Malignant otitis externa: What is the role of surgery?

Objective: Malignant otitis externa (MOE) is typically managed with long-term broad-spectrum antibiotics. The impact of surgical intervention on clinical outcomes is not well described. This study aims to compare clinical outcomes of MOE patients managed with or without surgery.

Bringing Inclusivity to "Ethnic" Rhinoplasty: A Novel Anatomical Classification System.

"Ethnic rhinoplasty" is a term that historically has been employed to categorize patterns in nasal anatomy, possible procedures to change appearance, and patient and surgeon expectations for expected outcomes for the multitude of patients with features that belong to non-White groups. Categorizing anatomical structures based on broad definitions of race or ethnicity may not be an accurate representation, nor give an accurate depiction of nasal anatomical features. A shift is needed regarding how race and ethnicity are employed in describing nasal anatomy and rhinoplasty.

Insights into the Interaction Landscape of the EVH1 Domain of Mena.

The Enabled/VASP homology 1 (EVH1) domain is a small module that interacts with proline-rich stretches in its ligands and is found in various signaling and scaffolding proteins. Mena, the mammalian homologue of Ena, is involved in diverse actin-associated events, such as membrane dynamics, bacterial motility, and tumor intravasation and extravasation. Two-dimensional (2D) H-N HSQC NMR was used to study Mena EVH1 binding properties, defining the amino acids involved in ligand recognition for the physiological ligands ActA and PCARE, and a synthetic polyproline-inspired small molecule (hereafter inhibitor ).

Anatomical Diversity of the Adult Corticospinal Tract Revealed by Single-Cell Transcriptional Profiling.

The corticospinal tract (CST) forms a central part of the voluntary motor apparatus in all mammals. Thus, injury, disease, and subsequent degeneration within this pathway result in chronic irreversible functional deficits. Current strategies to repair the damaged CST are suboptimal in part because of underexplored molecular heterogeneity within the adult tract.

Corneal Edema in Inducible Knockout Is Initiated by Mitochondrial Superoxide Induced Src Kinase Activation.

Purpose: Inducible KO leads to corneal edema by disruption of the pump and barrier functions of the corneal endothelium (CE). The loss of Slc4a11 NH-activated mitochondrial uncoupling leads to mitochondrial membrane potential hyperpolarization-induced oxidative stress. The goal of this study was to investigate the link between oxidative stress and the failure of pump and barrier functions and to test different approaches to revert the process.

Nanoliposomes for Sensing Local Osmolarity of the Tear Film on the Corneal Surface.

Local hotspots of elevated tear hyperosmolarity (exceeding 900 mOsM) are predicted in dry eye disease (DED) but have not been measured. This study aims to develop, characterize, and evaluate the suitability of fluorescent nanoliposomes for noninvasive sensing of the local osmolarity of the tear film. Fluorescent nanoliposomes, loaded with calcein (susceptible to self-quenching; sensor dye) and sulforhodamine 101 (SR101; reference dye), were produced by the thin-film hydration method.

Return to sport in elite gymnastics: Unprecedented training interruptions provide lessons for the future.

Introduction: Year-round training is standard for elite gymnasts in the United States, but the coronavirus disease 2019 (COVID-19) pandemic led to unprecedented training interruptions. The effect of these training disruptions is unknown.

Objective: This study aimed to describe and compare training interruptions in elite gymnasts before and during the pandemic, the time it took to return to the prior level of gymnastics training, the development of injuries during return to gymnastics training, and gymnast-reported difficulty in and nervousness about returning to prior level of gymnastics training.

Cell-impermeable staurosporine analog targets extracellular kinases to inhibit HSV and SARS-CoV-2.

Herpes simplex virus (HSV) receptor engagement activates phospholipid scramblase triggering Akt translocation to the outer leaflet of the plasma membrane where its subsequent phosphorylation promotes viral entry. We hypothesize that this previously unrecognized outside-inside signaling pathway is employed by other viruses and that cell-impermeable kinase inhibitors could provide novel antivirals. We synthesized a cell-impermeable analog of staurosporine, CIMSS, which inhibited outer membrane HSV-induced Akt phosphorylation and blocked viral entry without inducing apoptosis.

Rescue of the Congenital Hereditary Endothelial Dystrophy Mouse Model by Adeno-Associated Viruse-Mediated Replacement.

Purpose: Congenital hereditary endothelial dystrophy (CHED) is a rare condition that manifests at an early age showing corneal edema, increased oxidative stress, mitochondrial dysfunction, and eventually apoptosis of the endothelium due to loss of function of the membrane transport protein SLC4A11. This project tested whether replacing into the CHED mouse model can reverse the disease-associated phenotypes.

Design: Experimental study.

Mitochondrial ROS in KO Corneal Endothelial Cells Lead to ER Stress.

Recent studies from mice have identified glutamine-induced mitochondrial dysfunction as a significant contributor toward oxidative stress, impaired lysosomal function, aberrant autophagy, and cell death in this Congenital Hereditary Endothelial Dystrophy (CHED) model. Because lysosomes are derived from endoplasmic reticulum (ER)-Golgi, we asked whether ER function is affected by mitochondrial ROS in KO corneal endothelial cells. In mouse corneal endothelial tissue, we observed the presence of dilated ER and elevated expression of ER stress markers BIP and CHOP.

