Efficient conversion of Biginelli 3,4-dihydropyrimidin-2(1H)-one to pyrimidines via PyBroP-mediated coupling.

An efficient two-step procedure is described to convert the Biginelli 3,4-dihydropyrimidin-2(1H)-one to various multifunctionalized pyrimidines via the Kappe dehydrogenation and a new mild PyBroP-mediated coupling with C, N, O, and S nucleophiles, which provides a readily accessible multifunctionalized pyrimidine template for diversity-oriented synthesis.

The effect of percutaneous pin fixation of the interphalangeal joint on the thumb-tip force produced by the flexor pollicis longus: a cadaver study.

Purpose: Interphalangeal joint stabilization often is performed concomitantly with tendon transfers that restore key pinch (lateral pinch) to the paralyzed thumb. The goal of this study was to measure the effect of interphalangeal joint stabilization via percutaneous pin fixation on the thumb-tip force produced by the flexor pollicis longus (FPL).

Methods: We applied 10 N of force to the tendon of the FPL in 7 cadaveric specimens and measured the resulting thumb-tip force in the intact thumb and after stabilization of the interphalangeal joint.

Fabrication of large-area ferromagnetic arrays using etched nanosphere lithography.

Nanosphere lithography (NSL) is a simple, cost-effective, and powerful technique capable of producing large-area arrays of ferromagnetic nanostructures with dimensions below 100 nm. These properties make NSL an attractive process for the fabrication of arrays of magnetic elements with applications in magnetic data storage. The main disadvantage with conventional NSL is that the monolayer of spheres always contains imperfections that are transferred to the resulting nanostructures.

Identification of key pinch forces required to complete functional tasks.

Reconstructive hand surgeries restore key pinch to individuals with pinch force deficits caused by tetraplegia. Data that define the magnitudes of force necessary to complete functional key pinch tasks are limited. This study aims to establish target pinch forces for completing selected tasks that represent a range of useful functional activities.

Raccoon roundworm encephalitis.

The raccoon roundworm, Baylisascaris procyonis, is increasingly recognized as a cause of zoonotic visceral, ocular, and neural larva migrans and, in particular, of devastating encephalitis in young children. Exposure occurs mainly at raccoon latrines, where large numbers of infective eggs may be accidentally ingested. Risk factors for infection include contact with raccoon latrines, pica/geophagia, age of <4 years, and male sex.

Diagnostic application of Epstein-Barr virus-encoded RNA in situ hybridisation.

Aims: Epstein-Barr virus (EBV) has been implicated in the pathogenesis of nasopharyngeal carcinoma and a range of proliferative lymphoid conditions. In situ hybridisation (ISH) looking for virus-encoded RNA (EBER) transcripts is performed simply using a commercially available probe. We aimed to examine the application of this test in a routine diagnostic setting.

Serial mechanisms in lexical access: the rank hypothesis.

There is general agreement that the effect of frequency on lexical access time is roughly logarithmic, although little attention has been given to the reason for this. The authors argue that models of lexical access that incorporate a frequency-ordered serial comparison or verification procedure provide an account of this effect and predict that the underlying function directly relates access time to the rank order of words in a frequency-ordered set. For both group data and individual data, it is shown that rank provides a better fit to the data than does a function based on log frequency.

Interesting behavior of alpha,beta-unsaturated oximes in intramolecular [4 + 2] cycloaddition reactions.

[structure: see text] Intramolecular [4 + 2] cycloaddition using alpha,beta-unsaturated oximes was explored. The reactions proceeded under unusually facile conditions to furnish the nitrones. The latter were subsequently reacted with DMAD to afford [3 + 2] cycloaddition products.

Design, synthesis, and biological evaluation of novel 7-azaindolyl-heteroaryl-maleimides as potent and selective glycogen synthase kinase-3beta (GSK-3beta) inhibitors.

Two approaches were developed to synthesize the novel 7-azaindolyl-heteroarylmaleimides. The first approach was based upon the palladium-catalyzed Suzuki cross-coupling or Stille cross-coupling of 2-chloro-maleimide 5 with various arylboronic acids or arylstannanes. The second approach was based upon the condensation of ethyl 7-azaindolyl-3-glyoxylate 12 with various acetamides.

Synthesis and evaluation of nonpeptide substituted spirobenzazepines as potent vasopressin antagonists.

A series of substituted spirobenzazepines was prepared and evaluated as V(1a) and V(2) dual vasopressin receptor antagonists. Compounds 7p and 7q have been shown to be not only potent inhibitors of vasopressin receptors, but also have exhibited an excellent overall pharmaceutical suitability profile.

Synthesis and evaluation of spirobenzazepines as potent vasopressin receptor antagonists.

A novel series of spirobenzazepines was synthesized and evaluated for V1a and V2 receptor antagonist activity. Compounds 8b, 8i, and 8k have shown selective V1a receptor antagonist activity. Compounds 8p and 8q were shown to be dual V1a/V2 receptor antagonists.

Surface plasmon polaritons and their role in the enhanced transmission of light through periodic arrays of subwavelength holes in a metal film.

We present results of the transmitted, reflected, and absorbed power associated with the enhanced transmittance of light through a silver film pierced by a periodic array of subwavelength holes. Comparing experimentally acquired dispersion curves under different polarization conditions shows that the transmission features of the array are consistent with p-polarized resonant modes of the structure. By exploring the regime in which no propagating diffracted orders are allowed, we further show that the transmittance maxima are associated with both reflectance minima and absorption maxima.

Novel non-peptidic neuropeptide Y Y2 receptor antagonists.

Through SAR studies of a piperidinylindoline cinnamide HTS lead, the first potent, non-peptide, low molecular weight selective Neuropeptide Y Y2 (NPY Y2) antagonists have been synthesized. The SAR studies around the piperidinyl, the indolinyl, and the cinnamyl moieties are discussed.

Synthesis and biological evaluation of novel macrocyclic bis-7-azaindolylmaleimides as potent and highly selective glycogen synthase kinase-3 beta (GSK-3 beta) inhibitors.

Palladium catalyzed cross-coupling reactions were used to synthesize two key intermediates 3 and 5 that resulted in the synthesis of novel series of macrocyclic bis-7-azaindolylmaleimides. Among the three series of macrocycles, the oxygen atom and thiophene containing linkers yielded molecules with higher inhibitory potency at GSK-3 beta (K(i)=0.011-0.

Raccoon roundworm eggs near homes and risk for larva migrans disease, California communities.

The raccoon roundworm, Baylisascaris procyonis, is increasingly recognized as a cause of serious or fatal larva migrans disease in humans and animals. We assessed the potential for infection in three northern California communities by determining the density and distribution of raccoon latrines, where transmission primarily occurs, and the prevalence of eggs at private residences. We collected fecal samples from 215 latrines and found that 44%-53% of the latrines contained B.

Biomechanics of the Steindler flexorplasty surgery: a computer simulation study.

Purpose: Our goal was to investigate the capacity of a Steindler flexorplasty to restore elbow flexion to persons with C5-C6 brachial plexus palsy. In this procedure the origin of the flexor-pronator mass is moved proximally onto the humeral shaft. We examined how the choice of the proximal attachment site for the flexor-pronator mass affects elbow flexion restoration, especially considering possible side effects including limited wrist and forearm motion owing to passive restraint from stretched muscles.

Analysis of 153 deaths after upper gastrointestinal endoscopy: room for improvement?

Background: Upper gastrointestinal (GI) endoscopy is a widely used procedure that is generally considered to be safe.

Methods: Of a total of 33,854 patients who underwent upper gastrointestinal endoscopy during 1999 under the care of surgeons in Scotland, 153 (0.004%) died.

2,5-disubstituted 3,4-dihydro-2H-benzo[b][1,4]thiazepines as potent and selective V2 arginine vasopressin receptor antagonists.

A number of 2,5-disubstituted benzothiazepines were synthesized and screened for their ability to inhibit arginine vasopressin binding to the human V(2) and V(1a) receptor subtypes. The more active compounds were subsequently analyzed for their antagonist activity in in vitro functional assays. The SAR showed a preference for an acidic unit appended from the benzothiazepine scaffold.

