Search

This study examined the relationship of psychosocial factors with alcohol use for adolescents residing in rural Iowa. This association was also tested separately for boys and girls. Seventh graders (N = 1673) self-reported alcohol use, peer drinking norms, adult drinking norms, drug refusal assertiveness, drug refusal techniques, life skills, pro-drinking attitudes, risk-taking tendency, and perceived family management practices. Data were collected during a 45-minute class period. Multiple regressions indicated that: Peer drinking norms, drug refusal assertiveness, drug refusal techniques, life skills, pro-drinking attitudes and risk-taking tendency were related to drinking measures. Perceived family management skills and drug refusal techniques were associated with drinking for girls but not boys. Risk-taking tendency was related to drinking for boys but not girls. [ABSTRACT FROM AUTHOR]

Most research of ethnic differences in adolescent drug use resorts to combining all Hispanic individuals into one group. This study focused on polydrug use among adolescents residing in an innercity region by Hispanic ethnicity (Puerto Rican versus Dominican) and gender. Puerto Rican and Dominican students in 22 New York City middle schools participated. Sixth and seventh graders completed self-report questionnaires with measures of the three gateway drugs (cigarettes, alcohol, and marijuana) at baseline (N = 849) and at a one-year followup (N = 678). In the first year of middle school, gender moderated the effect of Hispanic ethnicity on lifetime polydrug use. Specifically, Dominican boys reported greater polydrug use than Dominican girls, but use was similar across gender for Puerto Rican adolescents. In the second year of middle school, this pattern extended to more serious levels of polydrug use as measured by current polydrug use and composite polydrug frequency. Consequently, both Hispanic ethnicity and gender mattered in determining adolescent polydrug use. [ABSTRACT FROM AUTHOR]

Previous research suggests that alcohol and drug use among youth may be a function of the total number of etiologic factors present, rather than a specific type of factor. Furthermore, a growing number of studies have found that psychosocial protective factors are important in countering the effects of psychosocial risk. The present study evaluated the buffering effect of cumulative protection on adolescent alcohol use in the presence of high and moderate cumulative risk. A sample of 4,851 7th graders from 37 inner-city schools participated. Students with high scores on the cumulative risk factor index engaged in more alcohol use compared to those with low scores; those with high scores on the cumulative protective factor index engaged in less alcohol use relative to those with low scores. For participants at low risk, level of protection did not affect most measures of alcohol use. However, for both moderate and high risk groups, adolescents with high protection engaged in less alcohol use than those with low protection. These findings suggest that comprehensive alcohol use prevention programs for youth should focus on enhancing a variety. of protective factors in addition to reducing risk. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the relationships among problem behaviors during early adolescence. Specifically this investigation examined the association between drug use and aggression among a sample of inner-city adolescents. Eighth graders (N = 517; 49% boys) attending three New York City schools completed an anonymous questionnaire. Self-reported aggressive and unsafe behavior were associated with initiation of drug use (smoking, drinking alcohol, smoking marijuana). Sex differences were also found for aggressive behavior, victimization, and unsafe behavior. The data have implications for prevention because reducing drug use might also decrease aggressive and unsafe behavior. Social competence skills training, which has been found effective in drug use prevention programs, can be expanded to cover aggressive behavior and engagement in unsafe behavior. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine if ethnic and gender differences in polydrug use exist among a cohort of inner-city adolescents during the three-year middle school period. Students in 22 urban schools completed self-report questionnaires with measures of drug use (smoking, drinking, and marijuana use) at three annual assessments. For participating students, (N=2354), analyses of variance were conducted to test for ethnic group (Asian, Black, Hispanic, White) and gender differences in polydrug use. Ethnic differences were found for polydrug use measures at each assessments point. Asian and Black adolescents generally reported less polydrug use than White and Hispanic youth. When gender differences were evident, boys engaged in more use than girls. The relatively high rates of polydrug use indicate that prevention intervention programs that target multiple substances may be more efficient in reducing overall risk than prevention programs that focus on a single substance (e.g., smoking prevention only). [ABSTRACT FROM AUTHOR]

Adolescent smoking continues to rise in the United States. Individual from economically-disadvantaged households appear at high risk for smoking. This study focused on a sample of economically-disadvantaged adolescents attending New York City schools (N = 1875). Longitudinal predictors of smoking from four domains (socio-demographic background information, social influences to smoke, social and personal competence, and individual differences) were tested. Social influences to smoke, from mothers and friends, both predicted smoking one year later. Poor decision-making skills, and low psychological well-being also predicted subsequent smoking. Conclusion: These findings support social learning theory (Bandura, 1977) and problem behavior theory (Jessor, 1991). Furthermore, the results suggest that training adolescents to resist social influences to smoke, to problem solve and make sound decisions, and how to cope with psychological distress are among the key components for effective smoking prevention. [ABSTRACT FROM AUTHOR]

