Characterization of 10MAG/LDAO reverse micelles: Understanding versatility for protein encapsulation.

Reverse micelles (RMs) are spontaneously organizing nanobubbles composed of an organic solvent, surfactants, and an aqueous phase that can encapsulate biological macromolecules for various biophysical studies. Unlike other RM systems, the 1-decanoyl-rac-glycerol (10MAG) and lauryldimethylamine-N-oxide (LDAO) surfactant system has proven to house proteins with higher stability than other RM mixtures with little sensitivity to the water loading (W, defined by the ratio of water to surfactant). We investigated this unique property by encapsulating three model proteins - cytochrome c, myoglobin, and flavodoxin - in 10MAG/LDAO RMs and applying a variety of experimental methods to characterize this system's behavior.

Structure and dynamics determine G protein coupling specificity at a class A GPCR.

G protein coupled receptors (GPCRs) exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of GPCR-G protein complexes, little is known about the mechanism of G protein coupling specificity. The β2-adrenergic receptor is an example of GPCR with high selectivity for Gαs, the stimulatory G protein for adenylyl cyclase, and much weaker for the Gαi family of G proteins inhibiting adenylyl cyclase.

Arthroscopy Association of Canada Position Statement on Opioid Prescription After Arthroscopic Surgery.

Background: Despite the ongoing opioid epidemic, most patients are still prescribed a significant number of opioid medications for pain management after arthroscopic surgery. There is a need for consensus among orthopaedic surgeons and solutions to aid providers in analgesic strategies that reduce the use of opioid pain medications.

Purpose: This position statement was developed with a comprehensive systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to synthesize the best available evidence for managing acute postoperative pain after arthroscopic surgery.

Determining the factors associated with a prolonged length of stay for adolescent idiopathic scoliosis patients undergoing posterior spinal instrumentation and fusion in a single-payer health care system: are these factors different than those in the United States?

Introduction: Rapid recovery pathways (RRP) for adolescent idiopathic scoliosis patients undergoing posterior spinal instrumentation and fusion (PSIF) have been shown to be successful in reducing hospital length of stay (LOS). Although the majority of patients are discharged within 3 days, some patients require longer hospital admission. Previous studies in the United States have identified predictors of prolonged LOS for this patient population.

Opioid-Sparing Strategies in Arthroscopic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Opioid overprescription is a problem in orthopaedic surgery. Arthroscopic surgery, given its minimally invasive nature, represents an opportunity to minimize opioid prescription and consumption by using effective pain management adjuncts. Thus, the primary question posed in this study was which noninvasive pain management modalities can effectively manage pain and reduce opioid intake after arthroscopic surgery.

Risk of complications with prolonged operative time in morbidly obese patients undergoing elective total knee arthroplasty.

Background: Patients with a high body-mass index (BMI) are at increased risk for significant complications after total knee arthroplasty (TKA). We explored whether operative time is a modifiable risk factor for infectious and thromboembolic complications.

Methods: A retrospective observational cohort study of the ACS-NSQIP registry, including all patients who underwent primary TKA (2015-2018), and were morbidly obese (BMI 40 kg/m or greater) was performed.

The Impact of Industry Funding on Randomized Controlled Trials of Biologic Therapies.

There has been substantial interest from the pharmaceutical industry to study and develop new biologic agents. Previous studies outside of the biologics field have demonstrated that industry funding has the potential to impact the design and findings of clinical trials. The objective of this study was to evaluate the impact of industry funding on randomized controlled trials (RCTs) that investigated the efficacy of biologic therapies.

Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System.

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules.

Do Adhesive Drapes Have an Effect on Infection Rates in Orthopaedic Surgery? A Systematic Review and Meta-Analysis.

Background: Adhesive surgical drapes are purported to reduce the rates of surgical site infection. Despite that, international surgical guidelines generally recommend against the use of such drapes; however, this is primarily based on nonorthopaedic evidence.

Questions/purposes: (1) Does the use of adhesive drapes decrease the risk of wound contamination? (2) Does intraoperative drape peeling (intentional or inadvertent) increase the risk of wound contamination? (3) Does the use of adhesive drapes decrease the risk of surgical site infection?

Methods: A systematic review of the MEDLINE and Embase databases was performed according to the Cochrane Handbook methods for randomized controlled trials (RCTs) published since 2000 and comparing adhesive drapes with controls.

Quantifying the Level of Evidence of Podium Presentations at the American Association of Hip and Knee Surgeons From 2015 to 2019.

Background: The American Association of Hip and Knee Surgeons (AAHKS) Annual Scientific Meeting is a leading forum for the presentation and dissemination of research regarding the management of hip and knee pathology making research presented at these meetings a representation of the current literature in the field. The purpose of this study was to quantify the level of evidence of podium presentations presented at the AAHKS annual meeting from 2015 to 2019.

Methods: Two reviewers evaluated the abstracts for the available presentations.

The Fragility of Statistically Significant Findings From Randomized Controlled Trials in Hip and Knee Arthroplasty.

Background: The Fragility Index (FI) is a method for evaluating the robustness of statistically significant findings from randomized controlled trials (RCTs) beyond the P value in trials with dichotomous outcomes. The FI is defined as the number of patients in one arm of a trial that would have to have a different outcome to change the results of the trial from statistically significant to nonsignificant. This review assessed the FI in arthroplasty RCTs.

Cannabinoids in the Management of Acute Pain: A Systematic Review and Meta-analysis.

To synthesize the best evidence surrounding the efficacy of cannabinoids for acute pain in the clinical setting based on subjective pain scores and observed adverse effects. Systematic review with meta-analysis. PubMed, Embase, Cochrane Databases, and Google Scholar.

Protein conformational entropy is not slaved to water.

Conformational entropy can be an important element of the thermodynamics of protein functions such as the binding of ligands. The observed role for conformational entropy in modulating molecular recognition by proteins is in opposition to an often-invoked theory for the interaction of protein molecules with solvent water. The "solvent slaving" model predicts that protein motion is strongly coupled to various aspects of water such as bulk solvent viscosity and local hydration shell dynamics.

Perioperative nonopioid analgesia reduces postoperative opioid consumption in knee arthroscopy: a systematic review and meta-analysis.

Purpose: The opioid epidemic has prompted an emphasis on investigating opioid-sparing alternatives for pain management following knee arthroscopy. This review evaluated the effects of perioperative nonopioid adjunct analgesia on postoperative opioid consumption and pain control in patients undergoing knee arthroscopy.

Methods: A systematic review and meta-analysis was performed using the following databases: PubMed, Embase, Web of Science, MEDLINE, and SCOPUS.

THERAPY OF ENDOCRINE DISEASE Immunotherapy of advanced thyroid cancer: from bench to bedside.

Immunotherapy has arisen in use in the field of oncology with seven immune checkpoint inhibitors approved for the treatment of a variety of cancer histologies. Depending on the cancer type, the success rate might be different, but in average it is about 20%, with some cases showing a durable response, lasting also after the interruption of the treatment, with a clear benefit on OS. The development of an efficacious cure for advanced thyroid carcinomas is still an unmet need and immunotherapy represents an interesting alternative option also for this cancer.

Trials and tribulations: so many potential treatments, so few answers.

Purpose: The purpose of this review is to quantify the landscape of current clinical trials ongoing for therapies in the treatment of COVID-19. A secondary purpose is to examine the relationship between public and scientific interests in potential therapies for COVID-19.

Methods: A systematic search of clinicaltrials.

Maximizing virtual meetings and conferences: a review of best practices.

Purpose: In the current COVID-19 pandemic, it is more important than ever to maximize communication in the scientific and medical community. In the context of academic meetings and conferences, there is the growing need for a set of guidelines secondary to the COVID-19 pandemic, and the growing environmental and economic challenges that large academic and medical conferences face. These Virtual Meetings Best Practices were established in response to the scant evidence and guidance on the topic.

Management of infected extremity endoprostheses: a systematic review.

Background: Endoprosthetic reconstructions have become increasingly common in the setting of significant bone loss. Indications include revision arthroplasty, trauma, and reconstruction in the setting of primary malignancies or bony metastases. Although the use of endoprostheses has several advantages, they carry a high risk of infection.

The Aryl Hydrocarbon Receptor Is Expressed in Thyroid Carcinoma and Appears to Mediate Epithelial-Mesenchymal-Transition.

Aryl hydrocarbon receptor (AhR) is expected to promote initiation, progression and invasion of cancer cells regulating proliferation, differentiation, gene expression, inflammation, cell motility and migration. Furthermore, an immunosuppressant function of AhR has been recognized. This study evaluated AhR expression and its role in thyroid cancer progression.

Immune Profiling of Thyroid Carcinomas Suggests the Existence of Two Major Phenotypes: An ATC-Like and a PDTC-Like.

Objectives: The understanding of the mechanisms underlying thyroid cancer immune escape can lead to the identification of new molecular targets and/or efficacy biomarkers. For this purpose, we performed immune expression profiling in thyroid cancers to obtain a comprehensive view on immune mechanisms activated during cancer progression.

Methods: The study was conducted retrospectively in 25 papillary thyroid carcinomas (PTCs), 14 poorly differentiated thyroid carcinomas (PDTC), 13 anaplastic thyroid carcinomas (ATCs), and 7 normal thyroid (NT) tissue samples.

Toward comprehensive measurement of protein hydration dynamics: Facilitation of NMR-based methods by reverse micelle encapsulation.

Protein-water interactions are a fundamental determinant of protein structure and function. Despite their importance, the molecular details of water orientations and dynamics near protein surfaces remain poorly understood, largely due to the difficulty of measuring local water mobility near the protein in a site-resolved fashion. Solution NMR-based measurement of water mobility via the nuclear Overhauser effect was presented as a method for performing comprehensive, site-resolved measurements of water dynamics many years ago.

New insight on the S100A1-STIP1 complex highlights the important relationship between allostery and entropy in protein function.

Calcium signaling serves as a nexus of many vital cellular processes. Of particular importance is the role the calcium signaling plays in the prevention of protein misfolding, and the S100 family of calcium-binding proteins is a key player in this pathway. While the S100 proteins carry out a range of roles, the interaction of S100A1 and the stress-inducible phosphoprotein 1 (STIP1) has been shown to be particularly important.

Signal Transducer and Activator of Transcription 1 Plays a Pivotal Role in RET/PTC3 Oncogene-induced Expression of Indoleamine 2,3-Dioxygenase 1.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a single chain oxidoreductase that catalyzes tryptophan degradation to kynurenine. In cancer, it exerts an immunosuppressive function as part of an acquired mechanism of immune escape. Recently, we demonstrated that IDO1 expression is significantly higher in all thyroid cancer histotypes compared with normal thyroid and that its expression levels correlate with T regulatory (Treg) lymphocyte densities in the tumor microenvironment.