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Deep Brain Stimulation: Comparison of Progressive Versus Nonprogressive Dystonias
No full textDystonia is a movement disorder characterized by involuntary muscle spasms and contractions which can lead to abnormal postures and repetitive movements which are associated with pain and dysfunction. Deep Brain Stimulation (DBS) was introduced in the 1990’s and approved for treatment of dystonias in 2003. We compare responses to DBS between non-progressive and progressive dystonias to elucidate its role in the treatment of pediatric patients. Analysis of data is available through the PEDiDBS registry, a shared registry of pediatric patients undergoing DBS. Of the 173 subjects, dystonia was the primary indication in 158 (91.3%). Etiology of dystonia was Cerebral Palsy 27.8% (44/158) and 46.8% (74/158) other acquired conditions. Patients were categorized into progressive or non-progressive dystonia, including CP. Outcomes were assessed using Barry Albright Scales (BAS), Burke Fahn-Marsden Motor (BFMM) and Disability (BFMD) measures. Independent t-test p values are applied to the differences between baseline and follow up scores between the groups at 6, 12 and > 12 months. Overall improvement was noted in all groups over time, however, there was statistically less improvement (p < 0.05) in motor scores between CP and other acquired conditions at 6 months and between other acquired conditions and all genetic dystonias at >12 months. CP vs Dyt1 and other genetic dystonias showed no statistical difference in DBS responsiveness. The results demonstrate responsiveness in various treatment groups based on the three scales of measurement. Improvement was seen over time for all groups, with a wide range of variability. These results suggest DBS can be used as a treatment for dystonic symptoms from a variety of progressive and non-progressive dystonias
Perceived technology usefulness for caregiving among unpaid caregivers: a National Cross-Sectional Study
Get PDFBACKGROUND: Technological advancements have the potential to improve caregiving quality and alleviate caregiver burden by providing tools for real-time communication, monitoring, and care coordination. To assist with technology adoption among the 53 million unpaid caregivers nationwide, efforts are needed to better understand caregivers' perceptions about the usefulness of certain technologies for caregiving. METHODS: Data were analyzed from a national sample of 483 unpaid caregivers using an internet-delivered questionnaire. All unpaid caregivers were eligible if they provided at least 8 h of weekly care for a care recipient aged 50 years or older. The primary dependent variable was the Perceived Technology Usefulness for Caregiving (PTUC) Scale, which is a composite score of six items ranging from 0 to 100. PTUC item responses were summed and averaged, and the overall PTUC scores were transformed into statistical tertiles (higher scores indicating more perceived technology usefulness for caregiving). An ordinal regression model was fitted to identify factors associated with higher PTUC tertiles. RESULTS: Across tertiles, unpaid caregivers who were younger (Beta = -0.018, p = 0.030) and male (Beta = 0.422, p = 0.048) reported higher PTUC Scale scores. Compared to non-Hispanic white caregivers, Hispanic/Latino (Beta = 0.779, p = 0.010), African American (Beta = 1.064, p < 0.001), and Asian (Beta = 0.958, p = 0.010) caregivers reported higher PTUC Scale scores. Unpaid caregivers with lower financial insecurity (Beta = -0.010, p = 0.003), higher caregiver strain (Beta = 0.149, p < 0.001), and more satisfaction with the support they receive for caregiving (Beta = 0.009, p = 0.002) reported higher PTUC Scale scores. Unpaid caregivers whose care recipients had less cognitive impairment reported higher PTUC Scale scores (Beta = -0.245, p = 0.048). CONCLUSION: Findings indicate caregiver characteristics, caregiving dynamics, and available resources (financial and caregiving support) are associated with perceptions about the usefulness of technology for caregiving. The utility of technology for caregiving may be higher among unpaid caregivers with more caregiver strain or positive experiences with caregiving support.The author(s) declare that financial support was received for the research and/or publication of this article. Rahemi was supported by Clemson University/Institute for Engaged Aging and the South Carolina Alzheimer's Disease Research Center's (ADRC) SPARK Grant Program, NIH National Institute on Aging (NIA) K01AG081485 and the Alzheimer's Association (grant number: 24AARG-D-1242910)
EpipwR: efficient power analysis for EWAS with continuous outcomes
