Influence of bone density on stability in TBW.

Osteoporosis is a common disease that leads to a reduction in bone density and increases the risk of fractures. Stable surgical treatment is particularly important for these fractures. The aim of this study was to examine the influence of bone density in the area of ​​the proximal ulna on the failure of the fixation technique of K-wires in tension band wiring (TBW).

A Case Showing a New Diagnostic Aspect of the Application of Radiofrequency Echographic Multi-Spectrometry (REMS).

Radiofrequency echographic multi-spectrometry (REMS) is an ultrasound technique that has been recently introduced in the medical field to detect osteoporosis and fracture risk at axial sites. The use of sonography to visualize the region of interest (ROI) of the hip neck provides the opportunity to identify occult fractures. A 91-year-old woman with persistent right leg pain was referred to rheumatologist due to a known history of arthritis and osteoporosis.

Effect of the body mass index, basal metabolic rate, and body fat on the radiofrequency echographic multi-spectrometry (REMS)-based bone mineral density and fracture risk: a cross-sectional study.

Radiofrequency echographic multi-spectrometry (REMS) is a method to assess bone mineral density (BMD) of the axial skeleton, fragility score (FS), body mass index (BMI), basal metabolic rate (BMR), and body fat (BF) in %. The aim of the study was to investigate the influence of the BMI, BMR, and BF on the BMD and fracture risk with REMS. We conducted a cross-sectional study among 313 women, aged 20-90 years who underwent a screening for osteoporosis with REMS.

Discovery of brain permeable 2-Azabicyclo[2.2.2]octane sulfonamides as a novel class of presenilin-1 selective γ-secretase inhibitors.

This paper describes the rational design, synthesis, structure-activity relationship (SAR), and biological profile of presenilin-1 (PSEN-1) complex selective γ-secretase inhibitors, assessed for selectivity using a unique set of four γ-secretase subtype complexes. A set of known PSEN-1 selective γ-Secretase inhibitors (GSIs) was analyzed to understand the pharmacophoric features required for selective inhibition. Conformational modeling suggests that a characteristic 'U' shape orientation between aromatic sulfone/sulfonamide and aryl ring is crucial for PSEN-1 selectivity and potency.

An observational study of the radiofrequency echographic multi-spectrometry (REMS)-based fragility score of the lumbar spine and total fracture risk at 5 years in women.

A novel fragility score (FS) parameter, obtained during radiofrequency echographic multi-spectrometry (REMS), was developed to estimate the ultrasound-based skeletal fragility. The aim of our study is to assess the REMS-based FS of the lumbar spine (LS) among the Bulgarian women and to compare their characteristics acquired with REMS between fracture risk classes corresponding to a total fracture risk at 5 years for major osteoporotic fractures (MOF). A total of 100 Bulgarian women, who underwent a screening for osteoporotic fracture risk using the REMS technology, were included in a prospective observational study.

Selective inhibitors of the PSEN1-gamma-secretase complex.

Clinical development of γ-secretases, a family of intramembrane cleaving proteases, as therapeutic targets for a variety of disorders including cancer and Alzheimer's disease was aborted because of serious mechanism-based side effects in the phase III trials of unselective inhibitors. Selective inhibition of specific γ-secretase complexes, containing either PSEN1 or PSEN2 as the catalytic subunit and APH1A or APH1B as supporting subunits, does provide a feasible therapeutic window in preclinical models of these disorders. We explore here the pharmacophoric features required for PSEN1 versus PSEN2 selective inhibition.

Prevalence of low bone mineral density at axial sites and fracture risk in Bulgarian population.

Background: Osteoporosis is a common chronic disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of the bone, which are associated with increased risk of fragility fractures. Currently the most popular tool is the fracture risk assessment model FRAX to calculate the 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HF).

Objective: To investigate the prevalence of low BMD at axial sites and fracture risk in Bulgarian population.

Infrared photodissociation spectroscopy of (AlO)FeO: influence of Fe-substitution on small alumina clusters.

