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Supporting Autistic Students\u27 Mental Wellness: A Community Readiness Model Approach
No full textAutism spectrum disorder or difference (ASD) is a lifelong neurodevelopmental disability, usually identified during childhood. However, many adults miss the opportunity for diagnosis during childhood due to previous misunderstandings about autism presentation, camouflaging behaviors, and misdiagnoses. While current diagnostic tools for assessing autism in children are more robust, similar measures are lacking for adults who were not diagnosed in childhood. This gap poses risks for poor mental health outcomes among adults who missed a timely ASD diagnosis, which can be especially challenging for autistic college students. Although some higher education institutions offer support programs for autistic students, most do not, and, to our knowledge, no institutions routinely screen for ASD. Following the Community Readiness Model, we assessed the University of Nebraska Medical Center’s (UNMC) current readiness to address the mental health needs of autistic students. The Community Readiness Model (CRM) helps determine which stage of readiness a community is in, enabling strategic planning of future interventions that match the community readiness stage. Six participants affiliated with UNMC were recruited through purposeful and snowball sampling and participated in a brief interview. Participants were asked about the five dimensions of community readiness: leadership, resources, efforts, knowledge of efforts, and community. The findings reveal that UNMC was at Stage 3, Vague Awareness, regarding autism and mental health. The Community Climate dimension was the highest ranked, at Stage 5, Preparation; meanwhile, the resources dimension had the lowest overall level at Stage 2, or Denial/Resistance. This study revealed several obstacles to community readiness, including challenges and disparities in accessing autism evaluations and, therefore, accommodation services. Remote students may have fewer mental health resources than students studying on campus. Recent federal changes have contributed to uncertainty surrounding funding for autism and mental health in higher education spaces. These findings help guide numerous recommendations for raising community readiness levels at UNMC. A small sample size and brief interviews limit this study. Future studies should include more diverse representation, especially the perspectives of more neurodivergent individuals
Evaluating Bimane-CGH as a Site-Specific Probe for the Active Site of Mycobacterium tuberculosis EgtD
Full text linkMycobacterium tuberculosis relies on ergothioneine (EGT), a low-molecular-weight thiol, to maintain redox balance and resist oxidative stress and anti-tubercular drugs. EGT biosynthesis begins with EgtD, an AdoMet-dependent methyltransferase that trimethylates L-histidine to form hercynine, making EgtD a promising therapeutic target. This study evaluated the binding potential of a synthetic bimane-CGH probe designed to mimic substrate interactions and occupy the EgtD active site, with a fluorescent bimane tag for detection in structural assays. EgtD was expressed in E. coli, purified via cobalt affinity and size-exclusion chromatography, and co-crystallized with bimane-CGH. X-ray diffraction data were collected to 2.0 Å resolution, and the structure was solved and refined. Results revealed partial binding of bimane-CGH within the EgtD active site, with well-defined density for the histidine and glycine residues but uncertainty in the bimane position, possibly due to dynamic movement around the cysteine sulfur. These findings suggest the need for modified probe designs to achieve stable binding and inform future structure-based inhibitor development against M. tuberculosis EgtD.https://digitalcommons.unmc.edu/surp2025/1004/thumbnail.jp
Editing Approaches to Treat Alpha-1 Antitrypsin Deficiency
Full text linkTOPIC IMPORTANCE: Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder most commonly due to a single G to A point mutation (E342K), leading to debilitating lung and/or liver disorders and is associated with increased mortality. The E342K point mutation causes a conformational change of the AAT protein resulting in its retention in liver hepatocytes. This reduces AAT secretion into the serum resulting in higher protease activities due to the lack of inhibition from AAT, causing damage to healthy lung tissue. The current standard of care for lung manifestations involves weekly IV augmentation therapy and is considered suboptimal for these patients. Furthermore, there is currently no approved treatment for liver manifestations. The unmet medical need for patients with AAT deficiency remains high, and new treatment options are needed to treat the underlying disease etiology.
REVIEW FINDINGS: Advances in genomic medicines may enable treatment by editing the DNA or RNA sequence to produce wild-type AAT instead of the mutated AAT caused by the E342K mutation. One approach can be achieved by directing endogenous adenosine deaminases that act on RNA to the E342K RNA site, where they catalyze adenosine to inosine conversion through a process known as RNA editing. The A-I RNA change will be read as a G during protein translation, resulting in an altered amino acid and restoration of wild-type AAT secretion and function.
SUMMARY: In this review, we will discuss the pathophysiology of AAT deficiency and emerging treatment options with particular focus on RNA editing as a disease-modifying treatment for both liver and lung disease
The Impact of Public Health Authority on Emergency Response in State Health Departments
No full textBackground
Public health authority plays a crucial role in enabling state health officials to implement emergency response measures such as isolation, quarantine, and vaccination campaigns. However, legislative changes following the COVID-19 pandemic have significantly curtailed these authorities in many states, raising concerns about the ability of public health officials to respond effectively to future health crises. The erosion of public health authority has highlighted gaps in the legal literacy of health officials and underscored the need for enhanced training in navigating political and legal challenges.
