Open Access Policy Articles

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The IUPUI Faculty Council adopted an open access policy on October 7th, 2014 (available from: https://openaccess.indianapolis.iu.edu/). This policy shows IUPUI's commitment to disseminating the fruits of research and scholarship as widely as possible. Open access policies increase authors’ rights, readership and citation rates for scholarly articles. The opt out provision ensures that all faculty authors have the freedom to publish in the journal of their choice.

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Now showing 1 - 10 of 24863

Successful Sequential Liver and Isolated Intestine Transplantation for Mitochondrial Neurogastrointestinal Encephalopathy Syndrome: A Case Report
(International Scientific Information, 2024-02-27) Kubal, Chandrashekhar A.; Mihaylov, Plamen; Snook, Riley; Soma, Daiki; Saeed, Omer; Rokop, Zachary; Lacerda, Marco; Graham, Brett H.; Mangus, Richard S.; Surgery, School of Medicine
Background: Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is an autosomal recessive disease caused by thymidine phosphorylase deficiency leading to progressive gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Although liver transplantation corrects thymidine phosphorylase deficiency, intestinal deficiency of the enzyme persists. Retrospective chart review was carried out to obtain clinical, biochemical, and pathological details. Case Report: We present a case of liver and subsequent intestine transplant in a 28-year-old man with MNGIE syndrome with gastrointestinal dysmotility, inability to walk, leukoencephalopathy, ptosis, cachexia, and elevated serum thymidine. To halt progression of neurologic deficit, he first received a left-lobe partial liver transplantation. Although his motor deficit improved, gastrointestinal dysmotility persisted, requiring total parenteral nutrition. After exhaustive intestinal rehabilitation, he was listed for intestine transplantation. Two-and-half years after liver transplantation, he received an intestine transplant. At 4 years after LT and 20 months after the intestine transplant, he remains off parenteral nutrition and is slowly gaining weight. Conclusions: This is the first reported case of mitochondrial neurogastrointestinal encephalomyopathy to undergo successful sequential liver and intestine transplantation.
Spatial transcriptomic patterns underlying amyloid-β and tau pathology are associated with cognitive dysfunction in Alzheimer’s disease
(Elsevier, 2024) Yu, Meichen; Risacher, Shannon L.; Nho, Kwangsik T.; Wen, Qiuting; Oblak, Adrian L.; Unverzagt, Frederick W.; Apostolova, Liana G.; Farlow, Martin R.; Brosch, Jared R.; Clark, David G.; Wang, Sophia; Deardorff, Rachael; Wu, Yu-Chien; Gao, Sujuan; Sporns, Olaf; Saykin, Andrew J.; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Radiology and Imaging Sciences, School of Medicine
Amyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts. We identify AD susceptibility genes and gene modules in a gene co-expression network with expression profiles specifically related to regional vulnerability to Aβ and tau pathologies in AD. In addition, we identify distinct biochemical pathways associated with the gene-to-Aβ and the gene-to-tau associations. These findings may explain the discordance between regional Aβ and tau pathologies. Finally, we propose an analytic framework, linking the identified gene-to-pathology associations to cognitive dysfunction in AD at the individual level, suggesting potential clinical implication of the gene-to-pathology associations.