Get PDFMOTIVATION: Epigenome-wide association studies (EWAS) have emerged as a popular way to investigate the pathophysiology of complex diseases and to assist in bridging the gap between genotypes and phenotypes. Despite the increasing popularity of EWAS, very few tools exist to aid researchers in power estimation and those are limited to case-control studies. The existence of user-friendly tools, expanding power calculation functionality to additional study designs, would be a significant aid to researchers planning EWAS. RESULTS: We introduce EpipwR, an open-source R-package that can efficiently estimate power for EWAS with continuous or binary outcomes. EpipwR uses a quasi-simulated approach, meaning that data is generated only for CpG sites with methylation associated with the outcome, while P-values are generated directly for those with no association (when necessary). Like existing EWAS power calculators, reference datasets of empirical EWAS are used to guide the data generation process. Two numerical studies show the effect of the selected empirical dataset on the generated correlations and power, while another explores the accuracy of EpipwR against case-control alternatives. EpipwR is shown to outperform existing alternatives on both simulated and real EWAS datasets. AVAILABILITY AND IMPLEMENTATION: The EpipwR R-package is currently available on Bioconductor or at github.com/jbarth216/EpipwR.This study was conducted without external financial support
What should patients learn? Co-designing patient education to improve medication safety, professional-patient communication, and partnership
Get PDFINTRODUCTION: Adverse drug events are a major focus of patient safety research, but work is often limited to healthcare professionals' actions and inpatient populations. The patient work system provides a framework to understand the work done by patients and other nonprofessionals. The authors aimed to improve medication safety through the development of short educational videos designed to facilitate professional-patient partnership and shared decision-making by addressing the knowledge gaps and information asymmetry that serve as barriers to productive primary care encounters. METHODS: The authors first performed a narrative review to identify knowledge gaps and the most important medication management principles for patients to learn. Next, the authors conducted participatory design workshops with professionals and patients to develop a list of topics for the educational videos. Lastly, the authors surveyed professionals (N = 44) and patients (N = 100) to measure interest in the proposed video topics. RESULTS: The narrative review identified two themes: (1) knowledge-based barriers and hazards, and (2) opportunities for education-based solutions. The design workshops resulted in a proposed list of 12 educational videos divided into four modules: ownership, partnership, system, and learning. Two-factor ANOVA testing of the survey results showed that there was a significant difference in interest with professionals being more interested than patients (p < 0.001). Post-hoc testing revealed that patients were significantly more interested in watching videos from the partnership module than from the system module (p < 0.05). DISCUSSION: Information asymmetry provides a framework to understand why some patients defer decision-making to professionals while also showing the greatest interest in the partnership module. It also highlights why it is important for professionals to tell patients about their desire for patient ownership of care-engaged patients provide better information to professionals, who might otherwise work with incomplete records. To improve medication safety, patient education efforts should include a focus on how patients can partner with HCPs and be mindful of the work system barriers that patients will encounter while performing the educational work. Successful efforts stand to improve patient outcomes by reducing information asymmetry and enabling shared decision-making.The author(s) declare that financial support was received for the research and/or publication of this article. This work was conducted as part of the Partnership for Resilience in Medication Safety (PROMIS) Patient Safety Learning Lab with funding from the Agency for Healthcare Research and Quality (AHRQ) (R18 HS027277)
Editorial: Translational research advancements utilizing the Iowa Gambling Task in preclinical and clinical studies: 30 years of the IGT
Get PDFEvidence for the long-distance transport of ticks and tick-borne pathogens by human travellers to Texas, USA
Get PDFBACKGROUND: The incidence of tick-borne diseases in the USA has surged in recent years, with >50 000 cases reported from an estimated half-million cases annually. While domestic vectors are well characterized, the role of human travel in transporting exotic ticks and pathogens remains poorly understood. METHODS: We analysed 4808 submissions of ticks removed from individuals to the Tick-Borne Disease Research Laboratory in Texas, USA, from 2004 to 2024. Tick species were identified phenotypically or through DNA-based sequencing, and pathogens (Borrelia spp., Rickettsia spp., Ehrlichia spp., Anaplasma phagocytophilum and Babesia microti) were detected using molecular assays. Submitter travel histories were cross-referenced with known tick geographic ranges to identify long-distance transport. RESULTS: We documented cases of intercontinental, international and domestic interstate transport of ticks by human travellers. Four Ixodes ricinus ticks-originating from Europe-were transported to Texas; one tick carried Borrelia afzelii, a Lyme disease pathogen not endemic