Eagle jugular syndrome presenting with intracranial hypertension - Diagnosis and illustration of pathophysiology by multi-modality imaging.

Eagle jugular syndrome is an uncommon condition caused by compression of an elongated styloid process onto the internal jugular vein. Its presentation is non-specific but may represent in severe clinical consequences including venous thrombosis and intracranial haemorrhage. Thorough understanding of local anatomy is important in understanding the pathogenesis and establishing the diagnosis. Our case reported here illustrates the use of multimodality imaging, including dynamic Computer tomography manoeuvre, in identifying the site of obstruction and guidance towards successful surgical treatment.

Cost-effectiveness of budesonide-formoterol vs inhaled epinephrine in US adults with mild asthma.

BACKGROUND: The management of mild asthma has lacked an over-the-counter (OTC) option aside from inhaled epinephrine, which is available in the United States. However, inhaled epinephrine use without an inhaled corticosteroid may increase the risk of asthma death. OBJECTIVE: To compare the cost-effectiveness of OTC as-needed budesonide-formoterol as a plausible alternative to inhaled epinephrine. METHODS: We developed a probabilistic Markov model to compare OTC as-needed budesonide-formoterol inhaler use vs inhaled epinephrine use in adults with mild asthma from a US societal perspective over a lifetime horizon, with a 3% annual discount rate (2022 US dollars). Inputs were derived from the SYmbicort Given as-needed in Mild Asthma (SYGMA) trials, published literature, and commercial costs. Outcomes were quality-adjusted life-years (QALY), costs, incremental net monetary benefit (INMB), severe asthma exacerbations, well-controlled asthma days, and asthma-related deaths. Microsimulation was used to evaluate underinsured Americans living with mild asthma (n = 5,250,000). RESULTS: Inhaled epinephrine was dominated (with lower QALYs gains at a higher cost) by both as-needed budesonide-formoterol (INMB, $15,541 at a willingness-to-pay of $100,000 per QALY) and the no-OTC inhaler option (INMB, $1023). Adults using as-needed budesonide-formoterol had 145 more well-controlled asthma days, 2.79 fewer severe exacerbations, and an absolute risk reduction of 0.23% for asthma-related death compared with inhaled epinephrine over a patient lifetime. As-needed budesonide-formoterol remained dominant in all sensitivity and scenario analyses, with a 100% probability of being cost-effective compared with inhaled epinephrine in probabilistic sensitivity analysis. CONCLUSION: If made available, OTC as-needed budesonide-formoterol for treating mild asthma in underinsured adults without HCP management improves asthma outcomes, prevents fatalities, and is cost-saving.

Hyper-entanglement between pulse modes and frequency bins.

Hyper-entanglement between two or more photonic degrees of freedom (DOF) can enhance and enable new quantum protocols by allowing each DOF to perform the task it is optimally suited for. Here we demonstrate the generation of photon pairs hyper-entangled between pulse modes and frequency bins. The pulse modes are generated via parametric downconversion in a domain-engineered crystal and subsequently entangled to two frequency bins via a spectral mapping technique. The resulting hyper-entangled state is characterized and verified via measurement of its joint spectral intensity and non-classical two-photon interference patterns from which we infer its spectral phase. The protocol combines the robustness to loss, intrinsic high dimensionality and compatibility with standard fiber-optic networks of the energy-time DOF with the ability of hyper-entanglement to increase the capacity and efficiency of the quantum channel, already exploited in recent experimental applications in both quantum information and quantum computation.

