used our tool each week. Anonymously surveyed clinicians (n = 53) reported a significant increase in awareness of homelessness resources (33% pre to 70% post, P<0.0001) and substance use resources (17% to 65%, P<0.0001); confidence in accessing resources (22% to 74%, P<0.0001); knowledge of eligibility criteria (13% to 75%, P<0.0001); and ability to refer patients always or most of the time (11% to 43%, P<0.0001). The average likelihood to recommend the tool was 7.8 of 10. CONCLUSION: Our design process and low-cost tool may be replicated at other institutions to improve knowledge and referrals to local community resources.

Antibiotic and antitussive prescribing among urgent care and emergency department visits for respiratory diagnoses in a large health system.

Objective: Urgent care centers (UCs) commonly evaluate patients with respiratory infections, and patients increasingly prefer UCs to emergency departments (EDs) because of their customer-centric approach. The aim of this study is to describe antibiotic and opioid prescribing among UC and ED visits with respiratory diagnoses. Methods: This is a cross-sectional study of visits to 7 EDs and 6 UCs in the greater Chicago area. We included visits from July 1, 2017, to June 30, 2019, with a primary diagnosis of upper or lower respiratory infection. We describe the proportion of visits resulting in an antibiotic or antitussive prescription as well as the most frequently prescribed medications in these categories. We also describe the demographic and clinical characteristics of visits. Results: Of 9134 ED visits, 32.9% were prescribed an antibiotic and 14.4% an antitussive (6.6% opioid). Of 41,380 UC visits for respiratory diagnoses, 57.9% were prescribed an antibiotic and 25.0% an antitussive (9.3% opioid). The most frequently prescribed antibiotics among ED and UC visits were penicillins (36.6% and 44.5%, respectively) and macrolides (44.1% and 35.3%, respectively). The most commonly prescribed opioid was codeine (55.6% and 91.0%, respectively). Median waiting room time was 16 and 5 minutes for ED and UC visits, respectively; median length of stay was 178 and 41 minutes, respectively. Conclusions: Antibiotics and antitussives, including opioids, are frequently prescribed for ED and UC visits with non-bacterial respiratory diagnoses. These findings suggest greater attention to the appropriateness of antibiotic prescribing in both settings and the incorporation of specific guidance on codeine products in opioid-prescribing guidelines.

Use of real-world evidence data to evaluate the comparative effectiveness of second-line type 2 diabetes medications on chronic kidney disease.

Chronic kidney disease (CKD) is a common complication of type 2 diabetes mellitus (T2DM). Approximately-one-third of patients with T2DM also have CKD. In clinical trial studies, several anti-diabetic medications (ADM) show evidence of preventing the progression of CKD. Biguanides (e.g., metformin) are widely accepted as the first line medication. However, the comparative effectiveness of second line ADMs on CKD outcomes in T2DM is unclear. In addition, results from clinical trials may not generalize into routine clinical practice. In this study, we aimed to investigate the association of second line ADMs with diagnosed incident CKD, CKD hospitalization, and eGFR < 45 mL/min in T2DM patients using real-world data from electronic health records. Our study found that treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors was significantly associated with lower risk of diagnosed CKD incidence in both primary analysis (hazard ratio, 0.43; 95 % CI, [0.22;0.87]; p-value,0.02) and secondary analysis (hazard ratio, 0.42; 95 % CI, [0.19;0.92]; p-value, 0.03) compared to use of Sulfonylureas (SU) as a second-line ADM. However, significant associations were not observed when using eGFR < 45 mL/min as the endpoint. Treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor was significantly associated with lower risk of diagnosed incident CKD (hazard ratio, 0.7; 95 % CI, [0.53;0.96]; p-value, 0.03) and lower risk of CKD hospitalization (hazard ratio, 0.6; 95 % CI, [0.37; 0.96]; p-value, 0.04) in the primary analysis. However, both associations were not significant in the sensitivity analysis. We did not observe significant association between use of glucagon-like peptide 1 receptor agonists (GLP-1RA), Thiazolidinediones (TZD), insulin and diagnosed CKD incidence, hospitalization or eGFR < 45 mL/min compared to use of SU as a second-line ADM.

