Inclusive Approaches for Measuring Demographics of Underrepresented Populations in STEM and Biomedical Research Training Programs.

As federal strategic plans prioritize increasing diversity within the biomedical workforce, and STEM training and outreach programs seek to recruit and retain students from historically underrepresented populations, there is a need for interrogation of traditional demographic descriptors and careful consideration of best practices for obtaining demographic data. To accelerate this work, equity-focused researchers and leaders from STEM programs convened to examine approaches for measuring demographic variables. Gender, race/ethnicity, disability, and disadvantaged background were prioritized given their focus by federal funding agencies.

Low-Volume Targeted Interscalene Brachial Plexus Block in the Emergency Department as a Safer Alternative for Pain Control for Glenohumeral Reduction: A Case Series.

Background: Acute glenohumeral dislocation is a common emergency department (ED) presentation, however, pain control to facilitate reduction in these patients can be challenging. Although both procedural sedation and peripheral nerve blocks can provide effective analgesia, both also carry risks. Specifically, the interscalene brachial plexus block carries risk of ipsilateral hemidiaphragmatic paralysis due to inadvertent phrenic nerve involvement.

A subjective evaluation of different music preprocessing approaches in cochlear implant listeners.

Cochlear implants (CIs) can partially restore speech perception to relatively high levels in listeners with moderate to profound hearing loss. However, for most CI listeners, the perception and enjoyment of music remains notably poor. Since a number of technical and physiological restrictions of current implant designs cannot be easily overcome, a number of preprocessing methods for music signals have been proposed recently.

Diaphragmatic Excursion as a Novel Objective Measure of Serratus Anterior Plane Block Efficacy: A Case Series.

Introduction: Pain scales are often used in peripheral nerve block studies but are problematic due to their subjective nature. Ultrasound-measured diaphragmatic excursion is an easily learned technique that could provide a much-needed objective measure of pain control over time with serial measurements.

Case Series: We describe three cases where diaphragmatic excursion was used as an objective measure of decreased pain and improved respiratory function after serratus anterior plane block in emergency department patients with anterior or lateral rib fractures.

Acute Myocarditis After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

This case report describes a young adult patient with post-severe acute respiratory syndrome coronavirus 2 acute viral myocarditis who initially presented to a local urgent care center. The patient decompensated and was transferred to our tertiary, intensive care setting.

A systematic review of the cost-effectiveness of ultrasound in emergency care settings.

Background: The use of ultrasound (US) in emergency departments (ED) has become widespread. This includes both traditional US scans performed by radiology departments as well as point-of-care US (POCUS) performed by bedside clinicians. There has been significant interest in better understanding the appropriate use of imaging and where opportunities to enhance cost-effectiveness may exist.

Phosphatidylserine and phosphatidylethanolamine regulate the structure and function of FVIIa and its interaction with soluble tissue factor.

Cell membranes have important functions in many steps of the blood coagulation cascade, including the activation of factor X (FX) by the factor VIIa (FVIIa)-tissue factor (TF) complex (extrinsic Xase). FVIIa shares structural similarity with factor IXa (FIXa) and FXa. FIXa and FXa are regulated by binding to phosphatidylserine (PS)-containing membranes via their γ-carboxyglutamic acid-rich domain (Gla) and epidermal growth-factor (EGF) domains.

Nonauditory Functions in Low-performing Adult Cochlear Implant Users.

Introduction: Despite substantial benefits of cochlear implantation (CI) there is a high variability in speech recognition, the reasons for which are not fully understood. Especially the group of low-performing CI users is under-researched. Because of limited perceptual quality, top-down mechanisms play an important role in decoding the speech signal transmitted by the CI.

"Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew": Defining Autistic Burnout.

