Estrogen induces two distinct cholesterol crystallization pathways by activating ERα and GPR30 in female mice.

To distinguish the lithogenic effect of the classical estrogen receptor α (ERα) from that of the G protein-coupled receptor 30 (GPR30), a new estrogen receptor, on estrogen-induced gallstones, we investigated the entire spectrum of cholesterol crystallization pathways and sequences during the early stage of gallstone formation in gallbladder bile of ovariectomized female wild-type, GPR30((-/-)), ERα((-/-)), and GPR30((-/-))/ERα((-/-)) mice treated with 17β-estradiol (E2) at 6 µg/day and fed a lithogenic diet for 12 days. E2 disrupted biliary cholesterol and bile salt metabolism through ERα and GPR30, leading to supersaturated bile and predisposing to the precipitation of cholesterol monohydrate crystals. In GPR30((-/-)) mice, arc-like and tubular crystals formed first, followed by classical parallelogram-shaped cholesterol monohydrate crystals.

Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results.

Introduction: Idiopathic intracranial hypertension (IIH) may result in a chronic debilitating disease. Dural venous sinus stenosis with a physiologic venous pressure gradient has been identified as a potential etiology in a number of IIH patients. Intracranial venous stenting has emerged as a potential treatment alternative.

Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation.

It was recently demonstrated that MCPIP1 is a critical factor that controls inflammation and immune homeostasis; however, the relationship between MCPIP1 and other members of this protein family is largely unknown. Here, we report that MCPIP1 interacts with MCPIP4 to form a protein complex, but acts independently in the regulation of IL-6 mRNA degradation. In an effort to identify MCPIP1-interacting proteins by co-immunoprecipitation (Co-IP) and mass-spec analysis, MCPIP4 was identified as a MCPIP1-interacting protein, which was further confirmed by Co-IP and mammalian two-hybrid assay.

Infundibular dilations of the posterior communicating arteries: pathogenesis, anatomical variants, aneurysm formation, and subarachnoid hemorrhage.

Background: Cerebrovascular infundibular dilations (IDs) are triangular-shaped widenings less than 3 mm in diameter, which are most commonly found at the posterior communicating artery (PCoA). The aims of this systematic review are to elucidate the natural histories of IDs, determine their risk of progression to significant pathology, and discuss potential management options.

Methods: A comprehensive literature search of PubMed was used to find all case reports and series relating to cerebral IDs.

Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

Background: We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC).

Methods: A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population.

Results: Median follow-up was 12 months.

The Energy Index Does Not Affect Local Control of Brain Metastases Treated by Gamma Knife Stereotactic Radiosurgery.

Background: The energy index (EI) is a measure of dose homogeneity within a target volume calculated by the integral dose divided by the product of prescription dose and tumor volume.

Objective: To assess whether a higher EI is associated with greater local control for brain metastases (BMs) treated by Gamma Knife radiosurgery (GKRS).

Methods: We reviewed all patients treated with GKRS for BM at our institution between January 2009 and February 2014.

Neurological applications of transcranial high intensity focused ultrasound.

Advances in transcranial MRI-guided focused ultrasound have renewed interest in lesioning procedures in functional neurosurgery with a potential role in the treatment of neurological conditions such as chronic pain, brain tumours, movement disorders and psychiatric diseases. While the use of transcranial MRI-guided focused ultrasound represents a new innovation in neurosurgery, ultrasound has been used in neurosurgery for almost 60 years. This paper reviews the major historical milestones that have led to modern transcranial focused ultrasound and discusses current and evolving applications of ultrasound in the brain.

Outcomes of gamma knife radiosurgery, bi-modality & tri-modality treatment regimens for patients with one or multiple brain metastases: the Columbia University Medical Center experience.

Optimal treatment of brain metastases (BMs) is debatable. However, surgery or gamma knife radiosurgery (GKRS) improves survival when combined with whole brain radiotherapy (WBRT) versus WBRT alone. We retrospectively reviewed an institutional database of patients treated with GKRS for BMs from 1998 to 2013 to explore effects of single or multi-modality therapies on survival.

Logical-rules and the classification of integral dimensions: individual differences in the processing of arbitrary dimensions.

A variety of converging operations demonstrate key differences between separable dimensions, which can be analyzed independently, and integral dimensions, which are processed in a non-analytic fashion. A recent investigation of response time distributions, applying a set of logical rule-based models, demonstrated that integral dimensions are pooled into a single coactive processing channel, in contrast to separable dimensions, which are processed in multiple, independent processing channels. This paper examines the claim that arbitrary dimensions created by factorially morphing four faces are processed in an integral manner.

Neurocognitive Deficits After Radiation Therapy for Brain Malignancies.

Radiotherapy (RT) has proven to be an effective therapeutic tool in treatment of a wide variety of brain tumors; however, it has a negative impact on quality of life and neurocognitive function. Cognitive dysfunction associated with both the disease and adverse effects of RT is one of the most concerning complication among long-term survivors. The effects of RT to brain can be divided into acute, early delayed, and late delayed.

SREBP-1 Mediates Angiotensin II-Induced TGF-β1 Upregulation and Glomerular Fibrosis.

Angiotensin II is an important mediator of CKD of diverse etiology. A common pathologic feature of CKD is glomerular fibrosis, a central mediator of which is the profibrotic cytokine TGF-β. The mechanisms underlying the induction of TGF-β and matrix by angiotensin II are not completely understood.

SREBP-1 is a novel mediator of TGFβ1 signaling in mesangial cells.

