APOE modulates the correlation between triglycerides, cholesterol, and CHD through pleiotropy, and gene-by-gene interactions.

Relationship loci (rQTL) exist when the correlation between multiple traits varies by genotype. rQTL often occur due to gene-by-gene (G × G) or gene-by-environmental interactions, making them a powerful tool for detecting G × G. Here we present an empirical analysis of apolipoprotein E (APOE) with respect to lipid traits and incident CHD leading to the discovery of loci that interact with APOE to affect these traits.

Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM gene in human cancers.

The M2 isoform of pyruvate kinase (PKM2) plays an important role in aerobic glycolysis and is a mediator of the Warburg effect in tumors. It was previously thought that tumor cells switch expression of PKM from normal tissue-expressed PKM1 to tumor-specific PKM2 via an alternative splicing mechanism. This view was challenged by a recent report demonstrating that PKM2 is already the major PKM isoform expressed in many differentiated normal tissues.

Peritoneal catheter for massive cardiac ascites.

Cardiac ascites represents 5% of all causes of ascites. Diuretics and salt restriction remain the cornerstone of management. Large volume paracentesis is needed among patients who do not respond to conservative management.

Dating violence among urban, minority, middle school youth and associated sexual risk behaviors and substance use.

Background: Whereas dating violence among high school students has been linked with sexual risk-taking and substance use, this association has been understudied among early adolescents. We estimated the prevalence of physical and nonphysical dating violence in a sample of middle school students and examined associations between dating violence, sexual, and substance use behaviors.

Methods: Logistic regression models for clustered data from 7th grade students attending 10 Texas urban middle schools were used to examine cross-sectional associations between dating violence victimization and risk behaviors.

Impact of Hispanic ethnic concentration and socioeconomic status on obesity prevalence in Texas counties.

The purpose of this study is to determine whether Hispanic ethnic concentration is associated with a higher prevalence of obesity and, if this relationship exists, whether it is affected by the socioeconomic environment. The study uses the Texas Behavioral Risk Factor Surveillance System (BRFSS) linked to 2000 census data to access the relationship between prevalence of obesity, Hispanic ethnic concentration, poverty and level of education at a county-level. The findings suggest that the association of Hispanic ethnic concentration and obesity varies by socioeconomic environment.

Economic considerations of the treatment of ankylosing spondylitis.

Ankylosing spondylitis (AS) is associated with both significant direct and indirect costs, which vary by country, and have generally increased dramatically since the introduction of anti-tumor necrosis factor therapy. The cost-effectiveness of biologic agents is controversial, although cost-effectiveness studies need to consider the potential impact of anti-tumor necrosis factor treatments on work ability. Alternatives to reduce costs associated with biologics have been examined, including on-demand dosing and lower dose alternatives.

Management of device-related wound complications in deep brain stimulation surgery.

Object: Wound complications are uncommon following deep brain stimulation (DBS) surgery. However, certain key technical steps can be performed in each procedure to minimize this still troublesome risk. The authors reviewed the incidence and management of all hardware-related wound dehiscences and infections in a large patient series.

Deep sequencing study of the MTHFR gene to identify variants associated with myelomeningocele.

Introduction: Neural tube defects (NTDs) are congenital anomalies caused by a combination of genetic and environmental influences. A defect below the head region resulting in protuberance of meninges and nervous tissue is termed myelomeningocele (MM). MM, the most common NTD compatible with survival, occurs in approximately 1 in 1000 births worldwide.

Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling.

AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis. The 475 amino acid sequence of AtxA reveals DNA binding motifs and regions similar to proteins associated with the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS). We used strains producing native and functional epitope-tagged AtxA proteins to examine protein-protein interactions in cell lysates and in solutions of purified protein.

The genetic basis of spondyloarthritis.

Modern technological innovations have advanced our understanding of the genetic basis of spondyloarthritis. In ankylosing spondylitis (AS), where the major histocompatibility complex (MHC) accounts for nearly half of the predisposition, most comes from HLA-B27, for which 65 subtypes are now recognised, although other genes are also at work including HLA-B60 (B*40:01). Other genes have been identified, including those involved in peptide editing for loading onto class I MHC molecules (ERAP1) and cytokine genes such as interleukin 1A (IL-1A) and those involved in the Th17 network (IL-23R, an association seen primarily in Caucasians) and others.

Regulation of DNA repair through deSUMOylation and SUMOylation of replication protein A complex.

The replication protein A complex (RPA) plays a crucial role in DNA replication and damage response. However, it is not known whether this complex is regulated by the SUMOylation pathway. Here, we show that the 70 kDa subunit of RPA (RPA70) associates with a Sentrin/SUMO-specific protease, SENP6, in the nucleus to maintain RPA70 in a hypoSUMOylated state during S phase.

Responses in mantle cell lymphoma cells to SNS-032 depend on the biological context of each cell line.

