Assessing the treatment response of lateral elbow tendinopathy using time-dependent ultrasonography, Doppler imaging, and elastography.

Objective: To investigate the structural alterations, neovascularity, and elasticity of tendons and the relationship between elasticity and the Patient Rated Tennis Elbow Evaluation score after undergoing US-guided fenestration or surgery in patients with chronic lateral elbow tendinopathy.

Methods: Participants from the per-protocol population of a randomized trial conducted between October 2016 and June 2020 were included. The surgery and fenestration groups included 24 (mean age, 50 ± 7 years [standard deviation], 10 men) and 29 (47 ± 8 years, 18 men) participants, respectively.

Pollen identification through convolutional neural networks: First application on a full fossil pollen sequence.

The automation of pollen identification has seen vast improvements in the past years, with Convolutional Neural Networks coming out as the preferred tool to train models. Still, only a small portion of works published on the matter address the identification of fossil pollen. Fossil pollen is commonly extracted from organic sediment cores and are used by paleoecologists to reconstruct past environments, flora, vegetation, and their evolution through time.

Use of semi-permeable bag materials to facilitate on-site treatment of biological agent-contaminated waste.

Clean up following the wide-area release of a persistent biological agent has the potential to generate significant waste. Waste containing residual levels of biological contaminants may require off-site shipment under the U.S.

Treatment of chronic lateral epicondylosis: a randomized trial comparing the efficacy of ultrasound-guided tendon dry needling and open-release surgery.

Objective: Evaluate the efficacy of ultrasound-guided dry needling and open-release surgery in reducing pain and improving function in workers with lateral epicondylosis refractory to at least 6 months of nonsurgical management.

Methods: We randomly assigned participants in a 1:1 ratio to receive dry needling or surgery. The primary outcome was the Patient Rated Tennis Elbow Evaluation (PRTEE) score at 6 months.

Role of Mixed-Species Stands in Attenuating the Vulnerability of Boreal Forests to Climate Change and Insect Epidemics.

We investigated whether stand species mixture can attenuate the vulnerability of eastern Canada's boreal forests to climate change and insect epidemics. For this, we focused on two dominant boreal species, black spruce [ (Mill.) BSP] and trembling aspen ( Michx.

-Halamine Polypropylene Nonwoven Fabrics with Rechargeable Antibacterial and Antiviral Functions for Medical Applications.

Embedding medical and hygiene products with regenerable antimicrobial functions would have significant implications for limiting pathogen contaminations and reducing healthcare-associated infections. Herein, we demonstrate a scalable and industrially feasible methodology to fabricate chlorine rechargeable melt-blown polypropylene (PP) nonwoven fabrics, which have been widely used in hygienic and personal protective products, via a combination of a melt reactive extrusion process and melt-blown technique. Methacrylamide (MAM) was employed as a precursor of halamine monomers and covalently grafted onto the PP backbone to form polypropylene-grafted methacrylamide (PP-g-MAM), which could be chlorinated, yielding biocidal acyclic halamines.

Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection.

In light of the recent accumulated knowledge on SARS-CoV-2 and its mode of human cells invasion, the binding of viral spike glycoprotein to human Angiotensin Converting Enzyme 2 (hACE2) receptor plays a central role in cell entry. We designed a series of peptides mimicking the N-terminal helix of hACE2 protein which contains most of the contacting residues at the binding site, exhibiting a high helical folding propensity in aqueous solution. Our best peptide-mimics are able to block SARS-CoV-2 human pulmonary cell infection with an inhibitory concentration (IC) in the nanomolar range upon binding to the virus spike protein with high affinity.

High-Throughput Manufacture of 3D Fiber Scaffolds for Regenerative Medicine.

Engineered scaffolds used to regenerate mammalian tissues should recapitulate the underlying fibrous architecture of native tissue to achieve comparable function. Current fibrous scaffold fabrication processes, such as electrospinning and three-dimensional (3D) printing, possess application-specific advantages, but they are limited either by achievable fiber sizes and pore resolution, processing efficiency, or architectural control in three dimensions. As such, a gap exists in efficiently producing clinically relevant, anatomically sized scaffolds comprising fibers in the 1-100 μm range that are highly organized.

Homotrimerization Approach in the Design of Thrombospondin-1 Mimetic Peptides with Improved Potency in Triggering Regulated Cell Death of Cancer Cells.

In order to optimize the potency of the first serum-stable peptide agonist of CD47 (PKHB1) in triggering regulated cell death of cancer cells, we designed a maturation process aimed to mimic the trimeric structure of the thrombospondin-1/CD47 binding epitope. For that purpose, an N-methylation scan of the PKHB1 sequence was realized to prevent peptide aggregation. Structural and pharmacological analyses were conducted in order to assess the conformational impact of these chemical modifications on the backbone structure and the biological activity.

Discovery and Lead-Optimization of 4,5-Dihydropyrazoles as Mono-Kinase Selective, Orally Bioavailable and Efficacious Inhibitors of Receptor Interacting Protein 1 (RIP1) Kinase.

RIP1 kinase regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including inflammatory and neurological diseases. Currently, RIP1 kinase inhibitors have advanced into early clinical trials for evaluation in inflammatory diseases such as psoriasis, rheumatoid arthritis, and ulcerative colitis and neurological diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. In this paper, we report on the design of potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitors starting from a high-throughput screen and the lead-optimization of this series from a lead with minimal rat oral exposure to the identification of dihydropyrazole 77 with good pharmacokinetic profiles in multiple species.

A new AMPK activator, GSK773, corrects fatty acid oxidation and differentiation defect in CPT2-deficient myotubes.

