TMEM16A Antagonism: Therapeutic Potential with Desensitization of β-agonist Responsiveness in Asthma.

The efficacy of β-agonists in asthma is severely limited by β-adrenoceptor desensitization which results in poorly managed symptoms and refractory bronchoconstriction. Thus, there is a need to identify novel therapeutic pathways and to clarify the relationship between novel therapeutics and functional β-adrenoceptor responsiveness. We have previously demonstrated that acute antagonism of the calcium activated chloride channel, transmembrane member 16A (TMEM16A), relaxes airway smooth muscle (ASM).

Mind-Body Interventions for Youth with Chronic Medical Conditions: A Scoping Review of the Literature.

Little is known about the applicability, utilization, and effectiveness of mind-body interventions (MBIs) for conditions that are not predominantly pain, neoplastic, or psychiatric, particularly in pediatric patients. This scoping review describes research pertaining to such interventions in youth with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Searches of EBSCO CINAHL, Elsevier Scopus, Ovid for MEDLINE, and Ovid PsycInfo were conducted to investigate MBIs in youth under 18 years of age with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions.

Insufflation via a peritoneal dialysis catheter is a safe way to achieve pneumoperitoneum: a case report.

A 66-year-old female with a preoperative high index hostile abdomen was incidentally found to have a right T1a 16 mm renal cell carcinoma mass. She safely underwent robot assisted partial nephrectomy after her peritoneal dialysis catheter was alternatively used for insufflation. This adjustment in technique reduced risk related morbidity and possible conversion to open laparotomy.

Multifaceted roles and regulation of nucleotide-binding oligomerization domain containing proteins.

Nucleotide-binding oligomerization domain-containing proteins, NOD1 and NOD2, are cytosolic receptors that recognize dipeptides and tripeptides derived from the bacterial cell wall component peptidoglycan (PGN). During the past two decades, studies have revealed several roles for NODs beyond detecting PGN fragments, including activation of an innate immune anti-viral response, NOD-mediated autophagy, and ER stress induced inflammation. Recent studies have also clarified the dynamic regulation of NODs at cellular membranes to generate specific and balanced immune responses.

Ruptured Appendicitis Within an Intussusception on Point-of-Care Ultrasound.

This case describes a 21-month-old girl who was transferred to our pediatric emergency department with daily fevers for 9 days and concern for intussusception on an ultrasound obtained at the outside hospital. Her examination was notable for diffuse tenderness to palpation with no rebound or guarding. Point-of-care-ultrasound (POCUS) revealed a noncompressible, target-shaped structure in the right midabdomen, which appeared to contain a dilated loop of bowel surrounded by a hypoechoic fluid collection.

Modified stepping behaviour during outdoor winter walking increases resistance to forward losses of stability.

Healthy humans are proficient at maintaining stability when faced with diverse walking conditions, however, the control strategies that lead to this proficiency are unclear. Previous laboratory-based research has predominantly concluded that corrective stepping is the main strategy, but whether this finding holds when facing everyday obstacles outside of the laboratory is uncertain. We investigated changes in gait stability behaviour when walking outdoors in the summer and winter, hypothesizing that as ground conditions worsened in the winter, the stepping strategy would be hindered.

A comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic.

Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all coronaviruses represented in the NCBI Virus database.

Validation of Inertial Sensors to Evaluate Gait Stability.

The portability of wearable inertial sensors makes them particularly suitable for measuring gait in real-world walking situations. However, it is unclear how well inertial sensors can measure and evaluate gait stability compared to traditional laboratory-based optical motion capture. This study investigated whether an inertial sensor-based motion-capture suit could accurately assess gait stability.

Telemedicine use among patients with metastatic breast cancer during the COVID-19 pandemic: Differences by race, age, and region.

Purpose: Our objective was to describe differences in telemedicine use among women with metastatic breast cancer (mBC) by race, age, and geographic region.

Methods: This was a retrospective cohort study of women with recurrent or de novo mBC treated in US community cancer practices that initiated a new line of therapy between March 2020 and February 2021. Multivariable modified Poisson regression models were used to calculate adjusted rate ratios (RR) and robust 95% confidence intervals (CI) associated with telemedicine visits within 90 days of therapy initiation.

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility Opsin 3.

Opsin photoreceptors outside of the central nervous system have been shown to mediate smooth muscle photorelaxation in several organs. We hypothesized that opsin receptor activation in the colon would have a similar effect and influence colonic motility. We detected Opsin 3 (OPN3) protein expression in the colonic wall and demonstrated that OPN3 was present in enteric neurons in the muscularis propria of the murine colon.

Human biomechanics perspective on robotics for gait assistance: challenges and potential solutions.

Technological advancements in robotic devices have the potential to transform human mobility through gait assistance. However, the integration of physical hardware and software control algorithms with users to assist with impaired gait poses several challenges, such as allowing the user to adopt a variety of gaits and the process for evaluating the efficacy and performance of these assistive devices. Here, I discuss some of the challenges in the development of assistive devices and the use of biomechanical concepts and tools for control and test validation.

Learning from and Leveraging Multi-Level Changes in Responses to the COVID 19 Pandemic to Facilitate Breast Cancer Prevention Efforts.

