The quantum Gaussian-Schell model: a link between classical and quantum optics.

The quantum theory of the electromagnetic field uncovered that classical forms of light were indeed produced by distinct superpositions of nonclassical multiphoton wave packets. This situation prevails for partially coherent light, the most common kind of classical light. Here, for the first time, to our knowledge, we demonstrate the extraction of the constituent multiphoton quantum systems of a partially coherent light field. We shift from the realm of classical optics to the domain of quantum optics via a quantum representation of partially coherent light using its complex-Gaussian statistical properties. Our formulation of the quantum Gaussian-Schell model (GSM) unveils the possibility of performing photon-number-resolving (PNR) detection to isolate the constituent quantum multiphoton wave packets of a classical light field. We experimentally verified the coherence properties of isolated vacuum systems and wave packets with up to 16 photons. Our findings not only demonstrate the possibility of observing quantum properties of classical macroscopic objects but also establish a fundamental bridge between the classical and quantum worlds.

Droxidopa for Vasopressor Weaning in Critically Ill Patients with Persistent Hypotension: A Multicenter, Retrospective, Single-Arm Observational Study.

BACKGROUND: Persistent vasopressor requirements are a common reason for delayed liberation from the intensive care unit (ICU) and adjunct oral agents are sometimes used to hasten time to vasopressor discontinuation. We sought to describe the use of droxidopa for vasopressor weaning in critically ill patients with prolonged hypotension. MATERIALS AND METHODS: This retrospective, single-arm, observational study included adult patients admitted to an ICU at two academic centers between 06/2016-07/2023 who received droxidopa for vasopressor weaning. Patients who received droxidopa prior to admission or for another indication were excluded. The primary outcome was time to vasopressor discontinuation, defined as when vasopressors were stopped and remained off for at least 24 h. Secondary outcomes included rates of tachycardia and hypotension post-initiation, norepinephrine equivalents pre- and post-initiation, concomitant oral agent use, and dosing. A subgroup analysis was conducted in patients receiving droxidopa via feeding tubes. RESULTS: A total of 30 patients met inclusion criteria. Median age was 62 years old, 12 (40%) were female, and 73% were in a cardiac/cardiac surgical ICU. Patients were on vasopressors for a median of 16 days prior to droxidopa initiation. Median (IQR) time to vasopressor discontinuation was 70 h (23-192) and norepinephrine equivalents decreased immediately after initiation (0.08 vs 0.02 mcg/kg/min, p < 0.001). MAP increased after droxidopa initiation (68.8 vs 66.5 mm Hg, p = 0.008) while heart rates were unchanged (86 vs 84 BPM, p = 0.37) after initiation. Patients who weaned from vasopressors within 72 h versus longer than 72 h after droxidopa initiation were more likely to be on lower norepinephrine equivalents prior to initiation (0.05 vs 0.12 mcg/kg/min, p = 0.013). Feeding tube administration did not impact time to vasopressor discontinuation (p = 0.93). CONCLUSIONS: Droxidopa may be considered an adjunct therapy for vasopressor weaning. Effects were similar when analyzing patients receiving droxidopa via feeding tube.

Key findings from the 2023 'ACT NOW on Global HIV Migration, Mobility and Health Equity' community forum.

Background People living with HIV continue to face laws, policies, and practices that impact their potential for travel and migration. These laws include: mandatory HIV testing and involuntary disclosure of HIV; lack of access to affordable HIV-related health care, treatment and counselling during the migration process; deportation of foreign nationals living with HIV; and restrictions on the length of stays. Methods HIV migration laws were the topic of a half-day community forum held as part of the 12th International AIDS Society Conference on HIV Science held in Brisbane, Australia, in July 2023. Over 150 delegates attended and, after a series of presentations, delegates were invited to participate in structured, facilitated conversations about issues related to policy, health and law concerning migration of people living with HIV. In this paper, we report on key themes from those discussions and identify areas for ongoing investigation. Results Advocates recommended the removal of unfair and unjust migration laws and policies that contribute to HIV stigma and discrimination; updated migration policies that reflect the current context and cost of biomedical approaches to HIV management and prevention; expanded and equitable access to HIV-related care regardless of migration or residency status; and the development of advocacy networks to promote changes to migration policies. Conclusions Laws limiting the migration of people living with HIV actively discourage individuals from seeking HIV testing, treatment and care. Ultimately, restrictive migration laws and policies undermine global efforts to end AIDS as a public health concern and to virtually eliminate HIV transmission by 2030.

Pharmacological modulation of inflammatory oligodendrocyte progenitor cells using three multiple sclerosis disease modifying therapies in vitro.

Preclinical studies of pro-remyelinating therapies for multiple sclerosis tend to neglect the effect of the disease-relevant inflammatory milieu. Interferon-gamma (IFN-γ) is known to suppress oligodendrocyte progenitor cell (OPC) differentiation and induce a recently described immune OPC (iOPC) phenotype characterized by expression of major histocompatibility complex (MHC) molecules. We tested the effects of cladribine (CDB), dimethylfumarate (DMF), and interferon-beta (IFN-ß), existing anti-inflammatory therapies for MS, on the IFN-γ-induced iOPC formation and OPC differentiation block. In line with previous reports, we demonstrate that IFN-ß and DMF inhibit OPC proliferation, while CDB had no effect. None of the drugs exhibited cytotoxic effects at the physiological concentrations tested in vitro. In a differentiation assay, none of the drugs were able to promote differentiation, under inflammatory or basal conditions. To study drug effects on iOPCs, we monitored MHC expression in vitro with live cell imaging using cells isolated from MHC reporter mice. IFN-ß suppressed induction of MHC class II, and DMF led to suppression of both class I and II. CDB had no effect on MHC induction. We conclude that promoting proliferation and differentiation and suppressing iOPC induction under inflammatory conditions may require separate therapeutic strategies and must be balanced for maximal repair. Our in vitro MHC screening assay can be leveraged across cell types to test the effects of drug candidates and disease-related stimuli.

2023 Undetectable = Untransmittable global policy roundtable report: a multistakeholder perspective on Undetectable = Untransmittable research and policy priorities.

Background Launched in 2016 by Prevention Access Campaign, the 'Undetectable=Untransmittable' (U=U) campaign empowers people living with HIV to live full social, sexual and reproductive lives, dismantle stigma, promote increased treatment access, and advocate for updated HIV guidelines. Methods Key priorities for promoting improvements to community-centred, evidence-informed U=U policy and research were the focus of a half-day global roundtable held in 2023 alongside the 12th International AIDS Society Conference in Brisbane, Australia. After a series of presentations, experts in U=U research, policymaking, advocacy and HIV clinical care participated in facilitated discussions, and detailed notes were taken on issues related to advancing U=U policy and research. Results Expert participants shared that knowledge and trust in U=U remains uneven, and is largely concentrated among people living with HIV, particularly those connected to gay and bisexual networks. It was agreed that there is a need to ensure all members of priority populations are explicitly included in U=U policies that promote U=U. Participants also identified a need for policymakers, healthcare professionals, advocates and researchers to work closely with community-based organisations to ensure the U=U message is relevant, useful, and utilised in the HIV response. Adopting language, such as 'zero risk', was identified as crucial when describing undetectable viral load as an effective HIV prevention strategy. Conclusion U=U can have significant benefits for the mental and physical wellbeing of people living with HIV. There is an urgent need to address the structural barriers to HIV care and treatment access to ensure the full benefits of U=U are realised.

Journals must expand access to peer review data.

Empirical studies on peer review bias are primarily conducted by people from privileged groups and with affiliations with the journals studied. Data access is one major barrier to conducting peer review research. Accordingly, we propose pathways to broaden access to peer review data to people from more diverse backgrounds.

Pre-hospital ECPR in an Australian metropolitan setting: a single-arm feasibility assessment-The CPR, pre-hospital ECPR and early reperfusion (CHEER3) study.

INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.

Deep-Sea Sponges and Corals off the Western Coast of Florida-Intracellular Mechanisms of Action of Bioactive Compounds and Technological Advances Supporting the Drug Discovery Pipeline.