A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs.

Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems.

Droplet organelles?

Cells contain numerous, molecularly distinct cellular compartments that are not enclosed by lipid bilayers. These compartments are implicated in a wide range of cellular activities, and they have been variously described as bodies, granules, or organelles. Recent evidence suggests that a liquid-liquid phase separation (LLPS) process may drive their formation, possibly justifying the unifying term "droplet organelle". A veritable deluge of recent publications points to the importance of low-complexity proteins and RNA in determining the physical properties of phase-separated structures. Many of the proteins linked to such structures are implicated in human diseases, such as amyotrophic lateral sclerosis (ALS). We provide an overview of the organizational principles that characterize putative "droplet organelles" in healthy and diseased cells, connecting protein biochemistry with cell physiology.

Combination Growth Factor Therapy via Electrostatically Assembled Wound Dressings Improves Diabetic Ulcer Healing In Vivo.

Chronic skin ulcerations are a common complication of diabetes mellitus, affecting up to one in four diabetic individuals. Despite the prevalence of these wounds, current pharmacologic options for treating them remain limited. Growth factor-based therapies have displayed a mixed ability to drive successful healing, which may be due to nonoptimal delivery strategies. Here, a method for coating commercially available nylon dressings using the layer-by-layer process is described to enable both sustained release and independent control over the release kinetics of vascular endothelial growth factor 165 and platelet-derived growth factor BB. It is shown that the use of strategically spaced diffusion barriers formed spontaneously by disulfide bonds enables independent control over the release rates of incorporated growth factors, and that in vivo these dressings improve several aspects of wound healing in db/db mice.

Triggered Ca2+ influx is required for extended synaptotagmin 1-induced ER-plasma membrane tethering.

The extended synaptotagmins (E-Syts) are ER proteins that act as Ca(2+)-regulated tethers between the ER and the plasma membrane (PM) and have a putative role in lipid transport between the two membranes. Ca(2+) regulation of their tethering function, as well as the interplay of their different domains in such function, remains poorly understood. By exposing semi-intact cells to buffers of variable Ca(2+) concentrations, we found that binding of E-Syt1 to the PI(4,5)P2-rich PM critically requires its C2C and C2E domains and that the EC50 of such binding is in the low micromolar Ca(2+) range. Accordingly, E-Syt1 accumulation at ER-PM contact sites occurred only upon experimental manipulations known to achieve these levels of Ca(2+) via its influx from the extracellular medium, such as store-operated Ca(2+) entry in fibroblasts and membrane depolarization in ß-cells. We also show that in spite of their very different physiological functions, membrane tethering by E-Syt1 (ER to PM) and by synaptotagmin (secretory vesicles to PM) undergo a similar regulation by plasma membrane lipids and cytosolic Ca(2+).

Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.

Cells adapt to temperature shifts by adjusting levels of lipid desaturation and membrane fluidity. This fundamental process occurs in nearly all forms of life, but its mechanism in eukaryotes is unknown. We discovered that the evolutionarily conserved Caenorhabditis elegans gene acdh-11 (acyl-CoA dehydrogenase [ACDH]) facilitates heat adaptation by regulating the lipid desaturase FAT-7. Human ACDH deficiency causes the most common inherited disorders of fatty acid oxidation, with syndromes that are exacerbated by hyperthermia. Heat upregulates acdh-11 expression to decrease fat-7 expression. We solved the high-resolution crystal structure of ACDH-11 and established the molecular basis of its selective and high-affinity binding to C11/C12-chain fatty acids. ACDH-11 sequesters C11/C12-chain fatty acids and prevents these fatty acids from activating nuclear hormone receptors and driving fat-7 expression. Thus, the ACDH-11 pathway drives heat adaptation by linking temperature shifts to regulation of lipid desaturase levels and membrane fluidity via an unprecedented mode of fatty acid signaling.

Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation.

The Alzheimer's disease (AD)-associated ubiquilin-1 regulates proteasomal degradation of proteins, including presenilin (PS). PS-dependent γ-secretase generates ß-amyloid (Aß) peptides, which excessively accumulate in AD brain. Here, we have characterized the effects of naturally occurring ubiquilin-1 transcript variants (TVs) on the levels and subcellular localization of PS1 and other γ-secretase complex components and subsequent γ-secretase function in human embryonic kidney 293, human neuroblastoma SH-SY5Y and mouse primary cortical cells. Full-length ubiquilin-1 TV1 and TV3 that lacks the proteasome-interaction domain increased full-length PS1 levels as well as induced accumulation of high-molecular-weight PS1 and aggresome formation. Accumulated PS1 colocalized with TV1 or TV3 in the aggresomes. Electron microscopy indicated that aggresomes containing TV1 or TV3 were targeted to autophagosomes. TV1- and TV3-expressing cells did not accumulate other unrelated proteasome substrates, suggesting that the increase in PS1 levels was not because of a general impairment of the ubiquitin-proteasome system. Furthermore, PS1 accumulation and aggresome formation coincided with alterations in Aß levels, particularly in cells overexpressing TV3. These effects were not related to altered γ-secretase activity or PS1 binding to TV3. Collectively, our results indicate that specific ubiquilin-1 TVs can cause PS1 accumulation and aggresome formation, which may impact AD pathogenesis or susceptibility.

Interdependent self-construal moderates the age-related negativity reduction effect in memory and visual attention.

There is some debate concerning whether people selectively attend to and remember less negative relative to positive or neutral information with age. We argue that such an age-related negativity reduction effect may be attenuated among individuals who are more interdependent, as they are likely to perceive negative information as equally useful and important as positive information. In 2 studies, we tested this hypothesis by examining memory for (Study 1) and visual attention to (Study 2) emotional (positive vs. negative) stimuli among younger, middle-aged, and older Chinese participants. Findings revealed that the age-related negativity reduction effect was found to a lesser extent among older Chinese individuals who were more interdependent than among those who were less interdependent.

Effects of ubiquilin 1 on the unfolded protein response.

Previous studies have implicated the unfolded protein response (UPR) in the pathogenesis of Alzheimer's disease (AD). We previously reported that DNA variants in the ubiquilin 1 (UBQLN1) gene increase the risk for AD. Since UBQLN1 has been shown to play a role in the UPR, we assessed the effects of overexpression and downregulation of UBQLN1 splice variants during tunicamycin-induced ER stress. In addition to previously described transcript variants, TV1 and TV2, we identified two novel transcript variants of UBQLN1 in brain: TV3 (lacking exons 2-4) and TV4 (lacking exon 4). Overexpression of TV1-3, but not TV4 significantly decreased the mRNA induction of UPR-inducible genes, C/EBP homologous protein (CHOP), BiP/GRP78, and protein disulfide isomerase (PDI) during the UPR. Stable overexpression of TV1-3, but not TV4, also significantly decreased the induction of CHOP protein and increased cell viability during the UPR. In contrast, downregulation of UBQLN1 did not affect CHOP mRNA induction, but instead increased PDI mRNA levels. These findings suggest that overexpression UBQLN1 transcript variants TV1-3, but not TV4, exert a protective effect during the UPR by attenuating CHOP induction and potentially increasing cell viability.

Age-related positivity enhancement is not universal: older Chinese look away from positive stimuli.

Socioemotional selectivity theory postulates that with age, people are motivated to derive emotional meaning from life, leading them to pay more attention to positive relative to negative/neutral stimuli. The authors argue that cultures that differ in what they consider to be emotionally meaningful may show this preference to different extents. Using eye-tracking techniques, the authors compared visual attention toward emotional (happy, fearful, sad, and angry) and neutral facial expressions among 46 younger and 57 older Hong Kong Chinese. In contrast to prior Western findings, older but not younger Chinese looked away from happy facial expressions, suggesting that they do not show attentional preferences toward positive stimuli.

Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease families.

Insulin-degrading enzyme (IDE) is a zinc metalloprotease that degrades the amyloid beta-peptide, the key component of Alzheimer disease (AD)-associated senile plaques. We have previously reported evidence for genetic linkage and association of AD on chromosome 10q23-24 in the region harboring the IDE gene. Here we have presented the first functional assessment of IDE in AD families showing the strongest evidence of the genetic linkage. We have examined the catalytic activity and expression of IDE in lymphoblast samples from 12 affected and unaffected members of three chromosome 10-linked AD pedigrees in the National Institute of Mental Health AD Genetics Initiative family sample. We have shown that the catalytic activity of cytosolic IDE to degrade insulin is reduced in affected versus unaffected subjects of these families. Further, we have shown the decrease in activity is not due to reduced IDE expression, suggesting the possible defects in IDE function in these AD families. In attempts to find potential mutations in the IDE gene in these families, we have found no coding region substitutions or alterations in splicing of the canonical exons and exon 15b of IDE. We have also found that total IDE mRNA levels are not significantly different in sporadic AD versus age-matched control brains. Collectively, our data suggest that the genetic linkage of AD in this set of chromosome 10-linked AD families may be the result of systemic defects in IDE activity in the absence of altered IDE expression, further supporting a role for IDE in AD pathogenesis.

Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion.

Ubiquilin 1 (UBQLN1) is a ubiquitin-like protein, which has been shown to play a central role in regulating the proteasomal degradation of various proteins, including the presenilins. We recently reported that DNA variants in UBQLN1 increase the risk for Alzheimer disease, by influencing expression of this gene in brain. Here we present the first assessment of the effects of UBQLN1 on the metabolism of the amyloid precursor protein (APP). For this purpose, we employed RNA interference to down-regulate UBQLN1 in a variety of neuronal and non-neuronal cell lines. We demonstrate that down-regulation of UBQLN1 accelerates the maturation and intracellular trafficking of APP, while not interfering with alpha-, beta-, or gamma-secretase levels or activity. UBQLN1 knockdown increased the ratio of APP mature/immature, increased levels of full-length APP on the cell surface, and enhanced the secretion of sAPP (alpha- and beta-forms). Moreover, UBQLN1 knockdown increased levels of secreted Abeta40 and Abeta42. Finally, employing a fluorescence resonance energy transfer-based assay, we show that UBQLN1 and APP come into close proximity in intact cells, independently of the presence of the presenilins. Collectively, our findings suggest that UBQLN1 may normally serve as a cytoplasmic "gatekeeper" that may control APP trafficking from intracellular compartments to the cell surface. These findings suggest that changes in UBQLN1 steady-state levels affect APP trafficking and processing, thereby influencing the generation of Abeta.

Kinetics of amyloid beta-protein degradation determined by novel fluorescence- and fluorescence polarization-based assays.

Proteases that degrade the amyloid beta-protein (Abeta) are important regulators of brain Abeta levels in health and in Alzheimer's disease, yet few practical methods exist to study their detailed kinetics. Here, we describe robust and quantitative Abeta degradation assays based on the novel substrate, fluorescein-Abeta-(1-40)-Lys-biotin (FAbetaB). Liquid chromatography/mass spectrometric analysis shows that FAbetaB is hydrolyzed at closely similar sites as wild-type Abeta by neprilysin and insulin-degrading enzyme, the two most widely studied Abeta-degrading proteases. The derivatized peptide is an avid substrate and is suitable for use with biological samples and in high throughput compound screening. The assays we have developed are easily implemented and are particularly useful for the generation of quantitative kinetic data, as we demonstrate by determining the kinetic parameters of FAbetaB degradation by several Abeta-degrading proteases, including plasmin, which has not previously been characterized. The use of these assays should yield additional new insights into the biology of Abeta-degrading proteases and facilitate the identification of activators and inhibitors of such enzymes.