This study tested the effectiveness of a drug abuse prevention intervention with a predominantly minority sample of seventh-grade students (N = 721) in 7 urban schools in New York City. The drug abuse prevention curriculum teaches social resistance skills within the context of a broader intervention promoting general personal and social competence and implemented by regular classroom teachers. Results indicated that this approach was effective on several behavioral measures of current drug use including measures of polydrug use and on intention measures relevant to future drug use. Furthermore, there was some evidence for factors presumed to mediate the effects of this type of intervention (normative expectations and refusal skills). The significance of these findings is that they provide further support for the generalizability to a minority inner-city adolescent population of an approach previously found to be effective with white middle-class adolescent populations. In addition, this is the first time that effects have been shown with inner-city minority youth for the use of multiple drugs. [ABSTRACT FROM AUTHOR]

This study examined the relationship between language use and initiation of alcohol use among Hispanic adolescents (Puerto Rican, Dominican, Colombian, Ecuadorian). Logistic regression analysis revealed that adolescents who spoke Spanish with their parents had lower odds of having a drink relative to adolescents who spoke English and Spanish with their parents. Adolescents who only spoke English with their friends had lower odds of ever drinking relative to adolescents who spoke English and Spanish with their friends. Social influences to drink and being Dominican or Colombian also predicted alcohol use. Analyses were conducted separately by sex. Results are discussed in terms of the implications for prevention. [ABSTRACT FROM AUTHOR]

Adolescent alcohol use remains a pressing problem. Identifying which groups are at greater risk of alcohol use helps in understanding the etiology of drinking and the development of alcohol prevention programs. Little epidemiologic information regarding alcohol use among inner-city minority adolescents is available. This study examined the relationship between patterns of alcohol use and ethnic group, a black group consisting primarily of African-Americans and Caribbean/West Indians and a Hispanic group of predominantly Puerto Ricans and Dominicans, among urban youth. Hispanic youth reported greater experience with alcohol than black youth. Dominican adolescents drank more frequently, drank more per drinking occasion, and planned to drink more in the future than Puerto Rican adolescents. Similarly, Caribbean/West Indian youth drank more frequently, became drunk more often, drank more per drinking occasion, and planned to drink more in the future relative to African-American youth. In general, gender did not moderate the relationship with alcohol. This study indicates that only considering ethnic group membership is not sufficient because there were important subgroup differences in patterns of alcohol use for both Hispanics and Blacks. Implications for prevention are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine if ethnic and gender differences in alcohol use exist among a cohort of inner-city adolescents during each of the 3 years of middle school. Students in 22 urban schools completed selfreport questionnaires with measures of alcohol use (frequency of drinking, amount of drinks per occasion, and frequency of drunkenness) at three annual assessments. Of the participating students, 2312 identified themselves as Asian, Black, Hispanic or White. Analyses of variance were conducted to test for ethnic group (Asian, Black, Hispanic, White) and gender differences in alcohol use. Ethnic differences were found for all three alcohol measures at each assessment point. Boys drank more frequently than girls during the first 2 years. Asian and Black adolescents appeared to be at lower risk for alcohol use. [ABSTRACT FROM AUTHOR]

To explore the attitudes of a multi-ethnic sample (African-American, Caucasian, Latino) of parents, a telephone survey was conducted with 297 parents whose children attend school in New York City (98 African-Americans, 100 Latinos, and 99 Caucasians). The survey interview assessed a wide range of issues related to AIDS and AIDS education. In a series of logistic regressions that controlled for education, we compared each ethnic group (African-Americans, Latinos) with Caucasians as the reference. The majority of parents indicated that they supported AIDS education efforts in the schools, but there was considerable mistrust of the government and health professionals, particularly among the African-American parents. African-American and Latino parents were more likely to perceive AIDS as a threat and believe that AIDS education is more effective for Caucasians. We discuss implications for AIDS prevention and recommend strategies to overcome barriers to AIDS education and prevention in multi-ethnic communities. [ABSTRACT FROM AUTHOR]

Despite many innovative advances in cardiology over the past 50 years, heart disease remains a major killer. The steady progress that continues to be made in diagnostics and therapeutics is offset by the cardiovascular consequences of the growing epidemics of obesity and diabetes. Truly innovative approaches on the horizon have been greatly influenced by new insights in cardiovascular development. In particular, research in stem cell biology, the cardiomyocyte lineage, and the interactions of the myocardium and epicardium have opened the door to new approaches for healing the injured heart. [ABSTRACT FROM AUTHOR]

Hypothesis: The compaction of hydrogel films under permeation flow can be measured, in-situ, by tracking the internal displacements of their structure, thereby revealing the internal deformation profile. Additionally, monitoring the permeation flow rate and applied pressure over time enables determination of variations in the hydrogel's permeability due to flow-induced compaction. Hydrogels are soft porous materials capable of containing high amounts of water within their polymeric matrix. Flow-induced internal deformation can modify the hydrogel's permeability and selectivity, which are important attributes in separation processes, both industrial (e.g., membrane-based water purification) and natural (mucous filters in suspension feeders and intestinal lining) systems. Measuring the flow-induced compaction in thin hydrogels films can reveal the interplay between flow and permeability. However, the micro-scale internal compaction remains uncharted for due to experimental challenges., Experiments: A technique is demonstrated for analyzing the compaction and stratification of permeable soft materials, in-situ, created by a pressure-driven permeation flow. To this end, the internal deformations within a soft material layer are calculated, based on tracking the positions of fluorescent micro-tracers that are embedded within the soft material. We showcase the capabilities of this technique by examining a hundred-micron-thick calcium-alginate cake deposited on a nanofiltration membrane, emphasizing the achieved micro-scale resolution of the local compaction measurements., Findings: The results highlight the possibility to examine thin hydrogel films and their internal deformation produced by flow-induced stresses when varying the flow conditions. The method enables the simultaneous calculation of the soft material's permeance, as the pressure-driven flow conditions are continuously monitored. In summary, the proposed method provides a powerful tool for characterizing the behaviour of permeable soft materials under permeation conditions, with potential applications in engineering, biophysics and material science., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Rapid telehealth adoption happened at the onset of the coronavirus disease 2019 (COVID-19) pandemic, resulting in a move from in-person predominant to telehealth predominant care delivery. Later, in person visits rebounded with telehealth options remaining. This study aimed to assess differences in healthcare utilization during this changing landscape in terms of health equity determinants., Materials and Methods: This was an observational cohort study of Johns Hopkins Medicine (JHM) patients. We analyzed utilization of video, telephone, and in-person patient-provider visits by eligible patients between March 16, 2019 and December 31, 2020. Percent changes in average weekly patient-provider visits from pre-pandemic (March 16, 2019-June 30, 2019) to early 2020 pandemic (March 16, 2020-June 30, 2020) and from pre-pandemic (July 1, 2019-December 31, 2019) to late 2020 pandemic (July 1, 2020-December 31, 2020). We used a quantile cut off technique to describe disproportionately smaller or greater drops in visits during the first year of the pandemic among health equity determinant groups and according to visit specialty, when compared to the total population., Results: There was a 39% drop in patient-provider visits from the pre-pandemic to the early 2020 pandemic period, and a 24% drop from pre-pandemic to the late 2020 pandemic period. We discovered 21 groups according to health equity determinates and visit departments with patterns of disproportionately smaller or greater drops in visits during the first year of the pandemic, when compared to the total population: Pattern 1 - smaller drop in visits early and late 2020 (age 45-64, Medicare insurance, high poverty and high unemployment; mental health and medical specialty visits - P  < .001); Pattern 2 - greater drop in visits early 2020 only (age 65-84; OB/GYN and surgical specialty visits- P  < .001); Pattern 3 - greater drop in visits early and late 2020 (age 0-5, age 6-17, age 85+, Asian race, Hispanic or Latino ethnicity, private insurance- P  < .001); and Pattern 4 -smaller drop in visits in early 2020 when compared to late 2020. The age 18-44 group showed a smaller drop in visits early 2020 and then visit levels similar to the total population late 2020. Primary care visits were similar to the total population early 2020 and then a smaller drop in visits late 2020 ( P  < .001)., Discussion: Our study provides evidence of health equity determinant groups having disproportionally smaller or greater drops in visits during the first year of the pandemic. The observed differences may have been influenced by changing telehealth offerings during the first year of the pandemic. Groups with disproportionately smaller drops in visits early 2020 ( Pattern #1 and age 18-44 group in Pattern #4 ), suggests more success with adopting telehealth among those groups. Whereas groups with disproportionately greater drops in visits early 2020 ( Pattern #2 and Pattern #3 ), suggests less success with telehealth adoption. For Pattern #4 , more clarification is needed on how changes in telehealth offerings contributed to the downward trend in visits observed from early to late 2020., Conclusion: We describe 4 main patterns to characterize groups with disproportionately smaller or greater drops in visits during the first year of the pandemic. While this work did not specifically study vulnerable populations, these patterns set the stage for further studies of such groups., Competing Interests: All authors declare that they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Ischemic heart disease is a leading cause of death worldwide, manifested clinically as myocardial infarction (and ischemic cardiomyopathy. Presently, there exists a notable scarcity of efficient interventions to restore cardiac function after myocardial infarction. Cumulative evidence suggests that impaired tissue immunity within the ischemic microenvironment aggravates cardiac dysfunction, contributing to progressive heart failure. Recent research breakthroughs propose immunotherapy as a potential approach by leveraging immune and stroma cells to recalibrate the immune microenvironment, holding significant promise for the treatment of ischemic heart disease. In this Primer, we highlight three emerging strategies for immunomodulatory therapy in managing ischemic cardiomyopathy: targeting vascular endothelial cells to rewire tissue immunity, reprogramming myeloid cells to bolster their reparative function, and utilizing adoptive T cell therapy to ameliorate fibrosis. We anticipate that immunomodulatory therapy will offer exciting opportunities for ischemic heart disease treatment., Competing Interests: J.A.E. is a scientific founder and holds equity in Capstan Therapeutics, which develops therapeutics to reprogram immune cells in vivo. The other authors report no conflicts.

