ScholarWorks IU Indianapolis
Not a member yet
51146 research outputs found
Sort by
Deep learning diagnosis plus kinematic severity assessments of neurodivergent disorders
No full textEarly diagnostic assessments of neurodivergent disorders (NDD), remains a major clinical challenge. We address this problem by pursuing the hypothesis that there is important cognitive information about NDD conditions contained in the way individuals move, when viewed at millisecond time scales. We approach the NDD assessment problem in two complementary ways. First, we applied supervised deep learning (DL) techniques to identify participants with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), comorbid ASD + ADHD, and neurotypical (NT) development. We measured linear and angular kinematic variables, using high-definition kinematic Bluetooth sensors, while participants performed the reaching protocol to targets appearing on a touch screen monitor. The DL technique was carried out only on the raw kinematic data. The area under the receiver operator characteristics curve suggests that we can predict, with high accuracy, NDD participant's conditions. Second, we filtered the high frequency electronic sensor noise in the recorded kinematic data leaving the participants' physiological characteristic random fluctuations. We quantified these fluctuations by their biometric Fano Factor and Shannon Entropy from a histogram distribution built from the magnitude difference between consecutive extrema unique to each participant, suggesting a relationship to the severity of their condition. The DL may be used as complementary tools for early evaluation of new participants by providers and the new biometrics allow for quantitative subtyping of NDDs according to severity
Medicine quality assessment in Nepal using semi randomised sampling and evaluation of a small scale dissolution test and portable Raman spectrometers
Get PDFSubstandard and falsified medicines threaten global health and require reliable data and screening technologies to combat their spread. This study examined the quality of 241 samples containing azithromycin, cefixime, esomeprazole and losartan collected from licenced private vendors in the Saptari (121 samples; convenience sampling) and Kathmandu (120 samples; randomised sampling) districts of Nepal. Nearly 10% (24 samples; 95% CI 6.5-14.5) of samples failed pharmacopoeial quality analysis and were classified as 'substandard' or 'probably substandard'. No falsified medicines were identified. Small-scale dissolution acceptance criteria were applied to all 20 three-unit combinations of 213 samples tested in the first stage of the United States Pharmacopoeia dissolution test. Approximately 1% of these results were false positives when compared with the final United States Pharmacopoeia dissolution test results, suggesting the test's usefulness in encouraging dissolution testing in resource-limited contexts. In the narrow sense of presence/absence, two portable Raman spectrometers reliably detected azithromycin, cefixime and losartan in most samples based on effective methods for detecting falsified medicines; however, none of the substandard samples were identified. The findings suggest that falsified medicines are less prevalent in Nepal and the surrounding region than suggested by regional concerns about Nepal and global concerns about low- and middle-income countries. Nevertheless, the Nepalese government should continue to ensure the quality of all distributed medicines
Impact of Neurodevelopmental Disorder-Associated Clinical Variants on the Catalytic Activity of KMT5B
Get PDFIUIKMT5B is a lysine methyltransferase that is known for its role in catalyzing H4K20 dimethylation. This post-translational modification is involved in DNA repair and heterochromatin formation. Missense variants found in KMT5B cause a related neurodevelopmental disorder in which patients experience neurodevelopmental phenotypes like developmental delay (DD), intellectual deficits (ID), autism spectrum disorder (ASD), seizures, and motor deficits. However, the impact of these variants on enzyme activity is unknown. In this work, we provide qualitative and quantitative evidence showing the differential impacts of four select clinical missense variants of KMT5B on its lysine methylation activity. Recombinant KMT5B was purified and used for in vitro KMT assays to assess enzyme activity on nucleosome and peptide substrates. While three of the four variants tested showed significant decreases in catalytic activity, one variant had a non-significant decrease. This differential KMT5B catalytic activity raises questions about the relationship between levels of catalytic activity and neurodevelopmental phenotypes. The methods established in this work lay the groundwork for testing additional clinically associated KMT5B variants. Understanding the impacts of these variants on catalytic activity is an important first step in determining their underlying mechanisms that contribute to neurodevelopmental dysfunction
In vitro effect of fluoride-free mouthwashes on Streptococcus mutans biofilm
No full textObjective: To evaluate the efficacy of commercially available, fluoride-free mouthwashes sold in Indianapolis, IN, on Streptococcus mutans biofilm.
Materials and methods: Eighty-one different mouthwashes were purchased. A 16-h culture of S. mutans UA159 was treated with the mouthwashes in three dilutions (1:3, 1:6, and 1:12), prepared in Tryptic Soy broth supplemented with 1% sucrose. The minimum inhibitory concentrations (MIC), planktonic, and biofilm growth were evaluated using a spectrophotometer. In addition, the growth for minimum bactericidal concentration (MBC) was evaluated using five μL of the dilution and incubated on blood agar. For the analysis of the results, the mouthwashes were separated into six groups according to their active ingredients (cetylpyridinium chloride/CPC, n = 25; essential oils/EO n = 10; whitening/W (hydrogen peroxide/ sodium hexametaphosphate), n = 12; Natural-Derived Actives / NDA, n = 15; zinc chloride/ZC, n = 3; others/O, n = 16). ANOVA followed by the Tukey test was performed (p < 0.05).
