Proteomic and phosphoproteomic landscapes of acute myeloid leukemia.

We have developed a deep-scale proteome and phosphoproteome database from 44 representative acute myeloid leukemia (AML) patients from the LAML TCGA dataset and 6 healthy bone marrow-derived controls. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by the proteomic data. We identified examples of posttranscriptionally regulated proteins both globally (ie, in all AML samples) and also in patients with recurrent AML driver mutations. For example, samples with IDH1/2 mutations displayed elevated levels of the 2-oxoglutarate-dependent histone demethylases KDM4A/B/C, despite no changes in messenger RNA levels for these genes; we confirmed this finding in vitro. In samples with NPMc mutations, we identified several nuclear importins with posttranscriptionally increased protein abundance and showed that they interact with NPMc but not wild-type NPM1. We identified 2 cell surface proteins (CD180 and MRC1/CD206) expressed on AML blasts of many patients (but not healthy CD34+ stem/progenitor cells) that could represent novel targets for immunologic therapies and confirmed these targets via flow cytometry. Finally, we detected nearly 30 000 phosphosites in these samples; globally, AML samples were associated with the abnormal phosphorylation of specific residues in PTPN11, STAT3, AKT1, and PRKCD. FLT3-TKD samples were associated with increased phosphorylation of activating tyrosines on the cytoplasmic Src-family tyrosine kinases FGR and HCK and related signaling proteins. PML-RARA-initiated AML samples displayed a unique phosphorylation signature, and TP53-mutant samples showed abundant phosphorylation of serine-183 on TP53 itself. This publicly available database will serve as a foundation for further investigations of protein dysregulation in AML pathogenesis.

Hospital-Based Community Gardens as a Strategic Partner in Addressing Community Health Needs.

As part of community health needs assessments, US nonprofit hospitals are identifying a high prevalence of chronic diseases associated with poor diets. Institutions have responded by establishing nutrition-related initiatives such as farmers' markets and community gardens. There is public health value in demonstrating how these partnerships can help hospitals address identified community health needs. Here we describe diverse strategies undertaken by a hospital-based community garden at Penn State Milton S. Hershey Medical Center, explore implications for US hospitals, and provide implementation guidance. (Am J Public Health. 2023;113(9):939-942. https://doi.org/10.2105/AJPH.2023.307336).

Remethylation of Dnmt3a-/- hematopoietic cells is associated with partial correction of gene dysregulation and reduced myeloid skewing.

Mutations in the DNA methyltransferase 3A (DNMT3A) gene are the most common cause of age-related clonal hematopoiesis (ARCH) in older individuals, and are among the most common initiating events for acute myeloid leukemia (AML). The most frequent DNMT3A mutation in AML patients (R882H) encodes a dominant-negative protein that reduces methyltransferase activity by ∼80% in cells with heterozygous mutations, causing a focal, canonical DNA hypomethylation phenotype; this phenotype is partially recapitulated in murine Dnmt3a-/- bone marrow cells. To determine whether the hypomethylation phenotype of Dnmt3a-/- hematopoietic cells is reversible, we developed an inducible transgene to restore expression of DNMT3A in transplanted bone marrow cells from Dnmt3a-/- mice. Partial remethylation was detected within 1 wk, but near-complete remethylation required 6 mo. Remethylation was accurate, dynamic, and highly ordered, suggesting that differentially methylated regions have unique properties that may be relevant for their functions. Importantly, 22 wk of DNMT3A addback partially corrected dysregulated gene expression, and mitigated the expansion of myeloid cells. These data show that restoring DNMT3A expression can alter the epigenetic "state" created by loss of Dnmt3a activity; this genetic proof-of-concept experiment suggests that this approach could be relevant for patients with ARCH or AML caused by loss-of-function DNMT3A mutations.

The transformative power of participating in Opening Minds Through Art (OMA), an expressive arts program for medical students.

