The effects of refractive index heterogeneity within kidney tissue on multiphoton fluorescence excitation microscopy.

Although multiphoton fluorescence excitation microscopy has improved the depth at which useful fluorescence images can be collected in biological tissues, the reach of multiphoton fluorescence excitation microscopy is nonetheless limited by tissue scattering and spherical aberration. Scattering can be reduced in fixed samples by mounting in a medium whose refractive index closely matches that of the fixed material. Using optical 'clearing', the effects of refractive index heterogeneity on signal attenuation with depth are investigated. Quantitative measurements show that by mounting kidney tissue in a high refractive index medium, less than 50% of signal attenuates in 100 µm of depth.

The effects of spherical aberration on multiphoton fluorescence excitation microscopy.

Multiphoton fluorescence excitation microscopy is almost invariably conducted with samples whose refractive index differ from that of the objective immersion medium, conditions that cause spherical aberration. Due to the quadratic nature of multiphoton fluorescence excitation, spherical aberration is expected to profoundly affect the depth dependence of fluorescence excitation. In order to determine the effect of refractive index mismatch in multiphoton fluorescence excitation microscopy, we measured signal attenuation, photobleaching rates and resolution degradation with depth in homogeneous samples with minimal light scattering and absorption over a range of refractive indices. These studies demonstrate that signal levels and resolution both rapidly decline with depth into refractive index mismatched samples. Analyses of photobleaching rates indicate that the preponderance of signal attenuation with depth results from decreased rates of fluorescence excitation, even in a system with a descanned emission collection pathway. Similar results were obtained in analyses of fluorescence microspheres embedded in rat kidney tissue, demonstrating that spherical aberration is an important limiting factor in multiphoton fluorescence excitation microscopy of biological samples.

Aircrew visors and color vision performance: a comparative and preliminary pilot study analysis.

BACKGROUND: A very important aspect of visual performance to consider, for present and future recommendations regarding aircrew visors, concerns their impact on color vision. The literature has remained mostly inconclusive with respect to the human perceptual process of colors during actual mission employment. OBJECTIVE: This study uses active duty military aircrews to provide objective and valuable information on the effects of Short Wavelength Absorbing Filters (SWAFs), such as the High Contrast Visor (HCV), and some selected waveband type Laser Eye Protection (LEP) visors on color vision. It provides a direct comparison of several current and proposed aircrew eye protective visors with respect to their effects on color vision. The data analyzed in this study will also be used to support a recommendation regarding a new optimal visor for aircrew wear during air to air (and ground) engagements, for sun protection, and possible visual enhancement in order to improve user compliance. METHODS: Seven volunteers on active flying status each underwent comprehensive color vision testing with and without seven of the U. S. Air Force's (USAF's) current or proposed aircrew visors/filters. Spectral transmissions of these visors/filters were obtained to identify and determine their individual characteristics which included their ability to induce acquired color vision decrements in "color normal" individuals. RESULTS: The widely utilized USAF HCV significantly degraded color vision more than luminosity matched neutral density visors. Abrupt color vision decrements for specifically fielded LEP visors were also noted. Their objective data supported theoretical and speculated color vision effects. Even though low transmittance neutral density visors did have some effect on color vision, decrement severity was not considered significant enough to affect overall performance during color vision testing. CONCLUSIONS AND DISCUSSION: Because of their ability to significantly affect color vision, concerns regarding the use of HCV and LEP visors should entail age, baseline color vision, environmental, and mission factors. Further testing should be done to evaluate the definitive effects that these visors actually have on the recognition of color symbology of Multi Function and Electronic Flight Information Displays. Findings in this study also support theoretical opinions that encourage the fielding of a neutral density filter (mildly tinted) with an overall transmission of 25-49%. Its use by flyers during low and bright illuminant conditions may greatly enhance visual performance by encouraging wearer compliance while allowing colors to be perceived normally.

Sparfloxacin selects gyrase mutations in first-step Mycoplasma hominis mutants, whereas ofloxacin selects topoisomerase IV mutations.

