Inactivation of the paraventricular nucleus attenuates the cardiogenic sympathetic afferent reflex in the spontaneously hypertensive rat.

Background: Myocardial ischemia causes the release of bradykinin, which stimulates cardiac afferents, causing sympathetic excitation and chest pain. Glutamatergic activation of the paraventricular hypothalamic nucleus (PVN) in the spontaneously hypertensive rat (SHR) drives elevated basal sympathetic activity. Thus, we tested the hypothesis that inactivation of the PVN attenuates the elevated reflex response to epicardial bradykinin in the SHR and that ionotropic PVN glutamate receptors mediate the elevated reflex.

Implications of the accuracy of diagnostic algorithms for systemic lupus on our understanding of racial disparities in pregnancy outcomes.

Objective: Disparities in pregnancy outcomes among women with SLE remain understudied, with few available racially diverse datasets. We sought to identify disparities between Black and White women in pregnancy outcomes within academic institutions in the United States.

Methods: Using the Common Data Model electronic medical record (EMR)-based datasets within the Carolinas Collaborative, we identified women with pregnancy delivery data (2014-2019) and ≥1 SLE International Classification of Diseases 9 or 10 code (ICD9/10) code.

Hotairm1 Controls S100A9 Protein Phosphorylation in Myeloid-Derived Suppressor Cells during Sepsis.

During the acute phase of sepsis, the S100A9 proinflammatory protein resides in the cytosol in a phosphorylated form. In contrast, S100A9 relocalizes to the nucleus in an unphosphorylated form during the late/chronic sepsis state of immunometabolic paralysis. We reported that Hotairm1, a long noncoding RNA, facilitates S100A9 nuclear location in myeloid-derived suppressor cells.

Rapid recovery pathway without epidural catheter analgesia for surgical treatment of adolescent idiopathic scoliosis: a comparative study.

Purpose: To assess effectiveness of a rapid recovery pathway (RRP) without epidural catheter analgesia (ECA) or intravenous patient controlled analgesia (PCA) in accelerating recovery and decreasing opioid consumption in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF).

Methods: A retrospective cohort study included collection of demographics, ECA use, IV PCA, postoperative opioid consumption, postoperative pain scores, and reoperation rate. Opioid consumption was calculated using morphine milligram equivalents (MME).

Inhibiting KDM6A Demethylase Represses Long Non-Coding RNA Hotairm1 Transcription in MDSC During Sepsis.

Myeloid-derived suppressor cells (MDSCs) prolong sepsis by promoting immunosuppression. We reported that sepsis MDSC development requires long non-coding RNA Hotairm1 interactions with S100A9. Using a mouse model that simulates the immunobiology of sepsis, we find that histone demethylase KDM6A promotes Hotairm1 transcription by demethylating transcription repression H3K27me3 histone mark.

KDM6A Lysine Demethylase Directs Epigenetic Polarity of MDSCs during Murine Sepsis.

Sepsis-induced myeloid-derived suppressor cells (MDSCs) increase mortality risk. We previously identified that long non-coding RNA Hotairm1 supports myeloid precursor shifts to Gr1+CD11b+ MDSCs during mouse sepsis. A major unanswered question is what molecular processes control Hotairm1 expression.

Changes in For-Profit Medication-Assisted Therapy Clinics in an Appalachian City.

Objectives: This study is a follow-up to previous research regarding buprenorphine medication-assisted therapy (MAT) in Johnson City, Tennessee. For-profit MAT clinics were surveyed to determine changes in tapering practice patterns and insurance coverage during the last 3 years.

Methods: Johnson City for-profit MAT clinics; also called office based opioid treatment centers, were surveyed by telephone.

Incidental Findings in the Trauma Population: Interdisciplinary Approach and Electronic Medical Record Reminder Association with Pre-Discharge Reporting and Medicolegal Risk.

Background: Incidental findings (IFs) are reported in 20% or more of trauma CT scans. In addition to the importance of patient disclosure, there is considerable legal pressure to avoid missed diagnoses. We reported previously that 63.

Long Non-Coding RNA Hotairm1 Promotes S100A9 Support of MDSC Expansion during Sepsis.

Myeloid-derived suppressor cells (MDSCs) expand during mouse and human sepsis, but the mechanism responsible for this is unclear. We previously reported that nuclear transport of S100A9 protein programs Gr1CD11b myeloid precursors into MDSCs in septic mice. Here, we show that long non-coding RNA Hotairm1 converts MDSCs from an activator to a repressor state.

