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Coping strategies, reasons for driving, and the effect of self-monitoring in drinking-driving situations.

Male and female volunteers, who were drinking regularly but had not been convicted of DUI, were recruited for interviews about their past drinking episodes in a variety of locations and the reasons why they had or had not driven after drinking. The results of the initial interviews were used to compile a catalog of reported strategies and reasons for not driving after drinking, reported reasons for driving after drinking, and reported strategies to avoid detection or arrest when driving after drinking. Following the initial interview, each subject was randomly assigned to either a self-monitoring group or a no self-monitoring control group for three monthly follow-up interviews. The results of the follow-up revealed no apparent effect of self-monitoring on a variety of both drinking and drinking-and-driving measures.

Accidents, Traffic↗

A rapid-afterloading vaginal cylinder for 137Cs brachytherapy.

A small diameter, single-step afterloading vaginal cylinder has been developed for 137Cs brachytherapy of the vaginal cuff and walls. The Lucite cylinder has an interior slot of rectangular cross section running along its length and opening to the outside of the patient. A single rectangular Lucite insert, containing preselected sources, fits into the slot. Two short sources in the tip form a T with the sources along the vaginal canal and provide a high, uniform dose rate across the spherical tip of the applicator. A catalog of 30 precalculated loadings provides surface dose rates at the tip which vary from 140 to 230 cGy/hr for standard source strengths, as well as a variety of dose rate profiles along the vaginal wall. The applicator is tapered at the base for comfortable and secure placement, and the single-step insertion reduces both patient discomfort and personnel radiation exposure for this procedure.

Brachytherapy↗

Broad range DNA probes for detecting and amplifying eubacterial nucleic acids.

In this report we describe and characterize two oligomer probes that are broadly homologous to conserved eubacterial 16S ribosomal RNA (rRNA) sequences not present in human 18 rRNA or human mitochondrial 12S rRNA. One or both of the probes can detect all of 23 phylogenetically diverse eubacterial nucleic acids against which they were tested by dot blot hybridization. A sensitivity of about 1 bacterium per 10 eukaryotic cells was achieved. By using these oligomer sequences or their complements as primers in the polymerase chain reaction (PCR), the equivalent of 1 pg of E. coli DNA was detected in the presence of a large excess of eukaryotic DNA. Information useful for partial phylogenetic classification of detected organisms may be obtained by direct sequence analysis of the amplified DNA and comparison with known sequences or catalogs. Such broadly homologous probes offer advantages over more narrowly specific probes for detecting organisms whose identity is unknown. They could thus be employed for recognizing infection by organisms that cannot be cultured as may occur, for example, in tissue culture or in plant or animal diseases of unknown cause, provided the probes fail to hybridize with host nucleic acids.

Base Sequence↗

Applications of asymmetric collimation on linear accelerators.

Frequency of use of asymmetric collimation (AC) at an academic radiation oncology center equipped with AC-capable linear accelerators was determined, and the type of use was cataloged. Records of patients beginning radiation treatment at U.C. Davis Cancer Center within a 3-month period (3/1/92 to 5/31/92) were reviewed. Forty-seven percent of 102 patients and 56% of 123 courses of treatment involved AC. Six common uses of AC were identified: beam-split field matching, planned boosts, other field size changes, adjustments to match divergent fields, matchline feathering, and opposed tangential fields. This study demonstrates that asymmetric collimation is a useful and powerful clinical treatment tool with widespread applications to radiation therapy.

Cohort Studies↗

The IVth Karlson Lecture: ecdysone-responsive genes.

