Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics.

Objective: To identify novel CSF biomarkers in -associated frontotemporal dementia (FTD) by proteomics using mass spectrometry (MS).

Methods: Unbiased MS was applied to CSF samples from 19 presymptomatic and 9 symptomatic mutation carriers and 24 noncarriers. Protein abundances were compared between these groups.

Smooth muscle atrophy and colon pathology in SMN deficient mice.

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterized by loss of motor neurons in the ventral horn of the spinal cord. Clinical features such as progressively lethal respiratory weakness and associated muscle wasting have been extensively studied but less attention has been given to gastrointestinal (GI) dysfunction, which is common symptomatology in SMA patients with 43% constipation, 15% abdominal pain, and 14% meteorism. In the current study, the PrP92-SMN mouse model of SMA was utilized, to complement previous studies in which cells of the Enteric Nervous system (ENS) were susceptible to Smn (survival motor neuron) deficiency and could possibly be the basis of the observed GI symptoms.

Impact of Diabetes Mellitus on Ventricular Structure, Arterial Stiffness, and Pulsatile Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Background Heterogeneity in the underlying processes that contribute to heart failure with preserved ejection fraction ( HF p EF ) is increasingly recognized. Diabetes mellitus is a frequent comorbidity in HF p EF , but its impact on left ventricular and arterial structure and function in HF p EF is unknown. Methods and Results We assessed the impact of diabetes mellitus on left ventricular cellular and interstitial hypertrophy (assessed with cardiac magnetic resonance imaging, including T1 mapping pregadolinium and postgadolinium administration), arterial stiffness (assessed with arterial tonometry), and pulsatile arterial hemodynamics (assessed with in-office pressure-flow analyses and 24-hour ambulatory monitoring) among 53 subjects with HF p EF (32 diabetic and 21 nondiabetic subjects).

Axial Muscle Size as a Strong Predictor of Death in Subjects With and Without Heart Failure.

Background The impact of skeletal muscle size, quantified using simple noninvasive images routinely obtained during cardiac magnetic resonance imaging studies on mortality in the heart failure ( HF ) population is currently unknown. Methods and Results We prospectively enrolled 567 subjects without HF (n=364), with HF with reduced ejection fraction (n=111), or with HF with preserved ejection fraction (n=92), who underwent a cardiac magnetic resonance imaging. Skeletal muscle cross-sectional area was assessed with manual tracing of major thoracic muscle groups on axial chest magnetic resonance images.

Accuracy of risk prediction scores in pregnant women with congenital heart disease.

Objective: To assess performance of risk stratification schemes in predicting adverse cardiac outcomes in pregnant women with congenital heart disease (CHD) and to compare these schemes to clinical factors alone.

Design: Single-center retrospective study.

Setting: Tertiary care academic hospital.

Measurement and immunophenotyping of pleural fluid EpCAM-positive cells and clusters for the management of non-small cell lung cancer patients.

Objectives: A malignant pleural effusion (MPE) is a common complication in non-small cell lung cancer (NSCLC) with important staging and prognostic information. Patients with MPEs are often candidates for advanced therapies, however, the current gold standard, cytological analysis of pleural fluid samples, has limited sensitivity. We aimed to demonstrate the feasibility of non-invasive enumeration and immunophenotyping of EpCAM-positive cells in pleural fluid samples for the diagnosis of a MPE in NSCLC patients.

Arterial Properties as Determinants of Left Ventricular Mass and Fibrosis in Severe Aortic Stenosis: Findings From ACRIN PA 4008.

Background The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement ( AVR ).

Phosphodiesterase-5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury.

Background: Traumatic cerebrovascular injury (TCVI), a common consequence of traumatic brain injury (TBI), presents an attractive therapeutic target. Because phosphodiesterase-5 (PDE5) inhibitors potentiate the action of nitric oxide (NO) produced by endothelial cells, they are candidate therapies for TCVI. This study aims to: (1) measure cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and change in CVR after a single dose of sildenafil (ΔCVR) in chronic TBI compared to uninjured controls; (2) examine the safety and tolerability of 8-week sildenafil administration in chronic symptomatic moderate/severe TBI patients; and as an exploratory aim, (3) assess the effect of an 8-week course of sildenafil on chronic TBI symptoms.

Reading LINEs within the cocaine addicted brain.

Introduction: Long interspersed element (LINE)-1 (L1) is a type of retrotransposon capable of mobilizing into new genomic locations. Often studied in Mendelian diseases or cancer, L1s may also cause somatic mutation in the developing central nervous system. Recent reports showed L1 transcription was activated in brains of cocaine-treated mice, and L1 retrotransposition was increased in cocaine-treated neuronal cell cultures.

Decision-Making Deficits Associated with Amyloidosis in Lewy Body Disorders.

Lewy body disorders (LBD) are clinical syndromes characterized by pathological inclusions containing α-synuclein. Cognitive deficits are common or diagnostic in LBD, and may be associated with the presence of beta-amyloid (Aβ), which is a hallmark histopathologic abnormality characteristic of Alzheimer's disease (AD) that can also co-occur with LBD. In the present study we evaluated whether social decision-making difficulties in LBD are associated with Aβ burden.

Olfactory Impairment Predicts Underlying Dopaminergic Deficit in Presumed Drug-Induced Parkinsonism.

Drug-induced parkinsonism (DIP) is common, and the motor symptoms can be indistinguishable from Parkinson's disease (PD). When symptoms persist after drug withdrawal, this may represent "unmasking" of underlying PD. We previously reported that hyposmia, a common nonmotor feature of PD, was associated with persistent DIP.

Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention.

The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy.