37495 research outputs found
Sort by
Unravelling the Erythropoietin Heterodimeric Complex: \u3cem\u3eIn Silico\u3c/em\u3e Analysis of Complex Assembly and Binding Interface
Get PDFErythropoietin (Epo), a glycosylated protein categorized as a member of the cytokine family, is responsible for the modulation of erythrogenesis. Besides this, the nonhaematopoietic effects of Epo are associated with tissue-protective activity via an antiapoptotic pathway. This function of Epo is linked with its heterodimeric form, i.e. EpoR/βcR belonging to the cytokine family as well. Both receptors are dissected into three domains: extracellular (also known as ligand-binding domain), transmembrane and cytoplasmic domain. The transmembrane and cytoplasmic domains are assumed to play a paramount role in dimerization and tissue protection. However, the tertiary structure of cytoplasmic domains of both EpoR and βcR was not reported in the literature. Inspired by the potential therapeutic applications, we aimed to investigate the interaction pattern of EpoR/βcR using in silico tools. Cytoplasmic domains of EpoR and βcR were modelled, structural refinement was carried out through Rosetta, and these were then quality verified by well-known quality matrices. The observed results were found to be structurally consistent with the amenable geometry showing stereochemical sustainability. The modelled cytoplasmic domains were then successfully merged with the remaining domains (extracellular and transmembrane domains) of the respective receptors through MOEv2019.01 and Modeller. The complete structures of EpoR and βcR were subjected to geometry optimization and energy minimization via dynamic studies. The refined structures were subjected to protein–protein docking to yield the heterocomplex. Here, we report on the optimized structure coordinates of EpoR/βcR, the plausible electrostatic interactions involving G191, V206, T214, S241, T244, E336, R337, M342, G348, T349, E362 and K373 of EpoR and D336, S337, Y338, K333, R391, M426, H494, Q495, S717, S722, Y750 and G758 of βcR. Subsequently, we performed screening utilizing the StraPep database to identify Epo mimetic agents with the potential to enhance their tissue-protective effects. Following the virtual screening, four hits (4HQX, 4XO8, 1TPO and 3EZM) were obtained based on the binding affinity and protein–ligand interaction fingerprinting (PLIF). The stability exhibited by the four selected peptides in the binding site of the EpoR/βcR heterocomplex became visible during visual inspection. We propose that the presented model can be harnessed for future characterization studies
Mitigating the Risk of QTc Prolongation When Using Haloperidol for Acute Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents and Young Adults
Get PDFBackground/Objectives: Cannabinoid Hyperemesis Syndrome (CHS), associated with long-term cannabinoid use, has been increasingly observed in emergency room visits as more states in the U.S. have legislatively permitted medical and recreational marijuana use. The acute management of CHS primarily focuses on antiemetic treatment and supportive care. However, both the condition itself and the antiemetic drugs, such as haloperidol, may cause QTc prolongation. Methods: We reported two adolescent cases admitted to the emergency department for acute antiemesis management of CHS who received haloperidol treatment. A literature review was performed through October 2024 for previously published cases of QTc prolongation and/or Torsades de Pointes (TdP) in adolescents and young adults. Results: A 15-year-old female presented with hypokalemia and hypomagnesemia upon admission. She complained of chest pain and tachycardia, and the electrocardiogram (EKG) showed prolonged QTc (528 msec). The haloperidol infusion was discontinued. She recovered well post-discharge without complaints. A 17-year-old female had a borderline prolonged QT interval (476 msec). Her nausea and vomiting improved with a three-dose course of intravenous fosaprepitant before discharge. Our literature search identified five severe cases with life-threatening episodes of QTc prolongation and/or TdP in adolescents and young adults. Conclusions: Patients with CHS are at higher risk of QTc prolongation due to cannabis use, electrolyte imbalance, and antiemetic medications. We recommend vigilant EKG monitoring, particularly before initiating and throughout haloperidol treatment. If the patient presents with an increased risk of QTc prolongation, consider using topical capsaicin, lorazepam, aprepitant/fosaprepitant, and olanzapine as alternatives
Examining the Diagnostic Accuracy of a Novel Performance-based Test for Alzheimer\u27s Disease Screening
Get PDFAffordable, rapid methods for identifying mild Alzheimer’s disease (AD) are needed. A simple, brief performance-based test involving the learning of functional upper-extremity movements has been developed and is associated with AD pathology and functional decline. However, its specificity to AD relative to other neurodegenerative diseases that present with motor impairment is unknown. This study examined whether this novel test could distinguish between 34 participants diagnosed with mild AD (Clinical Dementia Rating Scale = 0.5-1) from 23 participants with mild-to-moderate Parkinson’s disease (PD) (Hoehn & Yahr = 2-3) using Receiver Operating Characteristic analysis of secondary data from two separate clinical trials. Indicators of diagnostic accuracy demonstrated that the test identified participants with AD, who had worse scores than those with PD, suggesting it may be a viable screening tool for mild AD. Exploratory analyses with a control group (n=52) further showed that test scores were not sensitive to motor dysfunction
Evidence and Sources of Placebo Effects in Transcranial Direct Current Stimulation During Visuospatial Working Memory Training
Get PDFTranscranial direct current stimulation (tDCS) can be used to non-invasively augment cognitive training. However, the benefits of tDCS may be due in part to placebo effects, which have not been well-characterized. The purpose of this study was to determine whether tDCS can have a measurable placebo effect on cognitive training and to identify potential sources of this effect. Eighty-three right-handed adults were randomly assigned to one of three groups: control (no exposure to tDCS), sham tDCS, or active tDCS. The sham and active tDCS groups were double-blinded. Each group performed 20 min of an adapted Corsi Block Tapping Task (CBTT), a visuospatial working memory task. Anodal or sham tDCS was applied during CBTT training in a right parietal-left supraorbital montage. After training, active and sham tDCS groups were surveyed on expectations about tDCS efficacy. Linear mixed effects models showed that the tDCS groups (active and sham combined) improved more on the CBTT with training than the control group, suggesting a placebo effect of tDCS. Participants’ tDCS expectations were significantly related to the placebo effect, as was the belief of receiving active stimulation. This placebo effect shows that the benefits of tDCS on cognitive training can occur even in absence of active stimulation. Future tDCS studies should consider how treatment expectations may be a source of the placebo effect in tDCS research, and identify ways to potentially leverage them to maximize treatment benefit
Discordance Between Balance Ability and Perception is Associated with Falls in Parkinson’s Disease: A Coordinated Analysis
Get PDFBackground: The congruence or discordance between actual and perceived balance ability has been proposed to be linked to functional outcomes such as falls. However, gaps remain in our ability to quantify discordance, and its relationship to relevant outcomes.