Those of us who study ecdysone action share at least two important long-range goals: (i) to understand the developmental specificity of steroid action in full molecular detail, by integrating ecdysone action with our rapidly expanding knowledge of the molecular biology of insect development, and (ii) to better understand the nature of the steroid response and its evolution by taking advantage of the unparalleled opportunities for both genetic and comparative study afforded by the diversity of the "ecdysone world". However, until recently, the molecular fundamentals of the ecdysone system were unknown and our efforts have, of necessity, been devoted to their elucidation. Now that the situation has changed: we have a small but varied catalog of ecdysone-responsive genes for study and it is clear that some of these are tissue- and stage-specific in their expression. The ecdysone receptor (EcR), like other steroid receptors a member of the nuclear receptor family, is now accessible to molecular study, and we have a preliminary understanding of the DNA sequences (EcREs) that bind receptor and specify a gene as ecdysone-responsive. With these tools in hand and with the opportunity to turn to larger questions, it is a propitious moment to consider the nature of those questions and how ecdysone can contribute to the answers.

Amino Acid Sequence↗

Patenting genes. J. Craig Venter and the Human Genome Project.

He often begins to answer before you have finished asking your question, but his replies are to the point. He speaks with emotion about the people he hopes to help, particularly children with fatal genetic diseases. 'I prefer to do something: the outcome of doing nothing is perfectly clear', he says. He began sequencing human genes while others were discussing how and when to do so. His methods have been called inelegant, redundant, wasteful, and too 'industrial'. Will his method fail to detect some infrequently transcribed genes? That's all right with him. He is not concerned with finding all the human genes, but rather with the fastest possible route to a useful catalog of most human genes.

Chromosome Mapping↗

Prospective evaluation of digital non-stereo color fundus photography as a screening tool in age-related macular degeneration.

PURPOSE: To evaluate mydriatic, non-stereo digital color fundus photographs as a screening tool for identifying and classifying exudative age-related macular degeneration (AMD). DESIGN: Prospective case series. METHODS: Digital color fundus photographs were obtained from patients seen in the AMD screening clinic over a 9-month period at the Ivey Eye Institute in London, Ontario. Photographs for eligible patients were separated by eye, cataloged, blinded, and randomly labeled before interpretation by an experienced vitreoretinal surgeon. Exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value of the fundus photographs in diagnosing, classifying, and managing cases of suspected exudative AMD were then calculated against gold standard clinical examination and fluorescein angiography. RESULTS: A total of 223 images were used from 118 eligible patients. Exact agreement between photographic evaluation and gold standard ranged from 89.2% (presence of pigment epithelial detachment (PED)) to 82.5% (evidence of retinal pigment epithelium geographic atrophy). Sensitivities ranged from 89.2% (presence of choroidal neovascular membrane (CNVM)) to 40.0% (presence of PED). Specificities ranged from 94.1% (presence of PED) to 86.8% (presence of retinal pigment epithelium geographic atrophy). Positive predictive value ranged from 86.1% (presence of CNVM) to 40.0% (presence of PED). Negative predictive value ranged from 94.1% (presence of PED) to 88.9% (presence of CNVM). As a screening tool for high-risk dry changes and active exudative changes, overall sensitivity specificity, positive predictive value, and negative predictive value were 82.1%, 79.1%, 70.4%, and 88.0%, respectively. CONCLUSIONS: Digital, non-stereo color fundus photographs are highly sensitive and have high negative predictive value as a screening tool. Very few treatable lesions are missed using telemedicine in age-related macular degeneration.

Aged↗

Electrocardiographic findings in 888 patients > or =90 years of age.

The oldest old are the fastest growing component of many national populations. No large-scale analysis of electrocardiographic findings in this group exists to date. This study cataloged the frequencies of specific electrocardiographic (ECG) findings in the target population and compared the frequencies of these findings by gender and race. The electrocardiograms of 888 subjects aged > or =90 years presenting for any reason were retrospectively analyzed using standard criteria for 128 separate ECG findings. Left ventricular enlargement (28%), first-degree atrioventricular block (16%), and atrial fibrillation (15%) were the most common abnormalities found in the population as a whole. In contrast to previous studies, which demonstrated a predominance of left-axis deviation, 91% of the electrocardiograms analyzed in our study demonstrated a mean frontal QRS axis ranging from -30 degrees to +90 degrees . Sinus rhythm was observed in 79% of the population. More Caucasians than African-Americans had atrial fibrillation (19% vs 12%, p = 0.004). Women had more normal ECG results than men (6% vs 2%, p = 0.02), and more women demonstrated complete right bundle branch block (13% vs 7%, p = 0.002). In conclusion, few patients aged > or =90 years who have their electrocardiograms recorded at hospitals have completely normal ECG results. The frequencies of some ECG findings in the target population vary by gender and race.

