Wright State University
  • Dayton, United States
Recent publications
Patients with periodic paralysis have attacks of weakness precipitated by depolarization of muscle. Each form of periodic paralysis is associated with unique changes in serum K⁺ during attacks of weakness. In hypokalemic periodic paralysis (hypoKPP), the mutation-induced gating pore current causes weakness associated with low serum K⁺. In hyperkalemic periodic paralysis (hyperKPP), mutations increase a non-inactivating Na⁺ current (Na persistent or NaP), which causes weakness associated with elevation of extracellular K⁺. In Andersen–Tawil syndrome, mutations causing loss of Kir channel function cause weakness associated with either low or high K⁺. We developed a computer model to address two questions: (1) What mechanisms are responsible for the distinct K⁺ dependencies of muscle depolarization-induced weakness in the three forms of periodic paralysis? (2) Why does extracellular K⁺ become elevated during attacks of weakness in hyperKPP, reduced in hypoKPP, and both elevated and reduced in Andersen–Tawil syndrome? We experimentally tested the model assumptions about resting potential in normal K⁺ solution in hyperKPP and hypoKPP. Recreating the distinct K⁺ dependence of all three forms of periodic paralysis required including the K⁺ and voltage dependence of current through Kir channels, the extracellular K⁺ and intracellular Na⁺ dependence of the Na/K ATPase activity, and the distinct voltage dependencies of the gating pore current and NaP. A key factor determining whether muscle would depolarize was the direction of small net K⁺ and net Na⁺ fluxes, which altered ion concentrations over hours. Our findings may aid in development of novel therapy for diseases with dysregulation of muscle excitability.
Background and Purpose: Intracranial aneurysms (IAs) with daughter sacs (DSs) have an increased risk for rupture yet the hemodynamic factors contributing to DS pathophysiology are still under-investigated. This study aimed to investigate hemodynamic factors in DS generation and rupture using anatomic and ablated IA models under various DS scenarios. Methods: 113 computational models of 43 patients with at least one IA containing a DS were built based on 3D rotational angiographical images using benchmarked model reconstruction procedures. Of these 43 patients, there were 19 ruptured (RIAs) and 26 unruptured IAs (UIAs). Ablated models representing the aneurysm before the DS formation were rebuilt by virtually ablating the blebs from the anatomic models. In-vitro validated computational fluid dynamics simulations were conducted for both anatomic IA and ablated IA models under physiologically pulsatile flow conditions. Wall shear stress (WSS) associated parameters were used to analyze the hemodynamic factor on the DS pathophysiology statistically. Results and Discussion: There was a statistically significant difference seen between RIAs and UIAs in hemodynamic performances at the entire aneurysmal sac region (P<0.01). Specifically, there was a significant difference in maximum instantaneous WSS (MIWSS), maximum instantaneous WSS gradient (MIWSSG), maximum time-averaged WSS (MTAWSS), and maximum time-averaged WSS (MTAWSSG) observed between RIAs and UIAs arising from the internal carotid artery, anterior cerebral artery, and middle cerebral artery. The difference in maximum oscillatory shear index (OSI) between RIAs and UIAs was not consistent at these aneurysmal locations. In addition, on the local DS bleb region, the hemodynamic comparisons between UIAs and RIAs were not consistent with the comparisons on the entire aneurysmal sac region. Future studies include the introduction of new parameters (i.e., instantaneous/time-averaged surface-averaged WSS, WSSG, and OSI) to investigate specific hemodynamic factors associated with DS and IA rupture. Hemodynamics between anatomic and ablated IA models will also be compared to determine its contributions on DS bleb inception. In conclusion, these findings are significant as they do suggest possible factors contributing to IA rupture. Continued research in this area will help develop a diagnostic tool to analyze IA rupture risk better than current available methods.
