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 29315

Thalamic GABA Predicts Fine Motor Performance in Manganese-Exposed Smelter Workers
(Public Library of Science, 2014-02-04) Long, Zaiyang; Li, Xiang-Rong; Xu, Jun; Edden, Richard A. E.; Qin, Wei-Ping; Long, Li-Ling; Murdoch, James B.; Zheng, Wei; Jiang, Yue-Ming; Dydak, Ulrike; Radiology and Imaging Sciences, School of Medicine
Overexposure to manganese (Mn) may lead to parkinsonian symptoms including motor deficits. The main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is known to play a pivotal role in the regulation and performance of movement. Therefore this study was aimed at testing the hypothesis that an alteration of GABA following Mn exposure may be associated with fine motor performance in occupationally exposed workers and may underlie the mechanism of Mn-induced motor deficits. A cohort of nine Mn-exposed male smelter workers from an Mn-iron alloy factory and 23 gender- and age-matched controls were recruited and underwent neurological exams, magnetic resonance spectroscopy (MRS) measurements, and Purdue pegboard motor testing. Short-echo-time MRS was used to measure N-Acetyl-aspartate (NAA) and myo-inositol (mI). GABA was detected with a MEGA-PRESS J-editing MRS sequence. The mean thalamic GABA level was significantly increased in smelter workers compared to controls (p = 0.009). Multiple linear regression analysis reveals (1) a significant association between the increase in GABA level and the duration of exposure (R(2) = 0.660, p = 0.039), and (2) significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R(2) = 0.902, p = 0.001) in the smelter workers. In addition, levels of mI were reduced significantly in the thalamus and PCC of smelter workers compared to controls (p = 0.030 and p = 0.009, respectively). In conclusion, our results show clear associations between thalamic GABA levels and fine motor performance. Thus in Mn-exposed subjects, increased thalamic GABA levels may serve as a biomarker for subtle deficits in motor control and may become valuable for early diagnosis of Mn poisoning.
Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents
(American Scientific, 2013) Guidoboni, Giovanna; Harris, Alon; Arciero, Julia C.; Siesky, Brent A.; Amireskandari, Annahita; Gerber, Austin L.; Huck, Andrew H.; Kim, Nathaniel J.; Cassani, Simone; Carichino, Lucia; Mathematical Sciences, School of Science
Open angle glaucoma (OAG) is a severe ocular disease characterized by progressive and irreversible vision loss. While elevated intraocular pressure (IOP) is a well-established risk factor for OAG, the progression of OAG in many cases, despite IOP treatment, suggests that other risk factors must play significant roles in the development of the disease. For example, various structural properties of the eye, ocular blood flow properties, and systemic conditions have been identified as risk factors for OAG. Ethnicity has also been indicated as a relevant factor that affects the incidence and prevalence of OAG; in fact, OAG is the leading cause of blindness among people of African descent. Numerous clinical studies have been designed to examine the possible correlation and causation between OAG and these factors; however, these studies are met with the challenge of isolating the individual role of multiple interconnected factors. Over the last decade, various mathematical modeling approaches have been implemented in combination with clinical studies in order to provide a mechanical and hemodynamical description of the eye in relation to the entire human body and to assess the contribution of single risk factors to the development of OAG. This review provides a summary of the clinical evidence of ocular structural differences, ocular vascular differences and systemic vascular differences among people of African and European descent, describes the mathematical approaches that have been proposed to study ocular mechanics and hemodynamics while discussing how they could be used to investigate the relevance to OAG of racial disparities, and outlines possible new directions of research.
Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome
(Wiley, 2024) Derry, Paul J.; Liopo, Anton V.; Mouli, Karthik; McHugh, Emily A.; Vo, Anh T. T.; McKelvey, Ann; Suv, Larry J.; Wu, Gang; Gao, Yan; Olson, Kenneth R.; Tour, James M.; Kent, Thomas A.; Cellular and Integrative Physiology, School of Medicine
Hydrogen sulfide (H2 S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2 S is elevated and associated with degraded mitochondrial function. Therefore, removing H2 S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2 S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2 S) to polysulfides (HS2+n - ) and thiosulfate (S2 O3 2- ) by poly(ethylene glycol) hydrophilic carbon clusters (PEG-HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG-OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2 S to polysulfides and S2 O3 2- in a dose-dependent manner. The reaction is dependent on O2 and the presence of quinone groups on the OCNs. In DS donor lymphocytes we found that OCNs increased polysulfide production, proliferation, and afforded protection against additional toxic levels of H2 S compared to untreated DS lymphocytes. Finally, in Dp16 and Ts65DN murine models of DS, we found that OCNs restored osteoclast differentiation. This new action suggests potential facile translation into the clinic for conditions involving excess H2 S exemplified by DS.
