Establishment and characterization of an hhTMPRSS2 knock-in mouse model to study SARS-CoV-2.

Despite a substantial body of research, we lack fundamental understanding of the pathophysiology of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) including pulmonary and cardiovascular outcomes, in part due to limitations of murine models. Most models use transgenic mice (K18) that express the human (h) angiotensin converting enzyme 2 (), knock-in (KI) mice, or mouse-adapted strains of SARS-CoV-2. Further, many SARS-CoV-2 variants produce fatal neurologic disease in K18 mice and most murine studies focus only on acute disease in the first 14 days post inoculation (dpi).

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures.

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures.

A gated-time-of-flight top-hat electrostatic analyzer for low energy ion measurements.

When incorporated into a top-hat electrostatic analyzer, a gate electrode enables the separation of ions by their mass-per-charge with modest mass resolution (M/∆M ∼ 10). Gated-time-of-flight (TOF) instruments avoid the energy straggling and angular scattering effects prevalent in foil-based detection systems, providing more pristine measurements of three-dimensional distribution functions of incident ions. Gated-TOF implementations are ideal for measuring the properties of low-energy (i.

Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure.

Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant connection exists between inflammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In this study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring.

Increased Striatal Presynaptic Dopamine in a Nonhuman Primate Model of Maternal Immune Activation: A Longitudinal Neurodevelopmental Positron Emission Tomography Study With Implications for Schizophrenia.

Background: Epidemiological studies suggest that maternal immune activation (MIA) is a significant risk factor for future neurodevelopmental disorders, including schizophrenia (SZ), in offspring. Consistent with findings in SZ research and work in rodent systems, preliminary cross-sectional findings in nonhuman primates suggest that MIA is associated with dopaminergic hyperfunction in young adult offspring.

Methods: In this unique prospective longitudinal study, we used [F]fluoro-l-m-tyrosine positron emission tomography to examine the developmental time course of striatal presynaptic dopamine synthesis in male rhesus monkeys born to dams (n = 13) injected with a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid [poly(I:C)], in the late first trimester.

Regulation of beige adipocyte thermogenesis by the cold-repressed ER protein NNAT.

Objective: Cold stimuli trigger the conversion of white adipose tissue into beige adipose tissue, which is capable of non-shivering thermogenesis. However, what process drives this activation of thermogenesis in beige fat is not well understood. Here, we examine the ER protein NNAT as a regulator of thermogenesis in adipose tissue.

Effects of Music Therapy on Quality of Life in Adults with Sickle Cell Disease (MUSIQOLS): A Mixed Methods Feasibility Study.

Purpose: To investigate the feasibility, acceptability, and preliminary efficacy of a 6-session music therapy protocol on self-efficacy, quality of life, and coping skills in adults with sickle cell disease (SCD).

Patients And Methods: Using a mixed-methods intervention design, adults with SCD (ages 21-57; mean age 32.33) were randomized (1:1) to either 1) a 6-session music therapy (MT) intervention (n = 12) or 2) waitlist control (WLC) (n = 12) using stratified randomization where factors were age in years (≤30 vs >30), and sex (male, female).

Evaluation of Atmospheric 3-Day Waves as a Source of Day-to-Day Variation of the Ionospheric Longitudinal Structure.

We report for the first time the day-to-day variation of the longitudinal structure in height of the F layer (hF) in the equatorial ionosphere using multi-satellite observations of electron density profiles by the Constellation Observing System for Meteorology, Ionosphere and Climate-2 (COSMIC-2). These observations reveal a ~3-day modulation of the hF wavenumber-4 structure viewed in a fixed local time frame during January 30-February 14, 2021. Simultaneously, ~3-day planetary wave activity is discerned from zonal wind observations at ~100 km by the Ionospheric Connection Explorer (ICON) Michelson Interferometer for Global High-Resolution Thermospheric Imaging (MIGHTI).

Strain differences in the extent of brain injury in mice after tetramethylenedisulfotetramine-induced status epilepticus.

Acute intoxication with tetramethylenedisulfotetramine (TETS) can trigger status epilepticus (SE) in humans. Survivors often exhibit long-term neurological effects, including electrographic abnormalities and cognitive deficits, but the pathogenic mechanisms linking the acute toxic effects of TETS to chronic outcomes are not known. Here, we use advanced in vivo imaging techniques to longitudinally monitor the neuropathological consequences of TETS-induced SE in two different mouse strains.

Targeting the CCR6/CCL20 Axis in Entheseal and Cutaneous Inflammation.

Objective: To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target.

Methods: First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade.

The fall, recovery, classification, and initial characterization of the Hamburg, Michigan H4 chondrite.

The Hamburg meteorite fell on January 16, 2018, near Hamburg, Michigan, after a fireball event widely observed in the U.S. Midwest and in Ontario, Canada.

Acute administration of diazepam or midazolam minimally alters long-term neuropathological effects in the rat brain following acute intoxication with diisopropylfluorophosphate.