Chronic subdural hematoma (cSDH) represents a relatively treatment-resistant pathologic process with a large impact on quality-adjusted life years. This risk is increased in the elderly, and the prevalence is expected to rise as the population ages. Expectant management and classical surgical treatment are associated with increased recurrence rate as well as complications. Middle meningeal artery (MMA) embolization is being utilized more frequently as adjunctive and primary treatment. It has demonstrated beneficial effects on recurrence and progression of cSDH. Here, we present the outcomes of this technique with different embolic agents in our patient population. IRB approval was obtained for this study. Retrospectively, all patients at a single institution who underwent endovascular MMA embolization with or without open surgical intervention for cSDH were included. Vulnerable populations were excluded. Demographic and medical data were collected at initial, 1-month, and 3-month time points if available and analyzed for differences with unpaired T-test, paired-T test, and chi-square test. Between 2020 and 2024, a total of 50 patients were treated with MMA embolization for cSDH. Mean age was 73 years. Majority were male. Most were on antithrombotic therapy. Of these, 34 had history of prior SDH, and 38 had history of head trauma. Of the 50 patients, 29 patients underwent combined open surgery and MMA embolization, while 21 underwent MMA embolization alone. The cSDH was bilateral in 23 patients and unilateral in 27 (13 right, 14 left) for a total of 73 cSDHs. Surgical evacuation was performed in 44 cSDHs. Liquid embolic agent (Onyx) was utilized for 32 patients, while particulate embolic agents (250-500 um) were utilized for 18 patients. Of the patients who had follow-up CTs at 1 month, there were 21 cSDHs treated with particles and 39 with Onyx. There was no significant difference in the proportions of patients undergoing surgery in addition to MMA embolization between the groups treated with Onyx and those treated with particle embolization. Additionally, there was no significant difference in the proportions of treated hemispheres with ≥ 50% reduction or ≥ 75% reduction between those treated with Onyx and those treated with particles. At our institution, there was no difference in reduction of cSDH with Onyx as compared to particle embolization. MMA embolization was associated with no recurrence or progression of cSDH at 3 months.
The neuromuscular junction (NMJ) is the linchpin of nerve-evoked muscle contraction. Broadly, the function of the NMJ is to transduce nerve action potentials into muscle fiber action potentials (MFAPs). Efficient neuromuscular transmission requires both cholinergic signaling, responsible for generation of endplate potentials (EPPs), and excitation, the amplification of the EPP by postsynaptic voltage-gated sodium channels (Nav1.4) to generate the MFAP. In contrast to the cholinergic component, the signaling pathways that organize Nav1.4 and mediate muscle fiber excitability are poorly characterized. Muscle-specific kinase (MuSK), in addition to its Ig1 domain-dependent role as the main organizer of acetylcholine receptors AChRs), also binds BMPs via its Ig3 domain and shapes BMP-induced signaling and transcriptional output. Here, using mice lacking the MuSK Ig3 domain (‘ΔIg3-MuSK’), we probed the role of this domain at the NMJ. NMJs formed in ΔIg3-MuSK animals with pre- and post- synaptic specializations aligned at all ages examined. However, the ΔIg3-MuSK postsynaptic apparatus was fragmented from the first weeks of life. Synaptic electrophysiology showed that spontaneous and nerve-evoked acetylcholine release, AChR density, and endplate currents were comparable at WT and ΔIg3-MuSK NMJs. However, single fiber electromyography revealed that nerve-evoked MFAPs in ΔIg3-MuSK muscle were abnormal as evidenced by jitter and blocking. Further, nerve-evoked compound muscle action potentials and muscle force production were also diminished. Finally, Nav1.4 levels were reduced at ΔIg3-MuSK NMJs, but not at the sarcolemma broadly, indicating that the observed excitability defects result from impaired synaptic localization of this ion channel. We propose that MuSK plays distinct, domain-specific roles at the NMJ: the Ig1 domain mediates agrin-LRP4 mediated AChR localization, while the Ig3 domain maintains postsynaptic Nav1.4 density, conferring the muscle excitability required to amplify cholinergic signals and trigger action potentials. Significance Statement The neuromuscular junction (NMJ) is required for nerve-evoked muscle contraction and movement, and its function is compromised during aging and disease. Though the mechanisms underlying neurotransmitter release and cholinergic response at this synapse have been studied extensively, the machinery necessary for nerve-evoked muscle excitation are incompletely characterized. We show that the Ig3 domain of MuSK (muscle-specific kinase) regulates NMJ structure and the localization of voltage-gated sodium channels necessary for nerve-evoked muscle fiber excitation and force production. This function of MuSK is structurally and mechanistically distinct from its role in organizing cholinergic machinery. The Ig3 domain of MuSK thus emerges as a target for selectively modulating excitability, which is defective in conditions such as congenital myasthenic syndromes and age-related muscle weakness.
Over 60 million patients in the USA have limited English proficiency (LEP) and experience barriers in care. Still, there exists no standardized method of monitoring the utilization of language interpreting services (LIS). To introduce a methodological approach to systematically monitor utilization of LIS for LEP patients. We utilized a One-To-Many Match algorithm to align inpatient visits of LEP patients from the electronic health record (EHR) with corresponding calls from LIS billing logs, using a unique patient identifier (MRN) and LIS call dates within patient’s admit and discharge dates. Due to error when MRNs are recorded by LIS, the FuzzyWuzzy Probabilistic String-Matching technique was utilized to enhance match accuracy where exact matches were unattainable, addressing inherent complexities in language data matching. The study involved 5823 inpatient encounters with a non-English preference in an urban hospital system in 2020, representing a linguistically diverse patient base, and attempted to match these against 183,655 LIS call logs. Our approach successfully matched 83.1% (4389 out of 5823) of inpatient encounters to an LIS call. We observed significant language-specific disparities in LIS usage, with Spanish leading in call volume at 2737 calls (exact matches) and 845 (probabilistic matches). Concordance rates varied, exceeding 94% for all languages in exact matches and ranging from 53.9% for Arabic to 71.6% for Russian in probabilistic matches. The average frequency of LIS calls was about one call per day per language group in the inpatient setting. The study provides vital insights into language service preferences, frequency, and duration. These findings emphasize the need for standard methods in monitoring LIS usage to enhance patient outcomes for LEP patients.
This study compared maximum a posteriori (MAP), expected a posteriori (EAP), and Markov Chain Monte Carlo (MCMC) approaches to computing person scores from the Multi-Unidimensional Pairwise Preference Model. The MCMC approach used the No-U-Turn sampling (NUTS). Results suggested the EAP with fully crossed quadrature and the NUTS outperformed the others when there were fewer dimensions. In addition, the NUTS produced the most accurate estimates in larger dimension conditions. The number of items per dimension had the largest effect on person parameter recovery.
Objective To examine the impact of a new image enhancement technique on the distribution of NT measurements. Methods In this retrospective study, nuchal translucency (NT) images that were taken with the GE Voluson E22 ultrasound machine between May and September 2024 were collected. One operator took manual and automated NT measurements in an NT image without radiant enhancement mode followed by automated measurements in NT images with minimum, medium and maximum radiant mode. The automated measurement in the NT images without radiant mode were considered gold standard. The relative bias of the gold standard, the manual measurement and the automated measurements with the radiant enhancement technology were compared using median and 25–75th interquartile range as well as by the Wilcoxon test. Results The database search yielded 352 NT images from 101 pregnant women. Average maternal age of the study population was 34.0 years and average crown-rump length was 68.3. The median NT thickness was 1.7 mm for both the manual and automated measurements done without the use of radiant mode. The median automated measurement with minimum, medium and maximum radiant mode was 2.00, 2.05 and 2.10 mm, respectively. All automated measurements were significantly higher than the gold standard. Discussion The use of the radiant mode results in an increase in the NT thickness. This effect should be taken into account when calculating the risk for chromosomal abnormalities.