Connection to mental health care upon community reentry for detained youth: a qualitative study
(Springer Nature, 2014-02-05) Aalsma, Matthew C.; Brown, James R.; Holloway, Evan D.; Ott, Mary A.; Pediatrics, School of Medicine
Background: Although detained youth evidence increased rates of mental illness, relatively few adolescents utilize mental health care upon release from detention. Thus, the goal of this study is to understand the process of mental health care engagement upon community reentry for mentally-ill detained youth. Methods: Qualitative interviews were conducted with 19 youth and caregiver dyads (39 participants) recruited from four Midwest counties affiliated with a state-wide mental health screening project. Previously detained youth (ages 11-17), who had elevated scores on a validated mental health screening measure, and a caregiver were interviewed 30 days post release. A critical realist perspective was used to identify themes on the detention and reentry experiences that impacted youth mental health care acquisition. Results: Youth perceived detention as a crisis event and having detention-based mental health care increased their motivation to seek mental health care at reentry. Caregivers described receiving very little information regarding their child during detention and felt "out of the loop," which resulted in mental health care utilization difficulty. Upon community reentry, long wait periods between detention release and initial contact with court or probation officers were associated with decreased motivation for youth to seek care. However, systemic coordination between the family, court and mental health system facilitated mental health care connection. Conclusions: Utilizing mental health care services can be a daunting process, particularly for youth upon community reentry from detention. The current study illustrates that individual, family-specific and systemic issues interact to facilitate or impair mental health care utilization. As such, in order to aid youth in accessing mental health care at detention release, systemic coordination efforts are necessary. The systematic coordination among caregivers, youth, and individuals within the justice system are needed to reduce barriers given that utilization of mental health care is a complex process.
Seasonal variation in children with developmental dysplasia of the hip
(Sage, 2014) Loder, Randall T.; Shafer, Cody; Orthopaedic Surgery, School of Medicine
Background: It has been postulated that developmental dysplasia of the hip (DDH) is more frequent in infants born in the winter months. It was the purpose of this study to ascertain if there was any seasonal variation in DDH at the author's institution and compare/contrast our results with those in the literature using rigorous mathematical fitting. Methods: All children with DDH treated at the author's institution from 1993 to 2012 were identified. The month of birth was recorded and temporal variation was analyzed using cosinor analysis. Similar data from the literature was analyzed. Results: There were 424 children (363 girls, 61 boys). An additional 22,936 children were added from the literature for a total of 23,360. Pearson's Chi-square test demonstrated a non-uniform distribution in the month of birth for both our 424 children as well as the combined literature series in both the Northern and Southern hemispheres. Cosinor analysis of the 424 children demonstrated double peaks in mid-March and mid-October. For the entire 23,360 children, no seasonal variation was observed in 2,205 (9.4 %), a single winter peak in 16,425 (70.3 %), a single summer peak in 1,280 (5.5 %), and double peaks in the spring and autumn in 3,450 (14.8 %). Conclusions: This study partly supports the hypothesis of tight clothing/cold temperature as one factor in the etiology of DDH with the tighter clothing/swaddling increasing the risk of DDH. However ~20 % of the DDH births demonstrated a non-winter peak. The single summer and double spring/autumn peaks, as well as in those series where no seasonal variation was noted, refutes the cold winter clothing hypothesis. Perhaps these different patterns in seasonal variation represent the heterogeneity of the genetic factors in DDH interacting with external factors (temperature and clothing) and internal factors (metabolic). Further study will be required to understand these different patterns in DDH seasonal variation.
IVUS Validation of Patient Coronary Artery Lumen Area Obtained from CT Images
(Public Library of Science, 2014-01-29) Luo, Tong; Wischgoll, Thomas; Koo, Bon Kwon; Huo, Yunlong; Kassab, Ghassan S.; Surgery, School of Medicine
Aims: Accurate computed tomography (CT)-based reconstruction of coronary morphometry (diameters, length, bifurcation angles) is important for construction of patient-specific models to aid diagnosis and therapy. The objective of this study is to validate the accuracy of patient coronary artery lumen area obtained from CT images based on intravascular ultrasound (IVUS). Methods and results: Morphometric data of 5 patient CT scans with 11 arteries from IVUS were reconstructed including the lumen cross sectional area (CSA), diameter and length. The volumetric data from CT images were analyzed at sub-pixel accuracy to obtain accurate vessel center lines and CSA. A new center line extraction approach was used where an initial estimated skeleton in discrete value was obtained using a traditional thinning algorithm. The CSA was determined directly without any circular shape assumptions to provide accurate reconstruction of stenosis. The root-mean-square error (RMSE) for CSA and diameter were 16.2% and 9.5% respectively. Conclusions: The image segmentation and CSA extraction algorithm for reconstruction of coronary arteries proved to be accurate for determination of vessel lumen area. This approach provides fundamental morphometric data for patient-specific models to diagnose and treat coronary artery disease.