The infrared photodissociation spectra of He-tagged (AlO)FeO ( = 2-5), are reported in the Al-O and Fe-O stretching and bending spectral region (430-1200 cm) and assigned based on calculated harmonic IR spectra from density functional theory (DFT). The substitution of Fe for an Al center occurs preferentially at 3-fold oxygen coordination sites located at the cluster rim and with the Fe atom in the +III oxidation state. The accompanying elongation of metal oxygen bonds leaves the Al-O network structure nearly unperturbed (isomorphous substitution).

Automated Laser-Transfer Synthesis of High-Density Microarrays for Infectious Disease Screening.

Laser-induced forward transfer (LIFT) is a rapid laser-patterning technique for high-throughput combinatorial synthesis directly on glass slides. A lack of automation and precision limits LIFT applications to simple proof-of-concept syntheses of fewer than 100 compounds. Here, an automated synthesis instrument is reported that combines laser transfer and robotics for parallel synthesis in a microarray format with up to 10 000 individual reactions cm .

Single HER2-positive tumor cells are detected in initially HER2-negative breast carcinomas using the DEPArray™-HER2-FISH workflow.

Background: In breast cancer (BC), overexpression of HER2 on the primary tumor (PT) is determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) to stratify samples as negative, equivocal and positive to identify patients (pts) for anti-HER2 therapy. CAP/ASCO guidelines recommend FISH for analyzing HER2/neu (ERBB2) gene amplification and for resolving equivocal HER2 IHC results. However, pre-analytical and analytical aspects are often confounded by sample related limitations and tumor heterogeneity and HER2 expression may differ between the PT and circulating tumor cells (CTCs), the precursors of metastasis.

Surface-Mediated Ring-Opening and Porphyrin Deconstruction via Conformational Distortion.

The breakdown of macrocyclic compounds is of utmost importance in manifold biological and chemical processes, usually proceeding via oxygenation-induced ring-opening reactions. Here, we introduce a surface chemical route to selectively break a prototypical porphyrin species, cleaving off one pyrrole unit and affording a tripyrrin derivative. This pathway, operational in an ultrahigh vacuum environment at moderate temperature is enabled by a distinct molecular conformation achieved via the specific interaction between the porphyrin and its copper support.

Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer.

Reliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS.

Reduction of Hartree-Fock Wavefunctions to Kohn-Sham Effective Potentials Using Multiresolution Analysis.

We present a highly accurate numerical implementation for computing the Kohn-Sham effective potentials for molecules based on a Hartree-Fock wavefunction and density, following the RKS approach of Staroverov and co-workers [ 2014, 140, 18A535]. Potentials and orbitals are represented in a multiresolution wavelet basis, avoiding basis set incompleteness-related issues. Together with the RKS method, the often occurring problems of oscillating potentials are removed.

Dasatinib, paclitaxel, and carboplatin in women with advanced-stage or recurrent endometrial cancer: A pilot clinical and translational study.

Purpose: To evaluate the effect of dasatinib therapy on EphA2 signaling in cancers of women with measurable (biopsy amenable) advanced-stage, chemo-naïve primary or recurrent endometrial cancer. Preliminary efficacy was also assessed.

Patients And Methods: We performed a pilot study of single-agent dasatinib lead-in, followed by triplet dasatinib, paclitaxel, and carboplatin.

Effects of exercise training on bone mineral density and some health-related outcomes in HIV conditions: A randomized controlled trial.

Introduction: Human Immunodeficiency Virus (HIV) infection remains prevalent co-morbidity, and among fracture patients. Few studies have investigated the role of exercise interventions in preventing bone demineralization in people who have fractures and HIV. If exercise exposed, HIV-infected individuals may experience improved bone health outcomes (BMD), function, quality of life (QoL).

Valence and Structure Isomerism of AlFeO: Synergy of Spectroscopy and Quantum Chemistry.

We provide spectroscopic and computational evidence for a substantial change in structure and gas phase reactivity of AlO upon Fe-substitution, which is correctly predicted by multireference (MR) wave function calculations. AlO exhibits a cone-like structure with a central trivalent O atom (C symmetry). The replacement of the Al- by an Fe atom leads to a planar bicyclic frame with a terminal Al-O radical site, accompanied by a change from the Fe/O to the Fe/O valence state.