Opening Minds Through Art (OMA) is a standardized expressive arts-based program that improves student attitudes toward persons living with dementia. Understanding how this change occurs is important for both educators and clinicians. In this study, narrative analysis was used to explore the impact of OMA on participating medical students. 111 students at six medical schools accepted an invitation to be part of OMA during the 2018-2020 academic years. After completing the program, participants were asked to write briefly about the impact of their OMA experience on their work as future physicians. These narratives were analyzed to identify themes relevant to the impact of the program. Students described appreciating both pragmatic and novel creative experiences in OMA, which differed from their traditional studies. Themes from the evaluation included: Inter and Intrapersonal Connection and Growth; Mastery of Anticipated Challenges; Acquisition of Knowledge and Skills; and Appreciation of Health Care Team Members. Teaching students to embrace clinical work with challenging and perceived "difficult" patients is often unaddressed in the medical school curriculum. This study suggests that the combination of medical knowledge and artistic expression can be used to benefit both students and persons living with dementia.

Ancient Roots of Today's Emerging Renaissance in Psychedelic Medicine.

An international ban on psychedelics initiated by the United Nations' Convention on Psychotropic Substances in 1971 restricted the clinical use of these ancient psychoactive substances. Yet, in an era marked by rising mental health concerns and a growing "Deaths of Despair" epidemic (i.e., excess mortality and morbidity from suicide, drug overdose, and alcoholism), the structured psychedelic use that has long been a part of ritual healing experiences for human societies is slowly regaining credibility in Western medicine for its potential to treat various mental health conditions. We use a historical lens to examine the use of psychedelic therapies over time, translate ancient lessons to contemporary clinical and research practice, and interrogate the practical and ethical questions researchers must grapple with before they can enter mainstream medicine. Given the COVID-19 pandemic and its contributions to the global mental health burden, we also reflect on how psychedelic therapy might serve as a tool for medicine in the aftermath of collective trauma. Ultimately, it is argued that a "psychedelic renaissance" anchored in the lessons of antiquity can potentially help shift healthcare systems-and perhaps the broader society-towards practices that are more humane, attentive to underlying causes of distress, and supportive of human flourishing.

A Systematic Scoping Review of How Healthcare Organizations Are Facilitating Access to Fruits and Vegetables in Their Patient Populations.

BACKGROUND: There is compelling evidence on the impact of diet as preventative medicine, and with rising health care costs healthcare organizations are attempting to identify interventions to improve patient health outcomes. OBJECTIVES: The purpose of this systematic scoping review was to characterize existing healthcare organization-based interventions to improve access to fruits and vegetables (F&V) for their patient populations. In addition, we aimed to review the impact of identified interventions on dietary intake and health outcomes. METHODS: Titles and abstracts were searched in PubMed® (MEDLINE®), Embase®, CINAHL®, and the Cochrane Library® from 1 January 1990 to 31 December 2019. To be selected for inclusion, original studies must have included a healthcare organization and have had a programmatic focus on increasing access to or providing fresh F&V to patients in an outpatient, naturalistic setting. The Effective Public Health Practice Project tool was used to assess study quality in 6 domains (selection bias, study design, confounders, blinding, data collection methods, and withdrawals and dropouts). RESULTS: A total of 8876 abstracts were screened, yielding 44 manuscripts or abstracts from 27 programs. Six program models were identified: 1) a cash-back rebate program, 2) F&V voucher programs, 3) garden-based programs, 4) subsidized food box programs, 5) home-delivery meal programs, and 6) collaborative food pantry-clinical programs. Only 6 of 27 studies included a control group. The overall quality of the studies was weak due to participant selection bias and incomplete reporting on data collection tools, confounders, and dropouts. Given the heterogeneity of outcomes measured and weak study quality, conclusions regarding dietary and health-related outcomes were limited. CONCLUSIONS: Healthcare-based initiatives to improve patient access to F&V are novel and have promise. However, future studies will need rigorous study designs and validated data collection tools, particularly related to dietary intake, to better determine the effect of these interventions on health-related outcomes.

