Remimazolam: A Retrospective Study of Initial Safety and Recovery Data in Diverse Procedural Sedation.

Purpose: The new ultra-short-acting benzodiazepine, remimazolam, offers a pharmacokinetic and pharmacodynamic advantage over commonly used procedural sedation medication. This retrospective study explored the real-world utilization of remimazolam during procedural sedation to support the development of a nurse sedation protocol. The primary outcome was to identify associations between recovery time, adverse reactions, and dose-response in expanded patient populations.

A quality improvement initiative to reduce the time to initial maternal visit in the neonatal intensive care unit.

Objective: We aimed to reduce the time interval between an infant's admission to the Neonatal Intensive Care Unit (NICU) and first maternal interaction.

Methods: We identified three key drivers: 1. Collaboration with Labor and Delivery, 2.

Convergent antibody responses are associated with broad neutralization of hepatitis C virus.

Introduction: Early development of broadly neutralizing antibodies (bNAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein E2 is associated with spontaneous clearance of infection, so induction of bNAbs is a major goal of HCV vaccine development. However, the molecular antibody features important for broad neutralization are not known.

Methods: To identify B cell repertoire features associated with broad neutralization, we performed RNA sequencing of the B cell receptors (BCRs) of HCV E2-reactive B cells of HCV-infected individuals with either high or low plasma neutralizing breadth.

Single-cell atlas of epithelial and stromal cell heterogeneity by lobe and strain in the mouse prostate.

Background: Evaluating the complex interplay of cell types in the tissue microenvironment is critical to understanding the origin and progression of diseases in the prostate and potential opportunities for intervention. Mouse models are an essential tool to investigate the molecular and cell-type-specific contributions of prostate disease at an organismal level. While there are well-documented differences in the extent, timing, and nature of disease development in various genetically engineered and exposure-based mouse models in different mouse strains and prostate lobes within each mouse strain, the underlying molecular phenotypic differences in cell types across mouse strains and prostate lobes are incompletely understood.

Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen therapy through MYC.

Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined.

Increasing usage of mother's own milk in neonates at risk of neonatal abstinence syndrome: MOM-NAS quality improvement initiative.

Objective: To increase the usage rate of mothers' own milk (MOM) among neonates with prenatal opioid exposure from a baseline average of 47% to an average of 75% over two years.

Study Design: Between October 2018 and December 2020, we implemented various Plan-Do-Study-Act cycles that involved engaging providers in postpartum counseling for mothers with opioid dependence, using electronic medical records to track the rate of counseling, providing NAS educational materials to parents, and establishing a rooming-in unit. Our outcome measure was the provision of MOM to eligible neonates, while our process measure was the rate of postpartum counseling.

Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers.

PD-1 blockade unleashes CD8 T cells, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens, and little is known about transcriptional programs of MANA-specific TIL.

Pervasive promoter hypermethylation of silenced TERT alleles in human cancers.

Background: In cancers, maintenance of telomeres often occurs through activation of the catalytic subunit of telomerase, encoded by TERT. Yet, most cancers show only modest levels of TERT gene expression, even in the context of activating hotspot promoter mutations (C228T and C250T). The role of epigenetic mechanisms, including DNA methylation, in regulating TERT gene expression in cancer cells is as yet not fully understood.

Using the Nintendo Wii Fit and body weight support to improve aerobic capacity, balance, gait ability, and fear of falling: two case reports.

Background & Purpose: Lower limb amputation in older adults has a significant impact on balance, gait, and cardiovascular fitness, resulting in diminished community participation. The purpose of this case study was to describe the effects of a balance training program utilizing the Nintendo Wii™ Fit (Nintendo of America, Inc, Redmond, Washington) balance board and body-weight supported gait training on aerobic capacity, balance, gait, and fear of falling in two persons with transfemoral amputation.

Case Descriptions: Participant A, a 62 year-old male 32 months post traumatic transfemoral amputation, reported fear of falling and restrictions in community activity.

Advanced cardiac life support instruction: do we know tomorrow what we know today?

This study compared two instructional and evaluation methods for teaching advanced cardiac life support (ACLS) to health care professionals who were taking the ACLS course for the first time. Outcomes of the instruction were measured on completion of the course and at 3 months and 6 months postinstruction to identify differences in participants' knowledge retention, skills competency, and self-efficacy in performing ACLS. In addition, satisfaction with the teaching method was evaluated.

CpG oligodeoxynucleotides augment the murine immune response to the Yersinia pestis F1-V vaccine in bubonic and pneumonic models of plague.

The current U.S. Department of Defense candidate plague vaccine is a fusion between two Yersinia pestis proteins: the F1 capsular protein, and the low calcium response (Lcr) V-protein.