The role of mutations in the genes for GyrA and ParC in quinolone resistance in Mycoplasma hominis was studied. Selection with sparfloxacin gave mutations at GyrA83 (Ser-->Leu; Escherichia coli numbering) or GyrA87 (Glu-->Lys), and mutants had increased levels of resistance to sparfloxacin (8- to 16-fold) but not to ofloxacin. Selection with ofloxacin gave changes at ParC80 (Ser-->Ile) or ParC84 (Glu-->Lys), and mutants were four- to eightfold more resistant to ofloxacin but not to sparfloxacin. Selection of second-step mutants from strains with ParC mutations with either quinolone yielded double mutants with additional mutations at GyrA83 (Ser-->Trp or Ser-->Leu) or GyrA87 (Glu-->Lys). Second-step selection of GyrA mutants gave additional mutations at ParC80 (Ser-->Ile) or ParC84 (Glu-->Lys). Two-step mutants showed high levels of resistance to ofloxacin (MICs, 64 to 128 microg/ml) and moderate levels of resistance to sparfloxacin (MICs, 2 to 8 microg/ml). The primary target of ofloxacin in first-step mutants of Mycoplasma hominis was ParC, whereas that for sparfloxacin was GyrA.

New cyclooxygenase-2/5-lipoxygenase inhibitors. 3. 7-tert-butyl-2, 3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations at the 5 position.

We report an expansion of the scope of our initial discovery that 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) are antiinflammatory and analgesic agents. Several other functional groups have been introduced at the 5 position: amides, amidines, ureas, guanidines, amines, heterocycles, heteroaromatics, and heteroaryl ethenyl substituents in the 5 position all provide active compounds. These compounds are dual cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitors. They inhibit both COX-1 and COX-2 with up to 33-fold selectivity for COX-2.

New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent.

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were prepared and evaluated as potential nonsteroidal antiinflammatory and analgesic agents. Interest in this class of compounds arose when a DHDMBF was found to be an active metabolite of the di-tert-butylphenol antiinflammatory agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs have good in vivo antiinflammatory and analgesic activity after oral administration. These compounds inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) in vitro. The cyclooxygenase inhibition was found to be selective for the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX inhibition may be responsible for the gastrointestinal safety of compounds such as 30.

New cyclooxygenase-2/5-lipoxygenase inhibitors. 2. 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations of the dihydrobenzofuran ring.

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were found to be nonsteroidal antiinflammatory and analgesic agents. These compounds are inhibitors of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX) with selectivity for the COX-2 isoform. A series of analogues were prepared to investigate the scope of this lead. Five ketone side chains from active DHDMBFs were used to investigate the effects of changes in the DHDMBF "core": the size and identity of the heterocycle and the substituent requirements of the heterocycle and phenyl ring. Biological testing showed that a variety of structural changes can be accommodated, but no structure was clearly superior to the DHDMBF structure.

The performance of students selected through a special program at St. Louis University School of Medicine.

PURPOSE: To compare the performances of students selected through a special program, the Medical Anatomy Preparatory Program (MAPP), at St. Louis University School of Medicine with those of students admitted at the traditional way. METHOD: The students were members of the classes of 1993-1996 at the St. Louis University School of Medicine (N = 654). Of these, 52 (8%) were MAPP students. The MAPP students and the non-MAPP students were compared on the basis of various test scores and grades obtained from the admission office, the registrar's office, and the office of curricular affairs. Means and standard deviations were computed for each group, and the MAPP students and the non-MAPP students were compared using analysis of variance to assess the statistical significance of any differences. RESULTS: The non-MAPP students were significantly better than were the MAPP students in terms of Medical College Admission Test scores, undergraduate gradepoint averages, grades for three major second-year courses, and performances on Steps 1 and 2 of the U.S. Medical Licensing Examination (all p < .001). There was no significant difference between the groups in grades for three major first-year courses or five major third-year courses. None of the MAPP students has been dropped for academic reasons. CONCLUSION: The MAPP program takes medical school applicants who have been rejected because of their preadmission performances, given them the opportunity to show that they can perform at the medical school level by taking the anatomy courses with the regular medical students, and accepts those who are successful. The results suggest that those chosen can satisfactorily complete the requirements for the MD degree.

Geographically indirect immigration to Canada: description and analysis.

"This article is concerned with geographically indirect immigration to Canada over the period 1968-1988. A geographically indirect immigrant is an individual legally admitted to Canada whose country of last permanent residence differs from country of birth. Records maintained by Employment and Immigration Canada on every immigrant legally admitted over the period were used in the study. Relative to geographically direct immigrants, geographically indirect immigrants tend to be older, more educated, and more highly skilled. Moreover, if they were not born in an English or French speaking country, indirect immigrants are more likely to speak English and/or French capably than direct migrants born in such countries. The study also contains bivariate logit estimates of a model of geographically indirect Canadian immigration. This model suggests that indirect migrants tend to be influenced by personal characteristics (age, sex, marital status, occupation, language ability), as well as by various characteristics of the country of birth (distance from Canada, income level, political conditions)."

Role of the self-image and smoker stereotype in smoking onset during early adolescence: a longitudinal study.

