Haasmarker4739

inor contribution in intestinal Cl- secretion induced by lubiprostone and cAMP agonists. We also found that lubiprostone is a general activator of cAMP-gated ion channels in human intestinal epithelial cells (via EP4 receptors). Our findings clarify the roles of Clc-2 in intestinal Cl- secretion and elucidate the mechanism of action of approved-drug lubiprostone.

Information of collateral flow may help to determine eligibility for thrombectomy. Our aim was to identify CT perfusion-based surrogate parameters of good collateral status in acute anterior circulation ischemic stroke.

In this retrospective study, we assessed the collateral status of 214 patients who presented with acute ischemic stroke due to occlusion of the MCA M1 segment or the carotid terminus. Collaterals were assessed on dynamic CTA images analogous to the multiphase CTA score by Menon et al. CT perfusion parameters (time-to-maximum, relative CBF, hypoperfusion intensity ratio, and CBV-index) were assessed with RAPID software. The Spearman rank correlation and receiver operating characteristic analyses were performed to identify the parameters that correlate with collateral scores and good collateral supply (defined as a collateral score of ≥4).

The Spearman rank correlation was highest for a relative CBF < 38% volume (ρ = -0.66,

< .001), followed by the hypoperfusion intensity ratio (ρ m, the hypoperfusion intensity ratio, and the CBV-index.Quantitative MR imaging techniques allow evaluating different aspects of brain microstructure, providing meaningful information about the pathophysiology of damage in CNS disorders. In the study of patients with MS, quantitative MR imaging techniques represent an invaluable tool for studying changes in myelin and iron content occurring in the context of inflammatory and neurodegenerative processes. In the first section of this review, we summarize the physics behind quantitative MR imaging, here defined as relaxometry and quantitative susceptibility mapping, and describe the neurobiological correlates of quantitative MR imaging findings. In the second section, we focus on quantitative MR imaging application in MS, reporting the main findings in both the gray and white matter compartments, separately addressing macroscopically damaged and normal-appearing parenchyma.

Verbal declarative memory performance relies on frontotemporal connectivity. The uncinate fasciculus is a major association tract connecting the frontal and temporal lobes. Hemispheric asymmetries contribute to various cognitive and neurobehavioral abilities. Here we investigated microstructural alterations and hemispheric asymmetry of the uncinate fasciculus and their possible correlation to memory performance of children with learning disorders attributed to verbal memory deficits.

Two groups of right-handed children with learning disorders attributed to verbal memory deficits and typically developing children (

= 20 and 22, respectively) underwent DTI on a 1.5T scanner. Tractography of the uncinate fasciculus in both hemispheres was performed, and fractional anisotropy and diffusivity indices (radial diffusivity, axial diffusivity, and trace) were obtained. The asymmetry index was calculated. Verbal memory was assessed using subsets of the Stanford Binet Intelligence Scale, 4th edition, a dyslexia asthis disorder.

These findings demonstrated microstructural aberrations with reduction of hemispheric asymmetry of the uncinate fasciculus, which could disrupt the normal frontotemporal connectivity in children with learning disorders attributed to verbal memory deficits. This outcome gives more understanding of pathologic mechanisms underlying this disorder.A majority of soft-body creatures evolve armor or shells to protect themselves. Similar protection demand is for flexible electronics working in complex environments. Existing works mainly focus on improving the sensing capabilities such as electronic skin (E-skin). Inspired by snakeskin, a novel electronic armor (E-armor) is proposed, which not only possesses mechanical flexibility and electronic functions similar to E-skin, but is also able to protect itself and the underlying soft body from external physical damage. The geometry of the kirigami mechanical metamaterial (Kiri-MM) ensures auxetic stretchability and meanwhile large areal coverage for sufficient protection. Moreover, to suppress the inherent but undesired out-of-plane buckling of conventional Kiri-MMs for conformal applications, soft hinges are used to form a distinct soft (hinges)-rigid (tiles) configuration. Analytical, computational, and experimental studies of the mechanical behaviors of the soft-hinge Kiri-MM E-armor demonstrate the merits of this design, i.e., stretchability, conformability, and protectability, as applied to flexible electronics. Deploying a conductive soft material at the hinges enables facile wiring strategies for large-scale circuit arrays. Functional E-armor systems for controllable display and sensing purposes provide simple examples of a wide spectrum of applications of this concept.Circular RNAs (circRNAs) are endogenous, covalently circularised, non-protein-coding RNAs generated from back-splicing. Most circRNAs are very stable, highly conserved, and expressed in a tissue-, cell- and developmental stage-specific manner. circRNAs play a significant role in various biological processes, such as regulation of gene expression and protein translation via sponging of microRNAs and binding with RNA-binding proteins. circRNAs have become a topic of great interest in research due to their close link with the development of various diseases. Their high stability, conservation and abundance in body fluids make them promising biomarkers for many diseases. A growing body of evidence suggests that aberrant expression of circRNAs and their targets plays a crucial role in pulmonary vascular remodelling and pulmonary arterial hypertension (group 1) as well as other forms (groups 3 and 4) of pulmonary hypertension (PH). Here we discuss the roles and molecular mechanisms of circRNAs in the pathogenesis of pulmonary vascular remodelling and PH. We also highlight the therapeutic and biomarker potential of circRNAs in PH.

