Search

ObjectiveInadequate diversity in clinical trials is widely recognized as a significant contributing factor to health disparities experienced by racial/ethnic minorities and other diverse populations in the US. To address this in a scalable way, we sought to develop a web tool that could help enhance underserved minority participation in clinical research.MethodsWe used our research literacy support flashcard tool as the initial prototype for human-centered design and usability testing of the web tool Health for All in public library settings. After forming partnerships with leadership from Chicago Public Libraries (CPL), local medical libraries, and the Chicago Department of Public Health, we conducted seven iterative design sessions with focus groups of library patrons and library staff from six CPL branches serving underserved communities followed by two rounds of usability testing and website modification.ResultsBased on the qualitative research findings from Design Sessions 1-7, we enacted the design decision of a website that was a hybrid of fact-filled and vignette (personal stories) paper prototypes divided into 4 modules (trust, diversity, healthy volunteers, pros/cons), each with their own outcome metrics. The website was thus constructed, and navigation issues identified in two rounds of usability testing by library patrons were addressed through further website modification, followed by the launch of a beta version of a hybridized single-scrolling and guided module prototype to allow further development with website analytics.ConclusionsWe report the development of Health for All, a website designed to enhance racial/ethnic minority participation in clinical trials by imparting research literacy, mitigating distrust engendered by longstanding racism and discrimination, and providing connections to clinical trials recruiting participants.

Habitat fragmentation due to both natural and anthropogenic forces continues to threaten the evolution and maintenance of biological diversity. This is of particular concern in tropical regions that are experiencing elevated rates of habitat loss. Although less well-studied than tropical rain forests, tropical dry forests (TDF) contain an enormous diversity of species and continue to be threatened by anthropogenic activities including grazing and agriculture. However, little is known about the processes that shape genetic connectivity in species inhabiting TDF ecosystems. We adopt a landscape genetic approach to understanding functional connectivity for leaf-toed geckos (Phyllodactylus tuberculosus) at multiple sites near the northernmost limit of this ecosystem at Alamos, Sonora, Mexico. Traditional analyses of population genetics are combined with multivariate GIS-based landscape analyses to test hypotheses on the potential drivers of spatial genetic variation. Moderate levels of within-population diversity and substantial levels of population differentiation are revealed by FST and Dest. Analyses using structure suggest the occurrence of from 2 to 9 genetic clusters depending on the model used. Landscape genetic analysis suggests that forest cover, stream connectivity, undisturbed habitat, slope, and minimum temperature of the coldest period explain more genetic variation than do simple Euclidean distances. Additional landscape genetic studies throughout TDF habitat are required to understand species-specific responses to landscape and climate change and to identify common drivers. We urge researchers interested in using multivariate distance methods to test for, and report, significant correlations among predictor matrices that can impact results, particularly when adopting least-cost path approaches. Further investigation into the use of information theoretic approaches for model selection is also warranted.

Background: In recent years, cancer survival rates have increased exponentially. However, this rise in survival comes with a significant drawback. As the number of treatment lines has grown, so too have the side effects, which can severely impact patients' functionality and quality of life. One of the most concerning effects is dyspnoea, a serious health issue that imposes substantial limitations on individuals. While traditional clinical approaches, primarily focused on pharmacological interventions, are commonly employed to manage dyspnoea, we argue that these methods may not always provide optimal symptomatic relief. Therefore, we propose a study protocol to implement an interdisciplinary intervention for these patients. This protocol aims to enhance standard clinical practice by introducing a program of functional re-education and environmental adaptation. We believe this intervention is essential for the follow-up care of patients with respiratory conditions after hospital discharge., Methods: A two-arm, randomized, parallel, controlled clinical trial will be conducted by the University of Salamanca, Spain, in collaboration with the Medical Oncology Service of the University Health Care Complex of Salamanca. The trial aims to recruit 80 oncology patients who exhibit symptoms of dyspnoea during hospital admission. Participants will be randomly assigned to one of two groups: the control group, which will receive a health education program, and the experimental group, which will receive both the health education program and a functional re-education and environmental adaptation program. Assessments will be conducted at three time points: baseline (prior to hospital discharge), follow-up (15 days after discharge), and the end of the intervention (1 month after discharge). During these assessments, sociodemographic data will be collected, and the following scales will be administered: Barthel Index, Medical Research Council Dyspnoea Scale (mMRC), EuroQol 5-D questionnaire (EQ-5D), Visual Analogue Scale (VAS), Short Physical Performance Battery (SPPB), Tampa Scale for Kinesiophobia (TSK), and the Zarit Reduced Caregiver Burden Scale., Discussion: The findings of this research can be easily implemented in clinical settings by introducing a targeted intervention to improve the quality of life for this patient population. This study aims to advance traditional clinical approaches by facilitating the recovery or adaptation of cancer patients in their daily routines, in relation to the severity of their symptoms. Our primary goal is to enhance independence and functionality, ultimately improving their overall standard of living., Trial Registration: ClinicalTrials.gov; ID: NCT06035263. Registered on: September 19, 2023. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000DM2U&selectaction=Edit&uid=U0004OJ7&ts=6&cx=f7qqxo., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Fernandez-Rodriguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The thermocoagulation model, which consists of focal cerebral ischemia with craniectomy, is helpful in studying permanent ischemic brain lesions and has good reproducibility and low mortality. This study analyzed the best conditions for inducing a focal ischemic lesion by thermocoagulation. We investigated parameters such as temperature and thermal dissipation in the brain tissue during induction and analyzed real-time blood perfusion, histological changes, magnetic resonance imaging (MRI), and motor behavior in a permanent ischemic stroke model. We used three-month-old male Wistar rats, weighing 300-350 g. In the first experiment, the animals were divided into four groups (n = 5 each): one sham surgery group and three ischemic lesion groups having thermocoagulation induction (TCI) temperatures of 200°C, 300°C, and 400°C, respectively, with blood perfusion (basal and 30 min after TCI) and 2,3,5-Triphenyl-tetrazolium chloride (TTC) evaluation at 2 h after TCI. In the second experiment, five groups (n = 5 each) were analyzed by MRI (basal and 24 h after TCI) and behavioral tests (basal and seven days after TCI) with the control group added for the surgical effects. The MRI and TTC analyses revealed that ischemic brain lesions expressively evolved, especially at TCI temperatures of 300°C and 400°C, and significant motor deficits were observed as the animals showed a decrease frequency of movement and an asymmetric pattern. We conclude that a TCI temperature of 400°C causes permanent ischemic stroke and motor deficit., Competing Interests: The authors have declared that no competing interests exist.

