Activation of Dopamine D2 Receptor Suppresses Neuroinflammation Through αB-Crystalline by Inhibition of NF-κB Nuclear Translocation in Experimental ICH Mice Model.

Background And Purpose: Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced secondary brain injury. Recently, dopamine D2 receptor (DRD2) is identified as an important component controlling innate immunity and inflammatory response in central nervous system, and αB-crystallin (CRYAB) is a potent negative regulator on inflammatory pathways. Here, we sought to investigate the role of DRD2 on neuroinflammation after experimental ICH and the potential mechanism mediated by CRYAB.

Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models.

Background & Aims: Hepatic fibrosis, featured by the accumulation of excessive extracellular matrix in liver tissue, is associated with metabolic disease and cancer. Inhalation exposure to airborne particulate matter in fine ranges (PM2.5) correlates with pulmonary dysfunction, cardiovascular disease, and metabolic syndrome.

Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival.

Background: Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The aim of this study was to determine the significance of preoperative MRI variables, both quantitative and qualitative, with regard to overall and progression-free survival in GBM.

Methods: We retrospectively identified 94 untreated GBM patients from the Cancer Imaging Archive who had pretreatment MRI and corresponding patient outcomes and clinical information in The Cancer Genome Atlas.

Regional Nodal Irradiation in Early-Stage Breast Cancer.

Background: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.

Methods: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group).

Brain Default Mode Network Changes after Renal Transplantation: A Diffusion-Tensor Imaging and Resting-State Functional MR Imaging Study.

Purpose: To investigate structural and functional alterations of the default mode network (DMN) in the brain after renal transplantation in patients with end-stage renal disease by using diffusion-tensor imaging and resting-state functional MR imaging.

Materials And Methods: This prospective study was approved by the local medical research ethics committee, and written informed consent was obtained. Twenty-one patients with end-stage renal disease (15 men, six women; mean age ± standard deviation, 32 years ± 9.

Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II-Induced Hypertension.

Rationale: Inflammation and adaptive immunity play a crucial role in the development of hypertension. Angiotensin II and probably other hypertensive stimuli activate the central nervous system and promote T-cell activation and end-organ damage in peripheral tissues.

Objective: To determine if renal sympathetic nerves mediate renal inflammation and T-cell activation in hypertension.

High-Sensitivity Cardiac Troponin T and Risk of Hypertension.

Background: The diagnosis of hypertension is often preceded by cardiac structural abnormalities. Thus, we assessed whether high-sensitivity cardiac troponin T (hs-cTnT), a marker of subclinical myocardial damage, can identify individuals at risk for hypertension or left ventricular hypertrophy.

Methods And Results: We studied 6516 Atherosclerosis Risk in Communities (ARIC) Study participants who were free of prevalent hypertension and cardiovascular disease at baseline (1990-1992).

Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation.

Background: Metabolic complications such as obesity, hyperglycemia, and type 2 diabetes are associated with poor outcomes in patients with glioblastoma. To control peritumoral edema, use of chronic high-dose steroids in glioblastoma patients is common, which can result in de novo diabetic symptoms. These metabolic complications may affect tumors via profound mechanisms, including activation of insulin receptor (InsR) and the related insulin-like growth factor 1 receptor (IGF1R) in malignant cells.

Trauma Exposure and Posttraumatic Stress Disorder Symptoms Predict Onset of Cardiovascular Events in Women.

Background: Psychological stress is a proposed risk factor for cardiovascular disease (CVD), and posttraumatic stress disorder (PTSD), the sentinel stress-related mental disorder, occurs twice as frequently in women as men. However, whether PTSD contributes to CVD risk in women is not established.

Methods And Results: We examined trauma exposure and PTSD symptoms in relation to incident CVD over a 20-year period in 49 978 women in the Nurses' Health Study II.

Easy Come, Easy Go: Capillary Forces Enable Rapid Refilling of Embolized Primary Xylem Vessels.

Protoxylem plays an important role in the hydraulic function of vascular systems of both herbaceous and woody plants, but relatively little is known about the processes underlying the maintenance of protoxylem function in long-lived tissues. In this study, embolism repair was investigated in relation to xylem structure in two cushion plant species, Azorella macquariensis and Colobanthus muscoides, in which vascular water transport depends on protoxylem. Their protoxylem vessels consisted of a primary wall with helical thickenings that effectively formed a pit channel, with the primary wall being the pit channel membrane.

COPII-Dependent ER Export: A Critical Component of Insulin Biogenesis and β-Cell ER Homeostasis.

Pancreatic β-cells possess a highly active protein synthetic and export machinery in the endoplasmic reticulum (ER) to accommodate the massive production of proinsulin. ER homeostasis is vital for β-cell functions and is maintained by the delicate balance between protein synthesis, folding, export, and degradation. Disruption of ER homeostasis by diabetes-causing factors leads to β-cell death.

R331W Missense Mutation of Oncogene YAP1 Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability.

Purpose: Adenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential.

Characterization of Craniocervical Artery Dissection by Simultaneous MR Noncontrast Angiography and Intraplaque Hemorrhage Imaging at 3T.

Background And Purpose: Craniocervical artery dissection is the most common cause of ischemic stroke identified in young adults. For the diagnosis of craniocervical artery dissection, multisequence MR imaging is recommended but is time-consuming. Recently, investigators proposed a simultaneous noncontrast angiography and intraplaque hemorrhage imaging technique allowing simultaneous noncontrast MRA and vessel wall imaging in a single scan.

Evaluation of primary open-angle glaucoma clinical practice guidelines.

Objective: To evaluate the methodologic quality of 3 primary open-angle glaucoma (POAG) clinical practice guidelines (CPGs).