Glomerular matrix accumulation is a hallmark of diabetic nephropathy. Recent studies showed that overexpression of the transcription factor SREBP-1 induces glomerulosclerosis. TGFβ1 is a key profibrotic mediator of glomerulosclerosis, but whether SREBP-1 regulates its effects is unknown.

Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment.

Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum.

Adenosine deaminase acting on RNA 1 limits RIG-I RNA detection and suppresses IFN production responding to viral and endogenous RNAs.

Type I IFNs play central roles in innate immunity; however, overproduction of IFN can lead to immunopathology. In this study, we demonstrate that adenosine deaminase acting on RNA 1 (ADAR1), an RNA-editing enzyme induced by IFN, is essential for cells to avoid inappropriate sensing of cytosolic RNA in an inducible knockout cell model-the primary mouse embryo fibroblast derived from ADAR1 lox/lox and Cre-ER mice as well as in HEK293 cells. ADAR1 suppresses viral and cellular RNA detection by retinoic acid-inducible gene I (RIG-I) through its RNA binding rather than its RNA editing activity.

Fetal radiation monitoring and dose minimization during intensity modulated radiation therapy for glioblastoma in pregnancy.

We examined the fetal dose from irradiation of glioblastoma during pregnancy using intensity modulated radiation therapy (IMRT), and describe fetal dose minimization using mobile shielding devices. A case report is described of a pregnant woman with glioblastoma who was treated during the third trimester of gestation with 60 Gy of radiation delivered via a 6 MV photon IMRT plan. Fetal dose without shielding was estimated using an anthropomorphic phantom with ion chamber and diode measurements.

A nomogram to predict loco-regional control after re-irradiation for head and neck cancer.

Background And Purpose: Loco-regionally recurrent head and neck cancer (HNC) in the setting of prior radiotherapy carries significant morbidity and mortality. The role of re-irradiation (re-RT) remains unclear due to toxicity. We determined prognostic factors for loco-regional control (LRC) and formulated a nomogram to help clinicians select re-RT candidates.

3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo-resistant cancer cells.

Multidrug-resistance is a major cause of cancer chemotherapy failure in clinical treatment. Evidence shows that multidrug-resistant cancer cells are as sensitive as corresponding regular cancer cells under the exposure to anticancer ceramide analogs. In this work we designed five new ceramide analogs with different backbones, in order to test the hypothesis that extending the conjugated system in ceramide analogs would lead to an increase of their anticancer activity and selectivity towards resistant cancer cells.

Correlation of Planned Dose to Area Postrema and Dorsal Vagal Complex with Clinical Symptoms of Nausea and Vomiting in Oropharyngeal Cancer (OPC) patients treated with radiation alone using IMRT.

Objective: To correlate the planned dose to the nausea center (NC) - area postrema (AP) and dorsal vagal complex (DVC) - with nausea and vomiting symptoms in OPC patients treated with IMRT without chemotherapy. We also investigated whether it was possible to reduce doses to the NC without significant degradation of the clinically accepted treatment plan.

Methods: From 11/04 to 4/09, 37 OPC patients were treated with definitive or adjuvant IMRT without chemotherapy.

Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency.

The urea cycle functions to incorporate ammonia, generated by normal metabolism, into urea. Urea cycle disorders (UCDs) are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA). A prospective analysis of interim HA events in a cohort of individuals with ornithine transcarbamylase (OTC) deficiency, the most common UCD, revealed that intercurrent infection was the most common precipitant of acute HA and was associated with markers of increased morbidity when compared with other precipitants.

New insights into the molecular mechanism of intestinal fatty acid absorption.

Background: Dietary fat is one of the most important energy sources of all the nutrients. Fatty acids, stored as triacylglycerols (also called triglycerides) in the body, are an important reservoir of stored energy and derived primarily from animal fats and vegetable oils.

Design: Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, that is, fatty acid transporters on the apical membrane of enterocytes.

Hyperphosphorylation of glucosyl C6 carbons and altered structure of glycogen in the neurodegenerative epilepsy Lafora disease.

Laforin or malin deficiency causes Lafora disease, characterized by altered glycogen metabolism and teenage-onset neurodegeneration with intractable and invariably fatal epilepsy. Plant starches possess small amounts of metabolically essential monophosphate esters. Glycogen contains similar phosphate amounts, which are thought to originate from a glycogen synthase error side reaction and therefore lack any specific function.

Diazoxide and cyclosporin A protect primary cholinergic neurons against beta-amyloid (1-42)-induced cytotoxicity.

Objective: Activation of mitochondrial (MitoKATP) channels was found to protect against anoxic and chemical stress in brain. This present study sought to investigate the ability of diazoxide and cyclosporin A to antagonize cytotoxicity induced by beta-amyloid peptide (A-beta1-42) in cultured rat primary basal forebrain cholinergic neurons.

Methods: Cytotoxicity was induced by A-beta1-42 (2 μM) in the presence of either diazoxide (500 μM), a selective opener of the mitochondrial ATP-sensitive potassium channel (MitoKATP), or cyclosporin A (20 μM), an inhibitor of the mitochondrial permeability transition pore (MTP), or the combination of both the reagents.

Reduction of brain edema and expression of aquaporins with acute ethanol treatment after traumatic brain injury.

Object: Previous studies have demonstrated that traumatic brain injury (TBI) causes brain edema by allowing excessive water passage through aquaporin (AQP) proteins. To establish the potential neuroprotective properties of ethanol as a post-TBI therapy, in the present study the authors determined the effect of ethanol on brain edema, AQP expression, and functional outcomes in a post-TBI setting.

Methods: Adult male Sprague-Dawley rats weighing between 425 and 475 g received a closed head TBI in which Maramarou's impact-acceleration method was used.