Correlation of BAG-3 and Heat Shock Protein 70 with CD30 expression in T-cell Lymphomas
(Springer Nature, 2014-02-04) Jiang, L.; Zhao, Z.; Menke, D. M.; Rizzo, K. A.; Pathology and Laboratory Medicine, School of Medicine
T-cell lymphomas are aggressive lymphomas with decreased prognosis and resistance to therapy. BAG-3 and heat shock protein 70 (HSP70) function in chemotherapeutic resistance and cellular survival. Expression of BAG-3 has not been investigated in T cell lymphomas. We investigated fifty cases including benign, systemic and cutaneous T cell lymphomas. Benign T cells were negative for BAG-3 and HSP70 immunohistochemical staining. BAG-3 expression correlated with increased HSP70 expression in a subset of systemic T cell lymphoma cases co-expressing the CD30 antigen. Correlation between BAG-3, HSP70 and CD30 expression was not seen in cutaneous T cell lymphoma cases. However, these cases showed a significant increase in BAG-3 staining when compared to CD30 negative systemic T cell lymphoma cases. The differential protein expression profile of BAG-3 and HSP70 may indicate a specific role for these proteins and the ubiquitin-proteasome system/autophagy in T cell lymphomas which may help guide future targeted therapy.
Optimizing the Timing of Transplant Education: The Critical Role of Dialysis Care Professionals
(Wolters Kluwer, 2024) McDonnell, Jenny L.; Urbanski, Megan A.; Drewry, Kelsey M.; Pastan, Stephen O.; Lea, Janice P.; Jacob Arriola, Kimberly; Escoffery, Cam; Patzer, Rachel E.; Wilk, Adam S.; Surgery, School of Medicine
Utilizing Multiple in Silico Analyses to Identify Putative Causal SCN5A Variants in Brugada Syndrome
(Springer Nature, 2014-01-27) Juang, Jyh-Ming Jimmy; Lu, Tzu-Pin; Lai, Liang-Chuan; Hsueh, Chia-Hsiang; Liu, Yen-Bin; Tsai, Chia-Ti; Lin, Lian-Yu; Yu, Chih-Chieh; Hwang, Juey-Jen; Chiang, Fu-Tien; Yeh, Sherri Shih-Fan; Chen, Wen-Pin; Chuang, Eric Y.; Lai, Ling-Ping; Lin, Jiunn-Lee; Medicine, School of Medicine
Brugada syndrome (BrS) is an inheritable sudden cardiac death disease mainly caused by SCN5A mutations. Traditional approaches can be costly and time-consuming if all candidate variants need to be validated through in vitro studies. Therefore, we developed a new approach by combining multiple in silico analyses to predict functional and structural changes of candidate SCN5A variants in BrS before conducting in vitro studies. Five SCN5A non-synonymous variants (1651G>A, 1776C>G, 1673A>G, 3269C>T and 3578G>A) were identified in 14 BrS patients using direct DNA sequencing. Several bioinformatics algorithms were applied and predicted that 1651G>A (A551T) and 1776C>G (N592K) were high-risk SCN5A variants (odds ratio 59.59 and 23.93). The results were validated by Mass spectrometry and in vitro electrophysiological assays. We concluded that integrating sequence-based information and secondary protein structures elements may help select highly potential variants in BrS before conducting time-consuming electrophysiological studies and two novel SCN5A mutations were validated.
Overcoming recruitment barriers revealed high readiness to participate and low dropout rate among people with schizophrenia in a randomized controlled trial testing the effect of a Guided Self-Determination intervention
(Springer Nature, 2014-02-03) Jørgensen, Rikke; Munk-Jørgensen, Povl; Lysaker, Paul H.; Buck, Kelly D.; Hansson, Lars; Zoffmann, Vibeke; Psychiatry, School of Medicine
Background: Recruitment is one of the most serious challenges in performing randomized controlled trials. Often clinical trials with participants diagnosed with schizophrenia are terminated prematurely because of recruitment challenges resulting in a considerable waste of resources in the form of time, funding, and the participants' efforts. Dropout rates in schizophrenia trials are also high.Recruitment challenges are often due to patients not wanting to participate in research but can also be due to clinicians' concerns regarding individuals diagnosed with schizophrenia as participants in research. This paper reports how overcoming recruitment challenges not related to patients revealed high readiness to take part and low dropout rates in a one year long randomized controlled trial testing Guided Self-Determination (GSD) among outpatients with schizophrenia receiving treatment in Assertive Outreach Teams in the northern part of Denmark. Methods: GSD is a shared decision-making and mutual problem-solving method using reflection sheets, which was developed in diabetes care and adjusted for this study and utilized by patients with schizophrenia. Descriptive data on strategies to overcome recruitment challenges were derived from notes and observations made during the randomized controlled trial testing of GSD in six outpatient teams. Results: Three types of recruitment challenges not related to patients were identified and met during the trial: 1) organizational challenges, 2) challenges with finding eligible participants and 3) challenges with having professionals invite patients to participate. These challenges were overcome through: 1) extension of time, 2) expansion of the clinical recruitment area and 3) encouragement of professionals to invite patients to the study. Through overcoming these challenges, we identified a remarkably high patient-readiness to take part (101 of 120 asked accepted) and a low dropout rate (8%). Conclusion: Distinction between recruitment challenges was important in discovering the readiness among patients with schizophrenia to take part in and complete a trial with the GSD-intervention.

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