Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers.

Pulmonary arterial hypertension: Sex matters.

Pulmonary arterial hypertension (PAH) is a complex disease of multifactorial origin. While registries have demonstrated that women are more susceptible to the disease, females with PAH have superior right ventricle (RV) function and a better prognosis than their male counterparts, a phenomenon referred to as the 'estrogen paradox'. Numerous pre-clinical studies have investigated the involvement of sex hormones in PAH pathobiology, often with conflicting results.

Data for analysis of catechol estrogen metabolites in human plasma by liquid chromatography tandem mass spectrometry.

Analysis of catechol estrogens (2 & 4 hydroxy-estrone and estradiol) has proven troublesome by liquid chromatography tandem mass spectrometry due to their low concentrations, short half-lives and temperature-labile nature. Derivatization to methyl piperazine analogues has been reported for a panel of 9 estrogens in, "Derivatization enhances analysis of estrogens and their bioactive metabolites in human plasma by liquid chromatography tandem mass spectrometry" (Denver et al., 2019).

Derivatization enhances analysis of estrogens and their bioactive metabolites in human plasma by liquid chromatography tandem mass spectrometry.

Estrogens regulate many diverse biological processes in health and disease. They circulate at a wide range of concentrations in females generating several active metabolites (hydroxy and methoxyestrogens). The metabolites are assumed to be present in much lower levels and are thought to contribute to diseases such as pulmonary arterial hypertension (PAH).

Linearly polarized GHz magnetization dynamics of spin helix modes in the ferrimagnetic insulator CuOSeO.

Linear dichroism - the polarization dependent absorption of electromagnetic waves- is routinely exploited in applications as diverse as structure determination of DNA or polarization filters in optical technologies. Here filamentary absorbers with a large length-to-width ratio are a prerequisite. For magnetization dynamics in the few GHz frequency regime strictly linear dichroism was not observed for more than eight decades.

Room-temperature helimagnetism in FeGe thin films.

Chiral magnets are promising materials for the realisation of high-density and low-power spintronic memory devices. For these future applications, a key requirement is the synthesis of appropriate materials in the form of thin films ordering well above room temperature. Driven by the Dzyaloshinskii-Moriya interaction, the cubic compound FeGe exhibits helimagnetism with a relatively high transition temperature of 278 K in bulk crystals.

Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts.

Cyclooxygenase-2 (COX-2) is a critically important mediator of inflammation that significantly influences tumor angiogenesis, invasion, and metastasis. We investigated the role of COX-2 expressed by triple negative breast cancer cells in altering the structure and function of the extracellular matrix (ECM). COX-2 downregulation effects on ECM structure and function were investigated using magnetic resonance imaging (MRI) and second harmonic generation (SHG) microscopy of tumors derived from triple negative MDA-MB-231 breast cancer cells, and a derived clone stably expressing a short hairpin (shRNA) molecule downregulating COX-2.

Exchange anisotropy in the skyrmion host GaVS.

Using ferromagnetic resonance spectroscopy at 34 GHz we explored the magnetic anisotropy of single-crystalline GaVS in the field-polarized magnetic state. We describe the data in terms of an easy-axis type uniaxial anisotropy with an anisotropy constant [Formula: see text] erg cm at 2 K, corresponding to a relative exchange anisotropy [Formula: see text]%, and about [Formula: see text]erg cm near 11 K, i.e.

Comparison of effects of eccentric training, eccentric-concentric training, and eccentric-concentric training combined with isometric contraction in the treatment of lateral elbow tendinopathy.

Study Design: RCT.

Introduction: Lateral elbow tendinopathy is a common clinical condition. eccentric exercises.

The use of Bioptron light (polarized, polychromatic, non-coherent) therapy for the treatment of acute ankle sprains.

Purpose The purpose of this study was to investigate the efficacy of Bioptron light therapy for the treatment of acute ankle sprains. Method A parallel group, single-blind, controlled study was carried out in patients with grade II acute ankle sprains. Patients were randomly allocated into two treatment groups (n = 25 for each).

Universal helimagnon and skyrmion excitations in metallic, semiconducting and insulating chiral magnets.

Nearly seven decades of research on microwave excitations of magnetic materials have led to a wide range of applications in electronics. The recent discovery of topological spin solitons in chiral magnets, so-called skyrmions, promises high-frequency devices that exploit the exceptional emergent electrodynamics of these compounds. Therefore, an accurate and unified quantitative account of their resonant response is key.

COX-2 dependent regulation of mechanotransduction in human breast cancer cells.

The ability of living cells to exert physical forces upon their surrounding is a necessary prerequisite for diverse biological processes, such as local cellular migrations in wound healing to metastatic-invasion of cancer. How forces are coopted in metastasis has remained unclear, however, because the mechanical interplay between cancer cells and the various stromal components has not been experimentally accessible. Current dogma implicates inflammation in these mechanical processes.

Magnetic thin-film insulator with ultra-low spin wave damping for coherent nanomagnonics.

Wave control in the solid state has opened new avenues in modern information technology. Surface-acoustic-wave-based devices are found as mass market products in 100 millions of cellular phones. Spin waves (magnons) would offer a boost in today's data handling and security implementations, i.

COX-2 in cancer: Gordian knot or Achilles heel?

The networks of blood and lymphatic vessels and of the extracellular matrix and their cellular and structural components, that are collectively termed the tumor microenvironment, are frequently co-opted and shaped by cancer cells to survive, invade, and form distant metastasis. With an enviable capacity to adapt to continually changing environments, cancer represents the epitome of functional chaos, a stark contrast to the hierarchical and organized differentiation processes that dictate the development and life of biological organisms. The consequences of changing landscapes such as hypoxia and acidic extracellular pH in and around tumors create a cascade of changes in multiple pathways and networks that become apparent only several years later as recurrence and metastasis.