Aged, 80 and over↗

[What do we control in mammaplasty for hypertrophic and/or ptotic breasts?].

A retrospective view on the history of mammaplasties for hypertrophic and/or ptotic breasts, shows its evolutive sense, in which we attempted to describe the main stages, avoiding to make a long "catalog". The first period (the longest) was marked by progresses concerning the control of vascular security of the areola and the nipple. That stage was essential by the fact it permitted to liberate the attention of surgeons for other questions: those concerning the shape of the breast, means of fixity and the long term evolution, quality and length of scars... In the continuity of this long evolution, each one of the authors presents a personal reflexion about the elements of control (and of course their limits!), developing some concepts as: the supra-medical pedicle for the vascular security, the advantage of the association mammaplasty and breast implant in the long term evolution and attentive post operative care to improve the quality of the scar (J.Ohana); the usefulness of a geometrical methodology-in which the importance of parameters as congruence and base of mammary gland conservation ("BAMACO") for shortening the scar without compromising the quality of the operated breast is demonstrated and with a relatively good stability of correction of the ptosis (-58% after 2 years) (R. Selinger).

Breast↗

Contraindications for superficial heat and therapeutic ultrasound: do sources agree?

OBJECTIVES: To determine the amount of agreement among general rehabilitation sources for both superficial heating and therapeutic ultrasound contraindications. DATA SOURCES: English-language textbook and peer-reviewed journal sources, from January 1992 to July 2002. Searches of computerized databases (HealthSTAR, CINAHL, MEDLINE, Embase) as well as Library of Congress Online Catalogs, Books in Print, and AcqWeb's Directory of Publishers and Venders. DATA SELECTION: Sources were excluded if they (1) were published before 1992, (2) failed to address general rehabilitation audiences, or (3) were identified as a researcher's related publication with similar information on the topic. DATA EXTRACTION: Type and number of contraindications, type of audience, year of publication, number of references, rationales, and alternative treatment strategies. DATA SYNTHESIS: Eighteen superficial heat and 20 ultrasound sources identified anywhere from 5 to 22 and 9 to 36 contraindications/precautions, respectively. Agreement among sources was generally high but ranged from 11% to 95%, with lower agreement noted for pregnancy, metal implants, edema, skin integrity, and cognitive/communicative concerns. Seventy-two percent of superficial heat sources and 25% of ultrasound sources failed to reference at least 1 contraindication claim. CONCLUSIONS: Agreement among contraindication sources was generally good for both superficial heat and therapeutic ultrasound. Sources varied with regard to the number of contraindications, references, and rationales cited. Greater reliance on objective data and standardized classification systems may serve to develop more uniform guidelines for superficial heat and therapeutic ultrasound.

Contraindications↗

A guest molecule-host cavity fitting algorithm to mine PDB for small molecule targets.

Inhaled anesthetic molecule occupancy of a protein internal cavity depends in part on the volumes of the guest molecule and the host site. Current algorithms to determine volume and surface area of cavities in proteins whose structures have been determined and cataloged make no allowance for shape or small degrees of shape adjustment to accommodate a guest. We developed an algorithm to determine spheroid dimensions matching cavity volume and surface area and applied it to screen the cavities of 6,658 nonredundant structures stored in the Protein Data Bank (PDB) for potential targets of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane). Our algorithm determined sizes of prolate and oblate spheroids matching dimensions of each cavity found. If those spheroids could accommodate halothane (radius 2.91 A) as a guest, we determined the packing coefficient. 394,766 total cavities were identified. Of 58,681 cavities satisfying the fit criteria for halothane, 11,902 cavities had packing coefficients in the range of 0.46-0.64. This represents 20.3% of cavities large enough to hold halothane, 3.0% of all cavities processed, and found in 2,432 protein structures. Our algorithm incorporates shape dependence to screen guest-host relationships for potential small molecule occupancy of protein cavities. Proteins with large numbers of such cavities are more likely to be functionally altered by halothane.

