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Addressing Functional Cognition During Acute Psychiatric Hospitalization
No full textIUISerious mental illness (SMI) often presents with cognitive impairments that significantly impact occupational performance and quality of life. Occupational therapists (OTs) possess the training to address functional cognition, yet their role in acute psychiatric settings remains underdeveloped and ambiguous. This doctoral capstone project aimed to identify and implement evidence-based OT assessments and interventions to address functional cognition among inpatients with SMI at Eskenazi Health’s Mental Health Recovery Center (MHRC). Guided by an integrated Occupational Adaptation (OA) and Metacognitive Reflection and Insight Therapy (MERIT) framework, the student conducted a narrative review and synthesized findings into clinical practice over a 14-week experience. Weekly field notes outlining treatment approaches informed a discussion of practice implications in the context of evidence-based findings. Outcome measures were implemented to assess metacognition, insight, and judgment, while occupation-based interventions were used to improve participation and well-being through the development of metacognitive awareness, self-reflection, executive functioning, and social cognition. Results support the inclusion of functional cognitive assessment and intervention in acute psychiatric OT services and highlight the value of metacognitive and occupation-based approaches in promoting recovery for patients with SMI. Continued research, theory development, program advancement, and professional advocacy for OT’s role in mental health is warranted to advance quality of care and improve long-term outcomes for individuals with SMI.Occupational Therap
Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease
No full textThe oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD
Celiac Disease in Medical Curriculum
No full textIntroduction/Background: Students attending US medical schools are often turning to commercial resources as a primary learning tool during their preclinical years. However, the quality and content of the material presented within these sources has not been widely studied. This study sought to compare sources of preclinical medical education using celiac disease, a common autoimmune illness. Celiac disease has an exceedingly variable range of presentations across many body systems, including subclinical symptoms. Despite accessible testing and treatment, most individuals with celiac have not been diagnosed, imposing significant disease burden.
Study objective/Hypothesis: This study sought to evaluate and compare the IUSM preclinical curriculum and popular commercial resources regarding their presentation of celiac disease.
Methods: After conducting a literature review, an evidence-based rubric was created to evaluate information about celiac disease. The rubric was applied to the IUSM preclinical curriculum and USMLE World, First Aid for the USMLE Step 1, and Boards and Beyond, commercial resources widely used by preclinical medical students.
Results: The IUSM curriculum scored higher overall and higher in all but one category than all the commercial resources. USMLE World had the highest score of the commercial resources. All sources showed deficits in two or more categories.
Conclusions: All sources assessed exhibit opportunities for improvement. However, the IUSM curriculum presented more thorough information regarding celiac disease. Although the commercial resources included within this study are used by students to prepare for standardized exams, they may be more concerned with improving test scores than providing students with the information needed to become effective physicians. Students may gain more complete information regarding celiac disease from the IUSM curriculum
Implicit Racial Bias and Unintentional Harm in Vascular Care
No full textImportance: Implicit bias may influence physician treatment decisions and contribute to Black-White health disparities. There are limited data linking implicit bias with actual care delivery and outcomes.
Objective: To determine whether implicit racial bias is associated with potentially harmful surgical treatment selection for a cohort of patients with peripheral artery disease-related claudication.
Design, setting, and participants: This survey study, linked with observational registry data, included eligible clinicians who participate in the Vascular Quality Initiative (VQI) among 960 centers. The VQI includes academic medical centers, teaching hospitals, community hospitals, and private practices. Eligible participants included all vascular specialist VQI members (N = 2512), of whom 218 completed the race implicit association test (IAT) and were linkable to procedure-level data. The study was conducted between October 2021 and October 2022.
Exposure: Race IAT.
Main outcomes and measures: Clinician-level implicit bias results were linked to patient-level registry data of peripheral revascularization procedures performed for claudication. The adjusted odds of performance of any infrapopliteal procedure by specialist implicit bias and patient race were measured via mixed-effects logistic regression models. Implicit bias as a moderator of the association of infrapopliteal procedures for claudication and patient race with 1-year amputation was assessed as a secondary outcome.