Simple inhibitors of histone deacetylase activity that combine features of short-chain fatty acid and hydroxamic acid inhibitors.

Butyric acid and trichostatin A (TSA) are anti-cancer compounds that cause the upregulation of genes involved in differentiation and cell cycle regulation by inhibiting histone deacetylase (HDAC) activity. In this study we have synthesized and evaluated compounds that combine the bioavailability of short-chain fatty acids, like butyric acid, with the bidentate binding ability of TSA. A series of analogs were made to examine the effects of chain length, simple aromatic cap groups, and substituted hydroxamates on the compounds' ability to inhibit rat-liver HDAC using a fluorometric assay.

TIM-4 expressed on APCs induces T cell expansion and survival.

TIM (T cell, Ig, mucin) proteins can regulate T cell immune responses. Tim-4 mRNA is not expressed in T cells, but exclusively in APCs. Tim-4 is a ligand for Tim-1 and Tim-4.

Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy.

Human immunodeficiency virus (HIV) persists in peripheral blood mononuclear cells despite sustained, undetectable plasma viremia resulting from long-term antiretroviral therapy. However, the source of persistent HIV in such infected individuals remains unclear. Given recent data suggesting high levels of viral replication and profound depletion of CD4(+) T cells in gut-associated lymphoid tissue (GALT) of animals infected with simian immunodeficiency virus and HIV-infected humans, we sought to determine the level of CD4(+) T cell depletion as well as the degree and extent of HIV persistence in the GALT of infected individuals who had been receiving effective antiviral therapy for prolonged periods of time.

Detection of the host immune response to Burkholderia mallei heat-shock proteins GroEL and DnaK in a glanders patient and infected mice.

We examined, by enzyme-linked immunosorbent assay and Western blot analysis, the host immune response to 2 heat-shock proteins (hsps) in a patient and mice previously infected with Burkholderia mallei. The patient was the first reported human glanders case in 50 years in the United States. The expression of the groEL and dnaK operons appeared to be dependent upon a sigma(32) RNA polymerase as suggested by conserved heat-shock promoter sequences, and the groESL operon may be negatively regulated by a controlling invert repeat of chaperone expression (CIRCE) site.

Impact of HIV on cell survival and antiviral activity of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are important mediators of innate immunity that act mainly through secretion of interferon (IFN)-alpha. Previous studies have found that these cells can suppress HIV in vitro; additionally, pDCs have been shown to be severely reduced in the peripheral blood of HIV-infected individuals. In the present study, we sought to determine the ability of pDCs to directly suppress viral replication ex vivo and to delineate the potential mechanisms whereby pDCs are depleted in HIV-infected individuals.

TIM family of genes in immunity and tolerance.

T cells on activation differentiate into different subsets (Th1 or Th2) with distinct effector functions. These T cell subsets are primarily differentiated on the basis of the cytokines that they produce, however, we have identified a novel gene family called TIM (T cell, immunoglobulin, mucin domain-containing molecules), whose members are differentially expressed on Th1 and Th2 cells. Three of the family members (Tim-1, Tim-3, and Tim-4) are conserved between mouse and man.

Conserved and heterogeneous lipid antigen specificities of CD1d-restricted NKT cell receptors.

CD1d-restricted NKT cells use structurally conserved TCRs and recognize both self and foreign glycolipids, but the TCR features that determine these Ag specificities remain unclear. We investigated the TCR structures and lipid Ag recognition properties of five novel Valpha24-negative and 13 canonical Valpha24-positive/Vbeta11-positive human NKT cell clones generated using alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramers. The Valpha24-negative clones expressed Vbeta11 paired with Valpha10, Valpha2, or Valpha3.

Interleukin-12 induces a Th1-like response to Burkholderia mallei and limited protection in BALB/c mice.

We evaluated the effect of interleukin (IL)-12 on the immune response to Burkholderia mallei in BALB/c mice. Mice were vaccinated with non-viable B. mallei cells with or without IL-12.

CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions.

Surface molecules that are differentially expressed on Th1 and Th2 cells may be useful in regulating specific immune responses in vivo. Using a panel of mAbs, we have identified murine CD226 as specifically expressed on the surface of differentiated Th1 cells but not Th2 or Th0 cells. Although CD226 is constitutively expressed on CD8 cells, it is up-regulated on CD4 cells upon activation.

The TIM gene family regulates autoimmune and allergic diseases.

The recently identified TIM gene family encodes cell-surface receptors that are involved in the regulation of Th1- and Th2-cell-mediated immunity. Tim-3 protein is specifically expressed on Th1 cells and negatively regulates Th1 responses, whereas Tim-2 is preferentially expressed in Th2 cells. Tim-1, previously identified as the hepatitis A virus receptor, co-stimulates T-cell expansion and cytokine production.