Tandem Duplication of Exons 1-7 Neither Impairs ATP7A Expression Nor Causes a Menkes Disease Phenotype.

ATP7A duplications are estimated to represent the molecular cause of Menkes disease in 4-10% of affected patients. We identified a novel duplication of ATP7A exons 1-7 discovered in the context of a challenging prenatal diagnostic situation. All other reported ATP7A duplications (n = 24) involved intragenic tandem duplications, predicted to disrupt the normal translational reading frame and produce nonfunctional ATP7A proteins.

Exercise Hemodynamics and Quality of Life after Aortic Valve Replacement for Aortic Stenosis in the Elderly Using the Hancock II Bioprosthesis.

Background and Aim. While aortic valve replacement for aortic stenosis can be performed safely in elderly patients, there is a need for hemodynamic and quality of life evaluation to determine the value of aortic valve replacement in older patients who may have age-related activity limitation. Materials and Methods.

Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.

Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical.

Paraneoplastic granulocyte colony-stimulating factor secretion in soft tissue sarcoma mimicking myeloproliferative neoplasia: a case report.

Background: While paraneoplastic leukocytosis is a common phenomenon in solid tumors, extreme elevations of white blood counts (WBC) in the range of more than 100,000/μl are uncommon in patients with non-hematologic malignancies. Leukocytosis with mature neutrophils due to a granulocyte colony-stimulating factor (G-CSF) producing tumor is only seen on rare occasions.

Case Presentation: Massive neutrophil leukocytosis of approximately 100,000/μl was diagnosed in a 57-year-old Caucasian woman with metastatic undifferentiated endometrial sarcoma.

Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma.

Recently, SOX2 has been identified as a potential lineage-specific oncogene in lung squamous cell carcinomas. Since head and neck squamous cell carcinomas (HNSCC) are morphologically and clinically highly related to lung squamous cell carcinomas, we hypothesized that SOX2 also plays an oncogenic role in this tumor entity. We assembled a cohort of 496 patients with HNSCC, including 253 metastases and 135 recurrences.

Examining change in social support and fruit and vegetable consumption in African American adults.

Objective: To examine (a) inter-individual variation in African Americans' fruit and vegetable social support, behavior, and consumption trajectories by estimating latent growth curves (LGCs) and (b) the associations between these trajectories over time.

Design: As part of a larger intervention study, data were collected from mid-life and older African Americans yearly for three years. The study incorporated a quasi-experimental design with random selection of participants, stratifying for age and gender.

Assessing Smart Phones for Generating Life-space Indicators.

Life-space is a promising method for estimating older adults' functional status. However, traditional life-space measures are costly and time consuming because they often rely on active subject participation. This study assesses the feasibility of using the global positioning system (GPS) function of smart phones to generate life-space indicators.

Eating behaviors of older African Americans: an application of the theory of planned behavior.

Purpose: The study applies the theory of planned behavior to explain the fruit and vegetable eating behaviors, a broad construct consisting of preparing, self-monitoring, and consuming fruits and vegetables, of older African Americans.

Design And Methods: Structural equation modeling was used to examine the applicability of the theory of planned behavior with data from 211 older African American women and men (73% women, 26% men; median age range of 57-63 years) participating in a larger intervention study.

Results: Attitudes about eating fruit and vegetables, subjective social norms, and perceived behavioral control were related to older African Americans' intentions to consume fruits and vegetables.

Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling.

Unlabelled: Polymorphonuclear neutrophil granulocytes (neutrophils) are tightly controlled by an incompletely understood homeostatic feedback loop adjusting the marrow's supply to peripheral needs. Although it has long been known that marrow cellularity is inversely correlated with G-CSF levels, the mechanism linking peripheral clearance to production remains unknown. Herein, the feedback response to antibody induced neutropenia is characterized to consist of G-CSF–dependent shifts of marrow hematopoietic progenitor populations including expansion of the lin-/Sca-1/c-kit (LSK) and granulocyte macrophage progenitor (GMP) compartments at the expense of thrombopoietic and red cell precursors.

Life dissatisfaction and eating behaviors among older African Americans: the protective role of social support.

Objectives: To examine (a) the influences of life dissatisfaction and dietary social support on eating behaviors (a high-fat diet and fruit/vegetable consumption) of older African Americans and (b) the moderating role of perceived dietary social support on the association between their life dissatisfaction and unhealthy eating behaviors.

Design: Baseline data from a larger intervention study of mid-life and older African Americans. The study incorporated a quasi-experimental design with random selection of participants, stratifying for age and gender.

Zebrafish xenografts as a tool for in vivo studies on human cancer.