SNS-032 is a potent inhibitor of cyclin-dependent kinases (Cdk) 2, 7, and 9 that regulate the cell cycle and transcription. Our studies in indolent primary chronic lymphocytic leukemia cells showed that SNS-032 inhibited transcription, diminished the antiapoptotic protein Mcl-1, and induced apoptosis. The present study focuses on evaluating this compound in four proliferating mantle cell lymphoma lines (Jeko-1, Granta 519, Mino, and SP-53).

Wood smoke risk assessment: defining the questions.

Risk assessment provides a framework for combining and evaluating scientific data on source-to-health effects for contaminants that could potentially affect the health of human populations. It utilizes an integrated approach to hazard identification, dose response, exposure assessment, and risk characterization. Since the range of potential exposure scenarios is considerable, given the complexity of wood-smoke sources and emissions, there is a need for defining the critical characteristics for the key parameters leading to adverse health outcomes.

The history of articulators: the "Articulator Wars" phenomenon with some circumstances leading up to it.

At the dawn of the 20th century, all was not well with the practice of "plate prostheses." Removable prosthodontics had been degrading for several decades and was now generally in low esteem, even though there had been many significant advances. W.

Intracranial pressure waveform analysis during rest and suctioning.

Cerebral compliance is a measure of cerebral adaptability to increases in volume within the intracranial space and an indicator of risk for neurological deterioration. However, no direct measurement of compliance exists in clinical practice to guide nursing care or treatment decisions. Current use of mean intracranial pressure (MICP) and gross morphological intracranial pressure waveform (ICPW) analysis have great variability in predicting outcomes.

Nanomedicine and society.

Nanomedicine is a reality of medical research and clinical practice, and it offers new and promising approaches to fundamental problems in medicine. Most prominent are the early detection of neoplastic disease and the individualized treatment of metastases. These potentially transformational developments require careful scrutiny of the potential impact of nanomedicine on society, so that the community can guide its deployment in keeping with the fundamental tenets of medical ethics.

Is the drip-and-ship approach to delivering thrombolysis for acute ischemic stroke safe?

Background: The drip-and-ship method of treating stroke patients may increase the use of tissue plasminogen activator (t-PA) in community hospitals.

Objective: The safety and early outcomes of patients treated with t-PA for acute ischemic stroke (AIS) by the drip-and-ship method were compared to patients directly treated at a stroke center.

Methods: The charts of all patients who were treated with intravenous (i.

Binge use of crack cocaine and sexual risk behaviors among African-American, HIV-positive users.

This study describes binge use of crack cocaine, binge users, and their sexual risk behaviors in a sample of 303 African-American, HIV-positive users. Recent binge use was defined as, "using as much crack cocaine as you can, until you run out of crack or are unable to use any more" in the last 30 days. Fifty-one percent reported a recent crack binge.

The functional role of the renin-angiotensin system in pregnancy and preeclampsia.

During normal pregnancy, the renin-angiotensin system (RAS) plays a vitally important role in salt balance and subsequent well-being of mother and fetus. In this balance, one must consider not only the classical renal RAS but also that of the uteroplacental unit, where both maternal and fetal tissues contribute to the signaling cascade. Many studies have shown that in normal pregnancy there is an increase in almost all of the components of the RAS.

Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters.

The current model for virulence gene regulation in Bacillus anthracis involves several trans-acting factors, the most important of which appears to be the anthrax toxin activator encoded by the atxA gene. AtxA is a positive regulator of the toxin genes pagA, cya and lef, and of a number of other plasmid- and chromosome-encoded genes. The AtxA protein (56 kDa) possesses a predicted winged-helix DNA-binding domain and phosphotransferase system-regulated domains, but the mechanism for positive regulation of AtxA target genes is not known.

Nanotechnology for breast cancer therapy.

Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact.

Arrested development and disrupted callosal microstructure following pediatric traumatic brain injury: relation to neurobehavioral outcomes.

Chronic pediatric traumatic brain injury (TBI) is associated with significant and persistent neurobehavioral deficits. Using diffusion tensor imaging (DTI), we examined area, fractional anisotropy (FA), radial diffusion, and axial diffusion from six regions of the corpus callosum (CC) in 41 children and adolescents with TBI and 31 comparison children. Midsagittal cross-sectional area of the posterior body and isthmus was similar in younger children irrespective of injury status; however, increased area was evident in the older comparison children but was obviated in older children with TBI, suggesting arrested development.

Supraglottoplasty for laryngomalacia with obstructive sleep apnea.

Objectives/hypothesis: To determine if supraglottoplasty (SGP) is effective in reversing abnormal respiratory parameters in children with laryngomalacia and obstructive sleep apnea (OSA).

Study Design: Retrospective case series at a tertiary referral children's hospital.

Methods: Ten patients with laryngomalacia and OSA as documented by polysomnography underwent SGP between 2005 and 2007.