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At least 217 records · Page 12Linked to original sources

Evaluation of a new coprocessed compound based on lactose and maize starch for tablet formulation.

The development of new direct compression excipients should include a comprehensive and rapid determination of deformation properties. The aim of this study was to characterize StarLac, a new coprocessed compound for direct compression based on lactose and maize starch. For this purpose, the effects of the base materials (maize starch and spray-dried lactose) were considered and the influence of the spray-drying process was investigated. This was performed by comparing the physical mixture of starch and spray-dried lactose at the same ratio as for StarLac. For analysis of the deformation behavior, the 3-D model and the Walker equation were applied; for verification, the Heckel equation and the pressure time function (a modified Weibull equation) were used. The advantages of StarLac are its good flowability depending on the spray-drying process, an acceptable crushing force due to its lactose content, its rapid disintegration depending on starch, and a brilliant fast release of an active ingredient, such as theophylline monohydrate. The volume-pressure deformation properties of StarLac were dependent on the lactose properties. Only at high maximum relative density (rho(rel, max)) did the influence of starch cause a change in these properties. A network-like structure can be observed using scanning electron microscopy pictures. Overall, StarLac deformed plastically with a low portion of elasticity. The physical mixture exhibited a more elastic behavior than StarLac. However, the part of the powder that was irreversibly compressed was much lower than was observed for the single substances. This behavior is caused by an interaction between the components, which in StarLac is prevented by spray drying.

Compressive Strength↗

An algorithm for rapid calculation of a probabilistic functional atlas of subcortical structures from electrophysiological data collected during functional neurosurgery procedures.

The paper introduces an optimal algorithm for rapid calculation of a probabilistic functional atlas (PFA) of subcortical structures from data collected during functional neurosurgery procedures. The PFA is calculated based on combined intraoperative electrophysiology, pre- and intraoperative neuroimaging, and postoperative neurological verification. The algorithm converts the coordinates of the neurologically most effective contacts into probabilistic functional maps taking into account the geometry of a stimulating electrode. The PFA calculation comprises the reconstruction of the contact coordinates from two orthogonal projections, normalizing (warping) the contacts modeled as cylinders, voxelizing the contact models, calculating the atlas, and computing probability. In addition, an analytical representation of the PFA is formulated based on Gaussian modeling. The initial PFA has been calculated from the data collected during the treatment of 274 Parkinson's disease patients, most of them operated bilaterally (487 operated hemispheres). It contains the most popular stereotactic targets, the subthalamic nucleus, globus pallidus internus, and ventral intermedius nucleus. The key application of the algorithm is targeting in stereotactic and functional neurosurgery, and it also can be employed in human and animal brain research.

Algorithms↗

POXO: a web-enabled tool series to discover transcription factor binding sites.

We present POXO, a comprehensive tool series to discover transcription factor binding sites from co-expressed genes (www.bioinfo.biocenter.helsinki.fi/poxo). POXO manages tasks such as functional evaluation and grouping of genes, sequence retrieval, pattern discovery and pattern verification. It also allows users to tailor analytical pipelines from these tools, with single mouse clicks. One typical pipeline of POXO begins by examining the biological functions that a set of co-expressed genes are involved in. In this examination, the functional coherence of the gene set is evaluated and representative functions are associated with the gene set. This examination can also be used to group genes into functionally similar subsets, if several biological processes are affected in the experiment. The next step in the pipeline is then to discover over-represented nucleotide patterns from the upstream sequences of the selected gene sets. This enables to investigate the possibility that the genes are co-regulated by common cis-elements. If over-represented patterns are found, similar ones can then be clustered together and be verified. The performance of POXO is demonstrated by analysing expression data from pathogen treated Arabidopsis thaliana. In this example, POXO detected activated gene sets and suggested transcription factors responsible for their regulation.

Arabidopsis↗

Moisture sorption kinetics for water-soluble substances. II: Experimental verification of heat transport control.

The rates of water sorption as a function of relative humidity for water-soluble substances exhibiting deliquescence have been measured in an atmosphere of pure water vapor. The substances studied included a series of alkali halides, choline halides, and sugars. The results were compared with a theoretical model, previously described, which relates the rate of water uptake to the transport of heat produced during the process away from the surface. Taking into account the heat of water vapor condensation, heat of solution, and heat of hydration, when hydration occurs, the model allows excellent a priori prediction of water uptake rates as a function of relative humidity.