A Cost-Effectiveness Analysis of Azithromycin for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Rationale: Daily oral azithromycin therapy can reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (COPD). However, given its adverse events and additional costs, it is not known whether adding long-term azithromycin as an adjunct therapy to inhaled pharmacotherapy is cost effective. Objectives: The objective of this study was to evaluate the cost-effectiveness of add-on azithromycin therapy in COPD as recommended by contemporary COPD management guidelines. Methods: We extended a previously validated Canadian COPD policy model to include azithromycin-related inputs and outcomes. The cost-effectiveness of azithromycin was evaluated over a 20-year time horizon in patients who continue to exacerbate despite receiving maximal inhaled therapies. The benefit of azithromycin was modeled as a reduction in exacerbation rates. Adverse events included cardiovascular death, hearing loss, gastrointestinal symptoms, and antimicrobial resistance. The incremental cost-effectiveness ratio (ICER) was calculated with costs in 2020 Canadian dollars ($) and quality-adjusted life-years (QALYs) discounted at 1.5% per year. The analysis was stratified among patient subgroups based on exacerbation histories. Results: In patients with a positive exacerbation history (one or more events in the previous 12 mo), azithromycin was associated with $49,732 costs, 7.65 QALYs, and 10.95 exacerbations per patient over 20 years. The corresponding values were $48,436, 7.62, and 11.86 for the reference group, resulting in an ICER of $43,200 per QALY gained. In patients defined as frequent exacerbators (two or more moderate or one or more severe events in the past 12 mo), the ICER was reduced to $8,862 per QALY gained. In patients with no history of exacerbation, azithromycin had lower QALYs and higher costs than the reference group. Conclusions: Add-on azithromycin is cost effective in patients with a recent history of exacerbations at commonly accepted willingness-to-pay thresholds of $50,000-$100,000/QALY. Guidelines should consider recommending add-on azithromycin for patients who had at least one moderate or severe exacerbation in the past year, albeit more information about treatment efficacy would strengthen this recommendation.

Interferon ß-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial.

Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNß-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 µg subcutaneous pegylated IFNß-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNß-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNß-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = -0.2%, 95% CI = -8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = -3.6% to 11.3%). Treatment with IFNß-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNß-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.

Generalizability of Risk Stratification Algorithms for Exacerbations in COPD.

BACKGROUND: Contemporary management of COPD relies on exacerbation history to risk-stratify patients for future exacerbations. Multivariable prediction models can improve the performance of risk stratification. However, the clinical utility of risk stratification can vary from one population to another. RESEARCH QUESTION: How do two validated exacerbation risk prediction models (Acute COPD Exacerbation Prediction Tool [ACCEPT] and the Bertens model) compared with exacerbation history alone perform in different patient populations? STUDY DESIGN AND METHODS: We used data from three clinical studies representing populations at different levels of moderate to severe exacerbation risk: the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421; annual risk, 0.22), the Long-term Oxygen Treatment Trial (LOTT; N = 595; annual risk, 0.38), and Towards a Revolution in COPD Health (TORCH; N = 1,091; annual risk, 0.52). We compared the area under the receiver operating characteristic curve (AUC) and net benefit (measure of clinical utility) among three risk stratification algorithms for predicting exacerbations in the next 12 months. We also evaluated the effect of model recalibration on clinical utility. RESULTS: Compared with exacerbation history, ACCEPT showed better performance in all three samples (change in AUC, 0.08, 0.07, and 0.10, in SUMMIT, LOTT, and TORCH, respectively; P ≤ .001 for all). The Bertens model showed better performance compared with exacerbation history in SUMMIT and TORCH (change in AUC, 0.10 and 0.05, respectively; P < .001 for both), but not in LOTT. No algorithm was superior in clinical utility across all samples. Before recalibration, the Bertens model generally outperformed the other algorithms in low-risk settings, whereas ACCEPT outperformed others in high-risk settings. All three algorithms showed the risk of harm (providing lower net benefit than not using any risk stratification). After recalibration, risk of harm was mitigated substantially for both prediction models. INTERPRETATION: Exacerbation history alone is unlikely to provide clinical utility for predicting COPD exacerbations in all settings and could be associated with a risk of harm. Prediction models have superior predictive performance, but require setting-specific recalibration to confer higher clinical utility.

Treating Biliary Tract Cancers: New Targets and Therapies.

