Assessment of developmental neurotoxicology-associated alterations in neuronal architecture and function using .

Few of the many chemicals that regulatory agencies are charged with assessing for risk have been carefully tested for developmental neurotoxicity (DNT). To speed up testing efforts, as well as to reduce the use of vertebrate animals, great effort is being devoted to alternate laboratory models for testing DNT. A major mechanism of DNT is altered neuronal architecture resulting from chemical exposure during neurodevelopment.

An engineered prodrug selectively suppresses β-lactam resistant bacteria in a mixed microbial setting.

The rise of β-lactam resistance necessitates new strategies to combat bacterial infections. We purposefully engineered the β-lactam prodrug AcephPT to exploit β-lactamase activity to selectively suppress resistant bacteria producing extended-spectrum-β-lactamases (ESBLs). Selective targeting of resistant bacteria requires avoiding interaction with penicillin-binding proteins, the conventional targets of β-lactam antibiotics, while maintaining recognition by ESBLs to activate AcephPT only in resistant cells.

Discovery of Potent, Orally Bioavailable Sphingosine-1-Phosphate Transporter (Spns2) Inhibitors.

Targeting the S1P pathway has resulted in the development of S1P1 receptor modulators for the treatment of multiple sclerosis and ulcerative colitis. We hypothesize that targeting an upstream node of the S1P pathway may provide an improved adverse event profile. In this report, we performed a structure-activity relationship study focusing on the benzoxazole scaffold in , which lead to the discovery of () as a potent inhibitor of S1P release from HeLa cells (IC: 51 ± 3 nM).

Resistance of mitochondrial DNA to cadmium and Aflatoxin B1 damage-induced germline mutation accumulation in C. elegans.

Mitochondrial DNA (mtDNA) is prone to mutation in aging and over evolutionary time, yet the processes that regulate the accumulation of de novo mtDNA mutations and modulate mtDNA heteroplasmy are not fully elucidated. Mitochondria lack certain DNA repair processes, which could contribute to polymerase error-induced mutations and increase susceptibility to chemical-induced mtDNA mutagenesis. We conducted error-corrected, ultra-sensitive Duplex Sequencing to investigate the effects of two known nuclear genome mutagens, cadmium and Aflatoxin B1, on germline mtDNA mutagenesis in Caenorhabditis elegans.

Toward the Elimination of Colorectal Cancer Disparities Among African Americans.

Background: In the USA, race and socioeconomic status are well-known factors associated with colorectal cancer incidence and mortality rates. These are higher among blacks than whites and other racial/ethnic groups.

Methods: In this article, we review opportunities to address disparities in colorectal cancer incidence, mortality, and survivorship among African Americans.

Identification of early interactions between Francisella and the host.

The adaptive immune response to Francisella tularensis is dependent on the route of inoculation. Intradermal inoculation with the F. tularensis live vaccine strain (LVS) results in a robust Th1 response in the lungs, whereas intranasal inoculation produces fewer Th1 cells and instead many Th17 cells.

Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity.

The extracellular matrix (ECM) plays an important role in the maintenance of white adipose tissue (WAT) architecture and function, and proper ECM remodeling is critical to support WAT malleability to accommodate changes in energy storage needs. Obesity and adipocyte hypertrophy place a strain on the ECM remodeling machinery, which may promote disordered ECM and altered tissue integrity and could promote proinflammatory and cell stress signals. To explore these questions, new methods were developed to quantify omental and subcutaneous WAT tensile strength and WAT collagen content by three-dimensional confocal imaging, using collagen VI knockout mice as a methods validation tool.

An alternative to the balance error scoring system: using a low-cost balance board to improve the validity/reliability of sports-related concussion balance testing.

Objective: Recent guidelines advocate sports medicine professionals to use balance tests to assess sensorimotor status in the management of concussions. The present study sought to determine whether a low-cost balance board could provide a valid, reliable, and objective means of performing this balance testing.

Design: Criterion validity testing relative to a gold standard and 7 day test-retest reliability.

Vagus nerve stimulation: 2-year outcomes for bipolar versus unipolar treatment-resistant depression.

Background: The outcome of vagus nerve stimulation (VNS) for patients with bipolar treatment-resistant depression (TRD) has not been well characterized. This study describes the outcome of VNS for bipolar TRD patients participating in the acute and longitudinal pivotal trials and compares their outcome with unipolar TRD patients in the same trials.

Methods: Of 235 participants enrolled in the acute study, 25 (11%) were diagnosed with DSM-IV bipolar I or II disorder.

Treating chronic migraine headaches: an evidence-based practice approach.

Psychologists and other mental health care professionals are generally trained to incorporate empirical evidence into clinical practice, but few have been taught formal techniques for doing so. Given the rapidity of progress in the clinical sciences, there is a growing need among practitioners to access current, clinically relevant research and have strategies for integrating these research findings into the clinic. In the field of medicine, evidence-based medicine took hold in the early 1990s to provide a framework and skill set for translating research into practice.

A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder.

Background: Obsessive-compulsive disorder (OCD) is a chronic illness associated with substantial morbidity; it often requires long-term medication. The best-studied therapeutic agent in the treatment of this disorder is the tricyclic antidepressant clomipramine. Since other tricyclic antidepressants appear to lack efficacy in OCD, that of clomipramine has been linked to its potent effects on serotonin.

Problem in tracheostomy patient care: recognizing the patient with a displaced tracheostomy tube.

There are times when a tracheostomy tube slips out of the trachea. A displaced tracheostomy tube can occur in any patient but is frequently seen in the patient with a full neck. In the overweight patient or patient with a full neck, the tracheostomy tube must pass through a greater amount of soft tissue.

A placebo-controlled evaluation of the effects of buspirone on smoking cessation: differences between high- and low-anxiety smokers.

One hundred one smokers were divided into high and low trait anxiety groups on the basis of a normalized score on the Profile of Mood States Anxiety/Tension Scale and were randomly assigned to receive buspirone or placebo in a double-blind fashion. After a 1-week baseline, smokers were exposed to an 8-week drug and behavioral intervention involving buspirone or placebo (up to 60 mg/day) with concurrent group cognitive behavioral intervention. All smokers were to quit smoking on the target date, set at 4 weeks after the program began.

The effects of smoking schedules on cessation outcome: can we improve on common methods of gradual and abrupt nicotine withdrawal?

This study compared the efficacy of 2 traditional methods of smoking cessation, gradual reduction and "cold turkey," with a new approach involving variation in the intercigarette interval. One hundred twenty-eight participants quit smoking on a target date, after a 3-week period of (a) scheduled reduced smoking (progressive increase in the intercigarette interval), (b) nonscheduled reduced smoking (gradual reduction, no specific change in the intercigarette interval), (c) scheduled nonreduced smoking (fixed intercigarette interval, no reductions in frequency), or (c) nonscheduled nonreduced smoking (no change in intercigarette interval or smoking frequency). Participants also received cognitive-behavioral relapse prevention training.

Quantitation of mycobacteria in blood specimens from patients with AIDS.

Objective: To determine the effect of a delay in processing blood specimens, that may occur by mailing them to a specialized laboratory, on the quantitation of the number of mycobacteria.

Design: Simulated blood specimens in sodium polyanetholium sulfonate (SPS)-containing vacutainers were spiked with Mycobacterium avium, and stored for 4 days after addition of clarithromycin or rifabutin, or remained drug-free. Daily samples were lysed with sodium desoxycholate, and inoculated onto 7H11 agar plates for the subsequent colony-forming units (CFU)/ml count.

Rapid high-performance liquid chromatographic method for the determination of ketamine and its metabolite dehydronorketamine in equine serum.

A simple, rapid and sensitive high-performance liquid chromatographic procedure has been developed for the determination of ketamine and dehydronorketamine in equine serum. Sample preparation consisted of mixing equal volumes of serum and acetonitrile-phosphoric acid (85%)-water (20:2:78, v/v/v), followed by ultrafiltration through a 10,000 molecular mass cut-off filter. Separation of these two analytes in the ultrafiltrate was accomplished on a reversed-phase phenyl column eluted with methanol-acetonitrile-phosphate buffer solution.

Determination of ceftazidime in dolphin serum by liquid chromatography with ultraviolet-visible detection and confirmation by thermospray liquid chromatography-mass spectrometry.

A simple and sensitive liquid chromatographic method has been developed for the determination of therapeutic levels of ceftazidime in dolphin serum. The method involved an ultrafiltration of diluted serum with an equal amount of acetonitrile-ethanol-water (40:40:20, v/v/v) through a 10,000 daltons molecular mass cut-off filter. Separation of ceftazidime from the other serum components was performed by ion-paired (dodecanesulfonate) liquid chromatography using a reversed-phase column eluted with acetonitrile-water solution.

Pathologic and immunologic alterations in early stages of beryllium disease. Re-examination of disease definition and natural history.

Beryllium lung disease is a chronic granulomatous disorder in which a beryllium-specific immune response plays a central role. By using a measure of cellular immune response to beryllium salts, bronchoalveolar lavage (BAL), and lung biopsy, we have identified 12 new cases of beryllium disease. Each of these individuals had pathologic changes on biopsy, lymphocytic alveolitis on BAL, and positive BAL lymphocyte transformation tests (LTT) in response to beryllium sulfate.

Activation of luteinizing hormone release from pituitary cells by polycations.

In the present work we examined the effect of cationic polymers on the pituitary gonadotrope. Such polymers are widely used to anchor gonadotropes and other cell types to culture dishes and other substrata to which they are not normally adherent. Homopolymers of Lys (eight size classes from 4,000-700,000 daltons) stimulate Ca+2-dependent LH release from pituitary cell cultures.