Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.

An open-source, battery-powered, low-cost, and dual-channel pneumatic pulse generator for microfluidic cell-stretch assays.

Cells in the body are regularly subjected to mechanical forces that influence their biological fate in terms of morphology, gene expression, and differentiation. The current gold standard method to replicate these effects in vitro is to culture cells on devices with elastic substrates and to impart mechanical stretch using mechanical or pneumatic pull-push methods. Microfluidic device designs offer several advantages in this context for general uniform and controlled stretching.

Impact of Polypharmacy on Symptoms and Health Outcomes in Older Adults With and Without Alzheimer's Disease and Related Dementias.

Background: There is a critical gap in understanding the symptom experience and health outcomes of older adults with and without Alzheimer's Disease and related dementias (ADRD) and polypharmacy (PPY). The primary aim of the study was to compare the number of symptoms experienced over time in older adults with and without ADRD by polypharmacy status. The secondary aim was to examine the trajectory of physical function and health outcomes over time in each group.

Differential relationships between physical activity and pain phenotypes in individuals with spinal cord injury.

Background: Chronic pain affects 70% of individuals with spinal cord injury (SCI) and leads to declines in health and quality of life. Neuropathic and nociceptive pain are phenotypes derived from different mechanisms that contribute to pain perception. The objective of this research was to investigate differential pain responses to moderate-to-vigorous physical activity (MVPA) in two chronic pain phenotypes: neuropathic and nociceptive pain.

Identification of highly selective SIK1/2 inhibitors that modulate innate immune activation and suppress intestinal inflammation.

The salt-inducible kinases (SIK) 1-3 are key regulators of pro- versus anti-inflammatory cytokine responses during innate immune activation. The lack of highly SIK-family or SIK isoform-selective inhibitors suitable for repeat, oral dosing has limited the study of the optimal SIK isoform selectivity profile for suppressing inflammation in vivo. To overcome this challenge, we devised a structure-based design strategy for developing potent SIK inhibitors that are highly selective against other kinases by engaging two differentiating features of the SIK catalytic site.

Baseline Comparison of Exercisers and Nonexercisers With Spinal Cord Injury Enrolled in a Group Tele-Exercise Program.

Background: Individuals with SCI are 1.5 times more likely to be sedentary compared to adults without disabilities or chronic health conditions. It is therefore imperative to develop and evaluate innovative facilitation strategies for physical activity behavior in this population.

Effect of Tele-exercise to Promote Empowered Movement for Individuals With Spinal Cord Injury (TEEMS) Program on Physical Activity Determinants and Behavior: A Mixed Methods Assessment.

Objective: To assess the effects of group tele-exercise participation on physical activity (PA) determinants and behavior as identified by social cognitive theory (SCT) in individuals with spinal cord injury (SCI).

Design: This clinically registered non-randomized trial [NCT05360719] used a single-group parallel mixed methods design. Quantitative and qualitative primary measures were assessed at pre-program and after 8-week intervention completion (post-program), with an additional 8-week period retention to capture quantitative assessments only.

Development and Feasibility of a Group Tele-Exercise Program for Individuals With Spinal Cord Injury.

Background And Purpose: More than 50% of individuals with spinal cord injury (SCI) report no regular exercise due to numerous barriers to participation. Tele-exercise services offer viable solutions to reduce barriers. However, limited evidence for SCI-specific tele-exercise programs is available.

Perspectives on Health With Spinal Cord Injury Now and in the Future: A Qualitative Descriptive Study.

Objective: Over the past half century, the landscape of life and aging with spinal cord injury (SCI) has changed drastically, in part due to medical advancements and the rapidly increasing aging population. With these changes comes a critical need for rehabilitation professionals to understand aging with SCI in relation to strategies that support health maintenance over time. The purpose of this study was to identify and describe the meaning of health maintenance and aging outlook from the perspectives of individuals living with SCI.

Foveated 3D range geometry compression via loss-tolerant variable precision depth encoding.

The capacity of three-dimensional (3D) range geometry acquisition methods to capture high-precision scans at high frame rates increases every year. These improvements have influenced a broadening range of disciplines to implement 3D range geometry capture systems, including telepresence, medicine, the visual arts, and many others. However, its increased popularity, precision, and capture rates have caused mounting pressure on the storage and transmission of 3D range geometry, thus straining their capacities.

Current Considerations in Emergency Airway Management.

Purpose Of Review: Emergency airway management is populated by many new concepts, evolving equipment, and contemporary strategies for optimal procedural success. This review aims to discuss various topics within these realms and to continue the ongoing conversation regarding improvement of emergency airway management.

Recent Findings: Various literature, opinion pieces, podcasts, and trials have prompted renewed interest in the field of emergency airway management.

Cancer screening in prisons: lessons for health providers.

Background: Lifestyle factors place those who experience incarceration at increased risk of morbidity and mortality from a range of preventable diseases, including cancer.

Methods: Two nurses were employed for a period of 6months to facilitate bowel and breast cancer screening of prisoners across four correctional centres in Queensland. We identify factors impacting on cancer screening in prisons and document the outcomes for those screened.