Design: The CPGs were assessed with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.

Participants: Four authors (A.

Bioengineering Novel Chimeric microRNA-34a for Prodrug Cancer Therapy: High-Yield Expression and Purification, and Structural and Functional Characterization.

Development of anticancer treatments based on microRNA (miRNA/miR) such as miR-34a replacement therapy is limited to the use of synthetic RNAs with artificial modifications. Herein, we present a new approach to a high-yield and large-scale biosynthesis, in Escherichia coli using transfer RNA (tRNA) scaffold, of chimeric miR-34a agent, which may act as a prodrug for anticancer therapy. The recombinant tRNA fusion pre-miR-34a (tRNA/mir-34a) was quickly purified to a high degree of homogeneity (>98%) using anion-exchange fast protein liquid chromatography, whose primary sequence and post-transcriptional modifications were directly characterized by mass spectrometric analyses.

Identification of implanted mesh after incisional hernia repair using an automated breast volume scanner.

Objectives: This study aimed to evaluate the utility of an automated breast volume scanner (ABVS) versus handheld ultrasound (US) for identifying implanted mesh after incisional hernia repair.

Methods: In vitro, the appearances of 3 samples of different flat mesh and a mesh plug on both ABVS and handheld US examinations were evaluated. In vivo, 97 patients received both ABVS and handheld US examinations in the incisional region.

Differential diagnosis of polypoid lesions of the gallbladder using contrast-enhanced sonography.

Objectives: The purpose of this study was to evaluate the usefulness of real-time contrast-enhanced sonography and microvascular imaging for differential diagnosis of neoplastic and non-neoplastic polypoid lesions of the gallbladder.

Methods: Real-time contrast-enhanced sonography and microvascular imaging were performed in 128 patients with polypoid lesions of the gallbladder larger than 6 mm in diameter. The enhancement patterns, microvascular imaging types, and kinetic parameters were analyzed on contrast-enhanced sonography.

Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1 Receptors.

Background: Whether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the angiotensin II type I receptor (AT1R).

Methods And Results: Exosomes containing AT1Rs were isolated from the media overlying AT1R-overexpressing cells exposed to osmotic stretch and from sera of mice undergoing cardiac pressure overload.

Kansas City Cardiomyopathy Questionnaire Score Is Associated With Incident Heart Failure Hospitalization in Patients With Chronic Kidney Disease Without Previously Diagnosed Heart Failure: Chronic Renal Insufficiency Cohort Study.

Background: Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF.

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population.

Objective: To investigate whether rs12731181 (A→G) interrupted miR-590-3p-mediated suppression of the prostaglandin F2α receptor (FP) and whether it is associated with essential hypertension in the Chinese population.

Approach And Results: We found that miR-590-3p regulates human FP gene expression by binding to its 3'-untranslated region. rs12731181 (A→G) altered the binding affinity between miR-590-3p and its FP 3'-untranslated region target, thus reducing the suppression of FP expression, which, in turn, enhanced FP receptor-mediated contractility of vascular smooth muscle cells.

Propensity Score-matched Comparison of Postoperative Adverse Outcomes between Geriatric Patients Given a General or a Neuraxial Anesthetic for Hip Surgery: A Population-based Study.

Background: The effects of the mode of anesthesia on major adverse postoperative outcomes in geriatric patients are still inconclusive. The authors hypothesized that a neuraxial anesthetic (NA) rather than a general anesthetic (GA) would yield better in-hospital postoperative outcomes for geriatric patients undergoing hip surgery.

Methods: The authors used data from Taiwan's 1997-2011 in-patient claims database to evaluate the effect of anesthesia on in-hospital outcomes.

Identifying Corticothalamic Network Epicenters in Patients with Idiopathic Generalized Epilepsy.

Background And Purpose: Corticothalamic networks are considered core pathologic substrates for idiopathic generalized epilepsy; however, the predominant epileptogenic epicenters within these networks are still largely unknown. The current study aims to identify these epicenters by resting-state functional connectivity.

Materials And Methods: To identify epicenters within the corticothalamic networks in idiopathic generalized epilepsy, we retrospectively studied a large cohort of patients with this condition (n = 97) along with healthy controls (n = 123) by resting-state functional MR imaging.

Curcumin Analog L48H37 Prevents Lipopolysaccharide-Induced TLR4 Signaling Pathway Activation and Sepsis via Targeting MD2.

Endotoxin-induced acute inflammatory diseases such as sepsis, mediated by excessive production of various proinflammatory cytokines, remain the leading cause of mortality in critically ill patients. Lipopolysaccharide (LPS), the characteristic endotoxin found in the outer membrane of Gram-negative bacteria, can induce the innate immunity system and through the myeloid differentiation protein 2 (MD2) and Toll-like receptor 4 (TLR4) complex, increase the production of inflammatory mediators. Our previous studies have found that a curcumin analog, L48H37 [1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one], was able to inhibit LPS-induced inflammation, particularly tumor necrosis factor α and interleukin 6 production and gene expression in mouse macrophages.

Functional brain network modularity predicts response to cognitive training after brain injury.

Objective: We tested the value of measuring modularity, a graph theory metric indexing the relative extent of integration and segregation of distributed functional brain networks, for predicting individual differences in response to cognitive training in patients with brain injury.

Methods: Patients with acquired brain injury (n = 11) participated in 5 weeks of cognitive training and a comparison condition (brief education) in a crossover intervention study design. We quantified the measure of functional brain network organization, modularity, from functional connectivity networks during a state of tonic attention regulation measured during fMRI scanning before the intervention conditions.