Extracellular signals are transmitted through kinase cascades to modulate gene expression, but it remains unclear how epigenetic changes regulate this response. Here, we provide evidence that growth factor-stimulated changes in the transcript levels of many responsive genes are accompanied by increases in histone phosphorylation levels, specifically at histone H3 serine-10 when the adjacent lysine-9 is dimethylated (H3K9me2S10). Imaging and proteomic approaches show that epidermal growth factor (EGF) stimulation results in H3K9me2S10 phosphorylation, which occurs in genomic regions enriched for regulatory enhancers of EGF-responsive genes. We also demonstrate that the EGF-induced increase in H3K9me2S10ph is dependent on the nuclear kinase MSK2, and this subset of EGF-induced genes is dependent on MSK2 for transcription. Together, our work indicates that growth factor-induced changes in chromatin state can mediate the activation of downstream genes.

Background: Delays or failure to complete a dermatologic referral may affect health care outcomes. Factors associated with these delays remain understudied., Objective: This study investigated socioeconomic and demographic factors associated with delays or failure to complete dermatology referrals and potential impact on surgical outcomes., Methods: A retrospective chart review was performed for 400 patients internally referred to an academic dermatology center from 19 primary-care clinics from July 2018 to June 2019. Only patients referred after an in-person primary-care visit in which the provider documented a specific concerning lesion were included. Multivariate analyses were performed to explore variables associated with delays or failure to complete dermatology referrals., Results: Patients were more likely to complete their referral if they had a personal history (adjusted odds ratio [aOR] = 7.843, 95% CI 1.383-14.304) or family history (aOR = 11.307, 95% CI 2.344-20.27) of skin cancer. Patients were more likely to delay referral completion past 30 days if they were ages 18 to 34 (aOR = 6.665, 95% CI 1.285-12.044) and less likely to delay referral past 30 days if they had a previous history of skin cancer (aOR = 0.531, 95% CI 0.181-0.882)., Limitations: Single institution, retrospective study, limited surgical patients., Conclusion: Understanding factors associated with delays in dermatology referral completion can help identify at-risk patient populations., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Epigenetics is the study of heritable changes to the genome and gene expression patterns that are not caused by direct changes to the DNA sequence. Examples of these changes include posttranslational modifications to DNA-bound histone proteins, DNA methylation, and remodeling of nuclear architecture. Collectively, epigenetic changes provide a layer of regulation that affects transcriptional activity of genes while leaving DNA sequences unaltered. Sequence variants or mutations affecting enzymes responsible for modifying or sensing epigenetic marks have been identified in patients with congenital heart disease (CHD), and small-molecule inhibitors of epigenetic complexes have shown promise as therapies for adult heart diseases. Additionally, transgenic mice harboring mutations or deletions of genes encoding epigenetic enzymes recapitulate aspects of human cardiac disease. Taken together, these findings suggest that the evolving field of epigenetics will inform our understanding of congenital and adult cardiac disease and offer new therapeutic opportunities., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introduction: The objective of this study was to understand whether use of audio-only telemedicine visits differed by individual- and neighborhood-level patient characteristics during the COVID-19 pandemic. Methods: We conducted a retrospective cross-sectional study of telemedicine encounter data from a large academic health system. The primary outcome was rate of audio-only versus video visits. The exposures of interest were individual- (age, race, insurance, preferred language) and neighborhood-level (Social Deprivation Index [SDI]) patient characteristics. Results: Our study included 1,054,465 patient encounters from January 1, 2020 to December 31, 2021, of which 18.33% were completed via audio-only. Encounters among adults 75 years or older, Black patients, Spanish-speakers, and those with public insurance were more frequently conducted by audio-only ( p < 0.001). Overall, populations showed decreasing rates of audio-only visits over time. We also observed an increase in the rate of audio-only encounters as SDI scores increased. Discussion: We found that audio-only disparities exist in telemedicine utilization by individual and zip code level characteristics. Though these disparities have improved over time as seen by our temporal analysis, marginalized and minority groups still showed the lowest rates of video utilization. In conclusion, access to audio-only care is a critical component to ensure that telemedicine is accessible to all populations. State and federal policy should support continued reimbursement of audio-only care to ensure equitable access to care while the implications of different care modalities are further studied.