Expanding Access to Comprehensive Geriatric Evaluation via Telehealth: Development of Hybrid-Virtual Home Visits
(Springer, 2024) Schubert, Cathy C.; Penney, Lauren S.; Schwartzkopf, Ashley L.; Damush, Teresa M.; Preddie, Alaina; Flemming, Soyna; Myers, Jennifer; Myers, Laura J.; Perkins, Anthony J.; Zhang, Ying; Bravata, Dawn M.; Medicine, School of Medicine
Background: In response to the aging population, the Department of Veterans Affairs (VA) seeks to expand access to evidence-based practices which support community-dwelling older persons such as the Geriatric Resources for Assessment and Care of Elders (GRACE) program. GRACE is a multidisciplinary care model which provides home-based geriatric evaluation and management for older Veterans residing within a 20-mile drive radius from the hospital. We sought to expand the geographic reach of VA-GRACE by developing a hybrid-virtual home visit (TeleGRACE). Objectives: The objectives were to: (1) describe challenges encountered and solutions implemented during the iterative, pre-implementation program development process; and (2) illustrate potential successes of the program with two case examples. Design: Quality improvement project with longitudinal qualitative data collection. Program description: The hybrid-virtual home visit involved a telehealth technician travelling to patients' homes and connecting virtually to VA-GRACE team members who participated remotely. Approach & participants: We collected multiple data streams throughout program development: TeleGRACE staff periodic reflections, fieldnotes, and team meeting notes; and VA-GRACE team member interviews. Key results: The five program domains that required attention and problem-solving were: telehealth connectivity and equipment, virtual physical examination, protocols and procedures, staff training, and team integration. For each domain, we describe several challenges and solutions. An example from the virtual physical examination domain: several iterations were required to identify the combination of telehealth stethoscope with dedicated headphones that allowed remote nurse practitioners to hear heart and lung sounds. The two cases illustrate how this hybrid-virtual home visit model provided care for patients who would not otherwise have received timely healthcare services. Conclusions: These results provide a blueprint to translate an in-person home-based geriatrics program into a hybrid-virtual model and support the feasibility of using hybrid-virtual home visits to expand access to comprehensive geriatric evaluation and ongoing care for high-risk, community-dwelling older persons who reside geographically distant from the primary VA facility.
Influence of Choline Chloride/Urea and Glycerol Plasticizers on the Mechanical Properties of Thermoplastic Starch Plastics
(MDPI, 2024-03-09) Staker, Jacob; Schott, Sydney; Singh, Riya; Collier, Kourtney; Druschel, Gregory; Siegel, Amanda P.; Tovar, Andres; Chemistry and Chemical Biology, School of Science
Bio-based plastics made of food-safe compostable materials, such as thermoplastic starch (TPS), can be designed into films that have potential to replace many non-biodegradable single-use plastic (SUP) items. TPS film characteristics, such as elongation at break and tensile strength, are largely affected by the choice of the plasticizers used in formulation. Our work identifies the mechanical properties and the chemical structural differences between TPS films made with two different plasticizer mixtures that have not yet been compared alongside one another: deep eutectic solvent choline chloride/urea (1:2) (CC:U) and glycerol with an acetic acid catalyst (AA:G). Potato-based TPS samples were formed by mixing each plasticizer with a consistent amount of potato starch and distilled water with heat. After gelation formation, the viscous TPS mixture was centrifuged to degas and extruded. Films were dried at controlled room temperature. Characterization included the tensile testing of coupons according to ASTM (American Society of Testing and Materials) standard D638, attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), melting point (MP), and scanning electron microscopy (SEM). The AA:G films displayed significantly higher tensile strength (M = 2.04 ± 1.24 MPa) than the CC:U films (M = 0.18 ± 0.08 MPa); however, the CC:U films had higher elongation at break (M = 47.2 ± 3.6%) than the AA:G films (M = 31.1 ± 12.6%). This can be explained by the difference in functional groups, composition, and the degree of crystallinity evidenced by the FTIR, XRD, MP, and SEM results. Our findings suggest that potato-based TPS films with an AA:G plasticizer mixture hold promise for SUP applications that require more strength, while CC:U films may be more suited for wraps and bags that require flexibility. These innovations can aid to mitigate the environmental impact of harmful plastic waste.
Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice
(Elsevier, 2023) Bertolini, Thais B.; Herzog, Roland W.; Kumar, Sandeep; Sherman, Alexandra; Rana, Jyoti; Kaczmarek, Radoslaw; Yamada, Kentaro; Arisa, Sreevani; Lillicrap, David; Terhorst, Cox; Daniell, Henry; Biswas, Moanaro; Pediatrics, School of Medicine
Active tolerance to ingested dietary antigens forms the basis for oral immunotherapy to food allergens or autoimmune self-antigens. Alternatively, oral administration of anti-CD3 monoclonal antibody can be effective in modulating systemic immune responses without T cell depletion. Here we assessed the efficacy of full length and the F(ab')2 fragment of oral anti-CD3 to prevent anti-drug antibody (ADA) formation to clotting factor VIII (FVIII) protein replacement therapy in hemophilia A mice. A short course of low dose oral anti-CD3 F(ab')2 reduced the production of neutralizing ADAs, and suppression was significantly enhanced when oral anti-CD3 was timed concurrently with FVIII administration. Tolerance was accompanied by the early induction of FoxP3+LAP-, FoxP3+LAP+, and FoxP3-LAP+ populations of CD4+ T cells in the spleen and mesenteric lymph nodes. FoxP3+LAP+ Tregs expressing CD69, CTLA-4, and PD1 persisted in spleens of treated mice, but did not produce IL-10. Finally, we attempted to combine the anti-CD3 approach with oral intake of FVIII antigen (using our previously established method of using lettuce plant cells transgenic for FVIII antigen fused to cholera toxin B (CTB) subunit, which suppresses ADAs in part through induction of IL-10 producing FoxP3-LAP+ Treg). However, combining these two approaches failed to improve suppression of ADAs. We conclude that oral anti-CD3 treatment is a promising approach to prevention of ADA formation in systemic protein replacement therapy, albeit via mechanisms distinct from and not synergistic with oral intake of bioencapsulated antigen.
An Investigation of Employment Hope as a Key Factor Influencing Perceptions of Subjective Recovery among Adults with Serious Mental Illness Seeking Community Work
(MDPI, 2024-03-19) Kukla, Marina; McGuire, Alan B.; Weber, Kenneth C.; Hatfield, Jessi; Henry, Nancy; Kulesza, Eric; Rollins, Angela L.; Psychology, School of Science
Introduction: Employment is an important contributor to recovery in people with serious mental illness (SMI), yet studies have not explored how subjective elements of employment hope contribute to perceptions of global recovery in this population. Methods: The current study examined the relationship between employment hope and subjective recovery in 276 unemployed adults with SMI participating in a multi-site clinical trial of a cognitive behavioral group intervention tailored toward work and combined with vocational rehabilitation. Participants had diagnoses of schizophrenia spectrum, bipolar, depressive, and posttraumatic stress disorders, and were receiving services at three Veterans Affairs healthcare facilities in the United States. Data were collected at study baseline. Linear regression analysis examined the relationship between employment hope (Short Employment Hope Scale; EHS-14) and subjective recovery (Recovery Assessment Scale; RAS) after controlling for psychiatric symptom severity and mental-health-related burden on daily life. Results: After accounting for covariates, employment hope significantly contributed to the regression model explaining subjective recovery. The overall model of predictor variables explained 52.5% of the variance in recovery. The results further explore the relationships between EHS-14 and RAS subscales. Conclusions: The findings suggest that employment hope is a key intervention target to bolster subjective recovery in this vulnerable population.
Exploring the Demographic and Professional Characteristics of Physicians and Nurse Practitioners Associated With Providing Medication-Assisted Treatment: A Retrospective Observational Study
(Sage, 2024) Maxey, Hannah L.; Vaughn, Sierra X.; Dickinson, Analise; Newhouse, Robin; Medicine, School of Medicine
Integration of medication-assisted treatment (MAT) for opioid use disorder in primary care settings is an emerging health care delivery model that supports increased access to specialized care but requires primary care provider engagement. Examining the characteristics of providers who provide this service is key to informing targeted recruitment. Using administrative and supplemental data collected during license renewal, this study aimed to identify the characteristics of primary care physicians and nurse practitioners (NPs) associated with greater odds of providing MAT in their practice. A retrospective observational study was conducted using a descriptive correlational design. The analysis included 5259 physicians and 3486 NPs who renewed their licenses electronically in 2021 and specialized in primary care or psychiatry. Chi-square and logistic regression analyses were conducted to identify the demographic and clinical characteristics of physicians and NPs associated with MAT participation in their practice. Physicians had a higher odds ratio (OR) of providing MAT if they were younger than 35 years (OR = 1.334; P = .0443), practiced in a federally qualified health center (OR = 3.101, P < .0001), and offered a sliding fee scale in their practice (OR = 2.046; P < .0001). Likewise, NPs had higher odds of providing MAT if they practiced in a public or community health center (OR = 3.866; P < .0001). The results of this study highlight the personal and professional characteristics of physicians and NPs associated with higher odds of providing MAT. These findings may have implications for the recruitment and sustainability of MAT integration in primary care.