Objective: To investigate a novel quantification of concordance/discordance between balance performance and perception and determine the relationship to falls among people with Parkinson’s disease (PwPD).
Methods: Data from 244 PwPD were aggregated from 5 previously conducted studies. Variables extracted included age, sex, Activities-Specific Balance Confidence scale (ABC; perceived balance), Timed Up and Go (TUG; balance performance), Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III scores, and retrospective falls (6- or 12-month). Data validation between studies was established. Discordance was quantified as the difference between an individual’s predicted ABC, based upon their TUG score, to their reported ABC.
Results: Two methods for calculating discordance were tested: simple linear regression and segmented regression. As there were no differences between the bootstrap distributions of both approaches (P = .520), simple linear regression was utilized for the subsequent logistic regression model. Discordance was the only statistically significant predictor of fall status (OR = 0.98, P = .003), after controlling for age, MDS-UPDRS part III, sex, and TUG. The inclusion of discordance in the logistic regression model boosted the predictive accuracy by 58%.
Conclusions: Discordance between actual and perceived balance was uniquely related to retrospective fall history among PwPD. Clinicians and researchers should consider discordance between actual and perceived balance as a potentially modifiable target to minimize falls
What Self-determination Theory Can Do for Post-pandemic College Students
No full textThink back to your first days of college. How did you feel?
For most first-year and first-generation college students, starting university is a time of great excitement and anticipation. It’s a chance to make friends, explore ideas and diverse perspectives, and perhaps live away from home. This excitement, however, is often accompanied by stressors that challenge students’ psychosocial development
Predictive Residual Neural Networks for Optical Trapping of Small Particles
Get PDFOptical tweezers provide a non-contact method to trap, move, and manipulate micro- and nano-sized objects. Using properly designed dielectric and plasmonic nanostructure configurations, optical tweezers have been tailored to create stable and precise trapping for nanoscale objects. Recent advances in numerical optimization techniques allow further enhancement in nanoscale optical traps through inverse optimization of such configurations. One of the main challenges in such optimization approaches is the time-consuming nature of full-wave simulation of nanostructures and postprocessing steps to extract optical forces. To address this challenge, we introduce a surrogate solver based on residual neural networks that can accurately predict the forces exerted on a nanoparticle. Our results illustrate the possibility of capturing the highly nonlinear dynamics of local optical forces using moderate-sized datasets, particularly appealing to the inverse design of optical tweezers
A Trans-Theoretical Systematization of Clinical Interventions Based on Dynamical Systems Research (DSR)
Get PDFThe scientific literature focused on the categorization of therapists’ interventions in clinical sessions, and their effects on patients, is not very extensive and often autoreferential. The most relevant findings clearly show the eclecticism of clinicians, grounding only 10–14% of their interventions on the specific theoretical approach to which they belong. Despite that, a trans-theoretical systematization of clinical interventions is lacking. The present work aims to verify the feasibility of a trans-theoretical categorization of clinical interventions based on Dynamical Systems Research in psychotherapy (DSR). For this purpose, the authors present the results of three literature reviews. The first sections of this paper present the literature on the historical development of clinical interventions within the psychodynamic and cognitive-behavioral approaches. In the fourth section, the review of the DSR literature in psychotherapy and the systematization of clinical interventions according to such a unifying framework are introduced. Clinical interventions can be aimed at increasing the patient’s stability and flexibility, with the final objective of promoting H-L Synchronization and S-F Oscillations. The connections between the DSR-based categorization and the literature pertaining to the psychodynamic and cognitive-behavioral approaches are highlighted. Finally, in the conclusions, the limitations and potential developments of this scientific area are discussed
The Peace Project: Creating Elementary School Peace Spaces and Places
Get PDFIntroduction: This pilot case study paper demonstrates how school programming can be aligned and enhanced to better create a climate of peace on an elementary school campus by utilizing an integral peace leadership lens. Working collectively as a Peace Leadership Advisory Group, the elementary school leadership team, and the university research team helped to align existing programming and explore and implement new programming to create a comprehensive plan for bringing peace ideas together at the elementary school level.
Methods: This pilot was a single case study that utilized Participatory Action Research. Data were collected through observation, survey, and interviews with school leadership and analyzed using thematic analysis, descriptive statistics, and grounded theory methods, respectively.
Results: The pilot study revealed that the efforts to build peace on campus were successful overall, with students and staff having a positive experience with peace programming throughout the academic year.
Discussion: The findings indicate that aligning existing programming as a way to frame a culture of peace and then supplementing that programming with additional activities serves as a way to unite a campus around the idea of peace