Polychlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) are contaminants of concern in the New York/New Jersey Harbor and in the organisms of the Newtown Creek Superfund site, which lies within the harbor. Because PCDD/Fs are never intentionally produced, identifying their sources can be challenging. In this work, sources of PCDD/Fs to the sediment of Newtown Creek were investigated using Positive Matrix Factorization (PMF) to analyze two data sets containing data on concentrations of (1) PCDD/Fs and (2) PCDD/Fs plus polychlorinated biphenyls (PCBs).
View Article and Find Full Text PDFDescribed herein is a protocol for producing a synthetic extracellular matrix that can be modified in situ during three-dimensional cell culture. The hydrogel platform is established using modular building blocks employing bio-orthogonal tetrazine (Tz) ligation with slow (norbornene, Nb) and fast (trans-cyclooctene, TCO) dienophiles. A cell-laden gel construct is created via the slow, off-stoichiometric Tz/Nb reaction.
View Article and Find Full Text PDFFunctional characterization of enzymes/proteins requires determination of the binding affinity of small molecules or other biomolecules with the target proteins. Several available techniques, such as proteomics and drug discovery strategies, require a precise and high-throughput assay for rapid and reliable screening of potential candidates for further testing. Surface plasmon resonance (SPR), a well-established label-free technique, directly measures biomolecular affinities.
View Article and Find Full Text PDFThe friction of solids is primarily understood through the adhesive interactions between the surfaces. As a result, slick materials tend to be nonstick (e.g.
View Article and Find Full Text PDFPolychlorinated biphenyls (PCBs) are a primary contaminant of potential concern at the Newtown Creek superfund site. Measurements of PCBs in hundreds of samples of sediment (surface and cores) within Newtown Creek and at nearby reference locations were obtained from the Remedial Investigation (RI) databases. This data set was analyzed using Positive Matrix Factorization (PMF).
View Article and Find Full Text PDFArticular cartilage's remarkable low-friction properties are essential to joint function. In osteoarthritis (OA), cartilage degeneration (e.g.
View Article and Find Full Text PDFPsychopharmacology (Berl)
June 2024
Rationale: Arginine vasopressin (AVP) has dose- and sex-specific effects on social behavior, and variation in social responses is related to variation in the V1a receptor gene in animals. Whether such complexity also characterizes AVP effects on anxiety in humans, or whether V1a genotype is related to anxiety and/or AVP's ability to affect it, remains to be determined.
Objective: To test if AVP has dose-dependent effects on anxiety in men and/or women and if a particular allele within the RS3 promoter region of the V1a receptor gene is associated with anxiety and/or AVP effects on anxiety.
Healthy articular cartilage is a remarkable bearing material optimized for near-frictionless joint articulation. Because its limited self-repair capacity renders it susceptible to osteoarthritis (OA), approaches to reinforce or rebuild degenerative cartilage are of significant interest. While exogenous collagen crosslinking (CXL) treatments improve cartilage's mechanical properties and increase its resistance to enzymatic degradation, their effects on cartilage lubrication remain less clear.
View Article and Find Full Text PDFExpert Opin Investig Drugs
February 2024
Introduction: Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that inhibits HIV RT through multiple mechanisms. Contrary to all approved NtRTIs, islatravir retains a 3'OH group. and clinical data show that ISL is an ultrapotent investigational drug with high tolerability.
View Article and Find Full Text PDFBackground: People who inject drugs (PWID) are at risk for severe bacterial and fungal infections including skin and soft tissue infections, endocarditis, and osteomyelitis. PWID have high rates of self-directed discharge and are often not offered outpatient antimicrobial therapies, despite studies showing their efficacy and safety in PWID. This study fills a gap in knowledge of patient and community partner perspectives on treatment and discharge decision making for injection drug use (IDU)-associated infections.
View Article and Find Full Text PDFAdoptive T-cell therapies (ATCTs) are increasingly important for the treatment of cancer, where patient immune cells are engineered to target and eradicate diseased cells. The biomanufacturing of ATCTs involves a series of time-intensive, lab-scale steps, including isolation, activation, genetic modification, and expansion of a patient's T-cells prior to achieving a final product. Innovative modular technologies are needed to produce cell therapies at improved scale and enhanced efficacy.
View Article and Find Full Text PDFToward the goal of establishing an engineered model of the vocal fold lamina propria (LP), mesenchymal stem cells (MSCs) are encapsulated in hyaluronic acid (HA)-based hydrogels employing tetrazine ligation with strained alkenes. To mimic matrix stiffening during LP maturation, diffusion-controlled interfacial bioorthogonal crosslinking is carried out on the soft cellular construct using HA modified with a ferocious dienophile, trans-cyclooctene (TCO). Cultures are maintained in MSC growth media for 14 days to afford a model of a newborn LP that is homogeneously soft (nLP), a homogeneously stiffened construct zero (sLP0) or 7 days (sLP7) post cell encapsulation, and a mature LP model (mLP) with a stiff top layer and a soft bottom layer.
View Article and Find Full Text PDFBackground: The prevalence of injection drug use (IDU)-associated infections and associated hospitalizations has been increasing for nearly two decades. Due to issues ranging from ongoing substance use to peripherally inserted central catheter safety, many clinicians find discharge decision-making challenging. Typically, clinicians advise patients to remain hospitalized for several weeks for intravenous antimicrobial treatment; however, some patients may desire other antimicrobial treatment options.
View Article and Find Full Text PDFBackground: Patients with injection drug use (IDU)-associated infections traditionally experience prolonged hospitalizations, which often result in negative experiences and bad outcomes. Harm reduction approaches that value patient autonomy and shared decision-making regarding outpatient treatment options may improve outcomes. We sought to identify health care professionals (HCPs) perspectives on the barriers to offering four different options to hospitalized people who use drugs (PWUD): long-term hospitalization, oral antibiotics, long-acting antibiotics at an infusion center, and outpatient parenteral antibiotics.
View Article and Find Full Text PDFBackground: The impact of public health policies during the COVID-19 pandemic on people who inject drugs (PWID) has varied across regions. In other countries, recent research has shown that PWID access to harm reduction services, despite rapid adaptations, has been negatively impacted. Our study describes these impacts in a rural state.
View Article and Find Full Text PDFCrosslinked, degradable, and cell-adhesive hydrogel microfibers were synthesized via interfacial polymerization employing tetrazine ligation, an exceptionally fast bioorthogonal reaction between strained -cyclooctene (TCO) and -tetrazine (Tz). A hydrophobic TCO crosslinker and homo-difunctional poly(ethylene glycol) (PEG)-based macromers with the tetrazine group conjugated to PEG via a stable carbamate (PEG-Tz1) bond or a labile hydrazone (PEG-Tz2) linkage were synthesized. After laying an ethyl acetate solution of TCO over an aqueous solution of Tz macromers, mechanically robust microfibers were continuously pulled from the oil-water interface.
View Article and Find Full Text PDFCartilage loses, recovers, and maintains its thickness, hydration, and biomechanical functions based on competing rates of fluid loss and recovery under varying joint-use conditions. While the mechanics and implications of load-induced fluid loss have been studied extensively, those of fluid recovery have not. This study isolates, quantifies, and compares rates of cartilage recovery from three known modes: (1) passive swelling - fluid recovery within a static unloaded contact area; (2) free swelling - unrestricted fluid recovery by an exposed surface; (3) tribological rehydration - fluid recovery within a loaded contact area during sliding.
View Article and Find Full Text PDFHealthy articular cartilage supports load bearing and frictional properties unmatched among biological tissues and man-made bearing materials. Balancing fluid exudation and recovery under loaded and articulated conditions is essential to the tissue's biological and mechanical longevity. Our prior tribological investigations, which leveraged the convergent stationary contact area (cSCA) configuration, revealed that sliding alone can modulate cartilage interstitial fluid pressurization and the recovery and maintenance of lubrication under load through a mechanism termed 'tribological rehydration.
View Article and Find Full Text PDFUnlabelled: , articular cartilage is exceptionally resistant to wear, damage, and dysfunction. However, replicating cartilage's phenomenal tribomechanics (i.e.
View Article and Find Full Text PDFBackground: Increasing rates of injection drug use (IDU) associated-infections suggest significant syringe service program (SSP) underutilization. Our study objective was to assess practices of safe injection techniques and to determine predictors of SSP utilization in a rural state.
Patients And Methods: This was a fifteen-month cross-sectional study of participants hospitalized with IDU-associated infections in Maine.
Loading-induced cartilage exudation causes loss of fluid from the tissue, joint space thinning and, in a long term prospective, the insurgence of osteoarthritis. Fortunately, experiments show that joints recover interstitial fluid and thicken during articulation after static loading, thus reversing the exudation process. Here, we provide the first original theoretical explanation to this crucial phenomenon, by implementing a numerical model capable of accounting for the multiscale porous lubrication occurring in joints.
View Article and Find Full Text PDFArticular cartilage is a robust tissue that facilitates load distribution and wear-free articulation in diarthrodial joints. These biomechanical capabilities are fundamentally tied to tissue hydration, whereby high interstitial fluid pressures and fluid load support facilitate the maintenance of low tissue strains and frictions. Our recent studies of cartilage sliding biomechanics using the convergent stationary contact area (cSCA) configuration, first introduced by Dowson and colleagues, unexpectedly demonstrated that sliding alone can promote recovery of interstitial pressure and lubrication lost to static compression through a mechanism termed 'tribological rehydration.
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