Aneurysmal subarachnoid hemorrhage is a life-threatening, neurological emergency characterized by accumulation of blood in the subarachnoid space due to a ruptured aneurysm. Over the past several decades, improvements in the clinical management of aneurysmal subarachnoid hemorrhage have led to better patient outcomes. However, aneurysmal subarachnoid hemorrhage is still associated with high morbidity and mortality.
View Article and Find Full Text PDFUsing a comprehensive chemical genetics approach, we identified a member of the lignan natural product family, HTP-013, which exhibited significant cytotoxicity across various cancer cell lines. Correlation of compound activity across a panel of reporter gene assays suggested the vacuolar-type ATPase (v-ATPase) as a potential target for this compound. Additional cellular studies and a yeast haploinsufficiency screen strongly supported this finding.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2016
O-GlcNAc glycosylation (or O-GlcNAcylation) is a dynamic, inducible posttranslational modification found on proteins associated with neurodegenerative diseases such as α-synuclein, amyloid precursor protein, and tau. Deletion of the O-GlcNAc transferase (ogt) gene responsible for the modification causes early postnatal lethality in mice, complicating efforts to study O-GlcNAcylation in mature neurons and to understand its roles in disease. Here, we report that forebrain-specific loss of OGT in adult mice leads to progressive neurodegeneration, including widespread neuronal cell death, neuroinflammation, increased production of hyperphosphorylated tau and amyloidogenic Aβ-peptides, and memory deficits.
View Article and Find Full Text PDFImportance: Methotrexate is a first-line systemic agent for treating of psoriasis, although its onset of effects is slower and overall it is less effective than tumor necrosis factor blockers.
Objective: To differentiate the response of psoriatic disease to adalimumab and methotrexate sodium.
Design, Setting, And Participants: Single-center, randomized, assessor-blind, 2-arm clinical trial of 30 patients from the outpatient dermatology center of Tufts Medical Center, enrolled from August 18, 2009, to October 11, 2011.
Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS) and cardiovascular disease (CVD), but few studies have investigated the prevalence of MetS and other risk factors for CVD in children with psoriasis. In an assessor-blinded study, 20 children ages 9-17 years with a current or previously documented history of psoriasis involving 5% or more of their body surface area or psoriatic arthritis were compared with a cohort of age- and sex-matched controls with benign nevi, warts, or acne. MetS, our primary endpoint, was defined by the presence of abnormal values in at least three of the following measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), waist circumference, and blood pressure.
View Article and Find Full Text PDFThe σ subunits of bacterial RNA polymerase occur in many variant forms and confer promoter specificity to the holopolymerase. Members of the σ(54) family of σ subunits require the action of a 'transcriptional activator' protein to open the promoter and initiate transcription. The activator proteins undergo regulated assembly from inactive dimers to hexamers that are active ATPases.
View Article and Find Full Text PDFInfection with schistosomes results in a CD4 T cell-mediated inflammatory reaction against parasite eggs that varies greatly in magnitude both in humans as well as in mice. In the murine disease, the severe form of immunopathology correlates with high levels of IL-17. We now report that live schistosome eggs stimulate dendritic cells from high pathology-prone CBA mice to produce IL-12p40, IL-6, and TGF-beta, whereas those from low pathology-prone BL/6 mice only make TGF-beta.
View Article and Find Full Text PDFObjectives: To describe and test a model that compares the accuracy of data gathered prospectively versus retrospectively among adult emergency department patients admitted with chest pain.
Methods: The authors developed a model of information flow from subject to medical record to the clinical study case report form, based on a literature review. To test this model, a bidirectional (prospective and retrospective) study was conducted, enrolling all eligible adult patients who were admitted with a chief complaint of chest pain.
Background: Little is known about the duration of symptoms and follow-up patterns of patients seen in emergency departments for abdominal or flank pain.
Objective: We aimed to measure the duration of symptoms and follow-up rate of patients discharged home from the emergency department after presenting with non-traumatic abdominal or flank pain.
Methods: We conducted a single-centre, prospective descriptive study of adult patients who presented to our emergency department with non-traumatic abdominal or flank pain and were discharged from the emergency department.
The objective of the study was to measure the utilization and diagnostic value of tests used in the Emergency Department (ED) on patients with undifferentiated non-traumatic abdominal or flank pain. Specific goals were to measure how often these tests led to changes in diagnosis or disposition, which tests were most commonly used, and which tests providers considered most helpful. We conducted a pilot single-center, prospective descriptive study, enrolling all eligible adult patients who presented to our ED with non-traumatic abdominal or flank pain during defined hours of our intake period.
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