Influenza vaccine effectiveness in healthy 6- to 21-month-old children during the 2003-2004 season.

Objective: To assess the clinical effectiveness of influenza vaccine in preventing influenza-like illness (ILI) office visits.

Study Design: We analyzed billing and immunization registry data for healthy 6- to 21-month-olds from 5 Denver, Colorado pediatric practices (n = 5193). ILI and pneumonia/influenza (a subset of ILI) were defined from International Classification of Diseases, Ninth Revision, Clinical Modification codes for office visits occurring during peak influenza season.

Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice.

LKB1 has been identified as a component of the major upstream kinase of AMP-activated protein kinase (AMPK) in skeletal muscle. To investigate the roles of LKB1 in skeletal muscle, we used muscle-specific LKB1 knockout (MLKB1KO) mice that exhibit low expression of LKB1 in heart and skeletal muscle, but not in other tissues. The importance of LKB1 in muscle physiology was demonstrated by the observation that electrical stimulation of the muscle in situ increased AMPK phosphorylation and activity in the wild-type (WT) but not in the muscle-specific LKB1KO mice.

Wnt/PCP signaling: a veritable polar star in establishing patterns of polarity in embryonic tissues.

Embryonic patterning has traditionally been viewed as the establishment of spatially significant gene expression in response to secreted signals. Recent work has highlighted the role of the Wnt/planar cell polarity (PCP) pathway in patterning tissues. Rather than establishing characteristic arrays of gene expression, however, this pathway functions to institute uniform polarity of cells within a tissue.

Presence of endocrine and exocrine markers in EGFP-positive cells from the developing pancreas of a nestin/EGFP mouse.

In order to purify and characterize nestin-positive cells in the developing pancreas a transgenic mouse was generated, in which the enhanced green fluorescent protein (EGFP) was driven by the nestin second intronic enhancer and upstream promoter. In keeping with previous studies on the distribution of nestin, EGFP was expressed in the developing embryo in neurones in the brain, eye, spinal cord, tail bud and glial cells in the small intestine. In the pancreas there was no detectable EGFP at embryonic day 11.

Influenza among healthy young children: changes in parental attitudes and predictors of immunization during the 2003 to 2004 influenza season.

Background: In Colorado, the 2003 to 2004 influenza season was unusually early and severe and received substantial media attention.

Objectives: Among parents of healthy young children, to determine how parental knowledge and attitudes regarding influenza infection and immunization changed during the 2003 to 2004 influenza season and to identify factors predictive of influenza immunization.

Methods: The study was conducted in 5 metropolitan Denver pediatric practices.

Transcription factor cycling on the insulin promoter.

Using MIN6 beta-cells and chromatin immunoprecipitation (ChIP) assays, the chronological sequence of binding of MafA, E47/beta2 and PDX-1 to the insulin promoter in living beta-cells were investigated. All four factors were shown to bind to the mouse insulin 2 promoter in a cyclical manner with a periodicity of approximately 10-15 min. The cyclical binding of MafA, E47 and beta2 was largely unaffected by the glucose or insulin concentration in the media.

An ES cell system for rapid, spatial and temporal analysis of gene function in vitro and in vivo.

We describe a versatile genetic system for rapid analysis of mammalian gene function. In this, loss of reporter activity in a novel embryonic stem (ES) cell line enables rapid identification of targeting to the ubiquitously expressed Rosa26 locus. Subsequent regulation of gene activity is governed by a dual regulatory strategy utilizing two drugs, Tamoxifen and Doxycycline.

Missed opportunities for influenza vaccination in children with chronic medical conditions.

Objectives: To assess the frequency and characteristics of missed opportunities for influenza immunization in children with chronic medical conditions and, among unimmunized children in that group, to explore parent-reported reasons for not vaccinating their child.

Design: Prospective cohort study. Data were obtained from billing and immunization registry databases and telephone interviews of parents.

Varying constants.

We review properties of theories for the variation of gravitation and fine structure 'constants'. We highlight some general features of the cosmological models that exist in these theories with reference to recent quasar data that are consistent with time variation in the fine structure constant since a redshift of 3.5.

Provider adoption of pneumococcal conjugate vaccine and the impact of vaccine shortages.

Objectives: To 1) determine the factors associated with provider acceptance of pneumococcal conjugate vaccine and 2) describe how providers prioritize pneumococcal conjugate vaccine during shortages.

Design/methods: During April-November 2002, we conducted a mailed survey of rural and urban Colorado practitioners who provided routine pediatric immunizations. Three groups were surveyed: 1) all immunization providers (n = 51) in 2 geographically large rural areas, identified through a regional immunization registry; 2) all providers (n = 61) from private pediatric practices in metropolitan Denver that were actively participating in the same registry; and 3) all family physicians (n = 244) from the same urban areas as the pediatric practices.

Relative contribution of PDX-1, MafA and E47/beta2 to the regulation of the human insulin promoter.

The insulin promoter binds a number of tissue-specific and ubiquitous transcription factors. Of these, the homoeodomain protein PDX-1 (pancreatic duodenal homeobox factor-1), the basic leucine zipper protein MafA and the basic helix-loop-helix heterodimer E47/BETA2 (beta-cell E box transactivator 2; referred to here as beta2) bind to important regulatory sites. Previous studies have shown that PDX-1 can interact synergistically with E47 and beta2 to activate the rat insulin 1 promoter.

