Model of a miniature pig catheterized for pharmacokinetic and pharmacodynamic studies of anti-infective agents

The purpose of this study was to examine the role of sleep problems in the etiology of nursing caries. Two-hundred mothers of children (104 with nursing caries and 96 caries free) from ages 2 to 4.5 years were surveyed to determine whether difficulty with child sleep and ensuing sleep-associated feeding might be related to the presence of nursing caries. Differences were noted between these two groups regarding: average number of nights the child slept through the night (P < 0.001); total hours of sleep per night (P < 0.05); frequency of night waking episodes (P < 0.01); feeding on demand upon waking (P < 0.01); using a bottle to assist with falling asleep at night (P < 0.001); and feeding in association with nap time (P < 0.001). Differences also were noted in regard to average age of weaning (P < 0.001). Our findings suggest that sleep problems among young children are a behavioral risk factor for night-time bottle use and early childhood caries.     

Pyramid collaborative filtering technique for an intelligent autonomous guide agent

This article presents an autonomous guide agent that can observe a community of learners on the web, interpret the learners' inputs, and then assess their sharing. The goal of this agent is to find a reliable helper (tutor or other learner) to assist a learner in solving his task. Despite the growing number of Internet users, the ability to find helpers is still a challenging and important problem. Although helpers could have much useful information about courses to be taught, many learners fail to understand their presentations. For that, the agent must be able to deal autonomously with the following challenges: Do helpers have information that the learners need? Will helpers present information that learners can understand? And can we guarantee that these helpers will collaborate effectively with learners? We have developed a new filtering framework, called a pyramid collaborative filtering model, to whittle the number of helpers down to just one. We have proposed four levels for the pyramid. Moving from one level to another depends on three filtering techniques: domain model filtering, user model filtering, and credibility model filtering. A new technique is filtering according to helpers' credibilities. Our experiments show that this method greatly improves filtering effectiveness. © 2007 Wiley Periodicals, Inc. Int J Int Syst 22: 1065–1082, 2007.     

The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.     

The Calvin cycle enzyme sedoheptulose-1,7-bisphosphatase is encoded by a light-regulated gene in Chlamydomonas reinhardtii

OBJECTIVES: Current surgical treatment for a glottic cancer with significant subglottic extension is a total laryngectomy. The objective of this study was to expand laryngeal conservation procedures by using a reconstructive technique that allows for the repair of hemicricolaryngectomy defects. STUDY DESIGN: After resection of the ipsilateral thyroid, cricoid, and arytenoid for advanced T3 glottic cancer, the laryngeal defect was reconstructed by means of an autotransplanted segment of trachea in four patients. The reconstruction consisted of a transferable patch that was constructed from a segment of revascularized cervical trachea. METHODS: During a 14-day period, a 4-cm segment of cervical trachea was wrapped by a free radial forearm fascial flap. In the second stage, the glottic cancer was removed and the cervical trachea was isolated on its fascial blood supply and transformed into a patch that was used to repair the extended hemilaryngectomy defect. Two different patch designs were used. Two patients underwent reconstruction with a patch augmented at the glottic level (group A); two patients underwent reconstruction without glottic augmentation on the patch (group B). Tracheal continuity was restored by an end-to-end reanastomosis. The postreconstruction morphology of the two patch designs was compared with the preoperative laryngeal morphology. RESULTS: The autotransplantation technique led to complete restoration of the subglottic airway lumen in all four patients. Although the anterior-posterior glottic diameter was reduced by 36% in group A patients and by 43.5% in group B patients, a sufficient glottic airway lumen was obtained. The glottic sphincteric function was restored in both groups. CONCLUSIONS: Tracheal autotransplantation may be used reliably to repair hemicricolaryngectomy defects. Augmentation of the patch at the level of the glottis is not essential for successful rehabilitation.     

