Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607).
View Article and Find Full Text PDFWith the increasing age of the population in the USA, fall prevention events to target older patients are imperative. The American Association for the Surgery of Trauma hosted a fall prevention event at the host city of the 2023 Annual Meeting. We review the planning and implementation of this "Stop the Falls" event, in hopes that other institutions may benefit and sustainably effectuate fall prevention events for an increasingly geriatric population.
View Article and Find Full Text PDFThe development of perfusable and multiscale vascular networks remains one of the largest challenges in tissue engineering. As such, there is a need for the creation of customizable and facile methods to produce robustly vascularized constructs. In this study, secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads were produced and evaluated for their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature.
View Article and Find Full Text PDFBackground: Geriatric trauma patients are an increasing population of the United States (US), sustaining a high incidence of falls, and suffer greater morbidity and mortality to their younger counterparts. Significant variation and challenges exist to optimize outcomes for this cohort, while being mindful of available resources. This manuscript provides concise summary of locoregional and national practices, including relevant updates in the triage of geriatric trauma in an effort to synthesize the results and provide guidance for further investigation.
View Article and Find Full Text PDFDevelopmental venous anomalies (DVAs) are clinically benign, low-flow vascular malformations that classically hemorrhage only when associated with a cerebral cavernous malformation. It is very rare for an isolated DVA to hemorrhage. Resection of the DVA is generally contraindicated because of the high risk of venous infarct.
View Article and Find Full Text PDFThe DEAD (Asp-Glu-Ala-Asp)-box helicase 3 X-linked (DDX3X) protein participates in many aspects of mRNA metabolism and stress granule (SG) formation. DDX3X has also been associated with signal transduction and cell cycle regulation that are important in maintaining cellular homeostasis. Malfunctions of DDX3X have been implicated in multiple cancers, including brain cancer, leukemia, prostate cancer, and head and neck cancer.
View Article and Find Full Text PDFDEAD-box RNA helicases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box helicases unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened.
View Article and Find Full Text PDFThe KT3 antibody is a commercially available antibody that recognizes the P granule protein PGL-3 (Takeda et al., 2008). Using immunostaining and western blotting of purified peptide fragments, we show that KT3 recognizes both PGL-3 and its paralog PGL-1 , likely through a shared epitope in the intrinsically disordered region.
View Article and Find Full Text PDFStrategies to separately manufacture arterial-scale tissue engineered vascular grafts and microvascular networks have been well-established, but efforts to bridge these two length scales to create hierarchical vasculature capable of supporting parenchymal cell functions or restoring perfusion to ischemic tissues have been limited. This work aimed to create multiscale vascular constructs by assessing the capability of macroscopic vessels isolated from mice to form functional connections to engineered capillary networks ex vivo. Vessels of venous and arterial origins from both thoracic and femoral locations were isolated from mice, and then evaluated for their abilities to sprout endothelial cells (EC) capable of inosculating with surrounding human cell-derived microvasculature within bulk fibrin hydrogels.
View Article and Find Full Text PDFWhen asked to estimate how much their state or nation has contributed to history, people typically provide unreasonably large estimates, claiming that their group has contributed much more to history than nongroup members would estimate, demonstrating collective overclaiming. Why does such overclaiming occur? In the current study we examined factors that might predict collective overclaiming. Participants from 12 U.
View Article and Find Full Text PDFAllogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies for which graft-versus-host disease (GVHD) remains a major complication. The use of donor T-regulatory cells (Tregs) to prevent GVHD appears promising, including in our previous evaluation of an engineered graft product (T-reg graft) consisting of the timed, sequential infusion of CD34+ hematopoietic stem cells and high-purity Tregs followed by conventional T cells. However, whether immunosuppressive prophylaxis can be removed from this protocol remains unclear.
View Article and Find Full Text PDFThe application of molecular tools to population management can improve the long-term genetic viability of ex situ populations. In this study, we aimed to understand the implications of integrating empirical kinships into the genetic management of an ex situ population of the endangered waterfowl, Baer's pochard (Aythya baeri), in North America. Single nucleotide polymorphism data were generated for 141 Baer's pochard using double digest restriction site-associated DNA sequencing and empirical kinships were derived and integrated into the population management software PMx.