Identification of Two Non-Peptidergic Small Molecule Inhibitors of CBX2 Binding to K27 Trimethylated Oligonucleosomes.

The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing trimethylated lysine on histone 3 (H3K27me3) [2] and is overexpressed in metastatic neuroendocrine prostate cancer. [3,4] We implemented a screening strategy using nucleosome substrates to identify inhibitors of CBX2 binding to chromatin.

Reliability of Upper-Extremity Muscle Activity and Kinematics During Adaptive Rowing.

Context: The purpose of this study was to determine test-retest reliability of upper-extremity muscle activity and kinematics during submaximal adapted rowing.

Design: A repeated-measures design was used.

Methods: Data were collected on 10 individuals (7 male and 3 female) with mobility impairment.

Staying active after rehab: Physical activity perspectives with a spinal cord injury beyond functional gains.

Lifestyle physical activity following spinal cord injury (SCI) is critical for functional independence, mental wellness, and social participation, yet nearly 50% of individuals with SCI report no regular exercise. The objective of this study was to better understand factors leading to this participation gap by capturing the physical activity perspectives of individuals living with SCI. We completed small group interviews with nine individuals living with SCI across the United States.

-Heterocyclic Carbene Ligand Stability on Gold Nanoparticles in Biological Media.

The ability to functionalize gold nanoparticle surfaces with target ligands is integral to developing effective nanosystems for biomedical applications, ranging from point-of-care diagnostic devices to site-specific cancer therapies. By forming strong covalent bonds with gold, thiol functionalities can easily link molecules of interest to nanoparticle surfaces. Unfortunately, thiols are inherently prone to oxidative degradation in many biologically relevant conditions, which limits their broader use as surface ligands in commercial assays.

Quantitative Sensory Changes Related to Physical Activity in Adult Populations: A Scoping Review.

Exercise-induced hypoalgesia related to physical activity produces sensory adaptations, but its mechanism remains unclear. Quantitative sensory testing is an effective measurement tool to identify sensory changes, but the extent of evidence linking quantitative sensory testing and physical activity has not been explored. The purpose of this scoping review is to synthesize the evidence on using quantitative sensory testing to evaluate psychophysical changes related to physical activity in adult populations.

Relationship of psychosocial factors and musculoskeletal pain among individuals with newly acquired spinal cord injury.

Study Design: Cross-sectional analysis of baseline data of a longitudinal cohort study.

Objectives: Little evidence exists on pain-related psychosocial factors in individuals with newly acquired spinal cord injury (SCI). To understand a biopsychosocial model of pain, we must first understand the presenting psychological pain-related factors at injury onset.

Graph theoretical structural connectome analysis of the brain in patients with chronic spinal cord injury: preliminary investigation.

Study Design: Retrospective study.

Objectives: We aimed to characterize the convergent disruptions of the structural connectivity based on network modeling technique (i.e.

Widespread Seropositivity to Viral Hemorrhagic Septicemia Virus (VHSV) in Four Species of Inland Sport Fishes in Wisconsin.

Serological assays were conducted for anti-viral hemorrhagic septicemia virus (VHSV) antibodies in four species of fish in Wisconsin (Bluegill Lepomis macrochirus, Brown Trout Salmo trutta, Northern Pike Esox lucius, and Walleye Sander vitreus) to examine spatial and temporal distributions of exposure. Sera were tested for non-neutralizing anti-nucleocapsid antibodies to VHSV by blocking enzyme-linked immunosorbent assay (ELISA). Results (percent inhibition [%I]) were analyzed for differences among species, across geographic distance, and among water management units.

Integration of teaming therapy and mixed-reality simulation as remote learning modality for couple and family therapy graduate training programs.

In response to COVID-19, a couple and family therapy (CFT) graduate training program integrated a teaming therapy model with virtual technology using mixed-reality simulation software. By utilizing teaming therapy--a model with strong roots in systemic theory and practice-- combined with cutting-edge simulation technology, this distance learning modality provides distinctly relational therapy supervision and training for students at a time when their internships sites are struggling to offer remote clinical services due to the pandemic. This integrative framework offers a high degree of both realism and safety, allowing experiential learning to be appropriately scaffolded for optimum creativity and engagement in an online setting.

Movement Coordination During Humeral Elevation in Individuals With Newly Acquired Spinal Cord Injury.

Humeral elevation is a critical motion for individuals who use a manual wheelchair given that, in a typical day, wheelchair users reach overhead 5 times more often than able-bodied controls. Kinematic analyses in individuals with chronic spinal cord injury (SCI) have focused on weight-bearing tasks rather than overhead reaching. This technical report presents shoulder movement coordination during overhead reaching in individuals with newly acquired SCI.

Shoulder impairment and pain of individuals with newly acquired spinal cord injury compared to uninjured peers.

Study Design: Cohort study.

Objectives: Shoulder pain prevalence is high in those with spinal cord injury (SCI) and is associated with decreased function, participation restrictions and decreased quality of life. Limited evidence exists regarding physical impairments of newly acquired SCI.