Unlabelled: Although autistic adults often discuss experiencing "autistic burnout" and attribute serious negative outcomes to it, the concept is almost completely absent from the academic and clinical literature. We used a community-based participatory research approach to conduct a thematic analysis of 19 interviews and 19 public Internet sources to understand and characterize autistic burnout. Interview participants were autistic adults who identified as having been professionally diagnosed with an autism spectrum condition.

Depth-Dependent Membrane Ordering by Hemagglutinin Fusion Peptide Promotes Fusion.

Membrane fusion, one of the most fundamental processes in life, occurs when two separate lipid membranes merge into a single continuous bilayer. Membrane fusion is essential for the entry of lipid-sheathed viruses such as influenza and HIV. Influenza virus is internalized via receptor-mediated endocytosis and then fuses with the endosomal membrane at low pH.

Global Health and Emergency Care: Defining Clinical Research Priorities.

Objectives: Despite recent strides in the development of global emergency medicine (EM), the field continues to lag in applying a scientific approach to identifying critical knowledge gaps and advancing evidence-based solutions to clinical and public health problems seen in emergency departments (EDs) worldwide. Here, progress on the global EM research agenda created at the 2013 Academic Emergency Medicine Global Health and Emergency Care Consensus Conference is evaluated and critical areas for future development in emergency care research internationally are identified.

Methods: A retrospective review of all studies compiled in the Global Emergency Medicine Literature Review (GEMLR) database from 2013 through 2015 was conducted.

Phosphatidylserine-Dependent Catalysis of Stalk and Pore Formation by Synaptobrevin JMR-TMD Peptide.

Although the importance of a SNARE complex in neurotransmitter release is widely accepted, there exist different views on how the complex promotes fusion. One hypothesis is that the SNARE complex's ability to bring membranes into contact is sufficient for fusion, another points to possible roles of juxtamembrane regions (JMRs) and transmembrane domains (TMDs) in catalyzing lipid rearrangement, and another notes the complex's presumed ability to bend membranes near the point of contact. Here, we performed experiments with highly curved vesicles brought into contact using low concentrations of polyethylene glycol (PEG) to investigate the influence of the synaptobrevin (SB) TMD with an attached JMR (SB-JMR-TMD) on the rates of stalk and pore formation during vesicle fusion.

The lateral diffusion and fibrinogen induced clustering of platelet integrin αIIbβ3 reconstituted into physiologically mimetic GUVs.

Platelet integrin αIIbβ3 is a key mediator of platelet activation and thrombosis. Upon activation αIIbβ3 undergoes significant conformational rearrangement, inducing complex bidirectional signalling and protein recruitment leading to platelet activation. Reconstituted lipid models of the integrin can enhance our understanding of the structural and mechanistic details of αIIbβ3 behaviour away from the complexity of the platelet machinery.

Factor Xa dimerization competes with prothrombinase complex formation on platelet-like membrane surfaces.

Exposure of phosphatidylserine (PS) molecules on activated platelet membrane surface is a crucial event in blood coagulation. Binding of PS to specific sites on factor Xa (fXa) and factor Va (fVa) promotes their assembly into a complex that enhances proteolysis of prothrombin by approximately 10⁵. Recent studies demonstrate that both soluble PS and PS-containing model membranes promote formation of inactive fXa dimers at 5 mM Ca²⁺.

pH Alters PEG-mediated fusion of phosphatidylethanolamine-containing vesicles.

Here, we examine the different mechanisms of poly(ethylene glycol)-mediated fusion of small unilamellar vesicles composed of dioleoylphosphatidylcholine/dioleoylphosphatidylethanolamine (DOPE)/sphingomyelin/cholesterol in a molar ratio of 35:30:15:20 at pH 7.4 versus pH 5. In doing so, we test the hypothesis that fusion of this lipid mixture should be influenced by differences in hydration of DOPE at these two pH values.

The transmembrane domain peptide of vesicular stomatitis virus promotes both intermediate and pore formation during PEG-mediated vesicle fusion.

