Differential olfactory dysfunction and nasal tissue pathology in Syrian hamsters infected with SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, frequently induces olfactory dysfunction (OD), a symptom that significantly impacts patients' quality of life. Understanding the variability in OD and nasal tissue pathology across different SARS-CoV-2 variants may provide insights as to the mechanisms underlying this symptom and inform therapeutic strategies for COVID-19-related sequelae. This study examines the OD and associated nasal pathology in Syrian hamsters infected with SARS-CoV-2 variants, including Wuhan (WA-1), Alpha, Beta, Gamma, Delta, and Omicron, at 5 days post-infection.

"First Bite": An intervention to increase children's vegetable consumption in Early Childhood Education and Care (ECEC) services in areas of high socioeconomic disadvantage - a cluster randomized controlled trial protocol.

BackgroundOnly 2% of 4-8-year-old Australian children consume the daily recommended vegetable serves, with implications on the development of lifelong dietary behaviors. Evidence suggests that enhancing children's access, exposure and familiarity with vegetables can help increase their vegetable intake. Most children attend Early Childhood Education and Care (ECEC) services, which are well placed to increase vegetable consumption through curriculum change, play-based learning and parental education.

Real-Time SPR Biosensing to Detect and Characterize Fast Dissociation Rate Binding Interactions Missed by Endpoint Detection and Implications for Off-Target Toxicity Screening.

Accurate detection of biomolecular interactions is essential in many areas, from the detection of the presence of biomarkers in the clinic to the development of therapeutic drugs and biologics in biopharma to the understanding of various biological processes in basic research. Traditional endpoint approaches can suffer from false-negative results for biomolecular interactions with fast kinetics. By contrast, real-time detection techniques like surface plasmon resonance (SPR) monitor interactions as they form and disassemble, reducing the risk of false-negative results.

siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs.

Osteoarthritis and rheumatoid arthritis are debilitating joint diseases marked by pain, inflammation and cartilage destruction. Current osteoarthritis treatments only relieve symptoms, while rheumatoid arthritis therapies can cause immune suppression and provide variable efficacy. Here we developed an optimized small interfering RNA targeting matrix metalloproteinase 13 for preferential delivery to arthritic joints.

Gait compliance alters ground reaction forces in human walking: implications for the evolution of bipedalism.

Despite decades of inquiry, the evolution of bipedalism remains a mystery. Some have argued that a compliant walking gait, with deep hip and knee flexion to moderate ground reaction forces, was used by early human ancestors, marking our relatively stiff modern gait as a recently acquired feature of our genus. Building on previous compliant walking studies, we test the hypothesis that vertical ground reaction forces are attenuated in compliant walking through increases in contact time.

Bite force production and the origin of .

The divergence of from gracile australopiths has been described as a trend of decreasing dentognathic size and robusticity, precipitated by stone tool use and/or a shift to softer foods, including meat. Yet, mechanical evidence supporting this narrative is sparse, and isotopic and archaeological data have led to the suggestion that a shift away from a gracile australopith-like diet would not have occurred in the most basal members of but rather only with the appearance of implying that the origin of our genus is not rooted in dietary change. Here, we provide mechanical evidence that exhibits an australopith-like pattern of facial strain during biting but, unlike most australopiths, was not suited for a diet that required forceful processing by the molar teeth.

Polymeric Nanoparticles Enable Targeted Visualization of Drug Delivery in Breast Cancer.

We report the coencapsulation of fluorocoxib Q (FQ) and chemocoxib A (CA) in micellar nanoparticles (FQ-CA-NPs) of a new PPS--POEGA diblock polymer, which exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (ζ) of -1.

Multiplexed proteomic biosensor platform for label-free real-time simultaneous kinetic screening of thousands of protein interactions.

Studying protein interactions in high throughput (HTP) is critical for advancing many aspects of drug discovery, biomarker identification, and diagnostic development. However, existing methods for producing functional protein libraries are costly, time-consuming, and lack real-time kinetic screening capabilities. To address these limitations, we developed an automated platform for HTP production and screening of a library of proteins on biosensor surfaces, facilitating large-scale measurement of interaction kinetics.