The majority of natural products utilized to treat a diverse array of human conditions and diseases are derived from terrestrial sources. In recent years, marine ecosystems have proven to be a valuable resource of diverse natural products that are generated to defend and support their growth. Such marine sources offer a large opportunity for the identification of novel compounds that may guide the future development of new drugs and therapies. Using the National Oceanic and Atmospheric Administration (NOAA) portal, we explore deep-sea coral and sponge species inhabiting a segment of the U.S. Exclusive Economic Zone, specifically off the western coast of Florida. This area spans ~100,000 km2, containing coral and sponge species at sea depths up to 3000 m. Utilizing PubMed, we uncovered current knowledge on and gaps across a subset of these sessile organisms with regards to their natural products and mechanisms of altering cytoskeleton, protein trafficking, and signaling pathways. Since the exploitation of such marine organisms could disrupt the marine ecosystem leading to supply issues that would limit the quantities of bioactive compounds, we surveyed methods and technological advances that are necessary for sustaining the drug discovery pipeline including in vitro aquaculture systems and preserving our natural ecological community in the future. Collectively, our efforts establish the foundation for supporting future research on the identification of marine-based natural products and their mechanism of action to develop novel drugs and therapies for improving treatment regimens of human conditions and diseases.

Improved Cartilage Protection with Low Molecular Weight Hyaluronic Acid Hydrogel.

Traumatic joint injuries are common, leading to progressive tissue degeneration and the development of osteoarthritis. The post-traumatic joint experiences a pro-inflammatory milieu, initiating a subtle but deteriorative process in cartilage tissue. To prevent or even reverse this process, our group previously developed a tissue-penetrating methacrylated hyaluronic acid (MeHA) hydrogel system, crosslinked within cartilage to restore and/or protect the tissue. In the current study, we further optimized this approach by investigating the impact of biomaterial molecular weight (MW; 20, 75, 100 kDa) on its integration within and reinforcement of cartilage, as well as its ability to protect tissue degradation in a catabolic state. Indeed, the low MW MeHA integrated and reinforced cartilage tissue better than the high MW counterparts. Furthermore, in a 2 week IL-1ß explant culture model, the 20 kDa MeHA demonstrated the most protection from biphasic mechanical loss, best retention of proteoglycans (Safranin O staining), and least aggrecan breakdown (NITEGE). Thus, the lower MW MeHA gels integrated better into the tissue and provided the greatest protection of the cartilage matrix. Future work will test this formulation in a preclinical model, with the goal of translating this therapeutic approach for cartilage preservation.

Live-Cell SOFI Correlation with SMLM and AFM Imaging.

Standard optical imaging is diffraction-limited and lacks the resolving power to visualize many of the organelles and proteins found within the cell. The advent of super-resolution techniques overcame this barrier, enabling observation of subcellular structures down to tens of nanometers in size; however these techniques require or are typically applied to fixed samples. This raises the question of how well a fixed-cell image represents the system prior to fixation. Here we present the addition of live-cell Super-Resolution Optical Fluctuation Imaging (SOFI) to a previously reported correlative process using Single Molecule Localization Microscopy (SMLM) and Atomic Force Microscopy (AFM). SOFI was used with fluorescent proteins and low laser power to observe cellular ultrastructure in live COS-7 cells. SOFI-SMLM-AFM of microtubules showed minimal changes to the microtubule network in the 20 min between live-cell SOFI and fixation. Microtubule diameters were also analyzed through all microscopies; SOFI found diameters of 249 ± 68 nm and SMLM was 71 ± 33 nm. AFM height measurements found microtubules to protrude 26 ± 13 nm above the surrounding cellular material. The correlation of SMLM and AFM was extended to two-color SMLM to image both microtubules and actin. Two target SOFI was performed with various fluorescent protein combinations. rsGreen1-rsKAME, rsGreen1-Dronpa, and ffDronpaF-rsKAME fluorescent protein combinations were determined to be suitable for two target SOFI imaging. This correlative application of super-resolution live-cell and fixed-cell imaging revealed minimal artifacts created for the imaged target structures through the sample preparation procedure and emphasizes the power of correlative microscopy.

MHC class I and MHC class II reporter mice enable analysis of immune oligodendroglia in mouse models of multiple sclerosis.

Oligodendrocytes and their progenitors upregulate MHC pathways in response to inflammation, but the frequency of this phenotypic change is unknown and the features of these immune oligodendroglia are poorly defined. We generated MHC class I and II transgenic reporter mice to define their dynamics in response to inflammatory demyelination, providing a means to monitor MHC activation in diverse cell types in living mice and define their roles in aging, injury, and disease.