Results: Among 218 vascular specialists (mean [SD] age, 46 [9] years; 160 [73%] male), 157 (72%) had a pro-White bias. Black patients treated by a physician with pro-White bias had a significant increase in the odds of receiving an infrapopliteal procedure compared with the total sample (adjusted odds ratio [AOR], 1.67; 95% CI, 1.12-2.48). When treated by a specialist with pro-White bias, Black patients had increased odds of 1-year amputation, regardless of anatomic location treated, compared with White patients (AOR, 2.34; 95% CI, 1.20-4.55). Conversely, Black patients treated by a specialist with no bias had similar odds of an infrapopliteal procedure (AOR, 0.93; 95% CI, 0.68-1.26) as the full patient sample and similar odds of 1-year amputation (AOR, 1.29; 95% CI, 0.33-4.99) as White patients.
Conclusions and relevance: These findings indicate that implicit bias is associated with potentially harmful infrapopliteal procedures for Black patients and contributes to Black-White outcome disparities in the US. These results suggest the need for system-level interventions that transparently identify and warn of procedures not aligned with best practices to reduce the negative influence of implicit bias
Enhanced insights into the genetic architecture of 3D cranial vault shape using pleiotropy-informed GWAS
No full textLarge-scale GWAS studies have uncovered hundreds of genomic loci linked to facial and brain shape variation, but only tens associated with cranial vault shape, a largely overlooked aspect of the craniofacial complex. Surrounding the neocortex, the cranial vault plays a central role during craniofacial development and understanding its genetics are pivotal for understanding craniofacial conditions. Experimental biology and prior genetic studies have generated a wealth of knowledge that presents opportunities to aid further genetic discovery efforts. Here, we use the conditional FDR method to leverage GWAS data of facial shape, brain shape, and bone mineral density to enhance SNP discovery for cranial vault shape. This approach identified 120 independent genomic loci at 1% FDR, nearly tripling the number discovered through unconditioned analysis and implicating crucial craniofacial transcription factors and signaling pathways. These results significantly advance our genetic understanding of cranial vault shape and craniofacial development more broadly
Emotional Labor in Archives: Learn and Share
No full textArchivists often delve deeply into records, so how do archivists cope when they spend their time working with collections that hold painful, emotionally heavy or traumatic memories? For those archivists who strive to put into practice the ideas of radical empathy, how do they carry on with this emotional labor every day? Topics covered include the theories of ethics of care, radical empathy, and trauma-informed practices in archives, as well as ideas for support for archivists. This presentation is intended to ignite discussion for attendees during the presentation and going forward in their work
Frontal Memory‐related Brainwaves Differentially Correlate with AD and Astrocyte Plasma Biomarkers
No full textBackground:
We currently lack in the dementia field accurate, noninvasive, quick, and affordable screening tools for brain dysfunctions associated with early subtle risk of mild cognitive impairment (MCI). Our Kentucky aging cohort demonstrates that asymptomatic older individuals with MCI‐like frontal memory‐related brainwave patterns convert to MCI within a short 5‐year period, as opposed to individuals with NC‐like patterns (1) that remain normal 10 years later (2). Astrocyte reactivity influences amyloid‐β effects on tau pathology in preclinical Alzheimer’s disease (3). Leveraging blood‐based AD and astrocyte biomarkers and the cognitive electroencephalogram (EEG) signatures (4), we test the hypothesis that predictive frontal memory‐related EEG changes correlate with preclinical and early AD plasma biomarkers.
Method:
34 (19 women) older volunteers with or without MCI, average age 79 (SD 8.53) years old, from a longitudinal cohort followed by University of Kentucky ADRC participated. Each participant’s EEG was recorded (64‐ or 14‐channels) during a working memory (modified delayed match‐to‐sample) task. Principal component analysis (PCA) was performed on 64‐channel EEG data to create PC scores (PC1 & PC2). For multiple linear regression of EEG PC scores on multiple neurodegenerative plasma biomarkers including Aβ42/40, pTau181, total Tau, and GFAP (Astrocyte reactivity), we adjusted age, sex, education, and gap years between collection dates.