Background: The use of real-time benefit tool (RTBT) may help increase transparency of patients' out-of-pocket (OOP) costs, thereby reducing patients' OOP spend and increasing prescription obtainment., Objective: We have previously reported on the potential benefit of RTBT in electronic health records at a large health system. We explore the benefit of RTBT by subgroups of prescriptions (i.e., order types)., Methods: In a retrospective cohort, we reviewed orders generated with and without RTBT use. We compared the 2 groups on key metrics related to prescription obtainment (fill rate, modification rate, cancellation rate, time to ready, time to sold, abandonment rate, and cancellation and transfer rate). Subgroup analysis included orders without over-the-counter (OTC) medications, orders without specialty medications, and orders without OTC and specialty medications., Results: Fill rate, cancellation rate, time to ready, time to sold, abandonment rate, and cancellation and transfer rate were statistically significantly different between the RTBT and non-RTBT groups, favoring the RTBT group (all, P < 0.01). Differences in modification rates were not statistically significant between the 2 groups., Conclusion: RTBTs have the potential to increase prescription obtainment. A consistent difference in key outcome measures between the RTBT and the non-RTBT groups was apparent among prescription orders regardless of whether OTC and specialty medications were included in the analysis., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer., (© 2023. Springer Nature Limited.)

Objectives: The coronavirus disease 2019 (COVID-19) pandemic led to a rapid adoption of telehealth. For underserved populations lacking internet access, telemedicine was accomplished by phone rather than an audio-video connection. The latter is presumed a more effective form and better approximation of an in-person visit. We sought to provide a telehealth platform to overcome barriers for underserved groups to hold video visits with their health care providers and evaluate differences between the two telehealth modalities as assessed by physicians and patients., Methods: We designed a simplified tablet solution for video visits and piloted its use among patients who otherwise would have been completing audio-only visits. Patients consented to participation and were randomized in a 1:1 fashion to continue with their scheduled phone visit (control) versus being shipped a tablet to facilitate a video visit (intervention). Participants and providers completed communication and satisfaction surveys., Results: Tablet and connectivity design features included removal of all functions but for the telemedicine program, LTE always-on wireless internet connectivity, absence of external equipment (cords chargers and keyboard), and no registration with a digital portal. In total, 18 patients were enrolled. Intervention patients with video-enabled devices compared to control patients agreed more strongly that they were satisfied with their visits (4.75/5 vs. 3.75/5, p = 0.02)., Conclusion: The delivered simplified tablet solution for video visits holds promise to improve access to video visits for underserved groups. Strategies to facilitate patient acceptance of devices are needed to expand the scope and potential impact of this effort., Competing Interests: Conflict of Interest None declared.

Background: Medication price transparency tools are increasingly available, but data on their use, and their potential effects on prescribing behavior, patient out of pocket (OOP) costs, and clinician workflow integration, is limited., Objective: To describe the implementation experiences with real-time prescription benefit (RTPB) tools at 5 large academic medical centers and their early impact on prescription ordering., Design: and Participants: In this cross-sectional study, we systematically collected information on the characteristics of RTPB tools through discussions with key stakeholders at each of the five organizations. Quantitative encounter data, prescriptions written, and RTPB alerts/estimates and prescription adjustment rates were obtained at each organization in the first three months after "go-live" of the RTPB system(s) between 2019 and 2020., Main Measures: Implementation characteristics, prescription orders, cost estimate retrieval rates, and prescription adjustment rates., Key Results: Differences were noted with respect to implementation characteristics related to RTPB tools. All of the organizations with the exception of one chose to display OOP cost estimates and suggested alternative prescriptions automatically. Differences were also noted with respect to a patient cost threshold for automatic display. In the first three months after "go-live," RTPB estimate retrieval rates varied greatly across the five organizations, ranging from 8% to 60% of outpatient prescriptions. The prescription adjustment rate was lower, ranging from 0.1% to 4.9% of all prescriptions ordered., Conclusions: In this study reporting on the early experiences with RTPB tools across five academic medical centers, we found variability in implementation characteristics and population coverage. In addition RTPB estimate retrieval rates were highly variable across the five organizations, while rates of prescription adjustment ranged from low to modest., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: FAW, JIS, BHC, NK and ES were supported by a Donaghue Foundation Greater Value Portfolio research grant relating to this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The problem of unaffordable prescription medications in the United States is complex and can result in poor patient adherence to therapy, worse clinical outcomes, and high costs to the healthcare system. While providers are aware of the financial burden of healthcare for patients, there is a lack of actionable price transparency at the point of prescribing. Real-time prescription benefit (RTPB) tools are new electronic clinical decision support tools that retrieve patient- and medication-specific out-of-pocket cost information and display it to clinicians at the point of prescribing. The rise in US healthcare costs has been a major driver for efforts to increase medication price transparency, and mandates from the Centers for Medicare & Medicaid Services for Medicare Part D sponsors to adopt RTPB tools may spur integration of such tools into electronic health records. Although multiple factors affect the implementation of RTPB tools, there is limited evidence on outcomes. Further research will be needed to understand the impact of RTPB tools on end results such as prescribing behavior, out-of-pocket medication costs for patients, and adherence to pharmacologic treatment. We review the terminology and concepts essential in understanding the landscape of RTPB tools, implementation considerations, barriers to adoption, and directions for future research that will be important to patients, prescribers, health systems, and insurers., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Dysregulation of the imprinted H19/IGF2 locus can lead to Silver-Russell syndrome (SRS) in humans. However, the mechanism of how abnormal H19/IGF2 expression contributes to various SRS phenotypes remains unclear, largely due to incomplete understanding of the developmental functions of these two genes. We previously generated a mouse model with humanized H19/IGF2 imprinting control region ( hIC1 ) on the paternal allele that exhibited H19/Igf2 dysregulation together with SRS-like growth restriction and perinatal lethality. Here, we dissect the role of H19 and Igf2 in cardiac and placental development utilizing multiple mouse models with varying levels of H19 and Igf2 . We report severe cardiac defects such as ventricular septal defects and thinned myocardium, placental anomalies including thrombosis and vascular malformations, together with growth restriction in mouse embryos that correlated with the extent of H19/Igf2 dysregulation. Transcriptomic analysis using cardiac endothelial cells of these mouse models shows that H19/Igf2 dysregulation disrupts pathways related to extracellular matrix and proliferation of endothelial cells. Our work links the heart and placenta through regulation by H19 and Igf2 , demonstrating that accurate dosage of both H19 and Igf2 is critical for normal embryonic development, especially related to the cardiac-placental axis., Competing Interests: SC, DF, SH, JT, LL, YL, ER, NL, XC, JE, MB No competing interests declared, (© 2022, Chang et al.)