Biliary tract cancers (BTCs) are rare and aggressive tumors that typically present at an advanced stage when surgical resection is no longer considered a therapeutic option. While gemcitabine and cisplatin have been the mainstay of treatment, unique chemotherapy combination strategies, targeted therapies, and immunotherapies have had some clinical efficacy and remain promising areas for clinical research. The use of molecular profiling of BTCs has facilitated the development and subsequent clinical application of novel targeted therapy compounds. Among the many genomic alterations identified in BTCs, molecular abnormalities in the fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), human epidermal growth factor receptor 2 (HER2), and BRAF have been successfully targeted therapeutically in clinical trials. Furthermore, the expanded use of new chemotherapy combinations, targeted therapies, and immunotherapies into alternate clinical settings such as in the neoadjuvant and adjuvant spaces is an area of active investigation. The management of BTCs is rapidly evolving. In this article, we review the emerging targets and therapies in BTC.

ACCEPT 2·0: Recalibrating and externally validating the Acute COPD exacerbation prediction tool (ACCEPT).

Background: The Acute Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Prediction Tool (ACCEPT) was developed for individualised prediction of COPD exacerbations. ACCEPT was well calibrated overall and had a high discriminatory power, but overestimated risk among individuals without recent exacerbations. The objectives of this study were to 1) fine-tune ACCEPT to make better predictions for individuals with a negative exacerbation history, 2) develop more parsimonious models, and 3) externally validate the models in a new dataset. Methods: We recalibrated ACCEPT using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE, a three-year observational study, 1,803 patients, 2,117 exacerbations) study by applying non-parametric regression splines to the predicted rates. We developed three reduced versions of ACCEPT by removing symptom score and/or baseline medications as predictors. We examined the discrimination, calibration, and net benefit of ACCEPT 2·0 in the placebo arm of the Towards a Revolution in COPD Health (TORCH, a three-year randomised clinical trial of inhaled therapies in COPD, 1,091 patients, 1,064 exacerbations) study. The primary outcome for prediction was the occurrence of ≥2 moderate or ≥1 severe exacerbation in the next 12 months; the secondary outcomes were prediction of the occurrence of any moderate/severe exacerbation or any severe exacerbation. Findings: ACCEPT 2·0 had an area-under-the-curve (AUC) of 0·76 for predicting the primary outcome. Exacerbation history alone (current standard of care) had an AUC of 0·68. The model was well calibrated in patients with positive or negative exacerbation histories. Changes in AUC in reduced versions were minimal for the primary outcome as well as for predicting the occurrence of any moderate/severe exacerbations (ΔAUC<0·011), but more substantial for predicting the occurrence of any severe exacerbations (ΔAUC<0·020). All versions of ACCEPT 2·0 provided positive net benefit over the use of exacerbation history alone for some range of thresholds. Interpretation: ACCEPT 2·0 showed good calibration regardless of exacerbation history, and predicts exacerbation risk better than current standard of care for a range of thresholds. Future studies need to investigate the utility of exacerbation prediction in various subgroups of patients. Funding: This study was funded by a team grant from the Canadian Institutes of Health Research (PHT 178432).

Structural determinants of dual incretin receptor agonism by tirzepatide.

SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist.

Persistent opioid use in patients with multiple myeloma post-ASCT.

PURPOSE: Bone pain is a common presenting symptom of multiple myeloma (MM) and is frequently treated with opioids in addition to myeloma directed therapy. With improved response and survival with modern myeloma therapy, it is important to re-examine the role of opioids in managing symptomatic myeloma. PATIENTS AND METHODS: We performed a retrospective analysis of patients with myeloma at Rutgers Cancer Institute of New Jersey (RCINJ) who received an ASCT between January 1, 2012, and December 30, 2017, and who had subsequent follow-up (a total of 138 patients). We sought information specifically from the visits after induction therapy but prior to ASCT, at 100 days and 1-year post-ASCT follow-up visits. We compared opioid users and non-users in relation to treatment response, co-morbid conditions, and symptoms. We also examined amounts, duration, and odds of continued opioid use. RESULTS: At the time of the first analysis (before transplant), 34.8% of patients were using opioids and opioid use was more frequent in younger patients and, as expected, in patients with bone lesions. At 1 year, 31.9% of patients were still using opioids and continued opioid use was not correlated with disease response. Of the patients using opioids at the time of transplant, 58% either maintained their opioid dose or increased it at 1-year post-transplant. CONCLUSIONS: This retrospective analysis shows that despite a small decrease in opioid use over time, opioid use remains frequent in MM patients and is correlated with younger age and bone involvement but not with response to therapy. Over half the patients using opioids at the time of transplant continued or increased opioid use over the following year. With increasing survival in myeloma patients, further attention is required to distinguish cancer pain from chronic pain in cancer patients.