Carnitine palmitoyl transferase 2 (CPT2) deficiency is one of the most common inherited fatty acid oxidation (FAO) defects and represents a prototypical mitochondrial metabolic myopathy. Recent studies have suggested a pivotal role of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle plasticity and mitochondrial homeostasis. Thus, we tested the potential of GSK773, a novel direct AMPK activator, to improve or correct FAO capacities in muscle cells from patients harboring various mutations.

Drivers of postfire soil organic carbon accumulation in the boreal forest.

The accumulation of soil carbon (C) is regulated by a complex interplay between abiotic and biotic factors. Our study aimed to identify the main drivers of soil C accumulation in the boreal forest of eastern North America. Ecosystem C pools were measured in 72 sites of fire origin that burned 2-314 years ago over a vast region with a range of ∆ mean annual temperature of 3°C and one of ∆ 500 mm total precipitation.

Ultrasound-guided tendon fenestration versus open-release surgery for the treatment of chronic lateral epicondylosis of the elbow: protocol for a prospective, randomised, single blinded study.

Introduction: Chronic lateral epicondylosis (CLE) of the elbow is a prevalent condition among middle-aged people with no consensus on optimal care management but for which surgery is generally accepted as a second intention treatment. Among conservative treatment options, ultrasound (US)-guided fenestration has shown encouraging results that should be explored before surgery is considered. The primary objective of this study is to compare the efficacy of US-guided fenestration with open-release surgery in patients with failure to improve following a minimum 6 months of conservative treatment.

Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA).

Lp-PLA has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA. The starting fragment hit was discovered through an X-ray fragment screen and showed no activity in the bioassay (IC > 1 mM).

Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies.

Thrombospondin-1 (TSP-1) is a glycoprotein considered as a key actor within the tumor microenvironment. Its binding to CD47, a cell surface receptor, triggers programmed cell death. Previous studies allowed the identification of 4N1K decapeptide derived from the TSP-1/CD47 binding epitope.

Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening.

Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA2 in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain (approximately 13 Å from the catalytic residue Ser273).

Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers.

Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities.

Ecological gradients driving the distribution of four Ericaceae in boreal Quebec, Canada.

Understory species play a significant role in forest ecosystem dynamics. As such, species of the Ericaceae family have a major effect on the regeneration of tree species in boreal ecosystems. It is thus imperative to understand the ecological gradients controlling their distribution and abundance, so that their impacts can be taken into account in sustainable forest management.

Discovery of Pyridones As Oral AMPK Direct Activators.

AMP-activated protein kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme that is activated in shortage of energy and suppressed in its surfeit. AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity, alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory changes. Thus, AMPK is a well-received therapeutic target for type 2 diabetes and other metabolic disorders.

Comparison of soluble guanylate cyclase stimulators and activators in models of cardiovascular disease associated with oxidative stress.

Soluble guanylate cyclase (sGC), the primary mediator of nitric oxide (NO) bioactivity, exists as reduced (NO-sensitive) and oxidized (NO-insensitive) forms. We tested the hypothesis that the cardiovascular protective effects of NO-insensitive sGC activation would be potentiated under conditions of oxidative stress compared to those of NO-sensitive sGC stimulation. The cardiovascular effects of the NO-insensitive sGC activator GSK2181236A [a low, non-depressor dose, and a high dose which lowered mean arterial pressure (MAP) by 5-10 mmHg] and those of equi-efficacious doses of the NO-sensitive sGC stimulator BAY 60-4552 were assessed in (1) Sprague Dawley rats during coronary artery ischemia/reperfusion (I/R) and (2) spontaneously hypertensive stroke prone rats (SHR-SP) on a high salt/fat diet (HSFD).

Liquid-crystalline zinc(II) and iron(II) alkyltriazoles one-dimensional coordination polymers.

Several series of unidimensional coordination polymers of formula [Zn(C(n)H(2n+1)trz)(3)](Cl)(2)·xH(2)O (n = 18, 16, 13, 11, 10, trz = 4-substituted-1,2,4-triazole), [Zn(C(18)H(37)trz)(3)](ptol)(2)·xH(2)O, [Fe(C(n)H(2n+1)trz)(3)](X)(2)·xH(2)O (n = 18, 16, 13, 10; X = Cl(-) or ptol(-), where ptol(-) = p-tolylsulfonate anion), and [Fe(C(18)H(37)trz)(3)](X)(2)·xH(2)O (X = C(8)H(17)PhSO(3)(-) and C(8)H(17)SO(3)(-)) are reported with their thermal, structural, and magnetic properties. Most of these materials exhibit thermotropic lamellar mesophases at temperatures as low as 410 K, as confirmed by textures observed by polarized optical microscopy. The corresponding phase diagrams deduced by differential scanning calorimetry are also reported.

Multifunctional gels from polymeric spin-crossover metallo-gelators.

The gelation abilities toward organic solvents of a series of triazole-based coordination polymers of formula [M(C(n)trz)(3)]A(2) (M = Fe(II) or Zn(II); C(n)trz = 4-n-alkyl-1,2,4-triazole with n = 13, 16, 18; A = monovalent anions, abbreviated as MC(n)A) have been studied to form thermally responsive multifunctional metallogels, in particular for the iron polymers that present the spin-crossover phenomenon. Indeed thermo-reversible physical gels exhibiting thermally reversible magnetic and optical crossovers are formed in decane and toluene. The FeC(18)ptol/decane and FeC(18)ptol/toluene phase diagrams are described (ptol = p-toluene sulfonate anion), together with the rheological properties of the gels determined as a function of the solvent, the gelator concentration as well as temperature.

Shear-induced fractures and three-dimensional motions in an organogel.

The flow behavior of a viscoelastic organogel is investigated using ultrasonic velocimetry combined with rheometry. Our gel presents a decreasing flow curve, i.e.