The H Transporter SLC4A11: Roles in Metabolism, Oxidative Stress and Mitochondrial Uncoupling.

Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H transporter activated by NH and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice.

The determination of thiocyanate in the blood plasma and holding water of after exposure to cyanide.

The illegal practice of cyanide fishing continues throughout the Indo-Pacific. To combat this destructive fishing method, a reliable test to detect whether a fish has been captured using cyanide (CN) is needed. We report on the toxicokinetics of acute, pulsed CN exposure and chronic thiocyanate (SCN) exposure, the major metabolite of CN, in the clownfish species, .

RNA sequencing uncovers alterations in corneal endothelial metabolism, pump and barrier functions of Slc4a11 KO mice.

Slc4a11 KO mice show significant corneal edema, altered endothelial morphology, and mitochondrial ROS at an early age without a decrease in endothelial cell density. We examined the differential gene expression profile between wild type (WT) and KO with the goal of finding pathways related to corneal endothelial metabolic, pump and barrier function that can explain the corneal edema. Freshly dissected Corneal Endothelium-Descemet's Membrane (CEDM) and cultured Mouse Corneal Endothelial Cells (MCEC) were obtained from WT and Slc4a11 KO mice.

HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.

HVEM is a TNF (tumor necrosis factor) receptor contributing to a broad range of immune functions involving diverse cell types. It interacts with a TNF ligand, LIGHT, and immunoglobulin (Ig) superfamily members BTLA and CD160. Assessing the functional impact of HVEM binding to specific ligands in different settings has been complicated by the multiple interactions of HVEM and HVEM binding partners.

Mitochondrial ROS Induced Lysosomal Dysfunction and Autophagy Impairment in an Animal Model of Congenital Hereditary Endothelial Dystrophy.

Purpose: The Slc4a11 knock out (KO) mouse model recapitulates the human disease phenotype associated with congenital hereditary endothelial dystrophy (CHED). Increased mitochondrial reactive oxygen species (ROS) in the Slc4a11 KO mouse model is a major cause of edema and endothelial cell loss. Here, we asked if autophagy was activated by ROS in the KO mice.

Mitochondrial Targeting of the Ammonia-Sensitive Uncoupler SLC4A11 by the Chaperone-Mediated Carrier Pathway in Corneal Endothelium.

Purpose: SLC4A11, an electrogenic H+ transporter, is found in the plasma membrane and mitochondria of corneal endothelium. However, the underlying mechanism of SLC4A11 targeting to mitochondria is unknown.

Methods: The presence of mitochondrial targeting sequences was examined using in silico mitochondrial proteomic analyses.

Factors Associated With Achilles Tendon Rupture in Women's Collegiate Gymnastics.

Background: Achilles injury risk in women's collegiate gymnastics is 10-fold higher than in all other collegiate sports. This study aims to identify risk factors for Achilles tendon ruptures in collegiate female gymnasts.

Hypothesis: Gymnasts with Achilles tendon ruptures will be more likely to report early gymnastics specialization, elite-level training before college, and performance of high-difficulty skills on floor and vault.

Inducible Slc4a11 Knockout Triggers Corneal Edema Through Perturbation of Corneal Endothelial Pump.

Purpose: The conventional Slc4a11 knockout (KO) shows significant corneal edema at eye opening, a fact that complicates the study of the initial events leading to edema. An inducible KO would provide opportunities to examine early events following loss of Slc4a11 activity.

Methods: Slc4a11 Flox (SF) mice were crossed with mice expressing the estrogen receptor Cre Recombinase fusion protein and fed tamoxifen (Tm) for two weeks.

BCL11A enhancer-edited hematopoietic stem cells persist in rhesus monkeys without toxicity.

Gene editing of the erythroid-specific BCL11A enhancer in hematopoietic stem and progenitor cells (HSPCs) from patients with sickle cell disease (SCD) induces fetal hemoglobin (HbF) without detectable toxicity, as assessed by mouse xenotransplant. Here, we evaluated autologous engraftment and HbF induction potential of erythroid-specific BCL11A enhancer-edited HSPCs in 4 nonhuman primates. We used a single guide RNA (sgRNA) with identical human and rhesus target sequences to disrupt a GATA1 binding site at the BCL11A +58 erythroid enhancer.

Bicarbonate activates glycolysis and lactate production in corneal endothelial cells by increased pH.

Recent studies have shown that lactate coupled water flux is the underlying mechanism of the corneal endothelial pump, which is highly dependent on the presence of bicarbonate. In this study we test the hypothesis that the increased intracellular pH (pH) caused by bicarbonate stimulates glycolytic activity and the production of lactate by endothelial cells. Primary cultures of bovine corneal endothelial cells (BCEC) were incubated in bicarbonate-free (BF) ringer, a high [HEPES] ringer, and bicarbonate-rich (BR) ringer all at pH 7.

Mechanistic dissection of the PD-L1:B7-1 co-inhibitory immune complex.

The B7 family represents one of the best-studied subgroups within the Ig superfamily, yet new interactions continue to be discovered. However, this binding promiscuity represents a major challenge for defining the biological contribution of each specific interaction. We developed a strategy for addressing these challenges by combining cell microarray and high-throughput FACS methods to screen for promiscuous binding events, map binding interfaces, and generate functionally selective reagents.