Strain-dependent profile of misfolded prion protein aggregates.

Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations.

Modulating the endotheliopathy of trauma: Factor concentrate versus fresh frozen plasma.

Background: Transfusion of balanced ratios of plasma to platelets and red blood cells has been shown to reduce early death from exsanguination in trauma patients. Aside from hemostasis, recent work has shown that plasma reduces vascular endothelial permeability, inflammation, and organ edema after hemorrhagic shock (HS), all components of the endotheliopathy of trauma. We hypothesized that Kcentra could have protective effects on the endotheliopathy of trauma comparable with fresh frozen plasma (FFP).

Lactoferrin: A Modulator for Immunity against Tuberculosis Related Granulomatous Pathology.

There is great need for a therapeutic that would limit tuberculosis related pathology and thus curtail spread of disease between individuals by establishing a "firebreak" to slow transmission. A promising avenue to increase current therapeutic efficacy may be through incorporation of adjunct components that slow or stop development of aggressive destructive pulmonary pathology. Lactoferrin, an iron-binding glycoprotein found in mucosal secretions and granules of neutrophils, is just such a potential adjunct therapeutic agent.

Spontaneous Fluctuations in Visual Cortical Responses Influence Population Coding Accuracy.

Information processing in the cerebral cortex depends not only on the nature of incoming stimuli, but also on the state of neuronal networks at the time of stimulation. That is, the same stimulus will be processed differently depending on the neuronal context in which it is received. A major factor that could influence neuronal context is the background, or ongoing neuronal activity before stimulation.

Circadian gene expression predicts patient response to neoadjuvant chemoradiation therapy for rectal cancer.

Preoperative neoadjuvant chemoradiation therapy may be useful in patients with operable rectal cancer, but treatment responses are variable. We examined whether expression levels of circadian clock genes could be used as biomarkers to predict treatment response. We retrospectively analyzed clinical data from 250 patients with rectal cancer, treated with neoadjuvant chemoradiation therapy in a single institute between 2011 and 2013.

Substrate Selectivity of Lysophospholipid Transporter LplT Involved in Membrane Phospholipid Remodeling in Escherichia coli.

Lysophospholipid transporter (LplT) was previously found to be primarily involved in 2-acyl lysophosphatidylethanolamine (lyso-PE) recycling in Gram-negative bacteria. This work identifies the potent role of LplT in maintaining membrane stability and integrity in the Escherichia coli envelope. Here we demonstrate the involvement of LplT in the recycling of three major bacterial phospholipids using a combination of an in vitro lysophospholipid binding assay using purified protein and transport assays with E.

Assessment of Competence: The Accreditation Council for Graduate Medical Education/Residency Review Committee Perspective.

Competency is an individual trait. As an agency that accredits programs and institutions, the Accreditation Council for Graduate Medical Education (ACGME) does not define or access competency. However, in the past 15 years the ACGME has promulgated several initiatives to aid programs in the assessment of the competence of their residents and fellows.

Immune Activity of BCG Infected Mouse Macrophages Treated with a Novel Recombinant Mouse Lactoferrin.

Lactoferrin has been investigated for its adjuvant action to boost the BCG vaccine. Previous studies demonstrated that lactoferrin (LF) enhanced efficacy of the Bacillus Calmette-Guérin (BCG) vaccine to protect mice against the virulent Erdman Mycobacterium tuberculosis challenge. The studies here investigate the hypothesis that a novel CHO-derived recombinant mouse LF can modify cytokine production and antigen presentation molecules on macrophages.

Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine.

Background: Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy.

Patients And Methods: Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma.

A medical history of Governor John B. Connally and his gunshot wounds.

: On November 22, 1963, the Governor of Texas, John Connally, was injured during the assassination of President John F. Kennedy. Multiple authors have documented President Kennedy's injuries, the attempted resuscitation, and the controversies surrounding these events.

Autoantibodies to Dense Fine Speckles in Pediatric Diseases and Controls.

Objective: Autoantibodies to the dense fine speckled 70 kDa antigen (DFS70) are reported to be more common in individuals who do not have an antinuclear antibody (ANA)-associated rheumatic disease (AARD) than in patients with AARD. The frequency of anti-DFS70 antibodies has been thoroughly studied in adult but not in pediatric populations. The primary objective of this observational study was to determine the frequency of anti-DFS70 in pediatric AARD and reference cohorts.

IGK with conserved IGΚV/IGΚJ repertoire is expressed in acute myeloid leukemia and promotes leukemic cell migration.

We have previously reported that immunoglobulin heavy chain genes were expressed in myeloblasts and mature myeloid cells. In this study, we further demonstrated that rearranged Ig κ light chain was also frequently expressed in acute myeloid leukemia cell lines (6/6), primary myeloblasts from patients with acute myeloid leukemia (17/18), and mature monocytes (11/12) and neutrophils (3/12) from patients with non-hematopoietic neoplasms, but not or only rarely expressed in mature neutrophils (0/8) or monocytes (1/8) from healthy individuals. Interestingly, myeloblasts and mature monocytes/neutrophils shared several restricted IGKV and IGKJ gene usages but with different expression frequency.

