Nicotine intake and smoking topography in smokers with bipolar disorder.

Objectives: Cigarette smoking behavior in bipolar disorder (BPD), including the effects of mood-stabilizing medications, has not been well characterized.

Methods: We compared serum nicotine, nicotine metabolite levels, and smoking topography in 75 smokers with BPD to 86 control smokers (CON). For some comparisons, an additional control group of 75 smokers with schizophrenia (SCZ) were included.

Logical Analysis of Data in Structure-Activity Investigation of Polymeric Gene Delivery.

To date semi-empirical or surrogate modeling has demonstrated great success in the prediction of the biologically relevant properties of polymeric materials. For the first time, a correlation between the chemical structures of poly(β-amino esters) and their efficiency in transfecting DNA was established using the novel technique of logical analysis of data (LAD). Linear combination and explicit representation models were introduced and compared in the framework of the present study.

Resource utilization and cost of treatment with anidulafungin or fluconazole for candidaemia and other forms of invasive candidiasis: focus on critically ill patients.

Background: Candidaemia and other forms of invasive candidiasis (C/IC) are serious and costly events for hospitalized patients, particularly those in the ICU. Both fluconazole and the echinocandins are recommended as first-line therapy for C/IC. Resource use and cost considerations are important in selecting appropriate treatment but little information is available on the economic implications of using echinocandins in this setting.

Colorectal cancer screening among primary care patients: does risk affect screening behavior?

Lifestyle factors including smoking, obesity, and diabetes can increase colorectal cancer (CRC) risk. Controversy exists regarding screening rates in individuals at increased CRC risk. To examine the effect of risk on CRC screening in primary care, cross-sectional data collected during January 2006-July 2007 from 720 participants in 24 New Jersey primary care practices were analyzed.

Activity of a C-terminal plant homeodomain (PHD) of Msc1 is essential for function.

Msc1, a member of the Jarid1 family of putative histone demethylases, is required for chromosome stability in fission yeast. Msc1 associates with the Swr1 complex that facilitates deposition of histone H2A.Z into chromatin.

Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma.

The antiapoptotic Bcl-2 family member Bfl-1 is up-regulated in many human tumors in which nuclear factor-kappaB (NF-kappaB) is implicated and contributes significantly to tumor cell survival and chemoresistance. We previously found that NF-kappaB induces transcription of bfl-1 and that the Bfl-1 protein is also regulated by ubiquitin-mediated proteasomal degradation. However, the role that dysregulation of Bfl-1 turnover plays in cancer is not known.

Racial differences in adjuvant systemic therapy for early breast cancer among Medicaid beneficiaries.

Black breast cancer patients have shorter survival compared to whites. Lack of optimal treatment may be a potential explanation for this difference. Although racial disparities in surgical and radiation therapy have been studied extensively, there is little information on racial disparities in use of adjuvant systemic therapy.

Quantification of 1-aminopyrene in human urine after a controlled exposure to diesel exhaust.

Diesel exhaust (DE) is a significant source of air pollution that has been linked to respiratory and cardiovascular morbidity and mortality. Many components in DE, such as polycyclic aromatic hydrocarbons, are present in the environment from other sources. 1-Nitropyrene appears to be a more specific marker of DE exposure.

Hybrid scoring and classification approaches to predict human pregnane X receptor activators.

Purpose: The human pregnane X receptor (PXR) is a transcriptional regulator of many genes involved in xenobiotic metabolism and excretion. Reliable prediction of high affinity binders with this receptor would be valuable for pharmaceutical drug discovery to predict potential toxicological responses

Materials And Methods: Computational models were developed and validated for a dataset consisting of human PXR (PXR) activators and non-activators. We used support vector machine (SVM) algorithms with molecular descriptors derived from two sources, Shape Signatures and the Molecular Operating Environment (MOE) application software.

Therapeutic starvation and autophagy in prostate cancer: a new paradigm for targeting metabolism in cancer therapy.

Background: Autophagy is a starvation induced cellular process of self-digestion that allows cells to degrade cytoplasmic contents. The understanding of autophagy, as either a mechanism of resistance to therapies that induce metabolic stress, or as a means to cell death, is rapidly expanding and supportive of a new paradigm of therapeutic starvation.

Methods: To determine the effect of therapeutic starvation in prostate cancer, we studied the effect of the prototypical inhibitor of metabolism, 2-deoxy-D-glucose (2DG), in multiple cellular models including a transfected pEGFP-LC3 autophagy reporter construct in PC-3 and LNCaP cells.

Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials.

Microcirculatory dysfunction is a critical element of the pathogenesis of severe sepsis and septic shock. In this Bench-to-Bedside review, we present: 1) the central role of the microcirculation in the pathophysiology of sepsis; 2) new translational research techniques of in vivo video microscopy for assessment of microcirculatory flow in human subjects; 3) clinical investigations that reported associations between microcirculatory dysfunction and outcome in septic patients; 4) the potential role of novel agents to "rescue" the microcirculation in sepsis; 5) current challenges facing this emerging field of clinical investigation; and 6) a framework for the design of future clinical trials aimed to determine the impact of novel agents on microcirculatory flow and organ failure in patients with sepsis. We specifically focus this review on the central role and vital importance of the nitric oxide (NO) molecule in maintaining microcirculatory homeostasis and patency, especially when the microcirculation sustains an insult (as with sepsis).

New predictive models for blood-brain barrier permeability of drug-like molecules.

Purpose: The goals of the present study were to apply a generalized regression model and support vector machine (SVM) models with Shape Signatures descriptors, to the domain of blood-brain barrier (BBB) modeling.

