p38γ MAPK Is Essential for Aerobic Glycolysis and Pancreatic Tumorigenesis.

KRAS is mutated in most pancreatic ductal adenocarcinomas (PDAC) and yet remains undruggable. Here, we report that p38γ MAPK, which promotes PDAC tumorigenesis by linking KRAS signaling and aerobic glycolysis (also called the Warburg effect), is a novel therapeutic target. p38γ interacted with a glycolytic activator PFKFB3 that was dependent on mutated KRAS.

Novel Positive Allosteric Modulators of Glutamate Transport Have Neuroprotective Properties in an in Vitro Excitotoxic Model.

Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis of various neurological disorders, such as stroke, brain trauma, epilepsy, and several neurodegenerative disorders. EAAT2 is the main transporter subtype responsible for glutamate clearance in the brain, and plays a key role in regulating neurotransmission and preventing excitotoxicity. Therefore, compounds that increase the activity of EAAT2 have therapeutic potential for neuroprotection.

CT detection of primary and metastatic ileal carcinoid tumor: rates of missed findings and associated delay in clinical diagnosis.

Purpose: To determine the rate of missed CT findings of ileal carcinoid tumor prior to pathologic diagnosis and the resultant diagnostic delay.

Methods: Initially, 74 patients with abdominal and pelvic CT prior to pathologically-proven diagnosis of ileal carcinoid were identified. Patients were excluded when the original CT study (n = 6) or report (n = 4) was not available, resulting in a final cohort of 64 patients (mean age, 58.

Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy.

Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention.

A Phase II Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Study of Lenalidomide in Lumbar Radicular Pain with a Long-Term Open-Label Extension Phase.

Objective: This phase II study assessed lenalidomide efficacy and safety.

Design: Three-phase core study: 14-day prerandomization, 12-week treatment, and 52-week open-label extension.

Setting: Fourteen US centers from July 2005 to July 2007.

Endovascular abdominal aortic aneurysm repair: a community hospital's experience.

Endovascular abdominal aortic aneurysm repair (EVAR) has become the first-line approach for the treatment of abdominal aortic aneurysms. Outcomes outside of tertiary care settings remain unknown. The purpose of this study is to report the midterm outcomes of EVAR in a community hospital.

Aqueous humor sCD44 concentration and visual field loss in primary open-angle glaucoma.

Purpose: To correlate aqueous humor soluble CD44 (sCD44) concentration, visual field loss, and glaucoma risk factors in primary open-angle glaucoma (POAG) patients.

Methods: Aqueous samples were obtained by paracentesis from normal and glaucoma patients who were undergoing elective surgery and analyzed for sCD44 concentration by enzyme-linked immunosorbent assay.

Results: In normal aqueous (n=124) the sCD44 concentration was 5.

Utility of clinical swallowing examination measures for detecting aspiration post-stroke.

The purpose of this investigation was to determine the utility of clinical swallowing examination (CSE) measures for detecting aspiration as defined by videofluoroscopic swallowing examination (VFSE). This study, involving 165 participants, is a follow-up to a previously published investigation of 60 participants. Findings are compared with that investigation as well as with other research on CSEs.

Hypophosphorylation of aqueous humor sCD44 and primary open-angle glaucoma.

Purpose: The ectodomain of CD44, the principal receptor for hyaluronic acid (HA), is shed as a 32-kDa fragment-soluble CD44 (sCD44)-which is cytotoxic to trabecular meshwork (TM) cells and retinal ganglion cells (RGCs) in culture. The purpose of this study was to characterize sCD44 further by determining the phosphorylation of aqueous humor sCD44 in normal and primary open-angle glaucoma (POAG).

Methods: Aqueous humor samples of patients were subjected to CD44 enzyme-linked immunosorbent assay (ELISA) and two-dimensional (2-D) polyacrylamide gel electrophoresis, followed by Western blot analysis with anti-CD44, anti-serine/threonine, and anti-tyrosine phosphospecific antibodies, to determine sCD44 concentration, isoelectric point (pI), and phosphorylation, respectively.

Treatment efficacy research: a window into genetic and neurodevelopmental correlates of developmental disabilities.

This issue of MRDD research reviews is dedicated to treatment efficacy research. The treatment of MRDD conditions has long been a central question, but the clinical science of treatment efficacy has not yet been systematically applied to many MRDD typologies. The purpose of this paper is to provide an overview of this special issue and to provide a rationale for including treatment efficacy research as a tool for studying selected neurological development and genetic correlates of MRDD.

Is the information about a test important? Applying the methods of evidence-based medicine to the clinical examination of swallowing.

Unlabelled: A hotly debated topic in oropharyngeal dysphagia is the Clinical Swallowing Examination's (CSE) importance in clinical practice. That debate can profit from the application of evidence-based medicine's (EBM) principles and procedures. These can guide both appropriate data collection and interpretation as will be demonstrated in the present report.

Discriminative validity of selected measures for differentiating normal from aphasic performance.

Normal elderly and mildly aphasic individuals may exhibit similar impairments in comprehension and expression. The discriminative validity between normal and aphasic performance on most standardized measures of aphasia has not been reported. The authors compared the performance of 18 aphasic and 18 normal adults to determine the discriminative validity of 2 general language measures--the Porch Index of Communicative Ability (B.