Algorithms↗

Anticancer metal compounds in NCI's tumor-screening database: putative mode of action.

Clustering analysis of tumor cell cytotoxicity profiles for the National Cancer Institute (NCI)'s open compound repository has been used to catalog over 1100 metal or metalloid containing compounds with potential anticancer activity. The molecular features and corresponding reactivity of these compounds have been analyzed in terms of properties of their metals, their associated organic components (ligands) and their capacity to inhibit tumor cell growth. Cytotoxic responses are influenced by both the identity of the metal and the properties of its coordination ligand, with clear associations between structural similarities and cytotoxicity. Assignments of mechanisms of action (MOAs) for these compounds could be segregated into four broad response classes according to preference for binding to biological sulfhydryl groups, chelation, generation of reactive oxygen species (ROS), and production of lipophilic ions. Correlations between specific cytotoxic responses and differential gene expression profiles within the NCI's tumor cell panel serve as a validation for candidate biological targets and putative MOA classes. In addition, specific sensitivity toward subsets of metal containing agents has been found for certain tumor cell panels. Taken together, our results expand the knowledge base available for evaluating, designing and developing new metal-based anticancer drugs that may provide the basis for target-specific therapeutics.

Antineoplastic Agents↗

Puzzling out the reeler brainteaser: does reelin signal to unique neural lineages?

Much has been learnt about the reeler mutant since its inclusion in the celebrated Catalog of the Neurological Mutants of the Mouse in the mid-sixties. The pace of discovery was most definitively agitated after the identification of reelin, the genuine gene product mutated in reeler (first expressed by a monolayer of cells in the marginal zone of the developing brain), and the subsequent establishment of the so-called reelin signaling pathway (including the reelin receptor machinery expressed by migrating newborn neurons). Yet little is known as to how the reelin signaling events, which are critically involved in neuronal migration, are linked to the in vivo behavior of individual neurons. Lately, the results of the forced ectopic expression of reelin in the neurogenic zone jeopardized all proposed models regarding its mechanism of action. Our studies suggest that earlier than newborn neurons, the radial glia neuronal progenitors may receive a functional reelin signal. Here I show evidence of an enriched localization of the reelin receptor machinery in radial glial cells of the lateral, but not the median, ganglionic eminence. This precise compartmentalization suggests that, unlike radial migration of cortical projection neurons, reelin signaling is not directly related with the tangential migration of the bulk of cortical interneurons. I hereby submit a personal glimpse of reeler morphogenesis which embodies a testable hypothesis; namely, that reelin signals to unique neural lineages to regulate migration.

Animals↗

Male accessory gland proteins in Grapholita molesta: Identification and reproductive functional validation of four accessory gland-specific lipases.

Accessory gland proteins (Acps), synthesized in the male accessory glands (AGs), are transferred to females via spermatophores during mating and elicit diverse post-mating physiological and behavioral responses. However, Acps have not been comprehensively characterized in Grapholita molesta, a cosmopolitan orchard pest. Here, using data-independent acquisition mass spectrometry, we describe an integrated proteomic approach combining comparative AG analyses (virgin vs. newly mated) with spermatophore profiling to identify Acps in G. molesta. According to the established screening criteria, we identified 83 confirmed Acps, which were classified into nine categories. Tissue-specific expression patterns of 20 randomly selected Acp genes were evaluated, revealing that these genes were specifically or highly expressed in male AGs. Among the 83 confirmed Acps, four Acps harbored the PLN02872 superfamily domain and were classified into the canonical lipase family. Notably, their transcripts were all highly expressed in the AGs during the pre-maturation stage. These four Acps were selected for preliminary validation of their male reproductive functions. RNAi-mediated knockdown of three out of four lipase genes in G. molesta males significantly decreased the fertility of mated females, with phenotypes including a significant reduction in egg production and egg hatching rate. This study provides a comprehensive catalog of high-confidence Acps, lays a foundation for subsequent in-depth functional characterization of these reproductive proteins, and offers promising molecular targets for the development of novel genetic regulation-based integrated pest management strategies.