Economic Evidence on Potentially Curative Gene Therapy Products: A Systematic Literature Review.

OBJECTIVE: The aim of this review was to summarize all available evidence on the cost effectiveness of potentially curative gene therapies and identify challenges that economic evaluations face in this area. METHODS: We conducted a systematic review of four databases (PubMed/MEDLINE, Embase, CINAHL, EconLit) and grey literature sources. We conducted the search on August 23, 2019 and updated it on November 26, 2020. We included all English, French and Spanish language studies that addressed a gene therapy that had received regulatory approval or had entered a phase III trial, and also reported on costs related to the therapy. Critical appraisal was conducted to assess quality of reporting in included studies. RESULTS: Fifty-six studies were identified. Of the 42 full economic evaluations, 71% (n = 30) evaluated chimeric antigen receptor T-cell therapies, most used either a Markov model (n = 17, 40%) and/or a partitioned survival model (n = 17, 40%), and 76% (n = 32) adopted a public or private payer perspective. The model characteristics with the greatest impact on cost effectiveness included assumptions about the efficacy of the treatment and the comparators used. CONCLUSION: All gene therapies in this review were shown to be more effective than their comparators, although due to high costs not all were considered cost effective at standard cost-effectiveness thresholds. Despite their high cost, some gene therapies have the potential to dominate the alternatives in conditions with high mortality/disability. The choice of comparator and assumptions regarding long-term effectiveness had substantial impacts on cost-effectiveness estimates and need to be carefully considered. Both the quality of inputs and the quality of reporting were highly variable.

Experimental quantum conference key agreement.

Quantum networks will provide multinode entanglement enabling secure communication on a global scale. Traditional quantum communication protocols consume pair-wise entanglement, which is suboptimal for distributed tasks involving more than two users. Here, we demonstrate quantum conference key agreement, a cryptography protocol leveraging multipartite entanglement to efficiently create identical keys between N users with up to N-1 rate advantage in constrained networks. We distribute four-photon Greenberger-Horne-Zeilinger (GHZ) states, generated by high-brightness telecom photon-pair sources, over optical fiber with combined lengths of up to 50 km and then perform multiuser error correction and privacy amplification. Under finite-key analysis, we establish 1.5 × 106 bits of secure key, which are used to encrypt and securely share an image between four users in a conference transmission. Our work highlights a previously unexplored protocol tailored for multinode networks leveraging low-noise, long-distance transmission of GHZ states that will pave the way for future multiparty quantum information processing applications.

Influence of Caregiver Presence During Physician Office Visits on Patients Undergoing Chemoradiation Therapy for Esophageal Cancer.

PURPOSE: Although the association of marital status with outcomes for patients with cancer has been widely studied, the mechanisms underpinning the protective effect of marriage are still not fully understood. The social support that marriage imparts is often discussed as an explanation for why patients with cancer who are married have better outcomes. Social support has been difficult to objectively quantify. Accompaniment of the patient at physician visits may be more meaningful than marital status itself. This study investigated the effect of caregiver presence at physician visits on treatment tolerance and outcome in patients undergoing chemoradiation therapy (CRT) for esophageal cancer. METHODS AND MATERIALS: Patients who received a diagnosis of esophageal cancer who underwent CRT from January 1, 2005, to January 1, 2016, as part of their curative-intent management were retrospectively reviewed. Data collected included the patients' marital status, caregiver presence at each physician visit, baseline performance status, serum albumin values and leukocyte values throughout treatment, patient weight values throughout treatment, tumor response to therapy, and overall survival. Patients were divided into 2 groups based on frequency of caregiver presence at physician visits (<50% or ≥50% of visits). Using χ2 tests, Wilcoxon rank sum tests, and log-rank tests, the patients' characteristics, treatment tolerance and treatment outcome, and overall survival, respectively, were compared. RESULTS: In total, 35 of 59 patients were defined as having frequent caregiver presence at physician visits (≥50% of all documented visits), whereas 24 patients were categorized as having infrequent caregiver accompaniment. No significant difference in performance status or weight loss before the diagnosis of esophageal cancer was found. Patients who had frequent caregiver presence at physician visits maintained body weight better than those who had infrequent caregiver presence (median weight loss of 2.7 kg compared with 4.9 kg; P = .04). There was no difference in overall survival between the 2 groups. CONCLUSIONS: Although patients with esophageal cancer undergoing CRT who had frequent caregiver presence at physician visits were not found to have an overall survival benefit, they had less weight loss, which may confer favorable treatment tolerance and maintenance of nutritional status during cancer treatment.