Materials And Methods: The Shape Signatures method is a novel computational tool that was used to generate molecular descriptors utilized with the SVM classification technique with various BBB datasets. For comparison purposes we have created a generalized linear regression model with eight MOE descriptors and these same descriptors were also used to create SVM models.

Inhibition of apoptosis prevents shear-induced detachment of endothelial cells.

Background: Biomaterials placed into the vasculature in man fail to develop an endothelial lining. Attempts to seed endothelial cells (ECs) on prosthetic vascular grafts have failed due to flow-induced detachment. The mechanism of flow-induced detachment of ECs from biomaterials is undefined.

Protease inhibitor associated mutations compromise the efficacy of therapy in human immunodeficiency virus-1 (HIV-1) infected pediatric patients: a cross-sectional study.

Background: Although the introduction of combined therapy with reverse transcriptase and protease inhibitors has resulted in considerable decrease in HIV related mortality; it has also induced the development of multiple drug-resistant HIV-1 variants. The few studies on HIV-1 mutagenesis in HIV infected children have not evaluated the impact of HIV-1 mutations on the clinical, virological and immunological presentation of HIV disease that is fundamental to optimizing the treatment regimens for these patients.

Results: A cross sectional study was conducted to evaluate the impact of treatment regimens and resistance mutation patterns on the clinical, virological, and immunological presentation of HIV disease in 41 children (25 male and 16 female) at the Robert Wood Johnson Pediatric AIDS Program in New Brunswick, New Jersey.

Protection of DNA ends by telomeric 3' G-tail sequences.

The extreme ends of eukaryotic chromosomes contain 3' extensions in the form of single-stranded G-rich repeats, referred to as telomeric 3' G-tails or overhangs. Increasing evidence has suggested that telomeric 3' G-tails can adopt a G-quadruplex conformation both in vitro and in vivo. However, the role of G-quadruplexes on the structure and function of telomeric 3' G-tails remains unclear.

The plant homeodomain fingers of fission yeast Msc1 exhibit E3 ubiquitin ligase activity.

The DNA damage checkpoint pathway governs how cells regulate cell cycle progression in response to DNA damage. A screen for suppressors of a fission yeast chk1 mutant defective in the checkpoint pathway identified a novel Schizosaccharomyces pombe protein, Msc1. Msc1 contains 3 plant homeodomain (PHD) finger motifs, characteristically defined by a C4HC3 consensus similar to RING finger domains.

The emergency department for routine healthcare: race/ethnicity, socioeconomic status, and perceptual factors.

Our objective was to study the role of race/ethnicity and socioeconomic status (SES) in the use of the emergency department (ED) as a source of routine healthcare. Adult patients presenting to an urban ED were surveyed. We assessed demographics, race/ethnicity, SES, and perceptional factors related to choosing the ED for the current visit.

Magnetic resonance imaging of aging, accommodating, phakic, and pseudophakic ciliary muscle diameters.

Purpose: To quantify in vivo accommodative changes in the aging human ciliary muscle diameter in phakic and pseudophakic eyes.

Setting: Department of Surgery/Bioengineering, UMDNJ-Robert Wood Johnson Medical School, Piscataway, and the Institute of Ophthalmology and Visual Science UMDNJ-New Jersey Medical School, Newark, New Jersey, USA.

Methods: Images were acquired from 48 eyes of 40 people between the ages of 22 and 91 years, 1 eye of 32 phakic volunteers and both eyes of 8 patients who had monocular implantation of a single-piece AcrySof intraocular lens (IOL) (Alcon Laboratories).

Ethanol decreases rat hepatic arylsulfatase A activity levels.

Background: Arylsulfatase A (ASA) is an enzyme that catalyzes the degradation of sulfatides, a glycosphingolipid found in many tissues, but predominantly in myelin and kidney. Arylsulfatase A is 1 member of a family of sulfatases that is activated by a required co- or posttranslational modification with the oxidation of cysteine to formylglycine. This conversion requires a novel oxygenase mechanism that can be inhibited by reactive oxygen species.

Conformational features of a natural break in the type IV collagen Gly-X-Y repeat.

Fibrillar collagens have an absolute requirement for Gly as every 3rd residue, whereas breaks in the Gly-X-Y repeating pattern are found normally in the triple helix domains of non-fibrillar collagens, such as type IV collagen in basement membranes. In this study, a model 30-mer peptide is designed to include the interruption GPOGAAVMGPOGPO found in the alpha5 chain of type IV collagen. The GAAVM peptide forms a stable triple helix, with Tm= 29 degrees C.

Acute respiratory failure with a single dose of quetiapine fumarate.

Objective: To report a case of acute respiratory failure after a single dose of quetiapine fumarate in an elderly patient with a history of chronic obstructive pulmonary disease (COPD).

Case Summary: A 92-year-old woman with a history of COPD was admitted to the hospital with pneumonia. Her symptoms improved with antibiotics.

Extended upstream A-T sequence increases T7 promoter strength.

Bacteriophage T7 promoters contain a consensus sequence from -17 to +6 relative to the transcription start site, +1. In addition, the strong class III promoters are characterized by an extended AT-rich region upstream of -17, which is often interrupted by one or more GC base pairs in the weaker class II promoters. Herein we studied the role of the AT-rich region upstream of -17 in transcription regulation of T7 RNA polymerase.

MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis.

During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members of the Msx homeoprotein family. By investigating Msx1 function in repression of myogenic gene expression, we identified a physical interaction between Msx1 and H1b, a specific isoform of mouse histone H1. We found that Msx1 and H1b bind to a key regulatory element of MyoD, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin.