Bone collagen tensile properties of the aging human proximal femur.

Despite the dominant role of bone mass in osteoporotic fractures, aging bone tissue properties must be thoroughly understood to improve osteoporosis management. In this context, collagen content and integrity are considered important factors, although limited research has been conducted on the tensile behavior of demineralized compact bone in relation to its porosity and elastic properties in the native mineralized state. Therefore, this study aims (i) at examining the age-dependency of mineralized bone and collagen micromechanical properties; (ii) to test whether, and if so to which extent, collagen properties contribute to mineralized bone mechanical properties.

Homogenized finite element analysis of distal tibia sections: Achievements and limitations.

High-resolution peripheral quantitative computed tomography (HR-pQCT) based micro-finite element (μFE) analysis allows accurate prediction of stiffness and ultimate load of standardised (∼1 cm) distal radius and tibia sections. An alternative homogenized finite element method (hFE) was recently validated to compute the ultimate load of larger (∼2 cm) distal radius sections that include Colles' fracture sites. Since the mechanical integrity of the weight-bearing distal tibia is gaining clinical interest, it has been shown that the same properties can be used to predict the strength of both distal segments of the radius and the tibia.

Clinical Implementation of Automated Oxygen Titration in a Tertiary Care Hospital.

Background: When treating acute respiratory failure, both hypoxemia and hyperoxemia should be avoided. S should be monitored closely and O flows adjusted accordingly. Achieving this goal might be easier with automated O titration compared with manual titration of fixed-flow O.

Discovery of Darovasertib (NVP-LXS196), a Pan-PKC Inhibitor for the Treatment of Metastatic Uveal Melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in the adult eye. Despite the aggressive local management of primary UM, the development of metastases is common with no effective treatment options for metastatic disease. Genetic analysis of UM samples reveals the presence of mutually exclusive activating mutations in the Gq alpha subunits GNAQ and GNA11.

Paradoxical Increase of Permeability and Lipophilicity with the Increasing Topological Polar Surface Area within a Series of PRMT5 Inhibitors.

An imidazolone → triazolone replacement addressed the limited passive permeability of a series of protein arginine methyl transferase 5 (PRMT5) inhibitors. This increase in passive permeability was unexpected given the increase in the hydrogen bond acceptor (HBA) count and topological polar surface area (TPSA), two descriptors that are typically inversely correlated with permeability. Quantum mechanics (QM) calculations revealed that this unusual effect was due to an electronically driven disconnect between TPSA and 3D-PSA, which manifests in a reduction in overall HBA strength as indicated by the HBA moment descriptor from COSMO-RS (conductor-like screening model for real solvation).

Unified validation of a refined second-generation HR-pQCT based homogenized finite element method to predict strength of the distal segments in radius and tibia.

Introduction: HR-pQCT based micro finite element (μFE) analyses are considered as "gold standard" for virtual biomechanical analyses of peripheral bone sites such as the distal segment of radius and tibia. An attractive alternative for clinical use is a homogenized finite element method (hFE) based on constitutive models, because of its much shorter evaluation times and modest computational resource requirements. Such hFE models have been experimentally validated for the distal segment of the radius, but neither for the distal segments of the tibia nor for both measurement sites together.

Fabric-elasticity relationships of tibial trabecular bone are similar in osteogenesis imperfecta and healthy individuals.

Osteogenesis Imperfecta (OI) is an inherited form of bone fragility characterised by impaired synthesis of type I collagen, altered trabecular bone architecture and reduced bone mass. High resolution peripheral computed tomography (HR-pQCT) is a powerful method to investigate bone morphology at peripheral sites including the weight-bearing distal tibia. The resulting 3D reconstructions can be used as a basis of micro-finite element (FE) or homogenized finite element (hFE) models for bone strength estimation.

Impact of Airway Humidification Strategy in Mechanically Ventilated COVID-19 Patients.

Background: Humidification of inspiratory gases is mandatory in all mechanically ventilated patients in ICUs, either with heated humidifiers (HHs) or with heat and moisture exchangers (HMEs). In patients with COVID-19, the choice of the humidification device may have relevant impact on patients' management as demonstrated in recent studies. We reported data from 2 ICUs using either HME or HH.

A Value-Based Comparison of the Management of Ambulatory Respiratory Diseases in Walk-in Clinics, Primary Care Practices, and Emergency Departments: Protocol for a Multicenter Prospective Cohort Study.

Background: In Canada, 30%-60% of patients presenting to emergency departments are ambulatory. This category has been labeled as a source of emergency department overuse. Acting on the presumption that primary care practices and walk-in clinics offer equivalent care at a lower cost, governments have invested massively in improving access to these alternative settings in the hope that patients would present there instead when possible, thereby reducing the load on emergency departments.

Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer.

SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein as well as a potential immunomodulator, controlling SHP2 activity is of high therapeutic interest.

The Discovery of SWI/SNF Chromatin Remodeling Activity as a Novel and Targetable Dependency in Uveal Melanoma.