Optimised domain-engineered crystals for pure telecom photon sources.

The ideal photon-pair source for building up multi-qubit states needs to produce indistinguishable photons with high efficiency. Indistinguishability is crucial for minimising errors in two-photon interference, central to building larger states, while high heralding rates will be needed to overcome unfavourable loss scaling. Domain engineering in parametric down-conversion sources negates the need for lossy spectral filtering allowing one to satisfy these conditions inherently within the source design. Here, we present a telecom-wavelength parametric down-conversion photon source that operates on the achievable limit of domain engineering. We generate photons from independent sources which achieve two-photon interference visibilities of up to 98.6 ± 1.1% without narrow-band filtering. As a consequence, we reach net heralding efficiencies of up to 67.5%, which corresponds to collection efficiencies exceeding 90%.

Structure-based, multi-targeted drug discovery approach to eicosanoid inhibition: Dual inhibitors of mPGES-1 and 5-lipoxygenase activating protein (FLAP).

BACKGROUND: Due to the importance of both prostaglandins (PGs) and leukotrienes (LTs) as pro-inflammatory mediators, and the potential for eicosanoid shunting in the presence of pathway target inhibitors, we have investigated an approach to inhibiting the formation of both PGs and LTs as part of a multi-targeted drug discovery effort. METHODS: We generated ligand-protein X-ray crystal structures of known inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) and the 5-Lipoxygenase Activating Protein (FLAP), with their respective proteins, to understand the overlapping pharmacophores. We subsequently used molecular modeling and structure-based drug design (SBDD) to identify hybrid structures intended to inhibit both targets. RESULTS: This work enabled the preparation of compounds 4 and 5, which showed potent in vitro inhibition of both targets. SIGNIFICANCE: Our findings enhance the structural understanding of mPGES-1 and FLAP's unique ligand binding pockets and should accelerate the discovery of additional dual inhibitors for these two important integral membrane protein drug targets.

Synthetic protease-activated class B GPCRs.

G-protein coupled receptors (GPCRs) are the ligand detection machinery of a majority of extracellular signaling systems in metazoans. Novel chemical and biological tools to probe the structure-function relationships of GPCRs have impacted both basic and applied GPCR research. To better understand the structure-function of class B GPCRs, we generated receptor-ligand fusion chimeric proteins that can be activated by exogenous enzyme application. As a prototype, fusion proteins of the glucagon-like peptide-1 receptor (GLP-1R) with GLP-1(7-36) and exendin-4(1-39) peptides incorporating enterokinase-cleavable N-termini were generated. These receptors are predicted to generate fusion protein neo-epitopes upon proteolysis with enterokinase that are identical to the N-termini of GLP-1 agonists. This system was validated by measuring enterokinase-dependent GLP-1R mediated cAMP accumulation, and a structure-activity relationship for both linker length and peptide sequence was observed. Moreover, our results show this approach can be used in physiologically relevant cell systems, as GLP-1R-ligand chimeras were shown to induce glucose-dependent insulin secretion in insulinoma cells upon exposure to enterokinase. This approach suggests new strategies for understanding the structure-function of peptide-binding GPCRs.

Structural insights into probe-dependent positive allosterism of the GLP-1 receptor.