Induction of Triple-Negative Breast Cancer Cell Death and Chemosensitivity Using mTORC2-Directed RNAi Nanomedicine.

Abstract: Alterations in the PI3K/mTOR signaling pathway are often seen in triple-negative breast cancers (TNBC), a breast cancer subtype characterized by limited molecularly targeted treatment options and poorer patient outcomes. We report that gene amplification or overexpression of the mTORC2-required cofactor RICTOR correlated with increased mTORC2 signaling and worse patient outcomes in clinical breast cancer expression datasets, supporting studies examining selective mTORC2 inhibition in TNBC. The mTOR kinase inhibitor PP242 blocks both mTORC1 and mTORC2, which decreases growth and survival of RICTOR-amplified TNBC cells.

An approach to produce thousands of single-chain antibody variants on a SPR biosensor chip for measuring target binding kinetics and for deep characterization of antibody paratopes.

Drug discovery continues to face a staggering 90% failure rate, with many setbacks occurring during late-stage clinical trials. To address this challenge, there is an increasing focus on developing and evaluating new technologies to enhance the "design" and "test" phases of antibody-based drugs (e.g.

Addressing Health-Related Social Needs During COVID-19 Through a Hospital-Based, Community Health Worker Program: A Case Study.

. Despite accounting for 34% of the population in Austin, Texas, Latinx individuals made up 50% of those who tested positive for coronavirus, 54% of COVID-related hospitalizations, and 51% of COVID-related deaths between March and June 2020. Of hospitalized Latinx patients, 40% had never seen a primary care provider and many had undiagnosed health conditions.

Histopathology of the tongue in a hamster model of COVID-19.

Objective: With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), the main objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection.

Methods: Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted.

Intravascular delivery of an MK2 inhibitory peptide to prevent restenosis after angioplasty.

Peripheral artery disease is commonly treated with balloon angioplasty, a procedure involving minimally invasive, transluminal insertion of a catheter to the site of stenosis, where a balloon is inflated to open the blockage, restoring blood flow. However, peripheral angioplasty has a high rate of restenosis, limiting long-term patency. Therefore, angioplasty is sometimes paired with delivery of cytotoxic drugs like paclitaxel to reduce neointimal tissue formation.

Histopathology of the Tongue in a Hamster Model of COVID-19.

Objective: With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), our objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection.

Methods: Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted.

Polymeric Micellar Nanoparticles Enable Image-guided Drug Delivery in Solid Tumors.

We report the development of a nanotechnology to co-deliver chemocoxib A with a reactive oxygen species (ROS)-activatable and COX-2 targeted pro-fluorescent probe, fluorocoxib Q (FQ) enabling real time visualization of COX-2 and CA drug delivery into solid cancers, using a di-block PPS - -POEGA copolymer, selected for its intrinsic responsiveness to elevated reactive oxygen species (ROS), a key trait of the tumor microenvironment. FQ and CA were synthesized independently, then co-encapsulated within micellar PPS - -POEGA co-polymeric nanoparticles (FQ-CA-NPs), and were assessed for cargo concentration, hydrodynamic diameter, zeta potential, and ROS-dependent cargo release. The uptake of FQ-CA-NPs in mouse mammary cancer cells and cargo release was assessed by fluorescence microscopy.

Dietary Intakes of Long-Chain Polyunsaturated Fatty Acids and Impulsivity: Comparing Non-Restricted, Vegetarian, and Vegan Diets.

Background: Research suggests a link between deficiencies in omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and impulsivity among psychiatric populations. However, this association is less evident in non-clinical populations. As omega-3 LCPUFAs are predominantly sourced through fish consumption, non-fish dieters may be more vulnerable to higher impulsivity.

Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery.

Novel sensor-integrated proteome on chip (SPOC) platform with thousands of folded proteins on a 1.5 sq-cm biosensor chip to enable high-throughput real-time label-free screening for kinetic analysis.