Uveal melanoma is a rare and aggressive cancer that originates in the eye. Currently, there are no approved targeted therapies and very few effective treatments for this cancer. Although activating mutations in the G protein alpha subunits, and , are key genetic drivers of the disease, few additional drug targets have been identified.

Small Animal Shanoir (SAS) A Cloud-Based Solution for Managing Preclinical MR Brain Imaging Studies.

Clinical multicenter imaging studies are frequent and rely on a wide range of existing tools for sharing data and processing pipelines. This is not the case for preclinical (small animal) studies. Animal population imaging is still in infancy, especially because a complete standardization and control of initial conditions in animal models across labs is still difficult and few studies aim at standardization of acquisition and post-processing techniques.

Evaluation of hyperoxia-induced hypercapnia in obese patients after cardiac surgery: a randomized crossover comparison of conservative and liberal oxygen administration.

Purpose: Recent studies on patients with stable obesity-hypoventilation syndrome have raised concerns about hyperoxia-induced hypercapnia in this population. This study aimed to evaluate whether a higher oxygen saturation target would increase arterial partial pressure of carbon dioxide (PaCO in obese patients after coronary artery bypass grafting surgery (CABG).

Methods: Obese patients having CABG were recruited.

Does the full-time presence of an intensivist lead to better outcomes in the cardiac surgical intensive care unit?

Objective: The study objective was to compare clinical outcomes in a dedicated adult cardiac surgery intensive care unit before and after the implementation of 24-hour intensivist coverage.

Methods: Between 2008 and 2016, 16,454 consecutive adult patients were admitted to the cardiac surgery intensive care unit after cardiac surgery. During this period, postoperative patients in the cardiac surgery intensive care unit were managed by intensivists during the day (group A); in July 2010, the nighttime coverage was transferred from the hands of residents and fellows to intensivists (group B).

Family medicine physician teachers and residents' intentions to prescribe and interpret spirometry: a descriptive cross-sectional study.

: Spirometry is the best test to demonstrate airway obstruction, but remains underused in primary care. : We assessed, among family medicine physician teachers and residents, their intention to prescribe spirometry in patients suspected of chronic obstructive pulmonary disease and their intention to interpret the results. This evaluation is based on the theoretical framework proposed by Godin et al.

Oxidative addition of carbon dioxide into mesoionics.

This work examines the prospect of making stable mesoionic compounds of the type mesomeric betaine R+-CO2- from direct oxidative additions of carbon dioxide to suitably-delocalized singlet carbene moieties, with bold objectives of carbon sequestration and overall energy storage. A set of possible candidates for such mesoionic compounds is theoretically explored through DFT calculations, inspecting coupling paths, thermodynamic and kinetic stabilities, and geometric and electronic structural features. Among others, the addressed cationic parts include aromatic rings in their broader sense, phenalene systems, and odd linear polyenic chains.

Objective Evaluation of Multiple Sclerosis Lesion Segmentation using a Data Management and Processing Infrastructure.

We present a study of multiple sclerosis segmentation algorithms conducted at the international MICCAI 2016 challenge. This challenge was operated using a new open-science computing infrastructure. This allowed for the automatic and independent evaluation of a large range of algorithms in a fair and completely automatic manner.

Indirect somatic embryogenesis of L in liquid medium and improvement of embryo-to-plantlet conversion rate.

The establishment of cocoa embryogenic cell lines in liquid medium starting from high frequency somatic embryogenesis (HFSE) callus is described. The growth kinetics of the cultures during the multiplication and the expression steps conducted in 250 mL Erlenmeyer flasks were described for three genotypes selected for their agronomical traits (EET95, EET96, and EET103). The glucose and dissolved oxygen concentrations and the absorption of Murashige and Skoog medium macronutrients (nitrate, ammonium, potassium, sulfate, calcium, phosphorus, and magnesium) were monitored.

Effects of High-Flow Nasal Cannula on the Work of Breathing in Patients Recovering From Acute Respiratory Failure.

Objectives: High-flow nasal cannula is increasingly used in the management of respiratory failure. However, little is known about its impact on respiratory effort, which could explain part of the benefits in terms of comfort and efficiency. This study was designed to assess the effects of high-flow nasal cannula on indexes of respiratory effort (i.

Unusual Cause of Life-Threatening Hemoptysis During Cardiac Operation: Surgical Management Revisited.

The surgical management of life-threatening perioperative hemoptysis has been vastly replaced by radiologic embolization. In some situations, surgical therapy can prove useful. This case report describes life-threatening hemoptysis of an unusual cause during coronary artery bypass grafting, managed through an original technique of temporary pulmonary vascular exclusion by thoracotomy.

Influence of trainee involvement on procedural characteristics for linear endobronchial ultrasound.

Background: Linear endobronchial ultrasound (EBUS) is a safe and effective method for the diagnostic sampling of mediastinal lymph nodes. However, there is a learning curve associated with the procedure and operator experience influences diagnostic yield. We sought to determine if trainee involvement during EBUS influences procedural characteristics, complication rate, and diagnostic yield.