Tobacco control policies and the concurrent use of smokeless tobacco and cigarettes among men, 1992-2002.

Accelerating the decline in smoking prevalence requires an understanding of changes in the concurrent use of and the substitution between different tobacco products, such as smokeless tobacco (SLT) and cigarettes. SLT could play an important role in reducing the toll of smoking-related illness and premature mortality. Research examining the role of tobacco control policies in explaining concurrent use of SLT and cigarettes has been minimal. Using the Current Population Survey Tobacco Use Supplements (CPS-TUS), we examined tobacco control policies in relationship with adult males' SLT use concurrent with smoking over the period 1992-2002. Consistent with the decline in smokeless-only and cigarette-only rates, concurrent use of SLT and cigarettes declined during the period. SLT users, faced with home or workplace smoking bans, are less likely to report smoking. Smokers with a home ban appear more likely to use SLT, but in more recent years, smokers with a workplace ban are less likely to use SLT. Tobacco excise taxes do not signal substitution between cigarettes and SLT products. Understanding current use patterns of the range of tobacco products, including their interaction with available policy levers, is vital in assessing whether changes that might promote substitution of arguably less toxic SLT products for highly toxic cigarettes are likely to lead to net public health gains or losses. Findings of the present study, in concert with other research about transitional probabilities between behavioral states, will inform the design of an effective policy framework that supports the objective of reducing tobacco-related death and disease.     

Isoflavones, soy-based infant formulas, and relevance to endocrine function

For more than 60 years, soy-based infant formulas have been fed to millions of infants worldwide and studied in controlled clinical research. These products provide essential nutrients required for normal growth and development. The safety of isoflavones in soy-based products, including infant formulas, has been questioned recently owing to reports of possible endocrine effects in animals and in cultured cells. The literature offers no evidence of endocrine effects in humans from infant consumption of modern soy-based formulas. Growth is normal and no changes in the timing of puberty or in fertility rates have been reported in humans who consumed soy formulas as infants. Consequently, soy-based infant formulas continue to be a safe, nutritionally complete feeding option for most infants.     

Use of an ultrasensitive recombinant cell bioassay to determine estrogen levels in girls with precocious puberty treated with a luteinizing hormone-releasing hormone agonist

Although treatment of girls with precocious puberty should ideally restore estradiol levels to the normal prepubertal range, treatment effectiveness has usually been monitored by gonadotropin levels because estradiol RIAs have lacked sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a recently developed ultrasensitive recombinant cell bioassay for estradiol would have sufficient sensitivity to demonstrate a dose-dependent suppression of estradiol during LH-releasing hormone agonist treatment and to determine whether currently used doses are able to suppress estradiol levels to the normal prepubertal range. Twenty girls with central precocious puberty were assigned randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 micrograms/ kg.day. A significant dose-response relationship was observed, with mean +/- SD estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the doses of 1, 2, and 4 micrograms/kg.day, respectively (P < 0.01). The highest dose suppressed estradiol levels to just above the 95% confidence limits for normal prepubertal girls (< 0.07-6.3 pmol/L). We conclude that the ultrasensitive bioassay for estradiol has sufficient sensitivity for monitoring the response to LH-releasing hormone agonist treatment of central precocious puberty. Additionally, the observation that the deslorelin dose of 4 micrograms/kg.day did not fully restore estradiol levels to the normal prepubertal range suggests that some girls with precocious puberty may require higher doses to receive the maximal benefit of treatment. We suggest that restoration of estradiol levels to the normal prepubertal range should be the ultimate biochemical measure of efficacy, as estradiol is the key hormone that accelerates growth rate, bone maturation rate, and breast development in girls with precocious puberty.     

High-resolution computed tomography in patients with bronchial asthma: correlation with clinical features, pulmonary functions and bronchial hyperresponsiveness

Phosphopeptides are a useful tool for the investigation of phosphorylation as a reversible posttranslational modification. There is a growing interest in using mimics of phosphoamino acids involved in phosphorylation in order to study the enzymes concerned in these processes. These mimics should contain a non-hydrolysable or isoelectrically modified phosphate moiety to be used as a specific inhibitor of phosphatases and kinases. We introduce sold-phase synthesis of H- and methylphosphonopeptides as a new class of mimics of phosphotyrosyl peptides. The peptides were synthesized on solid phase using the standard fluorenyl-methyloxycarbonyl (Fmoc) strategy. Tyrosine residues were incorporated as allyl-protected derivatives, which were selectively deprotected on the resin by treatment with Pd(PPh3)4. The peptide resin carrying the side-chain unprotected tyrosine of the model peptide Gly-Gly-Tyr-Ala was phosphonylated with di-tert-butyl-N,N-diethyl-phosphoramidite in the presence of 1H-tetrazole, yielding H-phosphonopeptides after trifluoroacetic acid (TFA) cleavage. Alternatively, phosphonylation of the unprotected tyrosine with O-tert-butyl-N,N-diethyl-P-methylphosphonamidite catalysed by 1H-tetrazole and followed by oxidation led to the methyphosphonopeptides after TFA cleavage. We obtained both the H-phosphonopeptides and the methylphosphonopeptides of the tetrapeptide in high yields and purities above 90%, according to reversed-phase high-performance liquid chromatography (RP-HPLC). To investigate the general applicability of our new methodology, we synthesized phosphonopeptides up to 13 amino acids long, corresponding to recognition sequences of tyrosine kinases. After cleavage and deprotection, all phosphonopeptides were obtained in high yields and purities of about 90%, as shown by mass spectrometry. The only by-product found was the unmodified peptide.     