Allele-specific expression of imprinted gene clusters is governed by gametic DNA methylation at master regulators called imprinting control regions (ICRs). Non-gametic or secondary differentially methylated regions (DMRs) at promoters and exonic regions reinforce monoallelic expression but do not control an entire cluster. Here, we unveil an unconventional secondary DMR that is indispensable for tissue-specific imprinting of two previously unlinked genes, Grb10 and Ddc. Using polymorphic mice, we mapped an intronic secondary DMR at Grb10 with paternal-specific CTCF binding (CBR2.3) that forms contacts with Ddc. Deletion of paternal CBR2.3 removed a critical insulator, resulting in substantial shifting of chromatin looping and ectopic enhancer-promoter contacts. Destabilized gene architecture precipitated abnormal Grb10-Ddc expression with developmental consequences in the heart and muscle. Thus, we redefine the Grb10-Ddc imprinting domain by uncovering an unconventional intronic secondary DMR that functions as an insulator to instruct the tissue-specific, monoallelic expression of multiple genes-a feature previously ICR exclusive., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the devastating global pandemic of coronavirus disease 2019 (COVID-19), in part because of its ability to effectively suppress host cell responses 1-3 . In rare cases, viral proteins dampen antiviral responses by mimicking critical regions of human histone proteins 4-8 , particularly those containing post-translational modifications required for transcriptional regulation 9-11 . Recent work has demonstrated that SARS-CoV-2 markedly disrupts host cell epigenetic regulation 12-14 . However, how SARS-CoV-2 controls the host cell epigenome and whether it uses histone mimicry to do so remain unclear. Here we show that the SARS-CoV-2 protein encoded by ORF8 (ORF8) functions as a histone mimic of the ARKS motifs in histone H3 to disrupt host cell epigenetic regulation. ORF8 is associated with chromatin, disrupts regulation of critical histone post-translational modifications and promotes chromatin compaction. Deletion of either the ORF8 gene or the histone mimic site attenuates the ability of SARS-CoV-2 to disrupt host cell chromatin, affects the transcriptional response to infection and attenuates viral genome copy number. These findings demonstrate a new function of ORF8 and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Further, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The nearest-neighbor algorithm (N-N) for single particle tracking (SPT) is widely employed for studying the deformation and mechanics of soft materials, or to detect flow in microfluidic systems. However, this algorithm may not perform well under certain conditions of oscillatory or directed motion of the studied tracers. Here, a method is presented with the goal of improving the performance of NN-SPT algorithms when studying directed and oscillatory motions. Specifically, the approach applies a change-of-basis matrix to the detected particles positions, prior to the calculations made by the NN-SPT algorithm. The presented results demonstrate the superior tracking efficiency when analyzing these systems, manifested via lower tracking mismatches and less spurious results than the original N-N algorithm.

Background: Total joint arthroplasty (TJA) is one of the most common procedures performed in the United States. Outcomes of this elective procedure may be improved via preoperative optimization of modifiable risk factors. Purposes: We sought to summarize the literature on the clinical implications of preoperative risk factors in TJA and to develop recommendations regarding preoperative optimization of these risk factors. Methods: We searched PubMed in August 2019 with an update in September 2020 for English-language, peer-reviewed publications assessing the influence on outcomes in total hip and knee replacement of 7 preoperative risk factors-obesity, malnutrition, hypoalbuminemia, diabetes, anemia, smoking, and opioid use-and recommendations to mitigate them. Results: Sixty-nine studies were identified, including 3 randomized controlled trials, 8 prospective cohort studies, 42 retrospective studies, 6 systematic reviews, 3 narrative reviews, and 7 consensus guidelines. These studies described worse outcomes associated with these 7 risk factors, including increased rates of in-hospital complications, transfusions, periprosthetic joint infections, revisions, and deaths. Recommendations for strategies to screen and address these risk factors are provided. Conclusions: Risk factors can be optimized, with evidence suggesting the following thresholds prior to surgery: a body mass index <40 kg/m 2 , serum albumin ≥3.5 g/dL, hemoglobin A1C ≤7.5%, hemoglobin >12.0 g/dL in women and >13.0 g/dL in men, and smoking cessation and ≥50% decrease in opioid use by 4 weeks prior to surgery. Surgery should be delayed until these risk factors are adequately optimized., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Julius K. Oni, MD, reports relationships with Zimmer, Smith and Nephew, and Omega, outside the submitted work. The other authors declare no potential conflicts of interest., (© The Author(s) 2021.)

The burgeoning field of immunomedicine is primed to expand beyond oncology (Aghajanian et al. , 2022). Over the past several decades, many cell-based therapies have been proposed, developed, and deployed in the clinic. The recent explosion of targeted cell therapies has primarily been aimed at oncological malignancies. In parallel, cardiology researchers have been investigating the various cell types that contribute to heart diseases, especially those responsible for tissue fibrosis and myocardial dysfunction. Our laboratory proposed in 2019 to unite these two disciplines: could a targeted cell therapy be used to ameliorate cardiac fibrosis (Aghajanian et al. , 2019). Although preliminary results were encouraging, the genetic engineering approach used to manufacture immune cells would result in persistent cytolytic T cell if directly translated to humans. This would pose a safety concern since activated fibroblasts are essential cells in the setting of acute injury. Therefore, we developed a novel technology to deliver modified RNA to T cells in vivo , resulting in a transient antiactivated fibroblast therapeutic (Rurik et al. , 2022). Although active for only a few days, these cells were sufficient to significantly improve cardiac function in a murine model of cardiac fibrosis. These results pave the way for low-cost and scalable, and dose-able and immune therapy for fibrotic disorders.

Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed 1 . Here we identify a metabolite signalling pathway that provides actionable insights towards this goal. We perform a dietary screen in autochthonous animal models of CRC and find that ketogenic diets exhibit a strong tumour-inhibitory effect. These properties of ketogenic diets are recapitulated by the ketone body β-hydroxybutyrate (BHB), which reduces the proliferation of colonic crypt cells and potently suppresses intestinal tumour growth. We find that BHB acts through the surface receptor Hcar2 and induces the transcriptional regulator Hopx, thereby altering gene expression and inhibiting cell proliferation. Cancer organoid assays and single-cell RNA sequencing of biopsies from patients with CRC provide evidence that elevated BHB levels and active HOPX are associated with reduced intestinal epithelial proliferation in humans. This study thus identifies a BHB-triggered pathway regulating intestinal tumorigenesis and indicates that oral or systemic interventions with a single metabolite may complement current prevention and treatment strategies for CRC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

One of the most exciting new therapies for cancer involves the use of autologous T cells that are engineered to recognize and destroy cancerous cells. Patients with previously untreatable B cell leukaemias and lymphomas have been cured, and efforts are underway to extend this success to other tumours. Here, we discuss recent studies and emerging research aimed to extend this approach beyond oncology in areas such as cardiometabolic disorders, autoimmunity, fibrosis and senescence. We also summarize new technologies that may help to reduce the cost and increase access to related forms of immunotherapy., (© 2022. Springer Nature Limited.)

Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified messenger RNA (mRNA) in T cell–targeted lipid nanoparticles (LNPs). The efficacy of these in vivo–reprogrammed CAR T cells was evaluated by injecting CD5-targeted LNPs into a mouse model of heart failure. Efficient delivery of modified mRNA encoding the CAR to T lymphocytes was observed, which produced transient, effective CAR T cells in vivo. Antifibrotic CAR T cells exhibited trogocytosis and retained the target antigen as they accumulated in the spleen. Treatment with modified mRNA-targeted LNPs reduced fibrosis and restored cardiac function after injury. In vivo generation of CAR T cells may hold promise as a therapeutic platform to treat various diseases.

Homeodomain only protein (Hopx) is a regulator of cell differentiation and function, and it has also emerged as a crucial marker of specific developmental and differentiation potentials. Hopx expression and functions have been identified in some stem cells, tumors, and in certain immune cells. However, expression of Hopx in immune cells remains insufficiently characterized. Here we report a comprehensive pattern of Hopx expression in multiple types of immune cells under steady state conditions. By utilizing single-cell RNA sequencing (scRNA-seq) and flow cytometric analysis, we characterize a constitutive expression of Hopx in specific subsets of CD4 + and CD8 + T cells and B cells, as well as natural killer (NK), NKT, and myeloid cells. In contrast, Hopx expression is not present in conventional dendritic cells and eosinophils. The utility of identifying expression of Hopx in immune cells may prove vital in delineating specific roles of Hopx under multiple immune conditions., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Shear stress forces instruct valve formation during cardiac development.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has given rise to the devastating global pandemic. In most cases, SARS-CoV-2 infection results in the development of viral pneumonia and acute respiratory distress syndrome, known as 'coronavirus disease 2019' or COVID-19. Intriguingly, besides the respiratory tract, COVID-19 affects other organs and systems of the human body. COVID-19 patients with pre-existing cardiovascular disease have a higher risk of death, and SARS-CoV-2 infection itself may cause myocardial inflammation and injury. One possible explanation of such phenomena is the fact that SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the receptor required for viral entry. ACE2 is expressed in the cells of many organs, including the heart. ACE2 functions as a carboxypeptidase that can cleave several endogenous substrates, including angiotensin II, thus regulating blood pressure and vascular tone. It remains largely unknown if the SARS-CoV-2 infection alters the enzymatic properties of ACE2, thereby contributing to cardiovascular complications in patients with COVID-19. Here, we demonstrate that ACE2 cleavage of des-Arg9-bradykinin substrate analogue is markedly accelerated, while cleavage of angiotensin II analogue is minimally affected by the binding of spike protein. These findings may have implications for a better understanding of COVID-19 pathogenesis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)