The present study utilized a longitudinal design to assess whether self-consistency or self-enhancement motives are predictive of future smoking onset. Participants were 1,222 nonsmoking 5th through 8th graders who were followed into the next academic year. The results showed that teens who were above the median in similarity between their self-image and smoker stereotype on coolness, sociability, and intelligence were almost twice as likely to show smoking onset at the 2nd measurement. This is supportive of a self-consistency motive for adolescent smoking. The results of this study provide an important extension to previous cross-sectional research in this area.

Preschoolers' strategic behavior and performance on a same-different task.

Preschoolers' strategic behavior was examined on a task in which they must decide whether two arrays are the same. Fifty-six 3- and 4-year-olds selected doors to open which exposed parts of the arrays. Children made moderate use of an appropriate "vertical-pairs" strategy - viewing spatially corresponding parts of the two arrays - and it facilitated performance. Telling nonstrategic children to use the strategy or executing it for them improved their same-different judgments. However, increased spontaneous production of the vertical-pairs strategy over trials did not consistently improve judgments, which suggests a strategy utilization deficiency. Other microgenetic analyses revealed that children tended to use several strategies over the trials and that strategy changes often were not developmentally progressive or driven by failure of another strategy. The discussion addressed production and utilization deficiencies and the diversity of strategy development.

The minimal sequence needed to define a functional DNA terminator in Bacillus subtilis.

The 47 bp DNA replication terminator (IRI) of Bacillus subtilis, contains two binding sites, A and B, for the replication terminator protein (RTP). Each site binds a dimer of RTP. Removal of the first two base-pairs (bp 1-2) from IRI completely destroyed in vivo terminator (fork arrest) function and was accompanied by loss of RTP binding to the A site, which is distal to the approaching fork that is arrested. Removal of base-pairs 34 to 47 from the other end, proximal to the approaching fork, lowered in vivo function to approximately 50% of the complete IRI. RTP binding appeared to be largely unaffected. Terminator function remained at the approximately 50% level with further deletions that proceeded as far as to include base-pair 28; and RTP binding remained largely unaffected. Removal of more of the sequence beyond base-pair 27 and into the region that makes extensive contact with RTP resulted in a further impairment to in vivo function, and caused altered RTP binding. The base-pairs 1 to 24 segment retained only 16% fork arrest activity and the effect on RTP binding was largely evidenced by an elimination of the ability of this extensively truncated sequence to fill the B site alone. The behaviour of the various terminator deletions emphasize the importance of the previously defined RTP-DNA contacts which allow the binding of RTP to the two overlapping sites, A and B, of IRI for terminator function. A comparison of the affinities of selected truncated terminators for RTP raises the possibility that the overall affinity of RTP for its DNA terminator is not the sole determinant of terminator function.

The Bacillus subtilis replication terminator system functions in Escherichia coli.

The Bacillus subtilis DNA terminators, IRI + IRII, were inserted into the Escherichia coli plasmid pACYC184 such that the IRI terminator would be in its active orientation with respect to the approaching unidirectionally moving replication fork. When this new plasmid was transferred into E. coli, harbouring an expression plasmid producing the B. subtilis terminator protein RTP, fork arrest was observed to occur at the position of the inserted terminator region. Thus, the B. subtilis replication terminator system can function in E. coli. It was shown that the B. subtilis system operated with approximately 30% of the efficiency of the E. coli system utilizing the R6K TerR2 DNA terminator and the E. coli Tus terminator protein. Assuming that RTP and Tus have quite different folded structures these results suggest that fork arrest in B. subtilis is not dependent upon a highly specific recognition and interaction between RTP positioned on the DNA terminator and a component(s) of the approaching replisome.

Peer influence on smoking initiation during early adolescence: a comparison of group members and group outsiders.

In this study, the authors compared group members' and group outsiders' susceptibility to the influence of their friends' smoking. Ss were nonsmokers in Grade 7 who were observed for 1 year. Consistent with their hypothesis, the authors found that group outsiders (Ss who did not have reciprocal friends) were affected more by the smoking of their best friend and by the overall level of smoking among their friends than group members were. Furthermore, this peer influence was strongest for teens who were very concerned about their friends' reactions to their substance use. In addition, consistency in smoking status was related to the formation, but not the breakdown, of reciprocal friendships. Results indicated that teenagers may view smoking as a vehicle for entering a desired friendship group. The authors suggest ways that prevention programs might address this mechanism for adolescent smoking initiation.

Understanding death and grief for children three and younger.