Fluorescence microscopic observation of catalysis by single or few LDH-1 enzyme molecules

Lactate dehydrogenase (LDH-1) catalyzes the reaction of lactate and nonfluorescent NAD+ to pyruvate, NADH (fluorescence at lambda em = 455 nm, lambda em = 365 nm) and H+. The injection of highly diluted LDH-1 solution into a drop of substrate solution results in the formation of a bubble of enzyme inside the drop of substrate. At the contact surface between the enzyme solution and the substrate, discrete and statistically distributed zones of increasing fluorescence intensity and different size can be observed after enzyme injection. These zones can be interpreted as clouds of NADH around a single or a few enzyme molecules. The kinetics of the NADH formation in every fluorescent zone, and the size of the zone, can be described by a zero order production combined with a diffusion controlled loss of the reaction's product NADH from the reaction zone. From the dilution of the enzyme solution and from statistical analysis one can conclude that only few enzyme molecules in the center of the fluorescent reaction zones catalyze the NADH formation.     

The impact wedge-peel performance of structural adhesives

The impact wedge-peel (IWP) test is an International Standard (ISO 11343) method that is employed to measure the resistance to cleavage fracture of structural adhesives at a relatively high test-rate of 2 to 3 m/s. In the present work this test has been employed to evaluate the performance of a range of structural adhesives when used to bond either steel or aluminium-alloy substrates. Firstly, a novel test arrangement for performing these tests, using a high-speed servohydraulic machine, is described. Tests were performed at 10^–4 and 2 m/s and at test temperatures of –40 and 23°C. High-speed photography was also used to investigate the failure of the IWP test specimens. Both stable and unstable types of crack growth were recorded, with the crack propagating cohesively through the adhesive layer in all cases. The methods of data analysis recommended by the International Standard are critically reviewed, and some shortcomings are highlighted. Secondly, the results from the IWP test are then directly correlated to the measured values of the adhesive fracture energies, G_c, of the adhesives, which were determined using a fracture-mechanics approach. Finally, it is demonstrated that, from knowledge of the value of G_c of the adhesive, coupled with a finite-element analysis of the IWP test geometry, the failure behaviour of the IWP specimen may be successfully modelled and predicted.     

Fringe is essential for mirror symmetry and morphogenesis in the Drosophila eye

An early event in Drosophila eye development is the division of the eye disc into dorsoventral domains. The dorsoventral pattern is displayed in the adult compound eye as a distinct mirror symmetry across the dorsoventral midline or equator. The dorsoventral axis is also implicated in organizing early development of the eye, as retinal differentiation is initiated at the posterior dorsoventral midline. Here we show that Fringe is expressed specifically in the ventral half of the undifferentiated eye disc, thus creating a dorsoventral boundary. Ectopic Fringe borders that are generated by clones of fringe cells can reverse the planar polarity of photoreceptor clusters, indicating that the Fringe boundary is crucial for the induction of mirror symmetry. Lack of a Fringe boundary disrupts equatorial expression of Notch signalling proteins and causes a complete failure of eye development. Our results indicate that the formation of the Fringe boundary and subsequent Notch signalling at the equator are essential for organizing mirror symmetry and eye morphogenesis.     

Regional and distant metastases in laryngeal and hypopharyngeal sarcomas

OBJECTIVE: To determine risk of failure of the Synthes 4.5-mm cannulated screw system instrumentation in equine bone and to compare its application with the Synthes 4.5-mm standard cortex screw system. STUDY DESIGN: The maximum insertion torque of the cannulated and standard cortex screw systems were compared with the ultimate torsional strengths of the equipment. Pullout strength and ultimate tensile load of cannulated and standard cortex screws were also determined. SAMPLE POPULATION: Paired equine cadaver third metacarpal and third carpal bones. METHODS: Maximum insertion torque and ultimate torsional strengths were determined by using an axial-torsional, servohydraulic materials testing system and a hand-held torquometer. Pullout tests were performed by using a servohydraulic materials testing system. RESULTS: Maximum insertion torque of all cannulated instrumentation was less than ultimate torsional strength at all locations (P < .05). Maximum insertion torques of cannulated taps and screws were greater than for standard taps and screws in the third carpal bone (P < .002). Pullout strength of the cannulated screws was less than the standard cortex screws at all sites (P < .001). Cannulated screws broke before bone failure in all but one bone specimen. CONCLUSIONS: The risk of cannulated instrument or screw failure during insertion into bone is theoretically low. The relatively low pullout strength of the cannulated screws implies that the interfragmentary compression achievable is likely to be less than with standard cortex screws. CLINICAL RELEVANCE: The relatively low pullout strength of the cannulated screw suggests that its risk of failure during fracture repair is greater than with the standard cortex screw.