Synthesis and discovery of macrocyclic polyoxygenated bis-7-azaindolylmaleimides as a novel series of potent and highly selective glycogen synthase kinase-3beta inhibitors.

Attempts to design the macrocyclic maleimides as selective protein kinase C gamma inhibitors led to the unexpected discovery of a novel series of potent and highly selective glycogen synthase kinase-3beta (GSK-3beta) inhibitors. Palladium-catalyzed cross-coupling reactions were used to synthesize the key intermediates 17 and 22 that resulted in the synthesis of novel macrocycles. All three macrocyclic series (bisindolyl-, mixed 7-azaindoleindolyl-, and bis-7-azaindolylmaleimides) were found to have submicromolar inhibitory potency at GSK-3beta with various degrees of selectivity toward other protein kinases.

Moellerella wisconsensis isolated from the oral cavity of a wild raccoon (Procyon lotor).

This report describes the isolation of Moellerella wisconsensis from the oral secretions of a wild raccoon in Northern California. Human enteric disease has previously been associated with this organism. This represents the first isolation of this rare enterobacterial species from a non-captive animal and only the third from a non-human source.

Different patterns of regulation of Tyr-phosphorylated STAT1 and STAT3 in human hepatoma Hep3B cells by the phosphatase inhibitor orthovanadate.

The cellular physiology of signal transducer and activator of transcription protein family (STAT) transcription factors includes activation by Tyr-phosphorylation (PY) in cytokine and growth factor receptor complexes at the level of plasma membrane rafts, subsequent cytoplasmic transit and nuclear import, and transcriptional regulation of target genes, followed by dephosphorylation and export back to the cytoplasm. The ubiquitous protein tyrosine phosphatase (PTP) called "T-cell protein tyrosine phosphatase" has been reported to mediate Tyr-dephosphorylation of both interferon-gamma (IFN-gamma)-induced PY-STAT1 and interkleukin-6 (IL-6)-induced PY-STAT3 in some cell lines. To test whether the same PTP regulated both PY-STAT1 and PY-STAT3 in human hepatocytes we used orthovanadate (VO(4); 0.

Learning about new anesthetics using a model driven, full human simulator.

Objective: New pharmacological agents are introduced into medical practice at an ever-increasing pace. Teaching how to use new medications in the clinical setting presents educational challenges and puts patients at risk.

Methods: Patients and clinical settings in which remifentanil might provide clinical advantages over existing anesthetics were identified.

The unoperated hand: the role of passive forces in hand function after tetraplegia.

Passive forces play a large role in hand function after tetraplegia. Most individuals with tetraplegia choose not to undergo surgical reconstruction of hand function and, therefore, depend on the passive properties of their musculoskeletal system to perform functional tasks. Knowledge of the levels of force needed to perform many of these tasks is lacking.

The influence of elbow position on the range of motion of the wrist following transfer of the brachioradialis to the extensor carpi radialis brevis tendon.

Background: In patients who have an injury of the cervical spinal cord, the brachioradialis tendon may be transferred to the extensor carpi radialis brevis tendon to restore voluntary wrist extension. We hypothesized that the active range of motion of the wrist depends on the position of the elbow after this transfer because the brachioradialis changes length substantially during elbow flexion, which implies the maximum force that the muscle can produce varies with elbow position. The objectives of this study were to determine whether the position of the elbow influences the range of motion of the wrist following transfer of the brachioradialis to the extensor carpi radialis brevis tendon and to evaluate the effect of surgical tensioning.

Evaluation of anesthesia residents using mannequin-based simulation: a multiinstitutional study.

Background: Anesthesia simulators can generate reproducible, standardized clinical scenarios for instruction and evaluation purposes. Valid and reliable simulated scenarios and grading systems must be developed to use simulation for evaluation of anesthesia residents.

Methods: After obtaining Human Subjects approval at each of the 10 participating institutions, 99 anesthesia residents consented to be videotaped during their management of four simulated scenarios on MedSim or METI mannequin-based anesthesia simulators.