An automated proteomic platform for producing and screening an array of functional proteins on biosensor surfaces was developed to address the challenges of measuring proteomic interaction kinetics in high throughput (HTP). This technology is termed Sensor-Integrated Proteome On Chip (SPOC) which involves cell-free protein expression in nano-liter volume wells (nanowells) directly from rapidly customizable arrays of plasmid DNA, facilitating simultaneous capture-purification of up to 2400 unique full-length folded proteins onto a 1.5 sq-cm surface of a single gold biosensor chip.

Structural Factors Contributing to Compassion Fatigue, Burnout, and Secondary Traumatic Stress Among Hospital-Based Healthcare Professionals During the COVID-19 Pandemic.

High levels of burnout among healthcare providers (HCPs) have been a widely documented phenomenon, which have been exacerbated during the COVID-19 pandemic. In the United States, qualitative studies that are inclusive of HCPs in diverse professional roles have been limited. Therefore, we utilized a qualitative-quantitative design to examine professional quality of life in terms of compassion fatigue, burnout, and secondary traumatic stress among hospital-based HCPs, including social workers, hospitalists, residents, and palliative care team members during COVID-19.

Albumin-binding RNAi Conjugate for Carrier Free Treatment of Arthritis.

Unlabelled: Osteoarthritis (OA) and rheumatoid arthritis (RA) are joint diseases that are associated with pain and lost quality of life. No disease modifying OA drugs are currently available. RA treatments are better established but are not always effective and can cause immune suppression.

Evaluation of emergency care education and triage implementation: an observational study at a hospital in rural Liberia.

Introduction: In Liberia, emergency care is still in its early development. In 2019, two emergency care and triage education sessions were done at J. J.

Core polymer optimization of ternary siRNA nanoparticles enhances in vivo safety, pharmacokinetics, and tumor gene silencing.

Gene silencing with siRNA nanoparticles (si-NPs) is promising but still clinically unrealized for inhibition of tumor driver genes. Ternary si-NPs containing siRNA, a single block NP core-forming polymer poly[(2-(dimethylamino)ethyl methacrylate)-co-(butyl methacrylate)] (DMAEMA-co-BMA, 50B), and an NP surface-forming diblock polymer 20 kDa poly(ethylene glycol)-block-50B (20kPEG-50B) have the potential to improve silencing activity in tumors due to the participation of both 50B and 20kPEG-50B in siRNA electrostatic loading and endosome disruptive activity. Functionally, single block 50B provides more potent endosomolytic activity, while 20kPEG-50B colloidally stabilizes the si-NPs.

Structural Optimization of siRNA Conjugates for Albumin Binding Achieves Effective MCL1-Targeted Cancer Therapy.

The high potential for therapeutic application of siRNAs to silence traditionally undruggable oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, siRNAs were optimized for binding to albumin through C lipid modifications to improve pharmacokinetics and tumor delivery. Systematic variation of siRNA conjugates revealed a lead structure with divalent C lipids each linked through three repeats of hexaethylene glycol connected by phosphorothioate bonds.

Evaluating implementation of Diabetes Self-Management Education in Maryland County, Liberia: protocol for a pilot prospective cohort study.

Introduction: Achieving glycaemic targets for people living with diabetes (PLWD) is challenging, especially in settings with limited resources. Programmes need to address gaps in knowledge, skills and self-management. Diabetes Self-Management Education (DSME) is an evidence-based intervention to educate and empower PLWD to improve self-management activities.

Combined Dusp4 and p53 loss with Dbf4 amplification drives tumorigenesis via cell cycle restriction and replication stress escape in breast cancer.

Aim: Deregulated signaling pathways are a hallmark feature of oncogenesis and driver of tumor progression. Dual specificity protein phosphatase 4 (DUSP4) is a critical negative regulator of the mitogen-activated protein kinase (MAPK) pathway and is often deleted or epigenetically silenced in tumors. DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53.