View Article and Find Full Text PDFPremise: Many plant communities across the world are undergoing changes due to climate change, human disturbance, and other threats. These community-level changes are often tracked with the use of permanent vegetative plots, but this approach is not always feasible. As an alternative, we propose using photogrammetry, specifically photograph-based digital surface models (DSMs) developed using structure-from-motion, to establish virtual permanent plots in plant communities where the use of permanent structures may not be possible.
View Article and Find Full Text PDFAlterations of the extracellular matrix contribute to adipose tissue dysfunction in metabolic disease. We studied the role of matrix density in regulating human adipocyte phenotype in a tunable hydrogel culture system. Lipid accumulation was maximal in intermediate hydrogel density of 5 weight %, relative to 3% and 10%.
View Article and Find Full Text PDFThere is a significant clinical need to develop effective vascularization strategies for tissue engineering and the treatment of ischemic pathologies. In patients afflicted with critical limb ischemia, comorbidities may limit common revascularization strategies. Cell-encapsulating modular microbeads possess a variety of advantageous properties, including the ability to support prevascularization in vitro while retaining the ability to be injected in a minimally invasive manner in vivo.
View Article and Find Full Text PDFIn human vascular anatomy, blood flows from the heart to organs and tissues through a hierarchical vascular tree, comprising large arteries that branch into arterioles and further into capillaries, where gas and nutrient exchange occur. Engineering a complete, integrated vascular hierarchy with vessels large enough to suture, strong enough to withstand hemodynamic forces, and a branching structure to permit immediate perfusion of a fluidic circuit across scales would be transformative for regenerative medicine (RM), enabling the translation of engineered tissues of clinically relevant size, and perhaps whole organs. How close are we to solving this biological plumbing problem? In this review, we highlight advances in engineered vasculature at individual scales and focus on recent strategies to integrate across scales.
View Article and Find Full Text PDFMicroporosity in hydrogels is critical for directing tissue formation and function. We have developed a fibrin-based smart hydrogel, termed an acoustically responsive scaffold (ARS), which responds to focused ultrasound in a spatiotemporally controlled, user-defined manner. ARSs are highly flexible platforms due to the inclusion of phase-shift droplets and their tunable response to ultrasound through a mechanism termed acoustic droplet vaporization (ADV).
View Article and Find Full Text PDFThe formation of functional capillary blood vessels that can sustain the metabolic demands of transplanted parenchymal cells remains one of the biggest challenges to the clinical realization of engineered tissues for regenerative medicine. As such, there remains a need to better understand the fundamental influences of the microenvironment on vascularization. Poly(ethylene glycol) (PEG) hydrogels have been widely adopted to interrogate the influence of matrix physicochemical properties on cellular phenotypes and morphogenetic programs, including the formation of microvascular networks, in part due to the ease with which their properties can be controlled.
View Article and Find Full Text PDFA hallmark of all germ cells is the presence of germ granules: assemblies of proteins and RNA that lack a delineating membrane and are proposed to form via condensation. Germ granules across organisms share several conserved components, including factors required for germ cell fate determination and maintenance, and are thought to be linked to germ cell development. The molecular functions of germ granules, however, remain incompletely understood.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can elicit acute and long-term effects on the myocardium among survivors, yet effects among otherwise healthy young adults remains unclear. Young adults with mild symptoms of SARS-CoV-2 (8M/8F, age: 21 ± 1 years, BMI: 23.5 ± 3.
View Article and Find Full Text PDFResearch has clearly demonstrated that some study strategies (for example, self-testing and spaced studying) are effective, yet students often report studying ineffectively. Our focus with the current study is to update and extend the current literature on how college students study. We surveyed 484 introductory psychology students at a small liberal arts college-a different type of school from prior studies.
View Article and Find Full Text PDFPromoting immune tolerance to transplanted organs can minimize the amount of immunosuppressive drugs that patients need to take, reducing lifetime risks of mortality and morbidity. Regulatory T cells (T) are essential for immune tolerance, and preclinical studies have shown their therapeutic efficacy in inducing transplantation tolerance. Here, we report the results of a phase 1/2 trial (ARTEMIS, NCT02474199) of autologous donor alloantigen-reactive T (darT) therapy in individuals 2 to 6 years after receiving a living donor liver transplant.
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