Purpose
The purpose of this study is to assess legal literacy among state health officials, identify training needs, and develop a structured curriculum outline to enhance their ability to navigate public health authority within their jurisdictions. This research seeks to bridge the gap between statutory authority and practical implementation by equipping officials with critical knowledge and skills.
Methods
This study utilized an explanatory sequential mixed-methods approach beginning with a quantitative survey of current and former state health officials to assess their familiarity with legal frameworks, confidence in applying public health laws, and perceived training gaps. The survey was followed by qualitative interviews to gain deeper insights into the political, legal, and operational challenges faced by officials. Data were analyzed using statistical methods for the survey and thematic coding for interview transcripts.
Results
The quantitative survey (N=48) revealed that while most respondents had moderate to high familiarity with legal frameworks, confidence in applying them varied significantly. Key barriers included the complexity of legal structures, political interference, and lack of formal training. Thematic analysis of qualitative interviews provided deeper insights into these challenges, highlighting legislative restrictions, political pressure, and difficulties in intergovernmental coordination. These findings indicate significant gaps in legal literacy and preparedness among state health officials reinforcing the need for targeted training interventions.
Conclusions
The results of this study underscore an urgent need to enhance the legal literacy of state health officials to strengthen emergency preparedness and response efforts. This study proposes a structured training framework that focuses on foundational legal knowledge, political navigation, and crisis leadership skills. The curriculum will include practical applications such as real-world case analyses, interactive decision-making exercises, and strategies for effectively engaging with policymakers and stakeholders. By equipping health officials with the necessary legal and leadership competencies, this initiative aims to improve public health decision-making, advocacy, and crisis management in complex and politically dynamic environments
Sickness & Stigma at Sea View: The Black Angels
No full textDiscover the true story of the Black Angels at the 16th annual Richard B. Davis, MD, PhD History of Medicine Lecture.
Author Maria Smilios learned about the Black Angels while working as a science book editor at Springer Publishing. As a native New Yorker and lover of history, medicine, and women’s narratives, she became determined to tell their story.
“The Black Angels” is the true story of the Black nurses who, in 1929, wagered their lives by leaving the Jim Crow south and went north to work on an isolated hilltop in Staten Island at Sea View Hospital. The “pest house” was an overcrowded municipal tuberculosis sanatorium where the city sent its poorest residents, considered “uncouth and un-American consumptives” to languish and die.
Maria Smilios is an award-winning author, keynote speaker, and adjunct lecturer at Columbia University Mailman School of Public Health. She was born and raised in New York City. She holds a Master of Arts in American literature and religion from Boston University where she was a Luce and Presidential scholar. Her work has appeared in The Guardian, Narratively, The Forward, Lit Hub, Writers Digest, The Emancipator, Newsweek, and other publications.
The Black Angels won the 2024 Christopher Award in literature, which celebrates works that “affirm the highest values of the human spirit.” It was also a finalist for the prestigious Gotham Book Prize, an NASW Science in Society Journalism finalist, an NPR Science Friday Summer Read for 2024, and shortlisted for the English PEN literary award.
New York City and State recently honored Maria for “outstanding service” and “positive contribution” to the people of New York. The book greatly informed and inspired the Staten Island Museum’s exhibit “Taking Care: The Black Angels of Sea View,” which is on display through the end of 2025.