The coronavirus pandemic (COVID-19) has had multilevel effects on non-COVID-19 health and health care, including deferral of routine cancer prevention and screening and delays in surgical and other procedures. Health and health care use has also been affected by pandemic-related loss of employer-based health insurance, food and housing disruptions, and heightened stress, sleep disruptions and social isolation. These disruptions are projected to contribute to excess non-COVID-19 deaths over the coming decades.

Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle.

Background: Currently available tocolytic agents are not effective treatment for preterm labor beyond 48 h. A major reason is the development of maternal side effects which preclude the maintenance of an effective steady-state drug concentration. One strategy that can mitigate these side effects is utilizing synergistic drug combinations to reduce the drug concentrations necessary to elicit a clinical effect.

Opsin 3-G Promotes Airway Smooth Muscle Relaxation Modulated by G Protein Receptor Kinase 2.

Recently, we characterized blue light-mediated relaxation (photorelaxation) of airway smooth muscle (ASM) and implicated the involvement of opsin 3 (OPN3), an atypical opsin. In the present study, we characterized the cellular signaling mechanisms of photorelaxation. We confirmed the functional role of OPN3 in blue light photorelaxation using trachea from OPN3 null mice (maximal relaxation 52 ± 13% compared with wild-type mice 90 ± 4.

Upper body and ankle strategies compensate for reduced lateral stability at very slow walking speeds.

At the typical walking speeds of healthy humans, step placement seems to be the primary strategy to maintain gait stability, with ankle torques and upper body momentum providing additional compensation. The average walking speeds of populations with an increased risk of falling, however, are much slower and may require differing control strategies. The purpose of this study was to analyse mediolateral gait stability and the contributions of the different control strategies at very slow walking speeds.

Correction to: Activation of an Endogenous Opsin 3 Light Receptor Mediates Photo-Relaxation of Pre-Contracting Late Gestation Human Uterine Smooth Muscle Ex Vivo.

This article was updated to correct Joy Y. Vink's name in the author listing.

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by F-positron emitting tomography and fluorescence.

Purpose: Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS).

Methods: We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence.

A lysosome specific, acidic-pH activated, near-infrared Bodipy fluorescent probe for noninvasive, long-term, in vivo tumor imaging.

Long-term, in vivo, fluorescent cell tracking probes are useful for understanding complex cellular processes including tissue regeneration, communication, development, invasion, and cancer metastasis. A near-infrared fluorescent, water-soluble probe is particularly important for studying these biological events and processes. Herein, a lysosome specific, near-infrared Bodipy probe with increased fluorescent intensity in the acidic, lysosome environment is reported.

Activation of an Endogenous Opsin 3 Light Receptor Mediates Photo-Relaxation of Pre-Contracting Late Gestation Human Uterine Smooth Muscle Ex Vivo.

Spontaneous preterm birth (sPTB) remains a worldwide healthcare challenge. Preterm labor (PTL) is thought to be the largest reversible cause of sPTB, but current tocolytic therapies are ineffective and associated with systemic side effects from chronic use. Therefore, identifying novel mechanisms that promote human uterine smooth muscle (hUSM) relaxation is essential to improving clinical management of PTL.

Novel Expression of GABAA Receptors on Resistance Arteries That Modulate Myogenic Tone.

The clinical administration of GABAergic medications leads to hypotension which has classically been attributed to the modulation of neuronal activity in the central and peripheral nervous systems. However, certain types of peripheral smooth muscle cells have been shown to express GABAA receptors, which modulate smooth muscle tone, by the activation of these chloride channels on smooth muscle cell plasma membranes. Limited prior studies demonstrate that non-human large-caliber capacitance blood vessels mounted on a wire myograph are responsive to GABAA ligands.

Mechanics of very slow human walking.

Human walking speeds can be influenced by multiple factors, from energetic considerations to the time to reach a destination. Neurological deficits or lower-limb injuries can lead to slower walking speeds, and the recovery of able-bodied gait speed and behavior from impaired gait is considered an important rehabilitation goal. Because gait studies are typically performed at faster speeds, little normative data exists for very slow speeds (less than 0.

Stepping behaviour contributes little to balance control against continuous mediolateral trunk perturbations.

Human bipedal gait is exceptionally stable, but the underlying strategies to maintain stability are unclear, especially in the frontal plane. Our study investigated balance strategies of healthy adults subjected to continuous mediolateral oscillations at the trunk during walking. We used a backpack with a passive inverted pendulum to create perturbations that were fixed, in-phase or out-of-phase with subjects' trunk.

An [F]-Positron Emitting Fluorophore Allows Safe Evaluation of Small Molecule Distribution in the CSF, CSF Fistulas, and CNS Device Placement.

The small molecule fluorescein is commonly used to guide the repair of cerebral spinal fluid leaks (CSFLs) in the clinic. We modified fluorescein so that it is also visible by positron emission tomography (PET). This probe was used to quantitatively track the fast distribution of small molecules in the CSF of rats.

Haptic Feedback Perception and Learning With Cable-Driven Guidance in Exosuit Teleoperation of a Simulated Drone.

Robotics teleoperation enables human operators to control the movements of distally located robots. The development of new wearable interfaces as alternatives to hand-held controllers has created new modalities of control, which are more intuitive to use. Nevertheless, such interfaces also require a period of adjustment before operators can carry out their tasks proficiently.