Signalling through platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor kit (c-KIT) plays a critical role in pulmonary arterial hypertension (PAH). We examined the preclinical efficacy of inhaled seralutinib, a unique small-molecule PDGFR/CSF1R/c-KIT kinase inhibitor in clinical development for PAH, in comparison to a proof-of-concept kinase inhibitor, imatinib.

Seralutinib and imatinib potency and selectivity were compared. Inhaled seralutinib pharmacokinetics/pharmacodynamics were studied in healthy rats. Efficacy was evaluated in two rat models of PAH SU5416/Hypoxia (SU5416/H) and monocrotaline pneumonectomy (MCTPN). Effects on inflammatory/cytokine signalling were examined. Q-VD-Oph mw PDGFR, CSF1R and c-KIT immunohistochemistry in rat and human PAH lung samples and microRNA (miRNA) analysis in the SU5416/H model were performed.

Seralutinib potently inhibited PDGFRα/β, CSF1R and c-KIT. Inhaled seralutinib demonstrated dose-dependd seralutinib was an effective treatment of severe PAH in two animal models, with improved cardiopulmonary haemodynamic parameters, a reduction in NT-proBNP, reverse remodelling of pulmonary vascular pathology and improvement in inflammatory biomarkers. Seralutinib showed greater efficacy compared to imatinib in a preclinical study.The lack of knowledge about the effect of inspiratory hyperoxia on the lung-specific tumour microenvironment and progression of lung cancer has attracted considerable attention. This study proposes that inspiratory hyperoxia has special significance for the malignant phenotype of lung cancer cells. The effects of different oxygenation parameters on the proliferation, apoptosis, invasion and migration of lung cancer cells were systematically evaluated in vitro and in vivo Our results reveal that inspiratory hyperoxia treatment (60% oxygen, 6 h·day-1) not only has no tumour progression-promoting effects, but also suppresses lung cancer metastasis and promotes long-term survival. In addition, we combined transcriptome, proteome and metabolome analysis and found that hyperoxia treatment induced significant intracellular metabolic changes in lung cancer cells. Overall, we established that MYC/SLC1A5-induced metabolic reprogramming and glutamine addiction is a new mechanism that drives lung cancer metastasis, which can be significantly suppressed by inspiratory hyperoxia treatment. These findings are relevant to the debate on the perils, promises and antitumour effect of inspiratory hyperoxia, especially for patients with lung cancer.

Sarcopenia is prevalent among older patients with cancer and is associated with poor outcomes.

To explore the relationship between muscle mass, quality, and patient age with overall survival after surgery for advanced ovarian cancer.

Patients with advanced stage (IIIC/IV) ovarian cancer who underwent primary cytoreductive surgery between January 2006 and July 2016 were included. Body composition measures were calculated from pre-operative CT imaging skeletal muscle index (skeletal muscle index=skeletal muscle area normalized for height), skeletal muscle density, and skeletal muscle gauge (product of skeletal muscle index and skeletal muscle density). Each measure was transformed to a z-score and evaluated for association with risk of death using Cox proportional hazards models. Recursive partitioning was used to classify patients into homogeneous subgroups considering age and skeletal muscle gauge as predictors of overall survival.

The study included 429 patients (mean age 64.2 years). Increased age m-risk patients can modify our treatment approach.

Skeletal muscle gauge, a novel sarcopenia measure incorporating quantity and quality, was associated with poorer survival in patients with advanced ovarian cancer, particularly among patients older than 60. Expanding our knowledge of how sarcopenia relates to solid tumor outcomes among high-risk patients can modify our treatment approach.

Pelvic floor dysfunction is a common adverse effect of uterine cancer treatment. In this study we compared patient-reported outcomes regarding pelvic floor dysfunction among uterine cancer survivors after hysterectomy and bilateral salpingo-oophorectomy, surgery and brachytherapy, or surgery and external beam radiotherapy with or without brachytherapy versus women who had a hysterectomy for benign indications.

We used the validated 20-item Pelvic Floor Distress Inventory to assess lower urinary distress, colorectal distress, and pelvic organ prolapse dysfunction in each treatment group. Pelvic floor dysfunction-related quality of life in these domains was compared across treatment modalities using the Pelvic Floor Impact Questionnaire-7. Treatment type, body mass index, comorbidities, and number of vaginal births were obtained from medical records. A zero-inflated negative binomial regression model was used to assess the association of treatment regimens and covariates relative to the non-cancer cohort.

A total of 309 surveys were analyzed.