HuR promotes miRNA-mediated upregulation of NFI-A protein expression in MDSCs during murine sepsis.

Myeloid-derived suppressor cells (MDSCs) contribute to high mortality rates during sepsis, but how sepsis induces MDSCs is unclear. Previously we reported that microRNA (miR)-21 and miR-181b reprogram MDSCs in septic mice by increasing levels of DNA binding transcription factor, nuclear factor 1 (NFI-A). Here, we provide evidence that miR-21 and miR-181b stabilize NFI-A mRNA and increase NFI-A protein levels by recruiting RNA-binding proteins HuR and Ago1 to its 3' untranslated region (3'UTR).

Relationship between inorganic ion distribution, resting membrane potential, and the Δ' of ATP hydrolysis: a new paradigm.

Cell membrane potential and inorganic ion distributions are currently viewed from a kinetic electric paradigm, which ignores thermodynamics. The resting membrane potential is viewed as a diffusion potential. The 9 major inorganic ions found in blood plasma (Ca, Na, Mg, K, H, Cl, HCO, HPO, and HPO) are distributed unequally across the plasma membrane.

S100A9 maintains myeloid-derived suppressor cells in chronic sepsis by inducing miR-21 and miR-181b.

Myeloid-derived suppressor cells (MDSC) expand during sepsis, suppress both innate and adaptive immunity, and promote chronic immunosuppression, which characterizes the late/chronic phase of sepsis. We previously reported that the transcription factors Stat3 and C/EBPβ synergize to induces the expression of microRNA (miR)-21 and miR-181b to promote MDSC expansion in a mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive stage. We also showed that Gr1CD11b cells, the precursors of MDSCs, from mice genetically deficient in the inflammatory protein S100A9 lack miR-21 or miR-181b in late sepsis, and are not immunosuppressive.

The "great" controlling nucleotide coenzymes.

Nucleotide coenzymes dot the map of metabolic pathways providing energy to drive the reactions of the pathway and play an important role in regulating and controlling energy metabolism through their shared potential energy, which is widely unobserved due to the paradox that the energy in the coenzyme pools cannot be determined from the concentration of the coenzyme couples. The potential energy of the nucleotide couples in the mitochondria or the cytoplasm is expressed in the enzyme reactions in which they take part. The energy in these couples, [NAD+]/[NADH], [NADP+]/[NADPH], [acetyl CoA]/[CoA], and [ATP]/[ADP]x[Pi], regulates energy metabolism.

IL-10 induces an immune repressor pathway in sepsis by promoting S100A9 nuclear localization and MDSC development.

The myeloid-related protein S100A9 reprograms Gr1CD11b myeloid precursors into myeloid-derived suppressor cells (MDSCs) during murine sepsis. Here, we show that the immunosuppressive cytokine IL-10 supports S100A9 expression and its nuclear localization in MDSCs to function as immune repressors. To support this new concept, we showed that antibody mediated IL-10 blockade in wild-type mice after sepsis induction inhibited MDSC expansion during late sepsis, and that ectopic expression of S100A9 in Gr1CD11b cells from S100A9 knockout mice switched them into the MDSC phenotype only in the presence of IL-10.

Discrete mitochondrial aberrations in the spinal cord of sporadic ALS patients.

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord leading to muscle atrophy, paralysis, and death. Mitochondrial dysfunction is a major contributor to motor neuron degeneration associated with ALS progression. Mitochondrial abnormalities have been determined in spinal cords of animal disease models and ALS patients.

Intracellular S100A9 Promotes Myeloid-Derived Suppressor Cells during Late Sepsis.

Myeloid precursor cell reprogramming into a myeloid-derived suppressor cell (MDSC) contributes to high mortality rates in mouse and human sepsis. S100A9 mRNA and intracellular protein levels increase during early sepsis and remain elevated in Gr1CD11b MDSCs after pro-inflammatory sepsis transitions to the later chronic anti-inflammatory and immunosuppressive phenotype. The purpose of this study was to determine whether intracellular S100A9 protein might sustain Gr1CD11b MDSC repressor cell reprogramming during sepsis.

Nfia deletion in myeloid cells blocks expansion of myeloid-derived suppressor cells during sepsis.

Sepsis-induced immunosuppression increases the risk of chronic infection and reduces survival. Myeloid-derived suppressor cells (MDSCs) expand in the bone marrow and spleen during murine polymicrobial sepsis, contributing to immunosuppression. A better understanding of molecular controls of MDSC production is needed to identify treatment targets.