Although the average toddler's cognitive skills may be limited, children three and younger have emotional responses to the death of someone they have known. Theories and research indicate that children's individual characteristics, their developmental stage including cognitive level, and their environmental and familial experiences must be considered to understand their grief. Myriad misconceptions and euphemisms can complicate and exacerbate children's grief. The authors address the possibilities for age-appropriate, theory-based interventions by clinicians and parents to effectively assist children three and younger in their grief work.

Vanilloids. 1. Analogs of capsaicin with antinociceptive and antiinflammatory activity.

As part of a program to establish structure-activity relationships for vanilloids, analogs of the pungent principle capsaicin, the alkyl chain portion of the parent structure (and related compounds derived from homovanillic acid) was varied. In antinociceptive and antiinflammatory assays (rat and mouse hot plate and croton oil-inflamed mouse ear), compounds with widely varying alkyl chain structures were active. Short-chain compounds were active by systemic administration in the assays mentioned above but they retained the high pungency and acute toxicity characteristic of capsaicin. In contrast, the long chain cis-unsaturates, NE-19550 (vanillyloleamide) and NE-28345 (oleylhomovanillamide), were orally active, less pungent, and less acutely toxic than capsaicin. The potential of these compounds as antiinflammatory/analgesic agents is discussed in light of recent data on the mechanism of action of vanilloids on sensory nerve fibers.

Racial differences in sexual behaviors related to AIDS in a nineteen-city sample of street-recruited drug injectors. NADR Consortium.

Questionnaire data from almost 12,000 street-recruited drug injectors in 19 cities were analyzed to determine racial differences that may affect transmission of the human immunodeficiency virus (HIV). Self-reported sexual behaviors of drug injectors differ by city-type. White male drug injectors reported less unprotected vaginal sex than black or Latino males in multicultural--black/white/Mexican-origin and biracial cities. Black drug users of both sexes were less likely than white or Latino drug users to report unprotected and sex in multicultural--black/white/Mexican-origin and multicultural--black/white/Puerto Rican cities. The reported percentage of sex acts in which a condom was used was similar for black, white, and Puerto Rican men, and for black and white women, in all city types, but Puerto Rican women reported more condom use than black women. Mexican-origin drug injectors of each gender were least likely to report using condoms in multicultural--black/white/Mexican-origin cities. Black drug injectors are particularly likely to report having sex partners who do not inject drugs, as are Puerto Rican men and as are whites in multicultural--black/white/Mexican-origin cities. High-risk sex without condoms is widely reported among all groups of drug injectors studied: Each racial/gender group in each city-type averaged 15 or more episodes of unprotected vaginal sex per month, and 10% of most subgroups report having anal sex within the past 6 months. At least 45% of subjects in each city-type reported sex with noninjectors of the opposite gender. Without continued and expanded intervention, these data are consistent with HIV spreading to drug injectors, their sexual partners, and their future children, in all racial/ethnic groups.

Professional development framework. Pathway to the future.

Staff development educators in a large midwestern university hospital developed a framework for professional development. The framework, applicable to all nurses, has four levels of professional development, from professional awareness to professional mastery. Within each developmental level five dimensions of nursing practice are identified: nursing process and practice skills, communication/collaboration, leadership, professional integration, and research/evaluation. This framework for professional development is reported and its potential use in the areas of planning, development and evaluation of staff development programs; restructure of a clinical ladder for nurses; and individual career development is discussed.

High-potency dipeptide sweeteners. 2. L-aspartylfuryl-, thienyl-, and imidazolylglycine esters.

Eight L-aspartyl dipeptides derived from heterocyclic glycine esters were prepared and evaluated as sweeteners. The fenchyl esters of L-aspartyl-2-furyl-, 2- and 3-thienyl-, and imidazolylglycine were all potently sweet with the D-2-furylglycine (+)-beta-fenchyl ester being the most potent at 16,500 times the potency of sucrose. The requirement for a planar heterocyclic group directly attached to the glycine carbon atom was demonstrated by the observation that the tetrahydrofuryl and beta-thienylalanine fenchyl esters were not sweet. The heteroaromatic glycine esters join the phenylglycine esters as a novel class of dipeptide sweeteners with very high potency.

High potency dipeptide sweeteners. 1. L-aspartyl-D-phenylglycine esters.

Twenty esters of L-aspartyl-D-phenylglycine, as well as two substituted analogues, an o-fluoro and a p-hydroxy-phenylglycine ester, were prepared. The L-aspartyl-D-phenylglycine (-)-alpha- and (+)-beta-fenchyl esters had the highest sweetness potency at 1200 and 3700 times that of sucrose, respectively. The high potency of these sweeteners is surprising as the phenyl group occupies a position previously believed to accommodate only much smaller groups.