Acute intoxication with organophosphorus cholinesterase inhibitors (OPs) can trigger seizures that rapidly progress to life-threatening status epilepticus. Diazepam, long considered the standard of care for treating OP-induced seizures, is being replaced by midazolam. Whether midazolam is more effective than diazepam in mitigating the persistent effects of acute OP intoxication has not been rigorously evaluated.

Suppression of inflammation and fibrosis using soluble epoxide hydrolase inhibitors enhances cardiac stem cell-based therapy.

Stem cell replacement offers a great potential for cardiac regenerative therapy. However, one of the critical barriers to stem cell therapy is a significant loss of transplanted stem cells from ischemia and inflammation in the host environment. Here, we tested the hypothesis that inhibition of the soluble epoxide hydrolase (sEH) enzyme using sEH inhibitors (sEHIs) to decrease inflammation and fibrosis in the host myocardium may increase the survival of the transplanted human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in a murine postmyocardial infarction model.

Differential Requirement for CCR6 in IL-23-Mediated Skin and Joint Inflammation.

CCR6 is important for the trafficking of IL-17A-producing γδ T cells and required for the development of psoriasiform dermatitis in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23-mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type and CCR6-deficient (CCR6-knockout) mice to induce overexpression of IL-23 systemically.

The chemical convulsant diisopropylfluorophosphate (DFP) causes persistent neuropathology in adult male rats independent of seizure activity.

Organophosphate (OP) threat agents can trigger seizures that progress to status epilepticus, resulting in persistent neuropathology and cognitive deficits in humans and preclinical models. However, it remains unclear whether patients who do not show overt seizure behavior develop neurological consequences. Therefore, this study compared two subpopulations of rats with a low versus high seizure response to diisopropylfluorophosphate (DFP) to evaluate whether acute OP intoxication causes persistent neuropathology in non-seizing individuals.

Extensive Recontouring of the Femoral Head with Osteochondral Allografting: A Case Report with Histological and MicroCT Analysis.

Morphological abnormalities such as cam deformity or growth disturbances can have a detrimental effect on the smooth function of the hip joint. This case reports an attempt to salvage the hip joint of a young patient with a posttraumatic growth disturbance of the femoral head using a fresh osteochondral allograft. This treatment has been used very rarely in the femoral head due to the presumed tenuous blood supply of the head and the perceived risk of nonunion or progressive avascular necrosis.

Atopy patch tests may identify patients at risk for systemic contact dermatitis.

Background: A subset of patients with positive patch tests demonstrates systemic contact dermatitis (SCD) upon ingestion or inhalation of the allergen. Concern has been raised about the use of patch tests for protein allergens (APTs) to detect SCD in atopic dermatitis (AD) patients.

Methods: We present atopy patch test (APT) data for 97 people.

TSPO PET Using [18F]PBR111 Reveals Persistent Neuroinflammation Following Acute Diisopropylfluorophosphate Intoxication in the Rat.

Acute intoxication with organophosphates (OPs) can trigger status epilepticus followed by persistent cognitive impairment and/or electroencephalographic abnormalities. Neuroinflammation is widely posited to influence these persistent neurological consequences. However, testing this hypothesis has been challenging, in part because traditional biometrics preclude longitudinal measures of neuroinflammation within the same animal.

Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation.

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans.

Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele.

Introduction: The surgically induced fetal lamb model is the most commonly used large animal model of myelomeningocele (MMC) but is subject to variation due to surgical technique during defect creation.

Material And Methods: Thirty-one fetal lambs underwent creation of the MMC defect, followed by defect repair with either an extracellular matrix (ECM) patch (n = 10) or ECM seeded with placental mesenchymal stromal cells (n = 21). Postnatal hindlimb function was assessed using the Sheep Locomotor Rating (SLR) scale.

Atopy and Sensitization to Allergens Known to Cause Systemic Contact Dermatitis.

Background: Atopic dermatitis (AD) associated with respiratory atopy may represent a form of systemic contact dermatitis (SCD), whereby AD flares after ingestion or inhalation of allergens.

Objective: The aim of the study was to compare the prevalence of positive patch tests to allergens known to cause SCD in AD patients with and without respiratory atopy.

Methods: This is a retrospective study of patients with AD patch tested to 23 allergens known to cause SCD.

Imaging, Behavior and Endocrine Analysis of "Jealousy" in a Monogamous Primate.

Understanding the neurobiology of social bonding in non-human primates is a critical step in understanding the evolution of monogamy, as well as understanding the neural substrates for emotion and behavior. Coppery titi monkeys () form strong pair bonds, characterized by selective preference for their pair mate, mate-guarding, physiological and behavioral agitation upon separation, and social buffering. Mate-guarding, or the "maintenance" phase of pair bonding, is relatively under-studied in primates.

A magnetic resonance imaging study of early brain injury in a rat model of acute DFP intoxication.

Current treatments for seizures induced by organophosphates do not protect sufficiently against progressive neurodegeneration or delayed cognitive impairment. Developing more effective therapeutic approaches has been challenging because the pathogenesis of these delayed consequences is poorly defined. Using magnetic resonance imaging (MRI), we previously reported brain lesions that persist for months in a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP).