The glomerular circadian clock temporally regulates basement membrane dynamics and the podocyte glucocorticoid response.

Kidney physiology shows diurnal variation, and a disrupted circadian rhythm is associated with kidney disease. However, it remains largely unknown whether glomeruli, the filtering units in the kidney, are under circadian control. Here, we investigated core circadian clock components in glomeruli, together with their rhythmic targets and modes of regulation.

Dual activity of Minnelide chemosensitize basal/triple negative breast cancer stem cells and reprograms immunosuppressive tumor microenvironment.

Triple negative breast cancer (TNBC) subtype is characterized with higher EMT/stemness properties and immune suppressive tumor microenvironment (TME). Women with advanced TNBC exhibit aggressive disease and have limited treatment options. Although immune suppressive TME is implicated in driving aggressive properties of basal/TNBC subtype and therapy resistance, effectively targeting it remains a challenge.

IFN Receptor 2 Regulates TNF-α-Mediated Damaging Inflammation during Aspergillus Pulmonary Infection.

The increased incidence of invasive pulmonary aspergillosis, caused by Aspergillus fumigatus, occurring in patients infected with severe influenza or SARS-CoV-2, suggests that antiviral immune responses create an environment permissive to fungal infection. Our recent evidence suggests that absence of the type I IFN receptor 2 subunit (IFNAR2) of the heterodimeric IFNAR1/2 receptor is allowing for this permissive immune environment of the lung through regulation of damage responses. Because damage is associated with poor outcome to invasive pulmonary aspergillosis, this suggested that IFNAR2 may be involved in A.

Lower Extremity Amputation in Fracture-Related Infection.

Objectives: To analyze demographics, comorbidities, fracture characteristics, presenting characteristics, microbiology, and treatment course of patients with fracture-related infections (FRIs) to determine risk factors leading to amputation.

Design: Retrospective cohort.

Setting: Single Level I Trauma Center (2013-2020).

Chassis-based fiber-coupled optical probe design for reproducible quantitative diffuse optical spectroscopy measurements.

Advanced optical neuromonitoring of cerebral hemodynamics with hybrid diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) methods holds promise for non-invasive characterization of brain health in critically ill patients. However, the methods' fiber-coupled patient interfaces (probes) are challenging to apply in emergent clinical scenarios that require rapid and reproducible attachment to the head. To address this challenge, we developed a novel chassis-based optical probe design for DOS/DCS measurements and validated its measurement accuracy and reproducibility against conventional, manually held measurements of cerebral hemodynamics in pediatric swine (n = 20).

Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine.

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury.

Volenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial.

Background: Volenrelaxin is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration.

Methods: In this Phase 1, four-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n = 56) received an intravenous or subcutaneous dose of volenrelaxin or placebo in a dose-ascending manner.

Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine.

We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB.

Dual activity of Minnelide chemosensitize basal/triple negative breast cancer stem cells and reprograms immunosuppressive tumor microenvironment.

Triple negative breast cancer (TNBC) subtype is characterized with higher EMT/stemness properties and immune suppressive tumor microenvironment (TME). Women with advanced TNBC exhibit aggressive disease and have limited treatment options. Although immune suppressive TME is implicated in driving aggressive properties of basal/TNBC subtype and therapy resistance, effectively targeting it remains a challenge.

Anchor-Based Meniscal Ramp Repair.

Ramp lesions of the medial meniscus are underdiagnosed because of difficulty in visualizing via magnetic resonance imaging and during arthroscopy. They most often occur simultaneously with anterior cruciate ligament (ACL) injury but may also be associated with posterior plateau contusions, steeper medial tibial plateau slope, and excess varus alignment. Upwards of 24% of ACL reconstructions have concomitant ramp lesions.

Enhancing Neuronal Cell Uptake of Therapeutic Nucleic Acids with Tetrahedral DNA Nanostructures.

The successful translation of therapeutic nucleic acids (NAs) for the treatment of neurological disorders depends on their safe and efficient delivery to neural cells, in particular neurons. DNA nanostructures can be a promising NAs delivery vehicle. Nonetheless, the potential of DNA nanostructures for neuronal cell delivery of therapeutic NAs is unexplored.