Nerve cells in the brain and spinal cord are surrounded by a layer of insulation called myelin that allows cells to transmit messages to each other more quickly and efficiently. This protective sheath is produced by cells called oligodendrocytes which together with their immature counterparts can also repair damage caused to myelin. In the inflammatory disease multiple sclerosis (MS), this insulation is disrupted and oligodendroglia fail to repair breaks in the myelin sheath, leaving nerves vulnerable to further damage. Recently it was discovered that mature and immature oligodendrocytes (which are collectively known as oligodendroglia) sometimes express proteins normally restricted to the immune system called major histocompatibility complexes (or MHCs for short). Researchers believe that MHC expression may allow oligodendroglia to interact with immune cells, potentially leading to the removal of oligodendroglia by the immune system as well as inflammation that exacerbates damage to nerves and hinders myelin repair. Knowing when oligodendroglia start producing MHCs and where these MHC-expressing cells are located is therefore important for understanding their role in MS. However, it is difficult to identify the location of MHC-expressing oligodendroglia using methods that are currently available. To address this, Harrington, Catenacci et al. created a genetically engineered mouse model in which the MHC-expressing oligodendroglia also generated a red fluorescent protein that could be detected under a microscope. This revealed that only a small number of oligodendroglia in the nervous system had MHCs, but these cells were located in areas of the brain and spinal cord with the highest inflammatory activity. Further microscopy studies in mice that developed MS-like symptoms revealed that MHC production in oligodendroglia increased compared with healthy animals, and that the proportion of oligodendroglia that produced MHC was highest in mice with the most severe symptoms. MHC-expressing oligodendroglia also congregated in the most damaged areas of the brain and spinal cord. These results suggest that MHC expression may contribute to inflammation and impact the function of oligodendroglia that have these molecules. In the future, Harrington et al. hope that their new mouse model will help researchers study the role of MHC expression in different diseases, and in the case of MS, aid the development of new treatments.

Peer review perpetuates barriers for historically excluded groups.

Peer review is central to the scientific process and scientists' career advancement, but bias at various stages of the review process disadvantages some authors. Here we use peer review data from 312,740 biological sciences manuscripts across 31 studies to (1) examine evidence for differential peer review outcomes based on author demographics, (2) evaluate the efficacy of solutions to reduce bias and (3) describe the current landscape of peer review policies for 541 ecology and evolution journals. We found notably worse review outcomes (for example, lower overall acceptance rates) for authors whose institutional affiliations were in Asia, for authors whose country's primary language is not English and in countries with relatively low Human Development Indices. We found few data evaluating efficacy of interventions outside of reducing gender bias through double-blind review or diversifying reviewer/editorial boards. Despite evidence for review outcome gaps based on author demographics, few journals currently implement policies intended to mitigate bias (for example, 15.9% of journals practised double-blind review and 2.03% had reviewer guidelines that mentioned social justice issues). The lack of demographic equity signals an urgent need to better understand and implement evidence-based bias mitigation strategies.

Selecting Multitarget Peptides for Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disease with a complex pathogenesis. Developing multitarget drugs could be a powerful strategy to impact the progressive loss of cognitive functions in this disease. The purpose of this study is to select a multitarget lead peptide candidate among a series of peptide variants derived from the neutrophil granule protein cathepsin G. We screened eight peptide candidates using the following criteria: (1) Inhibition and reversion of amyloid beta (Aß) oligomers, quantified using an enzyme-linked immunosorbent assay (ELISA); (2) direct binding of peptide candidates to the human receptor for advanced glycation end-products (RAGE), the Toll-like receptor 4 (TLR4) and the S100 calcium-binding protein A9 (S100A9), quantified by ELISA; (3) protection against Aß oligomer-induced neuronal cell death, using trypan blue to measure cell death in a murine neuronal cell line; (4) inhibition of TLR4 activation by S100A9, using a human TLR4 reporter cell line. We selected a 27-mer lead peptide that fulfilled these four criteria. This lead peptide is a privileged structure that displays inherent multitarget activity. This peptide is expected to significantly impact cognitive decline in mouse models of Alzheimer's disease, by targeting both neuroinflammation and neurodegeneration.

Optimising correlative super resolution and atomic force microscopies for investigating the cellular cytoskeleton.

Correlative imaging methods can provide greater information for investigations of cellular ultra-structure, with separate analysis methods complementing each other's strengths and covering for deficiencies. Here we present a method for correlative applications of super resolution and atomic force microscopies, optimising the sample preparation for correlative imaging of the cellular cytoskeleton in COS-7 cells. This optimisation determined the order of permeabilisation and fixation, the concentration of Triton X-100 surfactant used and time required for sufficient removal of the cellular membrane while maintaining the microtubule network. Correlative SMLM/AFM imaging revealed the different information that can be obtained through each microscopy. The widths of microtubules and microtubule clusters were determined from both AFM height measurements and Gaussian fitting of SMLM intensity cross sections, these were then compared to determine the orientation of microtubules within larger microtubule bundles. The ordering of microtubules at intersections was determined from the AFM height profiles as each microtubule crosses the other. The combination of both microtubule diameter measurements enabled greater information on their structure to be found than either measurement could individually.

How Thrombomodulin Enables W215A/E217A Thrombin to Cleave Protein C but Not Fibrinogen.

The W215A/E217A mutant thrombin is called "anticoagulant thrombin" because its activity toward its procoagulant substrate, fibrinogen, is reduced more than 500-fold whereas in the presence of thrombomodulin (TM) its activity toward its anticoagulant substrate, protein C, is reduced less than 10-fold. To understand how these mutations so dramatically alter one activity over the other, we compared the backbone dynamics of wild type thrombin to those of the W215A/E217A mutant thrombin by hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS). Our results show that the mutations cause the 170s, 180s, and 220s C-terminal ß-barrel loops near the sites of mutation to exchange more, suggesting that the structure of this region is disrupted. Far from the mutation sites, residues at the N-terminus of the heavy chain, which need to be buried in the Ile pocket for correct structuring of the catalytic triad, also exchange much more than in wild type thrombin. TM binding causes reduced H/D exchange in these regions and also alters the dynamics of the ß-strand that links the TM binding site to the catalytic Asp 102 in both wild type thrombin and in the W215A/E217A mutant thrombin. In contrast, whereas TM binding reduces the dynamics the 170, 180 and 220 s C-terminal ß-barrel loops in WT thrombin, this region remains disordered in the W215A/E217A mutant thrombin. Thus, TM partially restores the catalytic activity of W215A/E217A mutant thrombin by allosterically altering its dynamics in a manner similar to that of wild type thrombin.

Methylation of the serotonin transporter gene moderates the depressive subjective effect of cocaine.

Genetic variation in the serotonin transporter (SLC6A4) has been shown to moderate the acute subjective effects of cocaine. Methylation of the SLC6A4 gene is associated with decreased transcription of the serotonin transporter, leading to increased serotonin in the synapse. In this study, methylation of the SLC6A4 gene was investigated in the moderation of the subjective effects of cocaine. Non-treatment-seeking cocaine-dependent individuals (N = 53) were intravenously administered cocaine (40 mg) and saline in a randomized order. The subjective effects of cocaine were self-reported using a visual analog scale starting prior to the administration of cocaine (-15 min) or saline and up to 20 min after infusion. Participants were evaluated for methylation of the SLC6A4 promoter region and 5-HTTLPR genotype. A series of ANCOVAs for SLC6A4 methylation (high/low) were run for each of ten subjective and three cardiovascular effects controlling for age, sex [utilizing the sex-determining region Y protein (SRY)], and population structure (determined from ancestry informative markers and STRUCTURE software). Participants with SLC6A4 hypermethylation reported greater subjective response to cocaine for 'depressed' relative to participants with SLC6A4 hypomethylation (experiment-wise p = 0.002). These findings indicate that SLC6A4 methylation moderates the 'depressed' subjective effect of cocaine in non-treatment-seeking cocaine-dependent participants.

Nanoscale characterization of drug-induced microtubule filament dysfunction using super-resolution microscopy.

BACKGROUND: The integrity of microtubule filament networks is essential for the roles in diverse cellular functions, and disruption of its structure or dynamics has been explored as a therapeutic approach to tackle diseases such as cancer. Microtubule-interacting drugs, sometimes referred to as antimitotics, are used in cancer therapy to target and disrupt microtubules. However, due to associated side effects on healthy cells, there is a need to develop safer drug regimens that still retain clinical efficacy. Currently, many questions remain open regarding the extent of effects on cellular physiology of microtubule-interacting drugs at clinically relevant and low doses. Here, we use super-resolution microscopies (single-molecule localization and optical fluctuation based) to reveal the initial microtubule dysfunctions caused by nanomolar concentrations of colcemid. RESULTS: We identify previously undetected microtubule (MT) damage caused by clinically relevant doses of colcemid. Short exposure to 30-80 nM colcemid results in aberrant microtubule curvature, with a trend of increased curvature associated to increased doses, and curvatures greater than 2 rad/µm, a value associated with MT breakage. Microtubule fragmentation was detected upon treatment with ≥ 100 nM colcemid. Remarkably, lower doses (< 20 nM after 5 h) led to subtle but significant microtubule architecture remodelling characterized by increased curvature and suppression of microtubule dynamics. CONCLUSIONS: Our results support the emerging hypothesis that microtubule-interacting drugs induce non-mitotic effects in cells, and establish a multi-modal imaging assay for detecting and measuring nanoscale microtubule dysfunction. The sub-diffraction visualization of these less severe precursor perturbations compared to the established antimitotic effects of microtubule-interacting drugs offers potential for improved understanding and design of anticancer agents.

Safety of Continuous Erector Spinae Catheters in Chest Trauma: A Retrospective Cohort Study.

BACKGROUND: The erector spinae block is an efficacious analgesic option for the management of rib fracture--related pain. Despite there being minimal published data specifically addressing the safety profile of this block, many societies have made statements regarding its safety and its use as an alternative to traditional regional anesthesia techniques in patients at risk of complications. The primary aim of this study was to characterize the safety profile of erector spinae plane block catheters by determining the incidence of early complications. The secondary aim of this study was to characterize the incidence of late adverse events, as well as the erector spinae plane block catheter failure rate. METHODS: We analyzed electronic medical record data of patients who had an erector spinae plane block catheter inserted for the management of rib fractures between November 2017 and September 2020. To assess early adverse events, data collection included hypotension, hypoxemia, local anesthetic systemic toxicity, and pneumothorax thought to be associated with erector spinae plane block catheter insertion. Late complications included catheter site infection and catheter site hematoma. RESULTS: A total of 224 patients received 244 continuous erector spinae catheters during the study period. After insertion of the erector spinae, there were no immediate complications such as hypotension, hypoxia, local anesthetic toxicity, or pneumothorax. Of all blocks inserted, 7.7% were removed due to catheter failure (8.4 per 100 catheters; 95% confidence interval [CI], 5.1-13.9 per 100 catheters). This resulted in a failure rate of 1.9 per 1000 catheter days (95% CI, 1.1-6.7 catheter days). Late complications included 2 erythematous catheter sites and 2 small hematomas not requiring intervention. The incidence of a minor late complication was 16.7 per 1000 catheters (95% CI, 6.1-45.5 per 1000 catheters). CONCLUSIONS: This study supports the statements made by regional anesthesia societies regarding the safety of the erector spinae plane block. Based on the results presented in this population of trauma patients, the erector spinae plane block catheter is a low-risk analgesic technique that may be performed in the presence of abnormal coagulation status or systemic infection.

Hydrogen/Deuterium Exchange and Nuclear Magnetic Resonance Spectroscopy Reveal Dynamic Allostery on Multiple Time Scales in the Serine Protease Thrombin.

A deeper understanding of how hydrogen/deuterium exchange mass spectrometry (HDX-MS) reveals allostery is important because HDX-MS can reveal allostery in systems that are not amenable to nuclear magnetic resonance (NMR) spectroscopy. We were able to study thrombin and its complex with thrombomodulin, an allosteric regulator, by both HDX-MS and NMR. In this Perspective, we compare and contrast the results from both experiments and from molecular dynamics simulations. NMR detects changes in the chemical environment around the protein backbone N-H bond vectors, providing residue-level information about the conformational exchange between distinct states. HDX-MS detects changes in amide proton solvent accessibility and H-bonding. Taking advantage of NMR relaxation dispersion measurements of the time scale of motions, we draw conclusions about the motions reflected in HDX-MS experiments. Both experiments detect allostery, but they reveal different components of the allosteric transition. The insights gained from integrating NMR and HDX-MS into thrombin dynamics enable a clearer interpretation of the evidence for allostery revealed by HDX-MS in larger protein complexes and assemblies that are not amenable to NMR.