Results: Regarding MIC, planktonic, and biofilm growth of S. mutans, there was a significant decrease for the W and CPC groups (p CPC > EO > NDA/ZC/O).
Conclusion: The mouthwashes demonstrated significant effect on S. mutans biofilm, especially in the 1:3 dilution. W and CPC groups had a more significant effect on S. mutans biofilm.
Clinical relevance: S. mutans is an important bacterium in dental caries and periodontal diseases. Our study showed that non-fluoridated mouthwashes affect the initial stages of biofilm formation
Comparison of mass spectrometry and fourier transform infrared spectroscopy of plasma samples in identification of patients with fracture-related infections
No full textObjectives: Fracture-related infections (FRIs) have significant impact on patient outcomes. Diagnosing FRIs is challenging due to lack of robust, minimally invasive diagnostic tests in the early stages of the disease. The objective of this study was to evaluate the ability of proteomic mass spectrometry (MS) (quantitative approach) and spectral pattern analysis based on fourier transform infrared (FTIR) spectroscopy of plasma samples (qualitative approach) in discriminating between FRI and controls.
Materials and methods: A prospective case-control study at a level 1 trauma center was conducted. Patients meeting confirmatory FRI criteria were matched with controls without infection based on age, time after surgery, and fracture region. Plasma samples were collected at the time of presentation for FRI and saved for batch analysis. Tandem mass tag liquid chromatography-mass spectrometry was used for proteomics, and FTIR spectroscopy of dried films was used to obtain mid-infrared spectra from samples. Mid-infrared spectra were preprocessed, and for MS data, protein abundance ratios of FRI and controls were compared. Multivariate analysis-based predictive models were developed separately for FTIR-based spectra and MS-based protein ratio data.
Results: Thirteen FRI and 13 controls were included in the study. The predictive models based on FTIR spectroscopy data had an average area under the receiver operating characteristic (AUROC) of ≈0.803, CI95(0.8, 0.81), the average sensitivity was ≈ 0. 0.755, CI95(0.75, 0.76), and the specificity was ≈ 0.677, CI95(0.672, 0.682). The MS-based predictive models from protein abundance ratio results had an average AUROC of ≈0.735, CI95(0.732, 0.737), the average sensitivity was ≈ 0.74, CI95 (0.739, 0.747), and the specificity was ≈ 0.653, CI95(0.649, 0.656).
Discussion and conclusions: Mass spectrometry and spectral pattern recognition based on FTIR spectroscopy can both be used to develop predictive models that can discriminate between FRI and control samples. There is potential for both analytical approaches as candidate diagnostic biomarkers in FRI patients that require further validation in future studies
Interpersonal violence moderates sustained-transient threat co-activation in the vmPFC and amygdala in a community sample of youth
No full textThe increased risk for psychopathology associated with interpersonal violence exposure (IPV, e.g., physical abuse, sexual assault) is partially mediated by neurobiological alterations in threat-related processes. Evidence supports parsing neural circuitry related to transient and sustained threat, as they appear to be separable processes with distinct neurobiological underpinnings. Although childhood is a sensitive period for neurodevelopment, most prior work has been conducted in adult samples. Further, it is unknown how IPV exposure may impact transient-sustained threat neural interactions. The current study tested the moderating role of IPV exposure on sustained vmPFC-transient amygdala co-activation during an fMRI task during which threat and neutral cues were predictably or unpredictably presented. Analyses were conducted in a sample of 212 community-recruited youth (M/SDage = 11.77/2.44 years old; 51.9% male; 56.1% White/Caucasian). IPV-exposed youth evidenced a positive sustained vmPFC-transient amygdala co-activation, while youth with no IPV exposure did not show this association. Consistent with theoretical models, effects were specific to unpredictable, negative trials and to exposure to IPV (i.e., unrelated to non-IPV traumatic experiences). Although preliminary, these findings provide novel insight into how childhood IPV exposure may alter neural circuity involved in specific facets of threat processing
Cardiopulmonary Exercise Testing in Patients with Chronic Kidney Disease
No full textBackground: Cardiopulmonary exercise testing (CPET) is an emerging tool in nephrology that has garnered significant interest among clinicians and investigators.
Summary: CPET technology enables the user to accurately assess cardiovascular functional capacity using an integrative approach, to identify multi-organ reserve capacities and interrogate pathophysiological mechanisms underpinning impaired exercise tolerance in patients with chronic kidney disease (CKD). These capabilities provide rationale for accumulating studies exploring the use of this existing technology for new applications in nephrology and to solve current clinical practice barriers. Examples of current clinical interest areas include its potential to help transform diagnostic approaches to cardiovascular complications in patients with CKD, to offer superior cardiovascular risk stratification and to provide a solution to current limitations of traditional resting endpoints in cardiorenal clinical trials.
Key messages: This article reviews the foundational principles, methodologic, and operational implementation of CPET in patients with CKD and those on dialysis