CPEB (Cytoplasmic Polyadenylation Element Binding) proteins are a family of four RNA-binding proteins that regulate the translation of maternal mRNAs controlling meiotic cell cycle progression. But CPEBs are not limited to the transcriptionally silent germline; they are also expressed, in various combinations, in somatic cells, yet their role in regulation of mitosis-related gene expression is largely unknown. Deregulation of CPEB1 and CPEB4 have been linked to tumor development. However, a systematic analysis addressing their requirements for the temporal regulation of mitotic gene expression has yet to be performed. This study addresses the requirements of each of the four CPEBs for mitotic phase transitions, with a particular focus on cytoplasmic polyadenylation and translational regulation. We demonstrate that CPEB3 is the only member dispensable for mitotic cell division, whereas the other three members, CPEB1, 2, and 4, are essential to successful mitotic cell division. Thus, CPEB1 is required for prophase entry, CPEB2 for metaphase and CPEB4 for cytokinesis. These three CPEBs have sequential non-redundant functions that promote the phase-specific polyadenylation and translational activation of CPE-regulated transcripts in the mitotic cell cycle.

Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC) injected into the vitreous body in a model of optic nerve injury. Adult (3-5 months old) Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1β expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime.

Background: Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN) remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression., Methods: We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total) of kidney transplant patients with biopsy-documented histology., Findings: Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild) and 63 (moderate/severe) final candidates as CAN markers with predictive accuracy of 80% (mild) and 92% (moderate/severe). Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN., Conclusions: This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

Induction of adult rat bone marrow mesenchymal stem cells (MSC) by means of chemical compounds (beta-mercaptoethanol, dimethyl sulfoxide and butylated hydroxyanizole) has been proposed to lead to neuronal transdifferentiation, and this protocol has been broadly used by several laboratories worldwide. Only a few hours of MSC chemical induction using this protocol is sufficient for the acquisition of neuronal-like morphology and neuronal protein expression. However, given that cell death is abundant, we hypothesize that, rather than true neuronal differentiation, this particular protocol leads to cellular toxic effects. We confirm that the induced cells with neuronal-like morphology positively stained for NF-200, S100, beta-tubulin III, NSE and MAP-2 proteins. However, the morphological and molecular changes after chemical induction are also associated with an increase in the apoptosis of over 50% of the plated cells after 24 h. Moreover, increased intracellular cysteine after treatment indicates an impairment of redox circuitry during chemical induction, and in vitro electrophysiological recordings (patch-clamp) of the chemically induced MSC did not indicate neuronal properties as these cells do not exhibit Na(+) or K(+) currents and do not fire action potentials. Our findings suggest that a disruption of redox circuitry plays an important role in this specific chemical induction protocol, which might result in cytoskeletal alterations and loss of functional ion-gated channels followed by cell death. Despite the neuronal-like morphology and neural protein expression, induced rat bone marrow MSC do not have basic functional neuronal properties, although it is still plausible that other methods of induction and/or sources of MSC can achieve a successful neuronal differentiation in vitro.