Repurposing Waste Streams: Lessons on Integrating Hospital Food Waste into a Community Garden.

There have been increasing efforts in recent decades to divert institutional food waste into composting programs. As major producers of food waste who must increasingly demonstrate community benefit, hospitals have an incentive to develop such programs. In this article, we explain the emerging opportunity to link hospitals' food services to local community gardens in order to implement robust composting programs. We describe a partnership model at our hospital in central Pennsylvania, share preliminary outcomes establishing feasibility, and offer guidance for future efforts. We also demonstrate that the integration of medical students in such efforts can foster systems thinking in the development of programs to manage hospital waste streams in more ecologically-friendly ways.

Engineering Online and In-Person Social Networks for Physical Activity: A Randomized Trial.

BACKGROUND: Social networks can influence physical activity, but little is known about how best to engineer online and in-person social networks to increase activity. PURPOSE: The purpose of this study was to conduct a randomized trial based on the Social Networks for Activity Promotion model to assess the incremental contributions of different procedures for building social networks on objectively measured outcomes. METHODS: Physically inactive adults (n = 308, age, 50.3 (SD = 8.3) years, 38.3 % male, 83.4 % overweight/obese) were randomized to one of three groups. The Promotion group evaluated the effects of weekly emailed tips emphasizing social network interactions for walking (e.g., encouragement, informational support); the Activity group evaluated the incremental effect of adding an evidence-based online fitness walking intervention to the weekly tips; and the Social Networks group evaluated the additional incremental effect of providing access to an online networking site for walking as well as prompting walking/activity across diverse settings. The primary outcome was mean change in accelerometer-measured moderate-to-vigorous physical activity (MVPA), assessed at 3 and 9 months from baseline. RESULTS: Participants increased their MVPA by 21.0 min/week, 95 % CI [5.9, 36.1], p = .005, at 3 months, and this change was sustained at 9 months, with no between-group differences. CONCLUSIONS: Although the structure of procedures for targeting social networks varied across intervention groups, the functional effect of these procedures on physical activity was similar. Future research should evaluate if more powerful reinforcers improve the effects of social network interventions. TRIAL REGISTRATION NUMBER: The trial was registered with the ClinicalTrials.gov (NCT01142804).

Impact of TimeSlips creative expression program on behavioral symptoms and psychotropic medication use in persons with dementia in long-term care: a cluster-randomized pilot study.

OBJECTIVES: To evaluate whether involvement in TimeSlips, a creative storytelling program, reduced mood and behavioral symptoms as well as psychotropic medication use in persons with dementia. METHODS: A cluster-randomized pilot study compared two discrete dementia care units in one nursing home. The control cohort (N = 10) received standard-of-care activity programming, and the intervention cohort (N = 10) received standard-of-care plus two one-hour TimeSlips sessions per week for six weeks. Data on mood and behavioral symptoms and psychotropic drug prescriptions were collected, and within-group and between-group comparisons were performed. RESULTS: Between-group comparisons did not reveal statistically significant differences in mood and behavioral symptoms. No differences in psychotropic drug prescriptions were found. CONCLUSIONS: Larger trials of longer duration are needed to determine whether involvement in TimeSlips reduces mood and behavioral symptoms that compromise quality of life for persons with dementia.

Medical student views on the use of Facebook profile screening by residency admissions committees.