The zebrafish has become a powerful vertebrate model for genetic studies of embryonic development and organogenesis and increasingly for studies in cancer biology. Zebrafish facilitate the performance of reverse and forward genetic approaches, including mutagenesis and small molecule screens. Moreover, several studies report the feasibility of xenotransplanting human cells into zebrafish embryos and adult fish.

EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia.

The transcriptional regulator ecotropic viral integration site-1 (EVI-1) has mainly been studied for its role in myeloid malignancies, in which high EVI-1 levels are associated with particularly aggressive disease. The role of EVI-1 in lymphoid cells, however, is largely unknown. Here we show that EVI-1 is indeed expressed in lymphoid malignancies such as acute lymphoblastic leukemia (ALL) and a subset of chronic lymphocytic leukemia.

Case study: to-BBB's G-Technology, getting the best from drug-delivery research with industry-academia partnerships.

To-BBB aims to develop efficacious treatments for patients with devastating neurological conditions based on to-BBB's proprietary G-Technology that safely enhances the delivery of drugs across the blood-brain barrier. Through strategic research collaborations, a small company such as to-BBB is able to deliver the high-quality research necessary to develop these novel treatments.

Evolution of strategies for modern rechargeable batteries.

This Account provides perspective on the evolution of the rechargeable battery and summarizes innovations in the development of these devices. Initially, I describe the components of a conventional rechargeable battery along with the engineering parameters that define the figures of merit for a single cell. In 1967, researchers discovered fast Na(+) conduction at 300 K in Na β,β''-alumina.

EGFR-TKI resistant non-small cell lung cancer (NSCLC): new developments and implications for future treatment.

Treatment with receptor-tyrosine kinase inhibitors (TKIs) has improved progression-free and overall survival in patients with advanced non-small cell lung cancer (NSCLC). One major target for treatment with TKI is the epidermal growth factor receptor (EGFR), particularly in patients harboring activating mutations. However, despite initial responses and long lasting remissions, the development of secondary resistance inevitably leads to treatment failure.

Targeted CRM197-PEG-PEI/siRNA Complexes for Therapeutic RNAi in Glioblastoma.

RNA interference (RNAi) allows the specific knockdown of tumor relevant genes. To induce RNAi, the delivery of small interfering RNAs (siRNAs) is of crucial importance. This is particularly challenging for their therapeutic applications in vivo.

Interactions between Cdx genes and retinoic acid modulate early cardiogenesis.

Cdx transcription factors regulate embryonic positional identities and have crucial roles in anteroposterior patterning (AP) processes of all three germ layers. Previously we have shown that the zebrafish homologues cdx1a and cdx4 redundantly regulate posterior mesodermal derivatives inducing embryonic blood cell fate specification and patterning of the embryonic kidney. Here we hypothesize that cdx factors restrict formation of anterior mesodermal derivatives such as cardiac cells by imposing posterior identity to developing mesodermal cells.

Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma.

Background: The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors.

Designing mobile support for glycemic control in patients with diabetes.

We assessed the feasibility and acceptability of using mobile phones as part of an existing Web-based system for collaboration between patients with diabetes and a primary care team. In design sessions, we tested mobile wireless glucose meter uploads and two approaches to mobile phone-based feedback on glycemic control. Mobile glucose meter uploads combined with graphical and tabular data feedback were the most desirable system features tested.

Autologous blood cell therapies from pluripotent stem cells.

The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.

Hematopoietic development from human induced pluripotent stem cells.

A decade of research on human embryonic stem cells (ESC) has paved the way for the discovery of alternative approaches to generating pluripotent stem cells. Combinatorial overexpression of a limited number of proteins linked to pluripotency in ESC was recently found to reprogram differentiated somatic cells back to a pluripotent state, enabling the derivation of isogenic (patient-specific) pluripotent stem cell lines. Current research is focusing on improving reprogramming protocols (e.

Disease models from pluripotent stem cells.

Murine models of congenital and acquired diseases are invaluable yet often do not faithfully mirror human pathophysiology. Embryonic stem (ES) cells differentiated in vitro recapitulate aspects of early embryogenesis and differentiate into multiple somatic tissues, thereby serving as a powerful platform for developmental studies in the human. Analysis of genetically modified ES cells (by lentiviral gene transduction or derivation from embryos carrying genetic diseases, for example) offers the unprecedented opportunity to study in detail disease initiation and progression during embryonic development.

Autonomic function and prognosis.

Autonomic nervous system function is assessed in the clinic by measuring resting heart rate, heart rate variability, or heart rate recovery following exercise. Each of these measures is a strong predictor of cardiovascular risk and all-cause mortality in primary and secondary prevention settings. These measures have been used to identify correlates of autonomic nervous system dysfunction at both the patient level (eg, obesity, diabetes, heart failure) and the environmental level (eg, smoking, social stress, air pollution).