Hearing, speech, language, and vestibular disorders in the fetal alcohol syndrome: a literature review

Fetal alcohol syndrome (FAS) is characterized in part by mental impairment, as well as craniofacial and ocular anomalies. These conditions are traditionally associated with childhood hearing disorders, because they all have a common embryonic origin in malformations of the first and second branchial arches, and have similar critical periods of vulnerability to toxic insult. A review of human and animal research indicates that there are four types of hearing disorders associated with FAS. These are: (1) a developmental delay in auditory maturation, (2) sensorineural hearing loss, (3) intermittent conductive hearing loss due to recurrent serous otitis media, and (4) central hearing loss. The auditory and vestibular systems share the same peripheral apparatuses (the inner ear and eighth cranial nerve) and are embryologically and structurally similar. Consequently, vestibular disorders in FAS children might be expected. The evidence for vestibular dysfunction in FAS is ambiguous, however. Like other syndromes associated with craniofacial anomalies, hearing disorders, and mental impairment, FAS is also characterized by a high prevalence of speech and language pathology. Hearing disorders are a form of sensory deprivation. If present during early childhood, they can result in permanent hearing, language, and mental impairment. Early identification and intervention to treat hearing, language, and speech disorders could therefore result in improved outcome for the FAS child. Specific recommendations are made for intervention and future research.     

Immediate sealing of arterial puncture sites after cardiac catheterization and coronary angioplasty using a biodegradable collagen plug: results of an international registry

Stimulus control was established in rats using either 8-hydroxy-2-[di-n-propylamino]tetralin (DPAT) (0.2 mg/kg) or yohimbine (3 mg/kg). Tests were then conducted with purported antagonists at 5-hydroxytryptamine1A (5-HT1A) receptors. Drugs studied were NAN-190, [+/-]-pindolol, and [-]-alprenolol. In addition, each drug was characterized in terms of its affinity for 5-HT1A and alpha 2-adrenoceptors by means of radioligand binding techniques. None of the antagonists tested provided complete blockade of the stimulus effects of either DPAT or yohimbine. However, [+/-]-pindolol produced a statistically significant intermediate degree of antagonism of both DPAT and yohimbine. The affinities of DPAT, yohimbine, and NAN-190 for the 5-HT1A and alpha 2-adrenergic receptors, respectively, were sufficiently high to lead to some ambiguity of interpretation of the behavioral data. However, the results with [+/-]-pindolol, which has high affinity for the 5-HT1A receptor (34 nM) and negligible affinity for the alpha 2-adrenoceptor (24,600 nM), indicate that a significant component of yohimbine-induced stimulus control is mediated by the 5-HT1A receptor.     

Development and optimisation of a defined high cell density yeast medium

Saccharomyces cerevisiae cells grown in a small volume of chemically defined media neither reach the desired cell density nor grow at a fast enough rate to scale down the volume and increase the sample number of classical biochemical assays, as the detection limit of the readout often requires a high number of cells as an input. To ameliorate this problem, we developed and optimised a new high cell density (HCD) medium for S. cerevisiae. Starting from a widely used synthetic medium composition, we systematically varied the concentrations of all components without the addition of other compounds. We used response surface methodology to develop and optimise the five components of the medium: glucose, yeast nitrogen base, amino acids, monosodium glutamate, and inositol. We monitored growth, cell number, and cell size to ensure that the optimisation was towards a greater density of cells rather than just towards an increase in biomass (i.e., larger cells). Cells grown in the final medium, HCD, exhibit growth more similar to the complex medium yeast extract peptone dextrose (YPD) than to the synthetic defined (SD) medium. Whereas the final cell density of HCD prior to the diauxic shift is increased compared with YPD and SD about threefold and tenfold, respectively. We found normal cell-cycle behaviour throughout the growth phases by monitoring DNA content and protein expression using fluorescent reporters. We also ensured that HCD media could be used with a variety of strains and that they allow selection for all common yeast auxotrophic markers.     

Angiography of left ventricle following volume load and physical work in coronary disease

In order to recognize and quantitate abnormalities in wall segment motion in 22 patients simultaneous measurements of isovolumic and ejection phase parameters were performed with the Millar-angiographic catheter at rest, after leg raising and during bicycle exercise. 6 patients had slight coronary heart disease (CHD) (group I), 16 patients had severe CHD (group II). During volume load in all patients of gr. II a decrease of peak measured velocity (Vpm) and the velocity of circumferential fiber shortening (Vcf from 1.4 to 1.1 circ/s, p less than 0.025) occurred. In gr. I Vcf increased (p less than 0.05). During exercise there was a high increase in Vpm and Vcf in gr. I (from 1.2 to 1.9 circ/s) whereas in gr. II no increase was observed. LVEDP rose to 29 mm Hg and ESV from 58 to 70 ml/1.73 m2. By increasing LVEDP during volume load underperfused areas became ischaemic and akinetic. During physical work the segmental abnormality can be less pronounced possibly due to the higher prestenotic pressure.