to North America. Central and South American Amblyomma species were repeatedly imported, raising concerns for pathogen transmission and tick establishment. Domestic travellers also carried Ixodes scapularis ticks infected with Borrelia burgdorferi sensu stricto, Babesia microti and A. phagocytophilum from Lyme-endemic regions of the USA to Texas, along with non-native species Ixodes pacificus, Dermacentor andersoni and Dermacentor occidentalis from endemic areas in the western United States. CONCLUSIONS: Long-distance transport of ticks by travellers represents an underrecognized pathway for the global spread of ticks and tick-borne pathogens. Clinicians should consider travel history in tick-borne illness diagnostics. Enhanced surveillance, public education and travel screening are critical to mitigating these risks.Funding for this work was provided by the State of Texas to the UNTHSC in support of the Tick-Borne Disease Research Laboratory
Fluorescence Resonance Energy Transfer for Drug Loading Assessment in Reconstituted High-Density Lipoprotein Nanoparticles
No full textReconstituted high-density lipoprotein nanoparticles (NPs), which mimic the structure and function of endogenous human plasma HDL, hold promise as a robust drug delivery system. These nanoparticles, when loaded with appropriate agents, serve as powerful tools for targeted drug delivery. The fundamental challenge lies in controlling and estimating the actual drug load and the efficiency of drug release at the target. In this report, we present a novel approach based on enhanced Forster Resonance Energy Transfer (FRET) to assess particle load and monitor payload release. The NPs are labeled with donor molecules embedded in the lipid phase, while the spherical core volume is filled with acceptor molecules. Highly enhanced FRET efficiency to multiple acceptors in the NP core has been observed at distances significantly larger than the characteristic Forster distance (R(0)). To confirm that the observed changes in donor and acceptor emissions are a result of FRET, we developed a theoretical model for nonradiative energy transfer from a single donor to multiple acceptors enclosed in a spherical core volume. The load-dependent shortening of the fluorescence lifetime of the donor correlated with the presence of a negative component in the intensity decay of the acceptor clearly demonstrates that FRET can occur at a large distance comparable to the nanoparticle size (over 100 A). Comparison of theoretical simulations with the measured intensity decays of the donor and acceptor fluorophores constitute a new method for evaluating particle load. The observed FRET efficiency depends on the number of acceptors in the core, providing a simple way to estimate the nanoparticle load efficiency. Particle disintegration and load release result in a distinct change in donor and acceptor emissions. This approach constitutes a novel strategy for assessing NP core load, monitoring NP integrity, and evaluating payload release efficiency to target cells. Significants: In the last decade, nanoparticles have emerged as a promising strategy for targeted drug delivery, with applications ranging from cancer therapy to ocular neurodegenerative disease treatments. Despite their potential, a significant issue has been the real-time monitoring of these drug delivery vehicles within biological systems. Effective strategies for monitoring NP payload loading, NP integrity, and payload release are needed to assess the quality of new drug delivery systems. In our study, we have found that FRET-enabled NPs function as an improved method for monitoring these aspects currently missing from current drug delivery efforts.This research was funded by the NIH T32AG020494 and the NIH 1F31EY035916-01. Z.G. acknowledges the support of the "Tex" Moncrief Jr. Endowment Fund
Closing the gap between implementation science and policy in Nigeria: lessons from the Nigeria implementation science alliance using a nominal group technique
No full textINTRODUCTION: Knowledge translation in healthcare has been of keen interest to researchers, practitioners, policymakers and administrators as it seeks to confront complex health issues within communities by closing the gap between knowledge generation through research and knowledge application. A paucity of information exists regarding nature of the relationship between Nigerian implementation science researchers and policymakers in the sphere of knowledge translation. This study aimed to identify and discuss barriers to successful engagement between implementation researchers and policymakers as well as to identify strategies for successful engagement between both parties in Nigeria. METHODS: A modified Nominal Group Technique was conducted with 259 diverse health research stakeholders attending the 7th Nigeria Implementation Science Alliance conference in Abuja, Nigeria, to identify barriers to knowledge translation in Nigerian healthcare settings. RESULTS: Lack of interest in non-aligned priorities of implementation researchers and policymakers, knowledge and capacity gap in stakeholder engagement, and non-existence of engagement framework were ranked as the top three