Animals↗

Discovery and engineering of enzymes for new-to-nature photobiocatalysis.

Photobiocatalysis integrates enzymatic catalysis with photochemistry, enabling challenging radical transformations with high selectivity under mild conditions. Early developments in this field were largely driven by the discovery that enzyme-bound cofactors can form photoactive charge-transfer complexes with substrates, thereby initiating radical chemistry upon light irradiation. Recent advances, however, have substantially expanded the mechanistic landscape of photobiocatalysis through diverse mechanisms. This review summarizes major developments in photobiocatalysis reported since 2024. Rather than cataloging individual reactions, we focus on the fundamental mechanisms of radical generation and interception within enzyme active sites, and discuss how these mechanistic principles guide the discovery, engineering, and design of enzymes for new-to-nature photobiocatalysis.

Protein Engineering↗

Factors determining types and morphologies of calcium oxalate crystals: molar concentrations, buffering, pH, stirring and temperature.

BACKGROUND: Calcium oxalate (CaOx) can be crystallized in several forms and morphologies. We evaluated factors that determine differential types and shapes of CaOx crystals generated in vitro. METHODS: CaCl2 and Na2C2O4 solutions at various molar concentrations were mixed in different conditions (with or without Tris-HCl buffer and varying pH, temperature and speed of stirring) and incubated overnight. RESULTS: A total of 78 conditions were evaluated. The most frequently observed type of CaOx crystals was calcium oxalate monohydrate (COM). In 18.2 MOmega.cm water, typical monoclinic prismatic form of COM was found when 0.5-1 mmol/l CaCl2 and 0.5-1 mmol/l Na2C2O4 were mixed, whereas the COM dendrites were found when higher concentrations were used. Calcium oxalate dihydrate (COD) crystals were observed when 5 mmol/l CaCl2 and 0.5 mmol/l Na2C2O4 were employed. With the same molar concentrations of CaCl2 and Na2C2O4, the sequence of adding these 2 chemicals into the chamber had some effects on crystal types and morphologies. The presence of Tris-HCl buffer in the solution enhanced COM crystal growth and aggregation. The pH greater than 5.0 was associated with the presence of weddellite COD. Magnetic stirring of the supersaturated solution resulted to reduction in size of all crystal forms; the higher speed provided the smaller crystals. Finally, crystallization of CaOx at 4 degrees C was more efficient than performing the experiment at 25 and 37 degrees C. CONCLUSIONS: Molar concentrations, order of adding the substrates, buffering, pH, stirring and temperature have significant effects on CaOx crystal formation, types and morphologies. Cataloging these differential forms of crystals generated in different conditions will be useful for further study on modulations of CaOx crystals and kidney stone disease.

Buffers↗

Toward a functional taxonomy of cancer.

Interrogating the genomes of tumor cells with genomic and proteomic methods is becoming a mainstay of modern cancer classification efforts. This notion is brought to a new level by a paper in the July 23 issue of Cell, in which the dynamic responses of leukemia cells to perturbation are cataloged by flow cytometry, and the leukemias classified in terms of their functional responses. This study paves the way for more systematic attempts to bring functional genomics to the study of human cancer.

Classification↗

Quantitative proteomics analysis of the secretory pathway.

We report more than 1400 proteins of the secretory-pathway proteome and provide spatial information on the relative presence of each protein in the rough and smooth ER Golgi cisternae and Golgi-derived COPI vesicles. The data support a role for COPI vesicles in recycling and cisternal maturation, showing that Golgi-resident proteins are present at a higher concentration than secretory cargo. Of the 1400 proteins, 345 were identified as previously uncharacterized. Of these, 230 had their subcellular location deduced by proteomics. This study provides a comprehensive catalog of the ER and Golgi proteomes with insight into their identity and function.

Animals↗