Absorption↗

A model for de novo synthesis and assembly of tight intercellular junctions. Ultrastructural correlates and experimental verification of the model revealed by freeze-fracture.

The structure and function of intercellular tight (occluding) junctions, which constitute the anatomical basis for highly regulated interfaces between tissue compartments such as the blood-testis and blood-brain barriers, are well known. Details of the synthesis and assembly of tight junctions, however, have been difficult to determine primarily because no model for study of these processes has been recognized. Primary cultures of brain capillary endothelial cells are proposed as a model in which events of the synthesis and assembly of tight junctions can be examined by monitoring morphological features of each step in freeze-fracture replicas of the endothelial cell plasma membrane. Examination of replicas of non-confluent monolayers of endothelial cells reveals the following intramembrane structures proposed as 'markers' for the sequential events of synthesis and assembly of zonulae occludentes: development of surface contours consisting of elongate terraces and furrows (valleys) orientated parallel to the axis of cytoplasmic extensions of spreading endothelial cells, appearance of small circular PF face depressions (or volcano-like protrusions on the EF face) that represent cytoplasmic vesicle-plasma membrane fusion sites, which are positioned in linear arrays along the contour furrows, appearance of 13-15 nm intramembrane particles at the perimeter of the vesicle fusion sites, and alignment of these intramembrane particles into the long, parallel, anastomosed strands characteristic of mature tight junctions. These structural features of brain endothelial cells in monolayer culture constitute the morphological expression of: reshaping the cell surface to align future junction-containing regions with those of adjacent cells, delivery and insertion of newly synthesized junctional intramembrane particles into regions of the plasma membrane where tight junctions will form, and aggregation and alignment of tight junction intramembrane particles into the complex interconnected strands of mature zonulae occludentes. The distribution of filipin-sterol complex-free regions on the PF intramembrane fracture face of junction-forming endothelial plasmalemmae corresponds precisely to the furrows, aligned vesicle fusion sites and anastomosed strands of tight junctional elements.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Genetic complementation in apicomplexan parasites.

A robust forward genetic model for Apicomplexa could greatly enhance functional analysis of genes in these important protozoan pathogens. We have developed and successfully tested a genetic complementation strategy based on genomic insertion in Toxoplasma gondii. Adapting recombination cloning to genomic DNA, we show that complementing sequences can be shuttled between parasite genome and bacterial plasmid, providing an efficient tool for the recovery and functional assessment of candidate genes. We show complementation, gene cloning, and biological verification with a mutant parasite lacking hypoxanthine-xanthine-guanine phosphoribosyltransferase and a T. gondii cDNA library. We also explored the utility of this approach to clone genes based on function from other apicomplexan parasites using Toxoplasma as a surrogate. A heterologous library containing Cryptosporidium parvum genomic DNA was generated, and we identified a C. parvum gene coding for inosine 5-monophosphate-dehydrogenase (IMPDH). Interestingly, phylogenetic analysis demonstrates a clear eubacterial origin of this gene and strongly suggests its lateral transfer from epsilon-proteobacteria. The prokaryotic origin of this enzyme might make it a promising target for therapeutics directed against Cryptosporidium.

Animals↗

Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer.

BACKGROUND: Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease's evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear. METHODS: In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells. RESULTS: The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency. CONCLUSIONS: Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Humans↗

[Profound study of respiratory biomechanics for diagnosis of chronic dust bronchitis].

Respiratory function studies play an important role in diagnosis of chronic dust bronchitis, both for the diagnosis verification and for determining the disease advance. The study is characterized by step-by-step assessment of respiratory function with body plethysmogram, flow/volume chart and bronchial spasmolytic test. Discrimination and regression analysis revealed leading functional parameters in chronic dust bronchitis: respiratory pathways resistance, pulmonary residual volume, bronchial spasmolytic test, forced vital lungs capacity, peak output flow.

Biomechanical Phenomena↗

American College of Surgeons Verification/Consultation Program: analysis of unsuccessful verification reviews.