The Richard B. Davis, MD, PhD, History of Medicine Lectureship brings national experts to the UNMC campus to discuss the history of medicine in support of special collections at the McGoogan Library, including rare books and works on the history of medicine. The lectureship is supported through an endowed fund given by the late Richard B. Davis (1926-2010), MD, PhD, who was a UNMC faculty member from 1969 to 1994 and professor emeritus of internal medicine at UNMC. Dr. Davis and his wife, Jean, provided support for the lectureship out of his longstanding interest in the history of medicine.https://digitalcommons.unmc.edu/davis/1004/thumbnail.jp
Leveraging Biomarkers to Accelerate Drug Development and Patient Care
Full text linkThe timely diagnosis of diseases is vital for administering appropriate treatment and improving patient healthcare. To this date, many diseases such as inflammatory bowel disease (IBD), cancer, non-alcoholic fatty liver disease (NAFLD), do not exhibit symptoms until progressing into advanced stages. As a result, physicians are unable to diagnose them and provide timely therapeutic treatment. Moreover, the “one size fits all” approach does always work for such diseases, often rendering the treatment ineffective, and resulting in poor patient compliance and increased medical costs. Thus, precision medicine has gained much importance in the last few years. Biomarkers are important tools that help in diagnosis, monitoring of diseases, and therapeutic response. For years, physicians have relied on biomarkers to assess patient well-being and selection of drugs. However, many diseases cannot be diagnosed in their earlier stage, due to a lack of reliable biomarkers. There is an unmet medical need for development of novel biomarkers for such complex and chronic disorders. This dissertation looks into the typical steps involved in biomarker development. The first chapter focuses on different types of biomarkers, their advantages and disadvantages, the challenges to biomarker discovery, and their potential applications. In second chapter focused on the typical workflow for assay development and validation for an endogenous biomarker indole, which is a potential biomarker for NAFLD, C.difficile infections, assessing the risk of cardiovascular disease in chronic kidney disease, among many others. The subsequent chapters dive into eicosanoids as potential novel non-invasive biomarkers to assess disease progression and drug response for IBD. The third chapter aims to establish the proof of concept for the same using a mouse model of IBD. The fourth chapter evaluates eicosanoids as potential biomarkers to assess disease severity in humans, thereby evaluating them as potential biomarkers of disease progression and resolution. Overall, our research aims to improve precision medicine for complex and chronic disorders by identifying novel potential biomarkers, thereby improving patient outcomes
Neoadjuvant Gene Therapy with Calreticulin and R848: A Novel Approach to Pancreatic Ductal Adenocarcinoma Treatment
No full textPancreatic ductal adenocarcinoma (PDAC) is a rare cancer with 66,440 new cancer cases and 51,750 estimated cancer deaths in the United States as of 2024, according to the American Cancer Society. The incidence rate of pancreatic cancer in the US for both sexes combined is 13.4 per 100,000 per year and is steadily increasing. With a 5-year survival rate of only 13% for all stages of PDAC, pancreatic cancer ranks third among cancer-related causes of death in the US and is expected to rise to the number two position by 2030. The detection of PDAC at an early stage has always been challenging, and hence, 90% of cases diagnosed are already at advanced and metastatic stage. The treatment options after diagnosis are also minimal. Even though there are several options ranging from chemotherapy to radiotherapy to targeted therapy, surgery remains the best and only curative treatment for PDAC, with several drawbacks. Efforts are being actively made to diagnose early and to develop a less invasive and more promising targeted therapy for PDAC. Immunogenic cell death (ICD) is a particular type of apoptosis pathway that can serve as a promising tool for pancreatic cancer treatment and prevent its recurrence later in life. Thus, an immunostimulator and delivery of mRNA for the protein, that can initiate the ICD pathway in the immunosuppressive tumor microenvironment, can be a potential approach to treat PDAC. In this dissertation research, I hypothesized that R848 (resiquimod; a TLR7/8 agonist) and recombinant mRNA for calreticulin (CALR)-loaded lipid nanoparticles could express this protein on the surface of the PDAC tumor cells, which while acting as “eat me” signal to the dendritic cells (DCs) for phagocytosis will also inducing the ICD response and simultaneously activate T cells to cytotoxic T cells and memory T cells to achieve enhanced combinational cancer therapy. To explore this hypothesis, the dissertation first discusses the nature of pancreatic cancer and its types, its risk factors, available treatment strategies, and the challenges linked to it. It then highlights immunotherapy as a growing field and discusses its advantages, and how it can be used as a promising treatment strategy for PDAC in the future. The development of lipid nanoparticles (LNP) for mRNA delivery has also been described with a special emphasis on its safety, enhanced tissue penetration, and efficiency especially when administered intraperitoneally, making it ideal for targeting solid tumors. Subsequently, in vitro findings demonstrate how an engineered mRNA led to CALR expression only on the cell surface of PDAC cells. This expression triggered phagocytosis and promoted apoptosis in the neighboring tumor cells. These findings were crucial evidence of the supporting hypothesis for the PDAC therapeutics. These findings were further validated in an in vivo system for which the C57BL/6 mouse model was utilized. The combination of FI-3/mCALR-Daf1 and R848 significantly reduced the tumor burden enhanced the immune cell infiltration, induced tumor apoptosis, remodeled tumor microenvironment, and modulated cytokine profile. These outcomes suggest that combinational therapy represents a promising and innovative treatment strategy for PDAC
Causal Mediation Analysis with Joint Modeling Framework for Recurrent Events Mediator and Survival Outcomes
No full textWith the increasing emphasis on longitudinal studies and patient monitoring, recurrent event data have become more frequently collected, particularly among patients with chronic diseases. Understanding the mediating role of recurrent events in the causal pathway between exposures and time-to-event outcomes has garnered increasing interest not only in clinical research but also in various other fields, including epidemiology, public health, and social sciences. For instance, Opportunistic Infections (OIs), a form of recurrent events, frequently occur in Human Immunodeficiency Virus (HIV)-infected patients and can substantially impact their health and survival, particularly for those diagnosed with Acquired Immunodeficiency Syndrome (AIDS). Investigating how OIs mediate the effects of treatments or baseline conditions on survival outcomes is of great interest. However, existing methods for causal inference in joint analyses of recurrent and terminal events remain limited, particularly in scenarios involving multiple mediators—such as different types of OIs or other time-dependent biomarkers—and in accounting for unmeasured confounding, which is particularly challenging in survival analysis. To address these challenges, we develop novel joint modeling approaches that simultaneously investigate recurrent event mediators and survival outcomes. Our framework is further extended to handle multiple mediators, whether causally or non-causally related, while estimating direct and indirect effects. In Chapter 2, we propose a joint modeling approach that incorporates recurrent events as mediators and survival end- points as outcomes. By relaxing the “sequential ignorability” assumption through shared random effects, our method accounts for time-independent unmeasured confounding between mediators and outcome. Simulation studies demonstrate the robustness of this approach, and an application to an AIDS study shows that the number of OIs mediates the effect of baseline CD4 count on survival outcomes. In Chapter 3, we extend this framework by modeling recurrent events using gap times rather than the total time scale, allowing for varying distribution and covariate effects for each gap time. This approach provides greater flexibility in understanding the differential impact of exposure on early and late OIs. In Chapter 4, we further advance the mediation framework to quantify causal mechanisms when multiple mediators exist between exposure and terminal events through joint modeling. This approach relaxes the assumption of confounding between mediators and outcomes by utilizing the latent shared random effect. Using this method, we analyze the distinct mediation effects of multiple types of OIs, providing a more nuanced understanding of their role in disease progression. In Chapter 5, we extended the model further by integrating repeated biomarker measurements with recurrent events, explicitly addressing their causal interdependence. Applied to the CPCRA study, our method quantifies how recurrent OIs and repeated CD4 counts jointly mediate the effect of treatment or prior AIDS-defining conditions on mortality. The results highlight the opposing mediation effects of these pathways, emphasizing the importance of controlling OIs while improving immune function. Our research contributes to the methodological development of mediation analysis in survival studies, offering a robust framework for investigating multiple mediators, whether causally or non-causally related. These findings provide deeper insights into treatment mechanisms and inform clinical strategies for managing HIV progression
Kansas City Health Department – Childhood Lead Poisoning Prevention Program – Quality Improvement
Full text linkThis capstone manuscript evaluates the Kansas City Health Department\u27s Childhood Lead Poisoning Prevention Program’s effectiveness. Through comprehensive data analysis of grant utilization, return-on-interest (ROI) and participant satisfaction evaluation, the project will provide actionable recommendations for improving sustainable long-term outcomes in lead poisoning prevention
Transgender and Gender-Diverse Health Care Access and Availability of Care according to Resident Leaders in the Mahoning County, Ohio
Full text linkBACKGROUND: Transgender and gender diverse health is significantly under attack in the United States and there is a continued need to further research to identify ways to increase their access to both inclusive care as well as gender affirming care. The purpose of this study was to explore barriers and supportive factors that professionals and community leaders perceive surrounding the availability and accessibility of inclusive and gender affirming care for transgender and gender diverse people in Mahoning County, Ohio.
METHODS: Key informant interviews were conducted with professionals and community leaders who could be considered “facilitators” helping transgender and gender diverse people in their community find what they need to access care. A semi-structured interview guide was created to understand the state of gender affirming care and inclusive care access in Mahoning County, Ohio. Interviews were conducted using a video conferencing platform or in-person and lasted between 15 to 45 minutes. Interviews were recorded, transcribed, and analyzed. A thematic analysis was conducted to identify key themes.
RESULTS: Most, but not all, interviewees felt distress concerning the state of gender affirming and inclusive care access in their community. Participants identified several social determinant factors that act as barriers and supportive factors to individuals seeking care. This includes social trust, fear of discrimination, provider risk aversion, lack of community knowledge, data limitations, and education. Numerous systemic, institutional, and informal institutions that function as barriers hampering providers’ ability to help transgender and gender diverse community members access care were also identified. (DISCUSSION) Overall, this study found a need for greater education for community members, providers, and leaders in their community and the need for increased access to care, as well as information about care that would be useful to them in their efforts to support care access for transgender and gender diverse community members. It also identified a need for policy change at the institutional and systems levels, including challenging persistent and harmful informal practices.
PUBLIC HEALTH IMPLICATIONS: These findings could help inform local institutional policy decisions to help make care more accessible for patients and information easier to find for the professionals that are helping them find access to care. Additionally, these findings have implications for health equity as they reveal existing disparities at the community level that need to be addressed to improve the public’s health for the transgender and gender diverse population. Further research will be needed to address remaining gaps in knowledge and explore the role of “facilitators” in helping people access gender affirming and inclusive care in greater detail