Aortic Arch Morphology and Aortic Length in Patients with Dissection, Traumatic, and Aneurysmal Disease.

Objectives: To assess aortic arch morphology and aortic length in patients with dissection, traumatic injury, and aneurysm undergoing TEVAR, and to identify characteristics specific to different pathologies.

Method: This was a retrospective analysis of the aortic arch morphology and aortic length of dissection, traumatic injury, and aneurysmal patients. Computed tomography imaging was evaluated of 210 patients (49 dissection, 99 traumatic injury, 62 aneurysm) enrolled in three trials that received the conformable GORE TAG thoracic endoprosthesis.

Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span.

In Saccharomyces cerevisiae, Pah1 phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol, plays a crucial role in the synthesis of the storage lipid triacylglycerol. This evolutionarily conserved enzyme also plays a negative regulatory role in controlling de novo membrane phospholipid synthesis through its consumption of phosphatidate. We found that the pah1Δ mutant was defective in the utilization of non-fermentable carbon sources but not in oxidative phosphorylation; the mutant did not exhibit major changes in oxygen consumption rate, mitochondrial membrane potential, F1F0-ATP synthase activity, or gross mitochondrial morphology.

CHO expressed recombinant human lactoferrin as an adjuvant for BCG.

Lactoferrin (LF), an iron binding protein with immune modulatory activities, has adjuvant activity to enhance vaccine efficacy. Tuberculosis (TB) is a pulmonary disease caused by the pathogen Mycobacterium tuberculosis (MTB). Progressive TB disease is clinically defined by damaging pulmonary pathology, a result of inflammation due to immune reactivity.

Electronic Trigger-Based Intervention to Reduce Delays in Diagnostic Evaluation for Cancer: A Cluster Randomized Controlled Trial.

Purpose: We tested whether prospective use of electronic health record-based trigger algorithms to identify patients at risk of diagnostic delays could prevent delays in diagnostic evaluation for cancer.

Methods: We performed a cluster randomized controlled trial of primary care providers (PCPs) at two sites to test whether triggers that prospectively identify patients with potential delays in diagnostic evaluation for lung, colorectal, or prostate cancer can reduce time to follow-up diagnostic evaluation. Intervention steps included queries of the electronic health record repository for patients with abnormal findings and lack of associated follow-up actions, manual review of triggered records, and communication of this information to PCPs via secure e-mail and, if needed, phone calls to ensure message receipt.

A wireless transmission neural interface system for unconstrained non-human primates.

Objective: Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications.

Approach: To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull.

Diagnosis of Atopic Dermatitis: Mimics, Overlaps, and Complications.

Atopic dermatitis (AD) is one of the most common skin diseases affecting infants and children. A smaller subset of adults has persistent or new-onset AD. AD is characterized by pruritus, erythema, induration, and scale, but these features are also typical of several other conditions that can mimic, coexist with, or complicate AD.

A Meta-Analysis of Mesenchymal Stem Cells in Animal Models of Parkinson's Disease.

Multiple studies have been performed to evaluate the effects of mesenchymal stem cells (MSCs) in animal models of Parkinson's disease (PD). We performed a meta-analysis to estimate the treatment effect of unmodified MSCs on behavioral outcomes in preclinical studies of PD. We performed a systematic literature search to identify studies that used behavioral testing to evaluate the treatment effect of unmodified MSCs in PD models.

The iDigoxin Assay is More Sensitive than LOCI Digoxin Assay for Rapid Detection of Convallatoxin, the Active Cardiac Glycoside of Lily of The Valley.

Objective: Lily of the valley is a poisonous plant due to the presence of the cardiac glycoside convallatoxin. We compared two immunoassays (LOCI digoxin assay and iDigoxin assay) for rapid detection of convallatoxin if present in human serum.

Materials And Methods: Aliquots of a drug free serum pool and a digoxin serum pool were supplemented with microliter amounts of lily of the valley extract or nanogram to microgram quantities of convallatoxin, followed by measurement of apparent digoxin concentrations using the LOCI and iDigxoin assays.

Exploring New Ways to Deliver Value to Healthcare Organizations: Algorithmic Testing, Data Integration, and Diagnostic E-consult Service.

As the USA Health Care System undergoes transformation and transitions to value-based models it is critical for laboratory medicine/clinical pathology physicians to explore opportunities and find new ways to deliver value, become an integral part of the healthcare team. This is also essential for ensuring financial health and stability of the profession when the payment paradigm changes from fee-for-service to fee-for-performance. About 5 years ago we started searching for ways to achieve this goal.