Background: Colon cancer in younger populations has risen in recent years, prompting changes in screening guidelines. Hemicolectomy remains integral for standard treatment for non-metastatic early-onset colon cancer, and many institutions have adopted robot-assisted approaches for this procedure. However, high costs associated with this technology along with mixed data regarding survival benefits and post-surgical complications warrant further investigations on the specific advantages of robot-assisted surgery. This study aims to examine the impact of unplanned readmission to the same facility within 30 days following surgery for patients receiving robot-assisted and laparoscopic hemicolectomy on long-term survival for early-onset non-metastatic colon cancer to see how current paradigms of colon cancer treatment extend to early-onset patients. Methods: The National Cancer Database was used to identify patients under the age of 50 receiving a minimally invasive hemicolectomy for primary non-metastatic colon cancer diagnosed between 2016-2020. Patients were stratified based on surgical approach and whether they underwent an unplanned readmission to the same facility within 30 days following surgery, and survival differences were calculated log-rank test and Cox regression analysis that included co-variates related to tumor characteristics, patient demographics, and facility characteristics. Results: 5,076 patients were identified, with 577 receiving a robot-assisted approach and 4,499 receiving a laparoscopic approach. Multivariate analysis found no significant difference in long-term survival between patients receiving a laparoscopic versus robot-assisted approach (HR: 0.893, 95% CI: 0.687-1.161, p=0.398). Additionally, multivariate analysis found that unplanned readmission within 30 days did not have a significant impact on long-term survival outcomes for patients receiving a robot-assisted approach (HR: 0.856, 95% CI: 0.257-2.848, p=0.800), but it did find worsened survival outcomes for the laparoscopic approach (HR: 1.535, 95% CI: 1.070-2.203, p=0.020). Conclusions: Patients receiving laparoscopic hemicolectomy for early-onset non-metastatic colon cancer appear to have worsened overall long-term survival outcomes when undergoing an unplanned readmission to the same facility within 30 days of surgery when compared to patients receiving a robot-assisted surgical approach. However, it also appears that overall, both surgical approaches have similar overall long-term survival. Further research on how robot-assisted surgery impacts survival and post-surgical complications in patients with early-onset non-metastatic colon cancer is warranted to examine how this advancing technology could improve cancer care.
Introduction We propose and assess the biomechanical stability of medial column screw supplementation in a synthetic distal femur fracture model. Materials and methods Twenty-four low density synthetic femora modeling osteoporotic, intraarticular distal femur fractures with medial metaphyseal comminution were split into two fixation groups: (1) lateral locking distal femur plate (PA– plate alone) and (2) lateral locking distal femur plate with a 6.5 mm fully threaded medial cannulated screw (PWS– plate with screw). Cyclic biomechanical testing included 5 steps of 10,000 cycles with each step increasing axial loads starting at 0.5xBW (BW = 80 kg) up to 2.5xBW. Discrete stiffness was calculated for each step and cumulative stiffness was calculated across the entire protocol. Outcomes of interest included cumulative stiffness, discrete stiffness, and instrumentation failure. Results Seven of the PA models had failure during testing. No failures were seen in the PWS group. PWS had 19.8% higher cumulative stiffness compared to PA (676.3 N/mm vs 809.8 N/mm; P = 0.014). Discrete stiffness showed < 1% differences at lower loads, but increasing loads found the PWS group with 12% greater discrete stiffness than the PA group (879.1 N/mm vs 983.8 N/mm; P = 0.028). Conclusion This is the first study to evaluate the contribution of a medial column screw in a distal femur fracture model. PWS had superior stiffness and few failures compared to PA. Applied clinically, a medial column screw can increase construct stability in the setting of complex distal femur fractures with minimal increase in operative time, patient morbidity and cost.
