DigitalCommons@The Texas Medical Center
Not a member yet
41791 research outputs found
Sort by
Histone H3 Cysteine 110 Enhances Iron Metabolism and Modulates Replicative Life Span In Saccharomyces cerevisiae
No full textThe discovery of histone H3 copper reductase activity provides a novel metabolic framework for understanding the functions of core histone residues, which, unlike N-terminal residues, have remained largely unexplored. We previously demonstrated that histone H3 cysteine 110 (H3C110) contributes to cupric (Cu2+) ion binding and its reduction to the cuprous (Cu1+) form. However, this residue is absent in Saccharomyces cerevisiae, raising questions about its evolutionary and functional significance. Here, we report that H3C110 has been lost in many fungal lineages despite near-universal conservation across eukaryotes. Introduction of H3C110 into S. cerevisiae increased intracellular Cu1+ levels and ameliorated the iron homeostasis defects caused by inactivation of the Cup1 metallothionein or glutathione depletion. Enhanced histone copper reductase activity also extended replicative life span under oxidative growth conditions but reduced it under fermentative conditions. Our findings suggest that a trade-off between histone copper reductase activity, iron metabolism, and life span may underlie the loss or retention of H3C110 across eukaryotes
SmartBoot: Real-Time Monitoring of Patient Activity via Remote Edge Computing Technologies
No full textDiabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system-a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch-for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and compared with staff-recorded adherence logs. Additionally, user experience was assessed using the Technology Acceptance Model (TAM) in healthy participants (n = 12) and patients with DFU (n = 81). The SmartBoot demonstrated high accuracy in cadence and step count across conditions (bias \u3c 5.5%), with an adherence detection accuracy of 96% (Össur) and 97% (Foot Defender). TAM results indicated strong user acceptance and perceived ease of use across both cohorts. These findings support the SmartBoot system\u27s potential as a valid, scalable solution for real-time remote monitoring of adherence and mobility in DFU management. Further clinical validation in ongoing studies involving DFU patients is underway
Ethical Considerations for Sharing Aggregate Results From Pragmatic Clinical Trials
No full textA growing literature has explored the ethical obligations and current practices related to sharing aggregate results with research participants. However, no prior work has examined these issues in the context of pragmatic clinical trials. Several characteristics of pragmatic clinical trials may complicate both the ethics and the logistics of sharing aggregate results. Among these characteristics include that pragmatic clinical trials may affect the rights, welfare, and interests of not only patient-subjects but also clinicians, meaning that results may be owed to a broader range of groups than typically considered in other research contexts. In addition, some pragmatic clinical trials are conducted under a waiver of informed consent, meaning sharing results may alert participants that they were enrolled without their consent. This article explores the ethical dimensions that can inform decision-making about sharing aggregate results from pragmatic clinical trials, and provides recommendations for that sharing. A central insight is that healthcare institutions-as key partners for the conduct of pragmatic clinical trials-must also be key partners in decision-making about sharing aggregate pragmatic clinical trial results. We conclude with insights for future research
Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes
No full textPurpose: Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.
Methods: The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes (KEGG).
Results: Screening of 587 late-adult mouse genes yielded 12 with abnormal retinal phenotypes, which corresponded to 20 human orthologs. Three of the 12 mouse genes and two of the 20 human orthologs were previously implicated in retinal pathology or physiology in a literature review. Although all of the genes demonstrated retinal pathology when deleted from the mouse genome, most do not have established roles in human retinal disease. Furthermore, human protein-protein analysis and biological pathway analysis yielded only a few relationships between the candidate gene list and that of known IRD and AMD genes, suggesting they may represent novel retinal functions.
Conclusions: We identified 12 mouse genes with significant late-adult abnormal retinal pathology, eight of which have not been previously implicated in either mouse or human retinal physiology or pathology. These serve as novel retinal disease gene candidates for late-onset retinal disease
Regional Anesthesia for Orthopedic Surgeries: A Guide for Upper and Lower Extremity Procedures
No full textPurpose of the review: Regional anesthesia has become a cornerstone in orthopedic surgeries due to its ability to provide precise, localized pain relief while minimizing the systemic risks associated with general anesthesia and opioid use. This review aims to provide a compact guide for anesthesia trainees and practicing anesthesiologists on the use of regional anesthesia techniques for upper and lower extremity procedures.
Summary: This guide outlines the main regional block options for orthopedic surgeries, detailing the targeted anatomy, common surgical indications, important adjacent structures, and potential complications for each technique. Key blocks for upper extremity surgeries include interscalene, supraclavicular, infraclavicular, axillary, and intercostobrachial blocks, while lower extremity techniques encompass femoral, adductor canal, sciatic, popliteal, and lumbar plexus blocks. Advances in ultrasound guidance have enhanced the safety and efficacy of these techniques, making them indispensable for modern anesthesiology practice. By mastering these approaches, providers can optimize patient outcomes, expand their skillset, and contribute to enhanced perioperative care in orthopedic surgery
Bright and Photostable Yellow Fluorescent Proteins for Extended Imaging
No full textFluorescent proteins are indispensable molecular tools for visualizing biological structures and processes, but their limited photostability restricts the duration of dynamic imaging experiments. Yellow fluorescent proteins (YFPs), in particular, photobleach rapidly. Here, we introduce mGold2s and mGold2t, YFPs with up to 25-fold greater photostability than mVenus and mCitrine, two commonly used YFPs, while maintaining comparable brightness. These variants were identified using a high-throughput pooled single-cell platform, simultaneously screening for high brightness and photostability. Compared with our previous benchmark, mGold, the mGold2 variants display a ~4-fold increase in photostability without sacrificing brightness. mGold2s and mGold2t extend imaging durations across diverse modalities, including widefield, total internal reflection fluorescence (TIRF), super-resolution, single-molecule, and laser-scanning confocal microscopy. When incorporated into fluorescence resonance energy transfer (FRET)-based biosensors, the proposed YFPs enable more reliable, prolonged imaging of dynamic cellular processes. Overall, the enhanced photostability of mGold2s and mGold2t enables high-sensitivity imaging of subcellular structures and cellular activity over extended periods, broadening the scope and precision of biological imaging
The Efficacy of Complementary and Alternative Medicines in Medical Dermatology: A Comprehensive Review
No full textBackground: In recent years, there has been a widespread patient use of complementary and alternative medicines (CAMs) for dermatological application, despite few RCT-level studies on these supplements. This creates a barrier for dermatologists and others in counseling patients who may be using or might be tempted to use these CAM agents. This review investigates various CAM modalities used by patients for medical dermatology, exploring their efficacy and toxicity profiles.
