Coactosin-like protein 1 regulates integrity and repair of model intestinal epithelial barriers via actin binding dependent and independent mechanisms.

The actin cytoskeleton regulates the integrity and repair of epithelial barriers by mediating the assembly of tight junctions (TJs), and adherens junctions (AJs), and driving epithelial wound healing. Actin filaments undergo a constant turnover guided by numerous actin-binding proteins, however, the roles of actin filament dynamics in regulating intestinal epithelial barrier integrity and repair remain poorly understood. Coactosin-like protein 1 (COTL1) is a member of the ADF/cofilin homology domain protein superfamily that binds and stabilizes actin filaments. COTL1 is essential for neuronal and cancer cell migration, however, its functions in epithelia remain unknown. The goal of this study is to investigate the roles of COTL1 in regulating the structure, permeability, and repair of the epithelial barrier in human intestinal epithelial cells (IEC). COTL1 was found to be enriched at apical junctions in polarized IEC monolayers in vitro. The knockdown of COTL1 in IEC significantly increased paracellular permeability, impaired the steady state TJ and AJ integrity, and attenuated junctional reassembly in a calcium-switch model. Consistently, downregulation of COTL1 expression in Drosophila melanogaster increased gut permeability. Loss of COTL1 attenuated collective IEC migration and decreased cell-matrix attachment. The observed junctional abnormalities in COTL1-depleted IEC were accompanied by the impaired assembly of the cortical actomyosin cytoskeleton. Overexpression of either wild-type COTL1 or its actin-binding deficient mutant tightened the paracellular barrier and activated junction-associated myosin II. Furthermore, the actin-uncoupled COTL1 mutant inhibited epithelial migration and matrix attachment. These findings highlight COTL1 as a novel regulator of the intestinal epithelial barrier integrity and repair.

Use of Naloxone in Angiotensin-Converting Enzyme Inhibitor Overdose: A Case Report.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor overdose is an uncommonly presenting toxicologic emergency. Management is primarily supportive care, but a small body of evidence exists to support naloxone for management of hypotension. CASE REPORT: We present a case of accidental ACE inhibitor overdose. The patient took approximately 300 mg lisinopril over 48 h and presented for evaluation of syncope. He was hypotensive and unresponsive to fluids. We administered naloxone with immediate and sustained resolution in hypotension. The mechanism of action is briefly discussed. WHY SHOULD AN EMERGENCY MEDICINE PHYSICIAN BE AWARE OF THIS?: Naloxone is a rapid, low-risk, low-cost, and effective intervention for hypotension due to ACE inhibitor toxicity. It is supported by basic science research and clinical experience.

Medical Leadership in Inpatient Rehabilitation Facilities in the United States.

OBJECTIVE: Inpatient rehabilitation facilities treat patients with extensive postacute care rehabilitation needs. Physiatrists are uniquely trained in the complexities of such patients; however, not all inpatient rehabilitation facilities use physiatrists as medical leadership. This study identifies the training background and credentials of medical directors in all inpatient rehabilitation facilities within the United States. DESIGN: Using Internet search, e-mail, and telephone communication, the following data were collected: medical director credential and specialty information, board certification rates and years of practice experience, as well as bed numbers for each inpatient rehabilitation facilities listed on The Centers for Medicare and Medicaid Services Website. Data were collected between November 2019 and November 2020. RESULTS: Of the 1114 open facilities, 85% have medical directors with a doctor of medicine degree, while 13% have a doctor of osteopathic medicine degree. Two percent reported no physician medical director. Physiatry is the most common specialty (80%), followed by internal medicine, family medicine, neurology, orthopedic surgery, general surgery, and medicine/pediatrics. The mean number of beds per facility is 35.6 (median, 24; range, 4-350). There is an average of 11.4 inpatient rehabilitation facility beds per 100,000 people nationally. CONCLUSIONS: Physiatry is the predominant specialty to fulfill medical leadership at inpatient rehabilitation facilities, although there remains room for growth. In addition, doctor of medicine degrees greatly outnumber doctor of osteopathic medicine degrees in medical leadership.

Recent Advances of In-Source Electrochemical Mass Spectrometry.

Hyphenation of electrochemistry (EC) and mass spectrometry has become a powerful tool to study redox processes. Approaches that can achieve this hyphenation include integrating chromatography/electrophoresis between electroinduced redox reactions and detection of products, coupling an EC flow cell to a mass spectrometer, and performing electrochemical reactions inside the ion source of a mass spectrometer. The first two approaches have been well reviewed elsewhere. This Minireview highlights the inherent electrochemical properties of many mass spectrometry ion sources and their roles in the coupling of electrochemistry and mass spectrometric analysis. Development of modified ion sources that allow the compatibility of electrochemistry with ionization processes is also surveyed. Applications of different in-source electrochemical devices are provided including intermediate capturing, bioanalytical studies, nanoparticle formation, electrosynthesis, and electrode imaging.