PURPOSE: Previous research has shown that >50% of residency programmes indicate that inappropriate Facebook postings could be grounds for rejecting a student applicant. This study sought to understand medical students' views regarding the impact of their Facebook postings on the residency admissions process. STUDY DESIGN: In 2011-2012, we conducted a national survey of 7144 randomly selected medical students representing 10% of current enrollees in US medical schools. Students were presented with a hypothetical scenario of a residency admissions committee searching Facebook and finding inappropriate pictures of a student, and were asked how the committee ought to regard these pictures. RESULTS: The response rate was 30% (2109/7144). Respondents did not differ from medical students nationally with regard to type of medical school and regional representation. Of the three options provided, the majority of respondents (63.5%) indicated 'the pictures should be considered along with other factors, but should not be grounds for automatic rejection of the application'. A third (33.7%) believed 'the pictures should have no bearing on my application; the pictures are irrelevant'. A small minority of respondents (2.8%) felt 'the pictures should be grounds for automatic rejection of the application'. CONCLUSIONS: That the views of students regarding the consequences of their online activity differ so greatly from the views of residency admissions committees speaks to the need for better communication between these parties. It also presents opportunities for medical schools to help students in their residency application process by increasing awareness of social media screening strategies used by some residency programmes, and fostering self-awareness around the use of social media during medical school and especially during the residency application process.

Characterizing customers at medical center farmers' markets.

Approximately 100 farmers' markets operate on medical center campuses. Although these venues can uniquely serve community health needs, little is known about customer characteristics and outreach efforts. Intercept survey of markets and market customers between August 2010 and October 2011 at three medical centers in different geographic regions of the US (Duke University Medical Center, Cleveland Clinic, and Penn State Hershey Medical Center) were conducted. Markets reported serving 180-2,000 customers per week and conducting preventive medicine education sessions and community health programs. Customers (n = 585) across markets were similar in sociodemographic characteristics--most were middle-aged, white, and female, who were employees of their respective medical center. Health behaviors of customers were similar to national data. The surveyed medical center farmers' markets currently serve mostly employees; however, markets have significant potential for community outreach efforts in preventive medicine. If farmers' markets can broaden their reach to more diverse populations, they may play an important role in contributing to community health.

Digging Deeper: What Can We Really Learn about Dementia from History?

In response to Finch and Burstein's provocative argument that the advanced dementias may result from environmental toxins and lifestyle factors associated with post-industrial societies, we call for a more rigorous historical approach, emphasizing the importance of situating ancient texts more fully in their historical and cultural context. Such an approach would also entail consideration of the declining relative rates of dementia in Western countries, which have been linked to population health-level factors and policies that appear to have reduced the risk of dementia by directly and indirectly influencing the social determinants of brain health.

Engineering online and in-person social networks to sustain physical activity: application of a conceptual model.

BACKGROUND: High rates of physical inactivity compromise the health status of populations globally. Social networks have been shown to influence physical activity (PA), but little is known about how best to engineer social networks to sustain PA. To improve procedures for building networks that shape PA as a normative behavior, there is a need for more specific hypotheses about how social variables influence PA. There is also a need to integrate concepts from network science with ecological concepts that often guide the design of in-person and electronically-mediated interventions. Therefore, this paper: (1) proposes a conceptual model that integrates principles from network science and ecology across in-person and electronically-mediated intervention modes; and (2) illustrates the application of this model to the design and evaluation of a social network intervention for PA. METHODS/DESIGN: A conceptual model for engineering social networks was developed based on a scoping literature review of modifiable social influences on PA. The model guided the design of a cluster randomized controlled trial in which 308 sedentary adults were randomly assigned to three groups: WalkLink+: prompted and provided feedback on participants' online and in-person social-network interactions to expand networks for PA, plus provided evidence-based online walking program and weekly walking tips; WalkLink: evidence-based online walking program and weekly tips only; Minimal Treatment Control: weekly tips only. The effects of these treatment conditions were assessed at baseline, post-program, and 6-month follow-up. The primary outcome was accelerometer-measured PA. Secondary outcomes included objectively-measured aerobic fitness, body mass index, waist circumference, blood pressure, and neighborhood walkability; and self-reported measures of the physical environment, social network environment, and social network interactions. The differential effects of the three treatment conditions on primary and secondary outcomes will be analyzed using general linear modeling (GLM), or generalized linear modeling if the assumptions for GLM cannot be met. DISCUSSION: Results will contribute to greater understanding of how to conceptualize and implement social networks to support long-term PA. Establishing social networks for PA across multiple life settings could contribute to cultural norms that sustain active living. TRIAL REGISTRATION: ClinicalTrials.gov NCT01142804.