Methods: A comprehensive review was performed on the effectiveness of several CAMs utilized in medical dermatology by patients. A literature search was conducted using PubMed, Embase, Google Scholar, Web of Science, and Cochrane.
Results: Most CAM modalities had statistically insignificant results, and for agents that had significant results in efficacy, these studies were questionable with flawed designs and methodologies.
Conclusion: These CAM supplements have promising potential in dermatologic use and are deserving of further investigation in well-crafted RCT-level studies. A more practical focus in future studies should involve a comparison of CAM agents to conventional therapies either alone or in an integrative fashion. This would accurately represent how these agents will be used clinically by actual patients and will be more helpful to clinicians. In the meantime, dermatologists should be aware of bias in published studies demonstrating the effectiveness of certain CAM modalities, and their corresponding toxicity. By doing so, physicians act as a valuable resource to patients who would like to explore various CAM products, better guiding patient interactions and treatment with improved patient outcomes
NOTICE-ED: Nurse or Technician Insights Into Cognitive Evaluations in the Emergency Department
No full textBackground: Several strategies have been proposed to increase chronic cognitive impairment (CI) screening in the emergency department (ED). Our goal was to assess the feasibility and acceptability of implementing specific CI screening tools and strategies in the ED from an ED registered nurse and technician perspective.
Methods: We performed a qualitative study using semi-structured interviews with a purposive sample of ED nurses and ED technicians (EDTs). Participants worked at an urban academic hospital and were interviewed between November 2023 and March 2024. Interviews assessed participants\u27 opinions on the feasibility and acceptability of CI screening and the use of machine learning (ML) tools to identify high-risk patients for targeted CI screening, tablet-based screenings, and two validated CI screenings: the Ottawa 3DY (O3DY) and Short Blessed Test (SBT). We used the Consolidated Framework for Implementation Research (CFIR) to develop our interview guide and performed a rapid analysis with deductive and inductive codes based on CFIR constructs.
Results: Four major themes related to CI screening tools arose: (1) Benefits of CI screening; (2) feasibility of integrating screening tools into existing workflows; (3) professional role limitations; and (4) implementation requirements. Participants perceived CI screening as important for allocating limited ED resources. Shorter, less specific testing, including the O3DY, was seen as feasible during triage, while longer, more specific screening, including the SBT, was seen as more feasible in roomed care areas. Both ED nurses and EDTs identified the need for electronic health record tools and dedicated screening teams to facilitate implementation.
Conclusion: ED nurses and EDTs support chronic CI screening if screening techniques and clinical teams can be optimized to make workflows feasible
Lack of Relationships Between Ketamine Treatment and Peripheral Neurotrophic and Inflammatory Factors in a Randomized Controlled Ketamine Trial of Major Depressive Disorder
No full textBackground: Ketamine is a rapid-acting treatment for treatment-resistant depression (TRD), though mechanisms related to ketamine\u27s effects remain unclear. Blood-based neurotrophic and inflammatory factors (NIFs; e.g., brain-derived neurotrophic factor, interleukin-6) have emerged as markers potentially linked to ketamine and ketamine treatment response.
Methods: In this secondary analysis of a randomized controlled trial (RCT), 133 adults with TRD received a single-dose infusion of ketamine (n = 89; 0.5 mg/kg) or saline (n = 44) and provided measures of peripheral blood NIF levels and depression severity across a five-day post-infusion period. Differences between ketamine and saline groups were examined for (1) NIF levels, (2) associations between NIF trajectories and depression score trajectories, and (3) associations between baseline NIF levels and depression score trajectories. Subgroup sensitivity analyses examined identical relationships within many (n = 28) discrete subgroups of individuals.
Results: No differences were found between ketamine and saline cohorts for NIF trajectories, associations of NIF and depression trajectories, or associations of baseline NIF levels and depression trajectories. On subgroup analyses, in participants with lower BMI (BMI \u3c 25; n = 66), increasing interleukin-1 receptor antagonist (IL-1RA) trajectories post-ketamine were associated with less improvement in depression in the first day post-infusion.
Discussion: Associations between ketamine treatment and peripheral neurotrophic/inflammatory factors were not detected in our RCT of 133 adults with TRD. The sole exception across exhaustive sensitivity analyses was that, in individuals with low BMI, increases in IL-1RA levels may be linked to worse immediate treatment response. Future research investigating CNS-specific NIF activity is needed to more definitively test the posited role of NIFs in ketamine\u27s antidepressant mechanisms