UNLABELLED: This study was designed to document the reasons hospitals have been unsuccessfully peer reviewed as potential trauma centers. METHOD: 120 trauma center reviews were performed by a peer review program between September 1987 and December 1992 using the American College of Surgeons (ACS) criteria. Fifty-four hospitals had criteria deficiencies. These reviews were studied for criteria deficiencies for each hospital with documentation of frequency and relationship to re-review outcome. RESULTS: There are 108 ACS criteria. The 54 hospitals had various combinations of 28 different criteria deficiencies. Deficiencies ranged from 1 to 15 per hospital. Thirty-one hospitals underwent a second review. Twenty-five hospitals had corrected the deficiencies and were verified. No hospital with over 8 deficiencies was subsequently verified. The Quality Improvement program was the most common deficiency (74%) and was correctable (50%). Other frequent deficiencies were no trauma service (46%), no surgeons in ED (41%), inadequate neurosurgeon response (35%), no trauma coordinator (31%), no trauma registry (28%), lack of surgical commitment (26%), and lack of 24 hour OR availability (24%). The lack of surgeon or hospital commitment accounted for most of the 28 criteria deficiencies. Subsequent verification was notably poorer for hospitals seeking verification for the purpose of designation versus verification only (29% versus 75%). Only 1 hospital with a prior ACS consultation visit failed the first verification review. CONCLUSIONS: A limited but critical set of criteria enable a hospital to function as a trauma center. Trauma quality improvement is a poorly understood but a correctable issue. Surgical and hospital commitment are essential for verification. Prior consultation may be of benefit.

General Surgery↗

Use of aminoglycosides in elderly patients. Pharmacokinetic and clinical considerations.

Aminoglycosides still represent a mainstay in the treatment of serious infections caused by Gram-negative bacilli in elderly patients. The aging process is accompanied by various physiological changes (e.g. alterations in body composition, impairments in certain organ functions), which may affect drug disposition and, subsequently, drug action. For aminoglycosides that are eliminated by the renal route, kidney function is the key parameter that should be taken into account when dosage regimens are calculated. Because there is a progressive decline in renal function with aging, the glomerular filtration rate should be estimated for each patient. Any change in creatinine clearance (CLCR) should result in a proportional correction of the dosage regimen. Such individualised dosage of aminoglycosides is particularly important because of their narrow therapeutic indices. There are no conclusive data which indicate that age per se affects the elimination of aminoglycoside antibiotics. Overdosage may result from overestimation of renal function if crude serum creatinine (SCr) levels are used as a guide. Nomograms for the relationship between SCr and CLCR have been developed. However, nomograms should be used with caution because substantial interindividual variability in the plasma concentration-clearance relationship is still observed. Therefore, the choice of a maintenance dose based on an assessment of renal function, which change rapidly, should always be considered as preliminary, and verification by serum concentration measurements is necessary. As a result, the use of aminoglycoside serum concentration monitoring during therapy as the most important guide for dosage adjustment is particularly important in the elderly, and is indispensable in conjunction with frequent assessment of renal function. Although a matter of debate, the value of serum concentration monitoring has been demonstrated. With traditional multiple daily dosage, monitoring peak and trough concentrations has been recommended. For once daily dosage, however, no guidelines relating to therapeutic and/or toxic concentrations are available yet. In the meantime, we recommend monitoring at least trough concentrations. Once daily administration of aminoglycosides has emerged as a new mode of treatment. Compared with multiple daily administration, once daily dosage may have a number of advantages, and many clinical trials comparing the efficacy or safety of both modes have shown either superiority or equivalence of the new mode in most indications. At present, however, no data from studies of once daily administration in young compared with elderly adults are available.

Aged↗

Primacy of functional knowledge in semantic representations: the case of living and nonliving things.

In 3 experiments, participants decided whether sensory and functional features were true of living and nonliving concepts. In Experiments 1 and 2, concepts were presented twice: test phase followed study phase after either 3 min (Experiment 1) or 3 s (Experiment 2). At test, concepts were paired with the same feature as that at study, or a different feature from either the same modality (within-modality priming) or another modality (cross-modality priming). In both experiments functional decisions were faster than sensory decisions for living and nonliving concepts. Whilst no semantic priming occurred between study and test in Experiment 1, the shorter study-test interval of Experiment 2 did lead to test phase semantic priming. Here there was greater within- than cross-modality priming for sensory decisions, but equivalent within- and cross-modality priming for functional decisions owing to significantly greater facilitation of functional decisions from prior sensory decisions than vice versa. Experiment 3 involved a single verification phase: For half the participants the feature name preceded the concept name, and for half the concept name preceded the feature name. The functional processing advantage persisted irrespective of presentation order. Results suggest that functional information is central to the representation of all concepts: Function is processed faster than sensory information and is activated obligatorily.

Adolescent↗

Disease profiling arrays: reverse format cDNA arrays complimentary to microarrays.

The identification of differentially expressed genes enables us to understand the molecular mechanisms associated with disease, conditions of stress, drug treatments and developmental processes. Microarrays provide a powerful tool for studying these complex phenomena. Verification of differentially expressed genes and correlation with biological function, which is usually done by northern blot analysis, RNase protection assay or RT-PCR, is the bottleneck in all these protocols. We developed a new type of cDNA array for high-throughput expression profiling of multiple tissues and blood samples (i) for confirmation analysis of statistically significant number of clinical samples (ii) from limited amount of starting material, and (iii) with detailed clinical data from each individual. In contrast to traditional cDNA arrays, these arrays are spotted with a complex cDNA representing the entire mRNA message expressed in a given tissue or blood sample. cDNAs for these arrays were generated using SMART technology and accurately represent the original mRNA population, producing specific and quantitative signals during hybridization. cDNAs on Disease Profiling Arrays were derived from total RNAs of diseased and normal tissues or different blood fractions of patients. These cDNAs were spotted onto nylon membranes along with positive and negative controls. The arrays were then hybridized with gene-specific probes. Hybridization results revealed disease-related as well as patient-specific gene expression patterns between different disease types for these genes. These studies demonstrate that Disease Profiling Arrays are suitable for high-throughput studies comparing the relative abundance of a target gene, for simultaneously detecting differentially expressed genes in a wide variety of tissues and blood samples, and can be used down-stream from cDNA microarrays for confirmation analysis.

Autoimmune Diseases↗

Thematic relations in adults' concepts.

Concepts can be organized by their members' similarities, forming a kind (e.g., animal), or by their external relations within scenes or events (e.g., cake and candles). This latter type of relation, known as the thematic relation, is frequently found to be the basis of children's but not adults' classification. However, 10 experiments found that when thematic relations are meaningful and salient, they have significant influence on adults' category construction (sorting), inductive reasoning, and verification of category membership. The authors conclude that concepts function closely with knowledge of scenes and events and that this knowledge has a role in adults' conceptual representations.

Adult↗

Design of a high resolution positron emission tomograph: the Neuro-PET.

The design of a high resolution positron emission tomograph is described. The scanner has four rings of detectors with an inside diameter of 38 cm and produces seven simultaneous slices, including three cross-slices. Each ring contains 128 bismuth germanate scintillation detectors with dimensions of 8.25 x 20 x 35 mm; adjacent crystals are separated by tapered tungsten septa that extend to within 7.5 mm of the front faces. The anticipated geometrical spatial resolution of the scanner is 4.5 mm full width at half maximum (FWHM) at the center of the image, and the sensitivity is 44,000 true counts/sec/ring (390,000 counts/sec total) for a uniform phantom 20 cm in diameter containing 1 muCi/cc activity. There are interchangeable collimators for use in high count rate studies, for narrowing the slice width from 1 cm FWHM to 5 mm FWHM, and for ultra-high resolution studies with a 2.5 mm FWHM geometrical point spread function. The electronic circuitry has separate timing and energy verification channels and can detect 95% of the coincidences with a timing window (twice the maximum time between two coincident pulses) of 14 nsec. The count rate capability of the electronics is 150,000 counts/sec/ring and 1.5 million counts/sec total.

Bismuth↗

Large-scale analysis of gene expression changes during acute and chronic exposure to [Delta]9-THC in rats.

Large-scale cDNA microarrays were employed to assess transient changes in gene expression levels following acute and chronic exposure to cannabinoids in rats. A total of 24,456 cDNA clones were randomly selected from a rat brain cDNA library, amplified by PCR, and arrayed at high density to investigate differential gene expression profiles following acute (24 h), intermediate (7 days), and chronic (21 days) exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient of marijuana. Hippocampal mRNA probes labeled with (33)P obtained from both vehicle and Delta(9)-THC-treated animals were hybridized with identical cDNA microarrays. Results revealed a total of 49 different genes altered by Delta(9)-THC exposure; of these, 28 were identified, 10 had homologies to expressed sequence tags (ESTs), and 11 had no homology to known sequences in the GenBank database. Chronic or acute cannabinoid receptor activation altered expression of several genes (i.e., prostaglandin D synthase, calmodulin) involved in biochemical cascades of cannabinoid synthesis or cannabinoid effector systems. Other genes [i.e., neural cell adhesion molecule (NCAM), myelin basic protein], whose relation to cannabinoid system function was not immediately obvious, were also significantly altered. Verification of the changes obtained with the large-scale screen was determined by RNA dot blots in different groups of animals treated the same as those in the large-scale screen. Results are discussed in terms of the different types of genes affected at different times during chronic Delta(9)-THC exposure.