Metabolic blood flow regulation in a hybrid model of the human retinal microcirculation
(Elsevier, 2023) Albright, Amanda; Fry, Brendan C.; Verticchio, Alice; Siesky, Brent; Harris, Alon; Arciero, Julia; Mathematical Sciences, School of Science
The retinal vascular network supplies perfusion to vital visual structures, including retinal ganglion cells responsible for vision. Impairments in retinal blood flow and oxygenation are involved in the progression of many ocular diseases, including glaucoma. In this study, an established theoretical hybrid model of a retinal microvascular network is extended to include the effects of local blood flow regulation on oxygenation. A heterogeneous representation of the arterioles based on confocal microscopy images is combined with a compartmental description of the downstream capillaries and venules. A Green’s function method is used to simulate oxygen transport in the arterioles, and a Krogh cylinder model is applied to the capillary and venular compartments. Acute blood flow regulation is simulated in response to changes in pressure, shear stress, and metabolism. Model results predict that both increased intraocular pressure and impairment of blood flow regulation can cause decreased tissue oxygenation, indicating that both mechanisms represent factors that could lead to impaired oxygenation characteristic of ocular disease. Results also indicate that the metabolic response mechanism reduces the fraction of poorly oxygenated tissue but that the pressure- and shear stress-dependent response mechanisms may hinder the vascular response to changes in oxygenation. Importantly, the heterogeneity of the vascular network demonstrates that traditionally reported average values of tissue oxygen levels hide significant localized defects in tissue oxygenation that may be involved in disease processes, including glaucoma. Ultimately, the model framework presented in this study will facilitate future comparisons to sectorial-specific clinical data to better assess the role of impaired blood flow regulation in ocular disease.
Microglial Phagocytosis/Cell Health High-Content Assay
(Wiley, 2023) Mason, Emily R.; Soni, Disha M.; Chu, Shaoyou; Medicine, School of Medicine
We report a microglial phagocytosis/cell health high-content assay that has been used to test small molecule chemical probes and support our drug discovery projects targeting microglia for Alzheimer's disease therapy. The assay measures phagocytosis and cell health (cell count and nuclear intensity) simultaneously in 384-well plates processed with an automatic liquid handler. The mix-and-read live cell imaging assay is highly reproducible with capacity to meet drug discovery research needs. Assay procedures take 4 days including plating cells, treating cells, adding pHrodo-myelin/membrane debris to cells for phagocytosis, staining cell nuclei before performing high-content imaging, and analysis. Three selected parameters are measured from cells: 1) mean total fluorescence intensity per cell of pHrodo-myelin/membrane debris in phagocytosis vesicles to quantify phagocytosis; 2) cell counts per well (measuring compound effects on proliferation and cell death); and 3) average nuclear intensity (measuring compound induced apoptosis). The assay has been used on HMC3 cells (an immortalized human microglial cell line), BV2 cells (an immortalized mouse microglial cell line), and primary microglia isolated from mouse brains. Simultaneous measurements of phagocytosis and cell health allow for the distinction of compound effects on regulation of phagocytosis from cellular stress/toxicity related changes, a distinguishing feature of the assay. The combination of cell counts and nuclear intensity as indicators of cell health is also an effective way to measure cell stress and compound cytotoxicity, which may have broad applications as simultaneous profiling measurements for other phenotypic assays.
Correlates of Gait Speed Among Older Adults From 6 Countries: Findings From the COSMIC Collaboration
(Oxford University Press, 2023) Sprague, Briana N.; Zhu, Xiaonan; Rosso, Andrea L.; Verghese, Joe; Delbaere, Kim; Lipnicki, Darren M.; Sachdev, Perminder S.; Ng, Tze Pin; Gwee, Xinyi; Yap, Keng Bee; Kim, Ki-Woong; Han, Ji Won; Oh, Dae Jong; Narazaki, Kenji; Chen, Tao; Chen, Sanmei; Brodaty, Henry; Numbers, Katya; Kochan, Nicole A.; Walker, Richard W.; Paddick, Stella-Maria; Gureje, Oye; Ojagbemi, Akin; Bello, Toyin; Rosano, Caterina; COSMIC Consortium; Medicine, School of Medicine
Background: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries. Methods: We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified. Results: Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women. Conclusions: This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia.

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