Wireless electrical stimulation: an innovative powerful tool for the treatment of a complicated chronic ulcer.

High-voltage electrical stimulation has been long proposed as a method of accelerating the wound healing process. Its beneficial effect has been successfully evaluated in the treatment of a number of chronic ulcers and burns. We present here the implementation of a new wireless electrical stimulation technique for the treatment of a complicated chronic ulcer of the lower limb.

Prostaglandin E2 promotes the nuclear accumulation of lymphoid enhancer factor-1 in poorly differentiated breast cancer cells.

Products of the COX reaction are frequently elevated in solid tumors and their roles in the malignant phenotype have been extensively investigated. We have shown that COX-2 is essential for the growth of MDA-MB-231 cells in the fat pad of SCID mice and for their extrapulmonary colonization following injection in the tail vein of SCID mice. The molecular changes that follow shRNA-mediated silencing of COX-2 include a significant downregulation of LEF-1, a transcription factor normally activated during development following the Wnt-induced nuclear translocation of β-catenin.

Noninvasive imaging identifies new roles for cyclooxygenase-2 in choline and lipid metabolism of human breast cancer cells.

The expression of cyclooxygenase-2 (COX-2) is observed in approximately 40% of breast cancers. A major product of the COX-2-catalyzed reaction, prostaglandin E(2), is an inflammatory mediator that participates in several biological processes, and influences invasion, vascularization and metastasis. Using noninvasive MRI and MRS, we determined the effect of COX-2 downregulation on the metabolism and invasion of intact poorly differentiated MDA-MB-231 human breast cancer cells stably expressing COX-2 short hairpin RNA.

Exploiting the tumor microenvironment for theranostic imaging.

The integration of chemistry and molecular biology with imaging is providing some of the most exciting opportunities in the treatment of cancer. The field of theranostic imaging, where diagnosis is combined with therapy, is particularly suitable for a disease as complex as cancer, especially now that genomic and proteomic profiling can provide an extensive 'fingerprint' of each tumor. Using this information, theranostic agents can be shaped for personalized treatment to target specific compartments, such as the tumor microenvironment (TME), whilst minimizing damage to normal tissue.

Hypoxic tumor microenvironments reduce collagen I fiber density.

Although the mechanisms through which hypoxia influences several phenotypic characteristics such as angiogenesis, selection for resistance to apoptosis, resistance to radiation and chemotherapy, and increased invasion and metastasis are well characterized, the relationship between tumor hypoxia and components of the extracellular matrix (ECM) is relatively unexplored. The collagen I (Col1) fiber matrix of solid tumors is the major structural part of the ECM. Col1 fiber density can increase tumor initiation, progression, and metastasis, with cancer cell invasion occurring along radially aligned Col1 fibers.

Molecular and functional imaging of invasion and metastasis: windows into the metastatic cascade.

The ability of cancer cells to invade, metastasize, and form distant colonies, is one of the key characteristics that confers lethality to cancer. Metastatic cancer cells typically become refractory to treatment. The metastatic cascade is a multi-step process that is governed by events within the cancer cell, the tumor microenvironment, and the distant environments that are invaded and colonized by the cancer cells.

Comparison of effects of a home exercise programme and a supervised exercise programme for the management of lateral elbow tendinopathy.

Background: Home and supervised exercise programmes consisting of stretching and eccentric exercises have been recommended for the management of lateral elbow tendinopathy (LET). No studies have examined their comparative efficacy effectiveness.

Objective: In this study, whether a home exercise programme is more successful than a supervised exercise programme in treating patients with LET was investigated.

Comparing the effects of exercise program and low-level laser therapy with exercise program and polarized polychromatic non-coherent light (bioptron light) on the treatment of lateral elbow tendinopathy.

Background Data: The use of low-level laser therapy (LLLT) and polarized polychromatic non-coherent light as supplements to an exercise program has been recommended for the management of lateral elbow tendinopathy (LET).

Objective: To investigate whether an exercise program supplemented with LLLT is more successful than an exercise program supplemented with polarized polychromatic non-coherent light in treating LET.

Materials And Methods: Patients with unilateral LET for at least 4 wk were sequentially allocated to receive either an exercise program with LLLT or an exercise program with polarized polychromatic non-coherent light.

Inflammation, but not hypoxia, mediated HIF-1alpha activation depends on COX-2.

The COX pathway has been a target for pharmaceutical intervention in diseases with a high inflammatory component ranging from asthma and Alzheimer's to arthritis and cancer. A major transcriptional promoter of the malignant phenotype, HIF-1alpha, has been observed to be regulated by the COX-2 product PGE2. Here we show that HIF-1alpha protein significantly accumulated in human breast cancer MDA-MB-231 cells in response to the pro-inflammatory cytokine IL-1beta, but not in COX-2-silenced MDA-MB-231 cells.

The malignant phenotype of breast cancer cells is reduced by COX-2 silencing.

The cyclooxygenase (COX) pathway is currently targeted for therapeutic intervention in different cancers. We have previously shown that silencing of COX-2 in the poorly differentiated metastatic breast cell line MDA-MB-231 by RNA interference markedly delayed tumor onset and inhibited metastasis. To understand the functional effects of COX-2 silencing underlying the inhibition of tumor growth and metastasis previously reported, we investigated changes in these cells for a number of cancer-associated phenotypes.