Long Noncoding RNA TYKRIL Plays a Role in Pulmonary Hypertension via the p53-mediated Regulation of PDGFRβ.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of diverse biological functions. Their role in pulmonary arterial hypertension (PAH) remains to be explored. To elucidate the role of TYKRIL (tyrosine kinase receptor-inducing lncRNA) as a regulator of p53/ PDGFRβ (platelet-derived growth factor receptor β) signaling pathway and to investigate its role in PAH.

Thermochemistry of FeOH Species: Assessment of Some DFT Functionals.

Thermochemical data for 20 anionic, cationic, and neutral gas-phase species, including Fe, FeO, FeOH, FeO, OFeOH, Fe(OH), Fe(HO), and Fe(HO) with oxidation states between +I and +IV for Fe and -I and -II for O, compiled by Schröder [ 2008, 112, 13215], are used to assess the performance of the "Jacob's ladder" functionals PBE, TPSS, PBE0, and TPSSh for the SVP, TZVP, and QZVP basis sets. In addition, the BP86 and B3LYP functionals are considered. The TPSSh functional performs best.

Direct determination of optimal pair-natural orbitals in a real-space representation: The second-order Moller-Plesset energy.

An efficient representation of molecular correlated wave functions is proposed, which features regularization of the Coulomb electron-electron singularities via the F12-style explicit correlation and a pair-natural orbital factorization of the correlation components of the wave function expressed in the real space. The pair-natural orbitals are expressed in an adaptive multiresolution basis and computed directly by iterative variational optimization. The approach is demonstrated by computing the second-order Moller-Plesset energies of small- and medium-sized molecules.

Temperature- and Structure-Dependent Optical Properties and Photophysics of BODIPY Dyes.

We report on the temperature- and structural-dependent optical properties and photophysics of a set of boron dipyrromethene (BODIPY) dyes with different substitution patterns of their meso-aryl subunit. Single-crystal X-ray diffraction analysis of the compounds enabled a classification of the dyes into a sterically hindered and a unhindered group. The steric hindrance refers to a blocked rotational motion of the aryl subunit around the bond connecting this moiety to the meso-position of the BODIPY core.

Evaluating the Solvent Stark Effect from Temperature-Dependent Solvatochromic Shifts of Anthracene.

The solvent Stark effect on the spectral shifts of anthracene is studied with temperature-dependent solvatochromic measurements. The Stark contribution Δv to the absorption shift Δv in polar solvents is measured to be Δv =(53±35) cm , in reasonable agreement with dielectric continuum theory estimate of 28 cm , whereas the major shift Δv ∼300 cm presumably originates from the solute quadrupole. We pay attention to the accurate correction of Δv for the nonpolar contribution that is crucial when the shifts are modest in magnitude.

Instability of the proximal radioulnar joint in Monteggia fractures-an experimental study.

Background: A Monteggia fracture is defined as a fracture of the proximal ulna combined with a luxation of the radial head. The aim of the present work is to evaluate the extent of instability of the radius head in the proximal radioulnar joint (PRUJ) as a function of the severity of elbow fracture and ligamentous injury in an experimental biomechanical approach.

Methods: Eight fresh-frozen cadaver arms were used.

Trifluoromethyl Dihydrothiazine-Based β-Secretase (BACE1) Inhibitors with Robust Central β-Amyloid Reduction and Minimal Covalent Binding Burden.

The β-site amyloid precursor protein cleaving enzyme 1 (BACE1, also known as β-secretase) is a promising target for the treatment of Alzheimer's disease. A pK lowering approach over the initial leads was adopted to mitigate hERG inhibition and P-gp efflux, leading to the design of 6-CF dihydrothiazine 8 (N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide). Optimization of 8 led to the discovery of 15 (N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide) with an excellent balance of potency, hERG inhibition, P-gp efflux, and metabolic stability.

Biomechanical comparison of bi- and tricortical k-wire fixation in tension band wiring osteosynthesis.

Background: Patients with a simple transversal fracture of the olecranon are often treated with a tension band wiring (TBW), because it is known as a biomechanically appropriate and cost-effective procedure. Nevertheless, the technique is in detail more challenging than thought, resulting in a considerable high rate of implant-related complications like k-wire loosening and soft tissue irritation. In the literature, a distinction is generally only made between transcortical (bi-) and intramedullary (mono-) fixation of the wires.