Dangers and opportunities for social media in medicine.

Health professionals have begun using social media to benefit patients, enhance professional networks, and advance understanding of individual and contextual factors influencing public health. However, discussion of the dangers of these technologies in medicine has overwhelmed consideration of positive applications. This article summarizes the hazards of social media in medicine and explores how changes in functionality on sites like Facebook may make these technologies less perilous for health professionals. Finally, it describes the most promising avenues through which professionals can use social media in medicine-improving patient communication, enhancing professional development, and contributing to public health research and service.

Medical center farmers markets: a strategic partner in the patient-centered medical home.

BACKGROUND: The number of medical center-based farmers markets has increased in the past decade, but little is known about how such organizations contribute to the preventive health goals of the patient-centered medical home. COMMUNITY CONTEXT: In 2010, we started a seasonal farmers market at Penn State Hershey Medical Center to help support the institution's commitment to the medical home. METHODS: We obtained descriptive data on the farmers market from hospital and market records and tracking information on the market's Facebook and Twitter sites. We computed summary measures to characterize how the market has begun to meet the 6 standards of the 2011 National Committee for Quality Assurance's report on the medical home. OUTCOME: During the 2010 and 2011 seasons, 146 medical center volunteers from 40 departments formed 23 interprofessional teams that spent an average of 551 volunteer hours per season at the market, providing health screenings (n = 695) and speaking to customers (n = 636) about preventive health. Fifty-five nonmedical community health partners provided 208 hours of service at the market alongside medical center staff. Market programming contributed to 5 regional preventive health partnerships and created opportunities for interprofessional mentoring, student leadership, data management, development of social media skills, and grant-writing experience. The market contributed to all 6 medical home standards outlined by the National Committee for Quality Assurance. INTERPRETATION: Medical center markets can support medical home standards. With systematic tracking of the health effects and integration with electronic medical health records, markets hold potential to contribute to comprehensive patient-centered care.

How we used two social media tools to enhance aspects of active learning during lectures.

BACKGROUND: Medical education is evolving to include active learning approaches, yet some courses will remain lecture-based. Social media tools used by students may foster collaborative learning during lectures. AIM: We present preliminary results from a pilot study that integrated two 'social' technologies, Google Docs and SurveyMonkey, into 22 hour-long lectures for a course called "Social Influences on Health" attended by 154 students. METHODS: At the conclusion of the semester, we reviewed student usage patterns with both technologies and collected data from students via course evaluations that included a standard Likert Scale. We used thematic analysis to identify emergent themes from evaluations. RESULTS: On average, students contributed 6 comments/questions to the Google Doc in each lecture, and 35 students participated in SurveyMonkey. Engagement with both technologies increased throughout the semester and no unprofessional incidents were observed. The mean student rating for integration of Google Docs and SurveyMonkey was 3.4 or "above average" (SD = 1.17). Thematic analysis identified perceived strengths of this approach as well as areas for improvement. CONCLUSIONS: Social media such as Google Docs and SurveyMonkey can facilitate interaction and provide students with control over content and flow of lecture-based courses, but educators must be mindful of practical and conceptual limitations.

What Can the Health Humanities Contribute to Our Societal Understanding of and Response to the Deaths of Despair Crisis?

Deaths of Despair (DoD), or mortality resulting from suicide, drug overdose, and alcohol-related liver disease, have been rising steadily in the United States over the last several decades. In 2020, a record 186,763 annual despair-related deaths were documented, contributing to the longest sustained decline in US life expectancy since 1915-1918. This forum feature considers how health humanities disciplines might fruitfully engage with this era-defining public health catastrophe and help society better understand and respond to the crisis.