RNA tape sampling in cutaneous lupus erythematosus discriminates affected from unaffected and healthy volunteer skin.

Objective: Punch biopsy, a standard diagnostic procedure for patients with cutaneous lupus erythematosus (CLE) carries an infection risk, is invasive, uncomfortable and potentially scarring, and impedes patient recruitment in clinical trials. Non-invasive tape sampling is an alternative that could enable serial evaluation of specific lesions. This cross-sectional pilot research study evaluated the use of a non-invasive adhesive tape device to collect messenger RNA (mRNA) from the skin surface of participants with CLE and healthy volunteers (HVs) and investigated its feasibility to detect biologically meaningful differences between samples collected from participants with CLE and samples from HVs.

Advancing the Science of Healthcare Service Delivery: The NHLBI Corporate Healthcare Leaders' Panel.

There is a growing gap between available science and evidence and the ability of service providers to deliver high-quality care in a cost-effective way to the entire population. We believe that the chasm between knowledge and action is due to a lack of concerted effort among all organizations that deliver health care services across the life span of patients. Broad participation is needed and necessitates a far more explicit and concerted public-private partnership focused on large-scale transformation.

Use of External Quality Control Material for HIV-1 RNA Testing To Assess the Comparability of Data Generated in Separate Laboratories and the Stability of HIV-1 RNA in Samples after Prolonged Storage.

The National Institute of Allergy and Infectious Diseases (NIAID) AIDS Clinical Trials Group (ACTG) stores specimens from its clinical trials in a biorepository and permits the use of these specimens for nonprotocol exploratory studies, once the studies for the original protocol are concluded. We sought to assess the comparability of the data generated from real-time HIV-1 RNA testing during two clinical trials with the data generated from the retesting of different aliquots of the same samples after years of storage at -80°C. Overall, there was 92% agreement in the data generated for 1,570 paired samples (kappa statistic = 0.

Association of peripheral microvascular dysfunction and erectile dysfunction.

Purpose: Increasing evidence of a link between erectile dysfunction and cardiovascular disease suggests a shared vascular etiology with endothelial dysfunction as a plausible underlying biological mechanism. To our knowledge whether this association is different for large arterial endothelium compared to microvascular endothelium has not yet been established. We investigated the association of erectile dysfunction with macrovascular and microvascular endothelial function.

Incidence of lower urinary tract symptoms in a population-based study of men and women.

Objective: To report the incidence of lower urinary tract symptoms (LUTS) in a racially and ethnically and age-diverse U.S. population-based sample of men and women.

Intake of caffeinated, carbonated, or citrus beverage types and development of lower urinary tract symptoms in men and women.

Evidence to substantiate recommendations for restriction of caffeinated or acidic beverages as self-management for lower urinary tract symptoms (LUTS) is limited. We examined longitudinal and acute associations between beverage intake and LUTS in the Boston Area Community Health (BACH) cohort (n = 4,144) between 2002 and 2010. Multivariable models tested associations between baseline intakes and progression of LUTS at 5-year follow-up, between follow-up intakes and International Prostate Symptom Scores at follow-up, and between 5-year intake changes and LUTS progression.

IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies.

Background: The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The evidence base is lacking for most analgesic practice in SCD, particularly for the optimal opioid dosing for patient-controlled analgesia (PCA), in part because of the challenges of the trial design and conduct for this rare disease.

Impact of PCA strategies on pain intensity and functional assessment measures in adults with sickle cell disease during hospitalized vaso-occlusive episodes.

Clinical trials of sickle cell disease (SCD) pain treatment usually observe only small decrements in pain intensity during the course of hospitalization. Sub-optimal analgesic management and inadequate pain assessment methods are possible explanations for these findings. In a search for better methods for assessing inpatient SCD pain in adults, we examined several pain intensity and interference measures in both arms of a randomized controlled trial comparing two different opioid PCA therapies.

Red blood cell alloimmunization in sickle cell disease: prevalence in 2010.

Background: Transfusion of red blood cells (RBCs) is frequently required for care of individuals with sickle cell disease (SCD). Alloimmunization rates are high and may be reduced by matching for RBC antigens that can cause alloimmunization.

Study Design And Methods: During the PROACTIVE Feasibility Study, patients with SCD age 2 years or older admitted for pain without acute chest syndrome were enrolled for possible randomization to preventive blood transfusion or standard care.

Cross-platform analysis of HIV-1 RNA data generated by a multicenter assay validation study with wide geographic representation.

HIV-1 RNA quantitation continues to be extremely important for monitoring patients infected with HIV-1, and a number of assays have been utilized for this purpose. Differences in assay performance with respect to log(10) recovery and HIV-1 subtype specificity have been well documented for commercially available assays, although comparisons are usually limited to one or two assay platforms. Two new FDA-approved assays, the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test (RT) and the Abbott RealTime HIV-1 assay (AR), that utilize real-time PCR have replaced previous HIV-1 RNA platforms.

Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE).

Acute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half of ACS episodes occur in SCD patients already hospitalized, potentially permitting pre-emptive therapy in high-risk patients. Simple transfusion of red blood cells may abort ACS if given to patients hospitalized for pain who develop fever and elevated levels of secretory phospholipase A2 (sPLA2).

Inpatient management of sickle cell pain: a 'snapshot' of current practice.

The Sickle Cell Disease Clinical Research Network (SCDCRN) designed the PROACTIVE Feasibility Study (ClinicalTrials.gov NCT00951808) to determine whether elevated serum levels of secretory phospholipase A2 (sPLA2) during hospitalization for pain would permit preemptive therapy of sickle cell acute chest syndrome (ACS) by blood transfusion. While PROACTIVE was not designed to assess pain management and was terminated early due to inadequate patient accrual, collection of clinical data allowed a "snapshot" of current care by expert providers.

Application of quantitative 19F and 1H NMR for reaction monitoring and in situ yield determinations for an early stage pharmaceutical candidate.

Quantitative NMR spectrometry (qNMR) is an attractive, viable alternative to traditional chromatographic techniques. It is a fast, easy, accurate, and nondestructive technique which allows an analyst to gain quantitative information about a component mixture without the necessity of authentic reference materials, as is the case with most other analytical techniques. This is ideal for the synthesis of active pharmaceutical ingredients (API) that are in the early stages of development where authentic standards of the analytes may not be available.

Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.

Split-plot designs for robotic serial dilution assays.

This article explores effective implementation of split-plot designs in serial dilution bioassay using robots. We show that the shortest path for a robot to fill plate wells for a split-plot design is equivalent to the shortest common supersequence problem in combinatorics. We develop an algorithm for finding the shortest common supersequence, provide an R implementation, and explore the distribution of the number of steps required to implement split-plot designs for bioassay through simulation.

Total synthesis of epothilones B and D: stannane equivalents for beta-keto ester dianions.

Studies leading to a total synthesis of epothilones B and D are described. The overall synthetic plan was based on late-stage fragment assembly of two segments representing C(1)-C(9) and C(10)-C(21) of the structure. The C(1)-C(9) fragment was prepared by elaboration of commercially available (2R)-3-hydroxy-2-methylpropanoate at both ends of the three-carbon unit.

Cells in midline thalamus, central amygdala, and nucleus accumbens responding specifically to antipsychotic drugs.

Rationale: Determining brain regions in which neuroleptic drugs of different types produce similar effects, especially where these effects are not shared with drugs lacking antipsychotic efficacy, provides evidence as to how and where the clinical effects of neuroleptic drugs are mediated.

Objective: For this study, the pattern of expression of the protein Fos, a marker of cellular activation, was compared after administration of the typical neuroleptic haloperidol, the antipsychotic drug clozapine, and the atypical neuroleptic olanzapine, as well as the sedative drug diphenhydramine and the anxiolytic lorazepam.

Methods: Animals (Sprague-Dawley rats, three per cohort) received intraperitoneal injections of haloperidol (1 mg/kg), clozapine (20 mg/kg), olanzapine (5 mg/kg), diphenhydramine hydrochloride (1 mg/kg), lorazepam (5 mg/kg) or vehicle (2% lactic acid, 1 ml/kg).