Result:
The 61% of variance in frontal signals can be explained by PC1 in normal cognition (NC) and MCI individuals, and PC2 counts for 35% of variance (Figure 1). The decreased brainwaves (MCI‐like) seen in left frontal sites significantly correlate with increased pTau181, GFAP, and PC2 (Figure 2). Curiously, right frontal EEG relations with pTau181, GFAP showed the opposite trend. Bilateral frontal signals showed negative correlations with Aβ42/40 and positive correlations with total Tau.
Conclusion:
Our results indicate that GFAP & pTau181 trend in similar asymmetry ways with frontal cognitive brainwaves, but Aβ42/40 & total Tau correlate to a different component of frontal EEG. That is, distinct cognitive brainwaves correlate with astrocyte reactivity differentially that influence pathologies of beta‐amyloid accumulations and Tau development. Cognitive pathophysiological signatures and AD–Astrocyte plasma biomarkers have great potential for predicting subtle cognitive decline and specific dementia risk in healthy normal individuals
Optimization of SHIP1 Inhibitors for the treatment of Alzheimer’s disease
No full textBackground:
SHIP1 is a phosphatidyl inositol phosphatase encoded by INPP5D, which has been identified as a risk gene for Alzheimer’s disease (AD). SHIP1 is expressed in microglia, the resident macrophage in brain. It is a complex, multidomain protein that acts as a negative regulator downstream from TREM2. SHIP1 possesses a phosphatase (Ptase) domain flanked by a pleckstrin‐homology (PH) domain that binds phosphatidylinositol (3,4,5)‐trisphosphate[PI(3,4,5)P3] and a C2 domain that binds phosphatidylinositol (3,4)‐bisphosphate [PI(3,4)P2]. The Ptase domain converts PI(3,4,5)P3 to PI(3,4)P2. SHIP1 also has an SH2 domain that binds to ITIMs and ITAMs where it competes with kinases. Inhibiting SHIP1 is hypothesized to have potential therapeutic benefits, as it may improve TREM2‐mediated microglial responses to neurotoxins and promote an overall neuroprotective microglial phenotype to maintain a more resilient brain and slow the rate of cognitive decline in AD patients.
Method:
The IUSM Purdue TREAT‐AD Center recently evaluated SHIP1 inhibitors and proposed 3‐((2,4‐Dichlorobenzyl)oxy)‐5‐(1‐(piperidin‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine for target validation studies. Structurally related analogs were synthesized and tested for SHIP1 enzyme inhibition, AKT signaling, and microglia activation in a high‐content imaging assay using HMC3 and BV2 microglia‐like cell lines. Primary microglia were treated with an optimized SHIP1 inhibitor, and subsequent changes in fibril Aβ uptake and cell viability were assessed. The NanoString nCounter Neuroinflammation assay was used to measure transcriptomic profiles. For comparison primary microglial derived from both wild‐type and Inpp5d‐haploinsufficient mice were assessed.
Result:
Novel SHIP1 inhibitors have been discovered and preliminary Structure Activity Relationship (SAR) studies have been completed. These compounds have shown positive results for biochemical activity, target engagement and cellular pharmacology. Both Inpp5d deficiency and pharmacological inhibition increase amyloid uptake and cell viability in primary microglia. Elevated ERK and AKT phosphorylation, after amyloid exposure, were decreased by Inpp5d deficiency. Functional pathways associated with phagocytosis, apoptosis, cytokine production, and complement system activity were altered.
Conclusion:
These data demonstrate that SHIP1 inhibition promotes amyloid uptake through the complement system. SHIP1 inhibition also enhances cell survival and homeostasis in primary microglia. Further studies of SHIP1 inhibition and INPP5D knockdown in animal models may provide a potential therapeutic strategy for Alzheimer’s disease