Zika virus (ZIKV) causes a variety of peripheral and central nervous system complications leading to neurological symptoms such as limb weakness. We used a mouse model to identify candidate genes potentially involved in causation or recovery from ZIKV-induced acute flaccid paralysis. Using Zikv and Chat chromogenic and fluorescence in situ RNA hybridization, electron microscopy, immunohistochemistry, and ZIKV RT-qPCR, we determined that some paralyzed mice had infected motor neurons, but motor neurons are not reduced in number and the infection was not present in all paralyzed mice; hence infection of motor neurons were not strongly correlated with paralysis. Consequently, paralysis was probably caused by by-stander effects. To address this, we performed bioinformatics analysis on spinal cord RNA to identify 2058 differentially expressed genes (DEGs) that were altered during paralysis and then normalized after paralysis. Of these “biphasic” DEGs, 951 were up-regulated and 1107 were down-regulated during paralysis, followed by recovery. To refine the search for candidate DEGs we used gene ontology analysis and RT-qPCR to select 3 DEGs that could be involved with the node of Ranvier function and 5 DEGs that could be involved with synaptic function. Among these, SparcL1:Sparc DEG ratios were identified to be inversely correlated with ZIKV-induced paralysis, which is consistent with the known function of SPARC protein to antagonize the synaptogenesis of SPARCL1. Ank3, Sptbn1, and Epb41l3 affecting the structures at and near the nodes of Ranvier were significantly downregulated during ZIKV-induced paralysis. The primary contribution is the identification of 8 candidate genes that may be involved in the causation or recovery of ZIKV-induced paralysis.
Oncocytoma is a rare benign neoplasm of the glandular tissue, most commonly found in the caruncle of the eye. These lesions have an excellent prognosis and have not been reported to recur after resection from the caruncle. Given the wide range of differentials and potential for malignancy, excision and histopathological examination are recommended to establish the diagnosis and guide proper treatment.
The economy‐wide economic surplus, defined as output beyond what is needed to sustain the labouring workforce, is one of the oldest ideas in Western political economy. Marx permanently changed economic thinking by characterising it as exploitation. As confidence in government management of economic affairs grew in the twentieth century, how to spend the surplus better than free individuals would spend it themselves became a growing theme among economists and among the broader public. While the role of the surplus in economic theory today is modest, its vibrancy in the public conversation remains.
OBJECTIVE Youth behavioral health inpatient beds are limited during a time of crisis. Around one-third of youth admitted to a behavioral health unit (BHU) will be readmitted within 1 year of discharge, with 8% to 13% being admitted within 30 days. In one study, they found that more than one-third of patients initially admitted for suicidal ideation or attempt were readmitted within 7 days. Our objective was to decrease 7-day and 30-day readmission rates to our BHU by 20% by May of 2023. METHODS We collected baseline data through medical record review for our pediatric BHU readmissions from July 2020 until July 2021. Interventions, such as standardized workflows and checklists, were trialed with Plan-Do-Study-Act (PDSA) cycles beginning October 2021 until November 2022. Performance was analyzed using statistical process control charts (U-charts). Sustainment was tracked through December 2023. Length of stay (LOS) was tracked as a balancing measure. Compliance with our readmission checklist was tracked as a process measure. RESULTS Both 7-day and 30-day readmission rates to the pediatric BHU decreased as interventions were initiated and adopted. The rates of patients readmitted within 7 and 30 days decreased from a baseline mean of 5.54 to 2.83 (49%) and 11.52 to 7.38 (36%) per 100 hospitalizations, respectively. The LOS for the BHU decreased from 5.58 to 5.09 days. The readmission checklist was used for 81 out of 83 patients, or 97.5%. CONCLUSION Adoption of multiple interventions produced a decrease in readmissions to a pediatric BHU.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.
4,201 members
Jason Deibel
  • Department of Physics
Jyothirmayee Aravind
  • Department of Chemistry
Rebecca L. Glaser
  • Department of Surgery
Gary Burns
  • Department of Psychology
Courtney E W Sulentic
  • Department of Pharmacology and Toxicology
Information
Address
Dayton, United States