Animals↗

Chronic hypothalamic stimulation in awake rats fails to induce hypertension.

Daily electrical stimulation of the posterior hypotalamus for 12 weeks in awake rats caused persistent cardioacceleration but barely increased systolic pressure. Subsequent postmortem examination showed extensive fibrosis at sites of electrode implantation in both stimulated and unstimulated rats. Because Folkow and Rubinstein had succeeded in elevating blood pressure progressively by stimulating the "hypothalamic defence area," chronic stimulation was repeated following their stereotaxic coordinates. Systolic pressure rose but the elevation was significant only on Weeks 8 and 10. To maintain behavioral effects during chronic stimulation, current strengths had to be increased periodically, and stimulated rats gained weight more rapidly than unstimulated controls. Both these findings indicated that electrical stimulation had damaged the brain, but since local fibrosis made histologic verification difficult, additional experiments were done to determine if functional deficits could be detected. Upon further hypothalamic stimulation, electrical thresholds were higher and pressor and sympathetic nerve responses were smaller in rats that had been stimulated chronically than in those that had not. Although our results do not disprove the hypothesis that centrally-induced sympathetic hyperactivity initiates hypertension, they show that blood pressure cannot be elevated by hypothalamic stimulation alone when the brain has been injured.

Animals↗

Communication of medication orders by telephone--"writing it right".

Communication is commonly cited as a contributing factor to adverse events causing patient harm (Baker et al., 2004). There are numerous ways and reasons that communication failures can occur, such as poor handwriting, transcription errors, lack of verification, lack of integration of information, and ineffective team functioning. Errors that can occur in critical care with the verbal communication and receipt of a telephone order will be highlighted. These examples, together with proposed strategies for improving telephone order safety, are intended to promote awareness and potential practice changes in the critical care environment.

Abbreviations as Topic↗

[Sensitivity to clavulanic acid of Escherichia coli isolated at the Henri Mondor hospital in 1986 according to phenotypes of beta-lactam antibiotic resistance].

Susceptibility to Augmentin (AUG) was studied as a function of resistance phenotypes toward amoxicillin (AMX), carbenicillin (CAR), cephalothin (CFT) and cefotaxime (CTX) for 1817 strains of Escherichia coli isolated at Henri-Mondor hospital during 1986. For strains susceptible to the 4 beta-lactams (phenotype SSSS: 66%), the median zone diameter observed with AUG was 26.4 mm. It was slightly inferior (22.1) for acquired - penicillinase producing strains (phenotype RRSS: 21.5%), but zone diameters were greater than or equal to 21 mm for over than 75% of these strains. Strains of phenotype RRIS (6%), probably high penicillinase-producers, were generally intermediate to AUG (median zone diameter: 17.8), showing partial inhibition of enzyme by clavulanic acid. Cephalosporinase hyperproducers mutants (phenotype RSRS: 4%) and strains with a RRRS phenotype (2.5%), probably penicillinase and cephalosporinase producers, were resistant to AUG (median zone diameters: 15.6 and 12.6 mm). Among rarely observed phenotypes, some were readily integrated to major phenotypes: RSIS, ISRS and ISIS to phenotype RSRS; RIRS to phenotype RRRS; IISS to phenotype RRSS; apparently "aberrants" phenotypes (ISSS, RSSS, SSIS, SSRS) required interpretation of results as a function of observed zone diameters and at time a verification of tests. This study confirms the in vitro activity of AUG on penicillinase producing E. coli; in addition simultaneous reading of zone diameters observed with AMX, CAR, CFT and CTX, permitted to infer the probable mechanism of resistance to beta-lactams and therefore to correct possible discrepancies observed in antibiogram results.

Amoxicillin↗