Changes in access, utilization, and quality of care after enrollment into a state child health insurance plan.

Background: There currently are few published data evaluating the effect of State Children's Health Insurance Programs on health care outcome measures in children. Colorado's Child Health Plan Plus (CHP+) is a non-Medicaid State Children's Health Insurance Program that began enrollment in April 1998. The objectives of this study were to compare reported (1) access to care, (2) utilization of health care, and (3) quality of care during the year before and the first year after enrollment into CHP+.

Implementation of universal influenza immunization recommendations for healthy young children: results of a randomized, controlled trial with registry-based recall.

Background: An Advisory Committee on Immunization Practices policy of encouraging influenza vaccination for healthy 6- to 23-month-old children was in effect during the 2003-2004 influenza season, which was unusually severe in Colorado. We collaborated with 5 pediatric practices to attempt universal influenza immunization in this age group.

Objectives: The objectives were (1) to assess the maximal influenza immunization rates that could be achieved for healthy young children in private practice settings, (2) to evaluate the efficacy of registry-based reminder/recall for influenza vaccination, and (3) to describe methods used by private practices to implement the recommendations.

Purification and Characterization of a Population of EGFP-Expressing Cells from the Developing Pancreas of a Neurogenin3/EGFP Transgenic Mouse.

Neurogenin 3 (ngn3) is a basic helix loop helix transcription factor that is transiently expressed in the developing mouse pancreas with peak expression around E15. In mice lacking the ngn3 gene the endocrine cells of the pancreas fail to develop suggesting that the ngn3-positive cell may represent a progenitor cell for the endocrine pancreas. In order to purify and characterize this cell in detail we have generated a transgenic mouse, in which the ngn3 promoter drives expression of enhanced green fluorescent protein (EGFP).

Non-peptidic small-molecule antagonists of the human platelet thrombin receptor PAR-1.

The thrombin receptor on human platelets is the first member identified of a new family of G-protein coupled receptors referred to as protease activated receptors (PARs). These receptors are activated by a unique mechanism involving proteolytic cleavage of a portion of the extracellular domain to generate a new N-terminus which then acts as a tethered or intramolecular ligand (agonist) for the receptor. The hexapeptide SFLLRN-NH2 comprising the new N-terminus is referred to as the Thrombin Receptor Activating Peptide, or "TRAP" Thrombin is the most potent agonist for platelet aggregation and selective blockade of the intramolecular activation step without effecting the proteolytic activity of thrombin should result in moderation of platelet activation and aggregation without interfering with the other coagulation cascade effects of thrombin.

Transition of care: health care professionals' view.

There is much anxiety regarding the transfer of adolescents with chronic illness to adult services. Transfer of patients can be haphazard if the transition has not been planned. Problems and obstacles to transition have been identified and discussed by various authors.

Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors.

In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P(1) region. Various benzylamines were coupled to a pyridine/pyrazinone P(2)-P(3) template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K(i) of 0.

Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P(1)(') group.

Structural modifications of the aminopyridine P(1)(') group of imidazole acetic acid based TAFIa inhibitors led to the discovery of the aminocyclopentyl analog 28, a 1 nM TAFIa inhibitor with CLT(50) functional activity of 14 nM but without selectivity against CPB. While not as active, aminobutyl derivative 27 provided an improved 6.7-fold selectivity for TAFIa versus CPB.

Disenrollment from a state child health insurance plan: are families jumping S(c)HIP?

Background: Colorado's Child Health Plan Plus (CHP+) is a non-Medicaid state child health plan that began enrollment in April 1998. Families are disenrolled 12 months after enrollment if they fail to re-enroll.

Objective: To assess insurance coverage before and 1 year after initial enrollment in CHP+; reasons for disenrollment; and factors associated with re-enrollment.

Identification and recall of children with chronic medical conditions for influenza vaccination.

Objectives: Despite long-standing recommendations to provide annual influenza vaccination to children with chronic medical conditions, immunization rates are <10% in most primary care settings. Many obstacles impede implementation of these recommendations, including the challenge of identifying targeted children and the need to immunize yearly in a short time interval. The objective of this study was to assess the accuracy of billing data for identifying children who have high-risk conditions (HRCs) and need influenza vaccination and 2) to evaluate the efficacy of reminder/recall for children with HRCs.

Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis, and inhibitors of this enzyme have potential use in antithrombotic and thrombolytic therapy. Appropriately substituted imidazole acetic acids such as 10j were found to be potent inhibitors of activated TAFI and selective versus the related carboxypeptidases CPA, CPN, and CPM but not CPB. Further, 10j accelerated clot lysis in vitro and was shown to be efficacious in a primate model of thrombosis.

Atypical morphology of dark septate fungal root endophytes of Bouteloua in arid southwestern USA rangelands.

Native grasses of semi-arid rangelands of the southwestern USA are more extensively colonized by dark septate endophytes (DSE) than by traditional mycorrhizal fungi. Roots of dominant grasses ( Bouteloua sp.) native to arid southwestern USA rangelands were prepared and stained using stains specific for fungi (trypan blue) and for lipids (sudan IV).

Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position.

Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the alpha-thrombin-hirugen complex provides an explanation for these unanticipated results.