barriers. Developing and sustaining an effective engagement framework, aligning researcher-policymaker interests through collaborative research projects, and joint capacity-building were ranked the topmost facilitators of researcher-policymaker engagement. CONCLUSION: This study highlights key barriers to research-to-policy engagement in Nigeria, namely the need for structured engagement frameworks, alignment of priorities, and targeted capacity development, and proposes actionable strategies to address them. Sustainable impact will depend on dedicated financing, governance reforms, and institutional changes, supported by long-term partnerships and robust evaluation systems to advance knowledge translation and improve health outcomes.The author(s) declare financial support was received for the research and/or publication of this article. This research was funded by the Nigeria Implementation Science Alliance (NISA)
The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats
No full textBACKGROUND: Obstructive sleep apnea (OSA) is an intermittent hypoxia disorder associated with cognitive dysfunction, including learning and memory impairments. There is evidence that alterations in protease activity and neuronal activation are associated with cognitive dysfunction, are dependent on sex, and may be brain region-specific. However, the mechanisms mediating OSA-induced cognitive impairments are unclear. Therefore, we used a rat model of OSA, chronic intermittent hypoxia (CIH) to investigate protease activity (e.g., calpain and caspase-3) on spectrin, a cytoskeletal protein associated with neurotransmitter release, and neuronal activation (early growth response protein 1, EGR-1) in brain regions associated with learning and memory. METHODS: Male and female Sprague Dawley rats were exposed to CIH or room air (normoxic) for 14 days. We quantified protease activity and cleaved spectrin products, along with EGR-1 protein expression in hippocampal subregions (CA1, CA3), cortical regions [entorhinal cortex (ETC), retrosplenial cortex (RSC), cerebellar cortex (CC)], and subcortical regions [raphe nucleus (RN), locus coeruleus (LC)] associated with learning and memory. Within each group, Pearson correlations of calpain activity, caspase-3 activity, and EGR-1 expression were performed between brain regions. Sex differences within normoxic and CIH correlations were examined. RESULTS: CIH dysregulated calpain activity in male ETC, and female CA1 and RSC. CIH dysregulated caspase-3 activity in male RN, and female CA1 and RSC. CIH decreased calpain and caspase-3 cleavage products in male ETC. CIH decreased calpain-cleaved spectrin in male RSC but increased these products in female RSC. EGR-1 expression was decreased in male and female RN. Correlational analysis revealed CIH increased excitatory connections in males and increased inhibitory connections in females. EGR-1 expression in males shifted from negative to positive correlations. CONCLUSIONS: Overall, these data indicate CIH dysregulates protease activity and impairs neuronal function in a brain region- and sex-dependent manner. This indicates that males and females exhibit sex-specific vulnerabilities to mild OSA. These findings concur with our previous behavioral studies that demonstrated memory impairment in CIH-exposed rats. Many adults have a sleeping condition called sleep apnea, which can cause memory problems. Importantly, these memory problems can be linked to specific parts of the brain, such as the hippocampus, which is responsible for the formation of memories and ability to remember these memories. The hippocampus is connected to multiple other parts of the brain, so memory problems could also be due to changes in these other brain regions. Though sleep apnea is more common in men than women, it is likely that the brains of men and women respond to sleep apnea differently. To determine which brain regions are impacted by sleep apnea and how male or female sex could alter this effect, we exposed adult male and female rats to chronic intermittent hypoxia (CIH), which is a rat model of sleep apnea. We measured the effect of CIH by looking at the activation of brain cells and proteases, which are specialized proteins that cut other proteins into smaller pieces to change how they work. We found that CIH effects were unique to specific parts of the brain, and these effects were mainly observed in female rats. CIH also changed the way that enzyme and brain cell activity in certain brain regions was related to other brain regions. These results mean that not only does sleep apnea change the way parts of the brain function, but these changes are different for males and females. This indicates that men and women could experience sex-specific memory problems from sleep apnea.This study was supported by NIH R01NS0091359, NIA 1R01AG085296, and UNTHSC Seed grant funding to RLC; NHLBI 5R01HL155977 to JTC; AHA 22PRE900431 to JJG; AHA 22POST-903250 to JLB; and NIA T32AG020494 to SM
32nd Annual Research Appreciation Day Abstract Book
No full textAbstracts submitted for the thirty-second annual Research Appreciation Day. RAD 2025 was the fifth all-virtual RAD. In total, 242 abstracts were submitted