The Influence of Psychosocial Factors on Patients Undergoing Anterior Cruciate Ligament Reconstruction.

Context: Anterior cruciate ligament (ACL) injuries greatly impact patients in terms of future performance, reduced physical activity and athletic participation, and overall economic burden. Decades of research have investigated how to improve ACL reconstruction (ACLR) outcomes. Recently, there has been growing interest to understand the effects of psychosocial factors on patient outcomes.

The Impact of Smoking on Hospital Course and Postoperative Outcomes in Patients With Fracture-Related Infections.

Objectives: To assess the relationship between patient smoking status and fracture-related infection (FRI) characteristics including patient symptoms at FRI presentation, bacterial species of FRI, and rates of fracture union.

Design: Retrospective cohort study.

Setting: Urban level 1 trauma center.

Multilayer DNA Origami with Terminal Interfaces That Are Flat and Wide-Area.

DNA origami is a popular nanofabrication strategy that employs self-assembly of a long single scaffold strand, typically less than 10 kilobases in length, with hundreds of shorter staple strands into a desired shape. In particular, origami arranged as a single-layer rectangle has proven popular as flat pegboards that can display functionalities at staple-strand breakpoints, off the sides of the constituent double helices, with a ∼5.3 nm rhombic-lattice spacing.

Diet-induced changes in metabolism influence immune response and viral shedding dynamics in Jamaican fruit bats.

Land-use change may drive viral spillover from bats into humans, partly through dietary shifts caused by decreased availability of native foods and increased availability of cultivated foods. We manipulated diets of Jamaican fruit bats to investigate whether diet influences shedding of a virus they naturally host. To reflect dietary changes experienced by wild bats during periods of nutritional stress, bats were fed either standard or putative suboptimal diets which were deprived of protein (suboptimal-sugar) and/or supplemented with fat (suboptimal-fat).

Rapid Environmental Contamination With Candida auris and Multidrug-Resistant Bacterial Pathogens Near Colonized Patients.

Background: Environmental contamination is suspected to play an important role in Candida auris transmission. Understanding speed and risks of contamination after room disinfection could inform environmental cleaning recommendations.

Methods: We conducted a prospective multicenter study of environmental contamination associated with C.

High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity.

Diet-induced obesity impairs mitochondrial respiratory responses in tissues that are highly metabolically active, such as the heart. However, less is known about the impact of obesity on the respiratory activity of specific cell types, such as splenic B cells. B cells are of relevance, as they play functional roles in obesity-induced insulin resistance, inflammation, and responses to infection.

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability.

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol).

Orthopaedic Trauma Association Global Outreach Task Force Proceedings.

Introduction: In 2020, the Orthopaedic Trauma Association (OTA) adopted an updated strategic plan emphasizing global outreach. A task force was appointed to better understand the current global orthopaedic trauma educational demand and how the organization may better partner with our global colleagues. This article provides a description of the process and the results of the findings.

Impact of a pyridazine derivative on tripartite synapse ultrastructure in hippocampus: a three-dimensional analysis.

Introduction: We previously discovered a pyridazine derivative compound series that can improve cognitive functions in mouse models of Alzheimer's disease. One of the advanced compounds from this series, LDN/OSU-0215111-M3, was selected as the preclinical development candidate. This compound activates local protein translation at the perisynaptic astrocytic process (PAP) and enhances synaptic plasticity sequentially.

Non-invasive diffuse optical monitoring of cerebral physiology in an adult swine-model of impact traumatic brain injury.

In this study, we used diffuse optics to address the need for non-invasive, continuous monitoring of cerebral physiology following traumatic brain injury (TBI). We combined frequency-domain and broadband diffuse optical spectroscopy with diffuse correlation spectroscopy to monitor cerebral oxygen metabolism, cerebral blood volume, and cerebral water content in an established adult swine-model of impact TBI. Cerebral physiology was monitored before and after TBI (up to 14 days post injury).