Drugs that promote the association of protein complexes are an emerging therapeutic strategy. We report discovery of a G protein-coupled receptor (GPCR) ligand that stabilizes an active state conformation by cooperatively binding both the receptor and orthosteric ligand, thereby acting as a 'molecular glue'. LSN3160440 is a positive allosteric modulator of the GLP-1R optimized to increase the affinity and efficacy of GLP-1(9-36), a proteolytic product of GLP-1(7-36). The compound enhances insulin secretion in a glucose-, ligand- and GLP-1R-dependent manner. Cryo-electron microscopy determined the structure of the GLP-1R bound to LSN3160440 in complex with GLP-1 and heterotrimeric Gs. The modulator binds high in the helical bundle at an interface between TM1 and TM2, allowing access to the peptide ligand. Pharmacological characterization showed strong probe dependence of LSN3160440 for GLP-1(9-36) versus oxyntomodulin that is driven by a single residue. Our findings expand protein-protein modulation drug discovery to uncompetitive, active state stabilizers for peptide hormone receptors.

Discovery and pharmacology of the covalent GLP-1 receptor (GLP-1R) allosteric modulator BETP: A novel tool to probe GLP-1R pharmacology.

The glucagon-like peptide-1 receptor (GLP-1R) is a significant therapeutic target for small molecule drug discovery given the therapeutic impact of peptide agonists in the diabetes sphere. We review the discovery and subsequent characterization of the small molecule GLP-1R allosteric modulator 4-(3-(Benzyloxy)phenyl)-2-(ethylsulfinyl)-6-(trifluoromethyl)pyrimidine (BETP). BETP is a covalent modulator of the GLP-1R, and we discuss the pharmacological implications and possible structural basis of this novel mode of action. We highlight the insights into class B G-protein coupled receptor pharmacology and biology provided by studies conducted with BETP. These include the descriptions of exquisite allosteric modulator probe dependence and biased signaling in vitro and in vivo. We conclude with an analysis of the utility of BETP as a chemical probe for the GLP-1R.

Post-modification of Cellulose Nanocrystal Aerogels with Thiol-Ene Click Chemistry.

The functionalization of cellulose nanocrystal (CNC) aerogels was achieved through a two-step synthetic procedure. CNC aerogels were prepared under hydrothermal conditions, followed by solvent exchange and critical point drying. The CNC aerogels were functionalized with a methacrylate group and then underwent thiol-ene click chemistry to impart a range of functionalities onto the surface of the CNC aerogel. The use of the functionalized aerogels as oil absorbents was then investigated, with the most hydrophobic CNC aerogel, 1 H,1 H,2 H,2 H-perfluorodecanethiol-functionalized CNC aerogel, exhibiting the highest absorption of xylenes at 2.9 mL g-1.

COMPARISON OF 3 MM × 3 MM VERSUS 6 MM × 6 MM OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SCAN SIZES IN THE EVALUATION OF NON-PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the utility of different optical coherence tomography angiography scan protocols in evaluating retinal changes in non-proliferative diabetic retinopathy. METHODS: Patients were imaged with the RTVue XR Avanti OCT 3 mm × 3 mm and 6 mm × 6 mm "Angio Retina" scan protocols. Ability to clearly delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms, capillary nonperfusion, motion, and doubling artifacts were evaluated. RESULTS: Forty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm × 3 mm versus 59% of 6 mm × 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty percent of 3 mm × 3 mm versus 43% of 6 mm × 6 mm scans demonstrated FAZ remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm × 6 mm and 35% of 3 mm × 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87% of 3 mm × 3 mm scans versus 89% of 6 mm × 6 mm scans (P = 0.99). No significant differences were noted in the incidence of artifacts between the scan sizes (motion artifact P = 0.29 and doubling artifact P = 0.29). CONCLUSION: 3 mm × 3 mm scan delineated FAZ and remodeling better than 6 mm × 6 mm scan, likely because of its higher scan density. 6 mm × 6 mm scans detected microaneurysms more readily than 3 mm × 3 mm, likely because of its larger scan area. There were utility for both 3 mm × 3 mm and 6 mm × 6 mm scans when evaluating these patients.