We propose mechanisms by which the transmembrane domain of vesicular stomatitis virus (VSV-TMD) promotes both initiation of fusion and formation of a fusion pore. Time courses of polyethyleneglycol (PEG)-mediated fusion of 25 nm small unilamellar vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine (DOPE), bovine brain sphingomyelin, and cholesterol (35:30:15:20 molar ratio) were recorded at pH 7.4 at five different temperatures (from 17°C to 37°C) and compared with time courses obtained with the same vesicles containing the fusion-active TMD of the G protein of VSV.

Soluble phosphatidylserine binds to two sites on human factor IXa in a Ca2+ dependent fashion to specifically regulate structure and activity.

Clinical studies have demonstrated a correlation between elevated levels of FIX and the risk of coronary heart disease, while reduced plasma FIX causes hemophilia B. FIXa interacts with FVIIIa in the presence of Ca2+ and phosphatidylserine (PS)-containing membranes to form a factor X-activating complex (Xase) that is key to propagation of the initiated blood coagulation process in human. We test the hypothesis that PS in these membranes up-regulates the catalytic activity of this essential enzyme.

Ca2+ switches the effect of PS-containing membranes on Factor Xa from activating to inhibiting: implications for initiation of blood coagulation.

Calcium (Ca2+) plays a pivotal role in cellular and organismal physiology. The Ca2+ ion has an intermediate protein-binding affinity and thus it can serve as an on/off switch in the regulation of different biochemical processes. The serum level of ionized Ca2+ is regulated with normal ionized Ca2+ being in the range 1.

Phosphatidylserine and FVa regulate FXa structure.

Human coagulation FXa (Factor Xa) plays a key role in blood coagulation by activating prothrombin to thrombin on 'stimulated' platelet membranes in the presence of its cofactor FVa (Factor Va). PS (phosphatidylserine) exposure on activated platelet membranes promotes prothrombin activation by FXa by allosterically regulating FXa. To identify the structural basis of this allosteric regulation, we used FRET to monitor changes in FXa length in response to (i) soluble short-chain PS [C6PS (dicaproylphosphatidylserine)], (ii) PS membranes, and (iii) FVa in the presence of C6PS and membranes.

Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development.

Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations.

Wild-type and mutant hemagglutinin fusion peptides alter bilayer structure as well as kinetics and activation thermodynamics of stalk and pore formation differently: mechanistic implications.

Viral fusion peptides are short N-terminal regions of type-1 viral fusion proteins that are critical for virus entry. Although the importance of viral fusion peptides in virus-cell membrane fusion is established, little is known about how they function. We report the effects of wild-type (WT) hemagglutinin (HA) fusion peptide and its G1S, G1V, and W14A mutants on the kinetics of poly(ethylene glycol)(PEG)-mediated fusion of small unilamellar vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine, sphingomyelin, and cholesterol (molar ratio of 35:30:15:20).

A novel assay for detecting fusion pore formation: implications for the fusion mechanism.

Membrane fusion is broadly envisioned as a two- or three-step process proceeding from contacting bilayers through one or two semistable, nonlamellar lipidic intermediate structures to a fusion pore. A true fusion event requires mixing of contents between compartments and is monitored by the movement of soluble molecules between trapped compartments. We have used poly(ethylene glycol) (PEG) to rapidly generate an ensemble aggregated state A that proceeds sequentially through intermediates (I₁ and/or I₂) to a final fusion pore state (FP) with rate constants k₁, k₂, and k₃.

APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress.

The base excision repair pathway is largely responsible for the repair of oxidative stress-induced DNA damage. However, it remains unclear how the DNA damage checkpoint is activated by oxidative stress at the molecular level. Here, we provide evidence showing that hydrogen peroxide (H2O2) triggers checkpoint kinase 1 (Chk1) phosphorylation in an ATR [ataxia-telangiectasia mutated (ATM) and Rad3-related]-dependent but ATM-independent manner in Xenopus egg extracts.