Aqueous humor in primary open-angle glaucoma contains an increased level of CD44S.

Purpose: To determine whether the cell adhesion molecule CD44, the principal receptor of hyaluronan, is altered in the aqueous humor and the anterior segment of patients with primary open-angle glaucoma (POAG).

Methods: The trabecular meshwork (TM), iris, ciliary body, and sclera of POAG and age-matched control eyes preserved in ethanol were microdissected and subjected to 1% Triton X-100 solubilization at 4 degrees C. Western blot analysis was performed using monoclonal antibodies that recognize either CD44H (hematopoietic; extracellular domain) or CD44S (soluble ectodomain).

Sensitivity and specificity of clinical/bedside examination signs for detecting aspiration in adults subsequent to stroke.

Unlabelled: While detecting the presence of aspiration is only one aspect of a noninstrumented examination of swallowing function, it is an important component due to its potential health status consequences. The purpose of this investigation was to investigate the sensitivity and specificity of clinical/bedside examination signs for predicting aspiration on videofluoroscopic examination of swallowing. Sixty consecutive, acute stroke patients were investigated with clinical/bedside and videofluoroscopic exams.

Possible demographic influences on differentiating normal from aphasic performance.

Unlabelled: To determine the psychometric validity of current language impairment, communication activity limitation, and quality of life measures for differentiating normal from chronically aphasic adults, we examined possible threats to test accuracy by the demographic variables age, educational level, and gender. A total of 18 chronically aphasic and 18 nonaphasic adults were evaluated with six measures. The results of correlational analyses indicated that, within the normal adult and aphasic adult groups, there exist significant relationships between some, but not all, demographic variables and performance on language impairment, communication activity limitation, and quality of life measures.

Inter- and intrajudge reliability for videofluoroscopic swallowing evaluation measures.

Interjudge reliability for videofluoroscopic (VFS) swallowing evaluations has been investigated, and results have, for the most part, indicated that reliability is poor. While previous studies are well-designed investigations of interjudge reliability, few reports of intrajudge reliability are available for VFS measures derived from frame-by-frame analysis that clinicians typically employ. The purpose of this study was to examine the inter- and intrajudge reliability of VFS examination measures commonly used to assess swallowing functions.

Inter- and intrajudge reliability of a clinical examination of swallowing in adults.

This study investigates inter- and intrajudge reliability of a clinical examination of swallowing in adults. Several investigations have sought correlations between clinical indicators of dysphagia and the actual presence of dysphagia as determined by videofluoroscopy. Whereas some investigations have reported interjudge reliability for the videofluoroscopic measures employed, none have reported reliability for clinical measures.

"Speech problem" subsequent to carbon monoxide exposure? I the jury.

Exposure to carbon monoxide can damage the nervous system. Sometimes that damage disrupts speech, and sometimes it does not. And, when it does, not all of what one hears may have an organic basis.

Promoting recovery in chronic aphasia with an interactive technology.

Objective: To assess chronic aphasic patients' responses to resumption of therapy using an innovative, computer-based treatment system.

Design: Patients were assessed pretreatment and posttreatment using standardized assessment tools. Pretreatment and posttreatment performance score means were computed and compared, with statistical significance of the differences established using a one-tailed, matched t test.

The efficacy of computer-provided reading treatment for chronic aphasic adults.

We examined the effects of computer-provided reading activities on language performance in chronic aphasic patients. Fifty-five aphasic adults were assigned randomly to one of three conditions: computer reading treatment, computer stimulation, or no treatment. Subjects in the computer groups used computer 3 hours each week for 26 weeks.

Crossed aphasia. Functional brain imaging with PET or SPECT.

Objectives: To study patients with crossed aphasia (aphasia secondary to lesions in the right hemisphere in right-handed patients) with functional brain imaging using positron emission tomography (PET) or single photon emission computed tomography (SPECT); to see whether left hemisphere structures were metabolically depressed during the acute phase and, in 1 patient, during recovery; and to review the modern literature on crossed aphasia, with special reference to left hemisphere involvement.

Design: Case studies of 3 patients with crossed aphasia, including language testing, computed tomographic scanning, and functional imaging with PET or SPECT.

Setting: Hospital case studies.

Fibrin sleeve stripping for salvage of failing hemodialysis catheters: technique and initial results.

Purpose: To evaluate percutaneous fibrin sleeve stripping (PFSS) to prolong functional patency in failing hemodialysis catheters.

Materials And Methods: Forty PFSS procedures were performed in 24 catheters in 23 consecutive patients with an inadequate blood flow rate (< 200 mL/min) during hemodialysis. The fibrin sleeve was mechanically stripped off the shaft of the catheter with a snare introduced via the common femoral vein.

Interventional procedures in the intensive care unit patient.

Image-guided interventional techniques have markedly altered the management of many cardiothoracic problems in the intensive care unit. These techniques are less invasive, more patient friendly, and cost-effective. This article covers venous line placement and management, transpleural and transpulmonary biopsy and drainage procedures and interventions for variceal bleeding, massive hemoptysis, massive pulmonary embolism, and veno-occlusive disease.