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Objective: To assess the degree to which information retrieved from a biomedical database can augment personal knowledge in addressing novel problems, and how the ability to retrieve information evolves over time.Design: This longitudinal study comprised three assessments of two cohorts of medical students. The first assessment occurred just before student course experience in bacteriology, the second occurred just after the course, and the third occurred five months later. At each assessment, the students were initially given a set of bacteriology problems to solve using their personal knowledge only. Each student was then reassigned a sample of problems he or she had answered incorrectly, to work again with assistance from a database containing information about bacteria and bacteriologic concepts. The initial pass through the problems generated a "personal knowledge" score; the second pass generated a "database-assisted" score for each student at each assessment.Results: Over two cohorts, students' personal knowledge scores were very low (approximately 12%) at the first assessment. They rose substantially at the second assessment (approximately 48%) but decreased six months later (approximately 25%). By contrast, database-assisted scores rose linearly: from approximately 44% at the first assessment to approximately 57% at the second assessment, to approximately 75% at the third assessment.Conclusion: The persistent increase in database-assisted scores, even when personal knowledge had attenuated, was the most remarkable finding of this study. While some of the increase may be attributed to artifacts of the design, the pattern seems to result from the retained ability to recognize problem-relevant information in a database even when it cannot be recalled. [ABSTRACT FROM AUTHOR]

Background and Aims: The Incentive Sensitization Theory (IST) offers a comprehensive framework that explains how attentional mechanisms contribute to the maintenance and relapse of addictive behavior. However, the extent to which the underlying neuropsychological mechanisms are consciously accessible for report remains unknown. Thus, the aim of this study was to investigate the association between self-reported wanting and liking among smokers and its relationship with detecting changes in smoking-related stimuli., Design: An online experiment was designed deploying a flicker paradigm with neutral and smoking-related changes, completed by 422 individuals (mean age = 29.1 years, 214 non-smokers, 123 current smokers, and 85 former smokers). Additionally, the Fagerström Test for Cigarette Dependence and the Imaginative Wanting and Liking Questionnaire were administered., Findings: Consistent with prior research findings, smokers exhibited faster detection of smoking-related changes compared to non-smokers, while former smokers displayed an intermediate level of attentional bias, falling between the levels observed in smokers and non-smokers. Further, higher levels of nicotine dependence were associated with a greater discrepancy between self-reported wanting and liking, which was associated with better change detection performance for high salience smoking-related stimuli in smokers., Conclusion: These findings support the predictions of IST and support the notion that attentional bias might develops early in the course of nicotine addiction. Furthermore, the results indicate that the underlying cognitive mechanisms might be partially within conscious awareness, which opens up potential avenues for research design, treatment, and interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 File, Petro, Kojouharova, Kővári, Gaál, Demetrovics and Czigler.)

To date, little research has been conducted to understand the role of psychological distances on smoking behaviour. Construal Level Theory posits that individuals mentally construe events, objects, or ideas based on their perceived distance in terms of spatial, temporal, social, and hypothetical dimensions, influencing their judgments and decision-making processes. The aim of the current study was (1) to provide a comprehensive exploration of psychological distances of costs and benefits of tobacco smoking and antismoking intention and (2) to examine whether smoking can be attributed to rational behaviour based on the psychological distance weighted balance of perceived costs and benefits of quitting and continuing smoking. Mediation models delineating the relationships among temporal and hypothetical psychological distances, personal relevance and antismoking intention were tested on cross-sectional survey data of 1486 smokers (880 men, M age  = 39.9 years, SD = 13.36). Psychological distances were shown to be important factors in the cognitive evaluation process of smoking behaviour. Perceived temporal distance to smoking continuation/cessation was related to personal importance and hypothetical psychological distances, which were associated with anti-smoking intention. Furthermore, antismoking intention was related to the psychological distance-weighted gain-cost balance of quitting and continuing smoking. The current findings enhance our knowledge of the cognitive evaluation of the outcomes of smoking, indicating that the choice of not quitting smoking may be partially based on a biased rational decision-making process., (© 2023. The Author(s).)

Background and Aims: The aim of the present study was to examine the mental representations of the use of different substances and other potentially addictive behaviors in order to explore meaningful similarities and differences that may contribute to a better understanding of behavioral addictions' representations and diagnostic criteria., Methods: The authors mapped the mental and emotional representations of 661 participants (70.5% women; Mage = 35.2 years, SD = 11.7) to the concept "your most disturbing excessive activity" using free-word associations combined with a network-based clustering method., Results: The network analyses identified four distinct mental representations, three implicating dominantly negative (Guilt/Shame/Relief, Addiction/Health, and Procrastination/Boredom) and one dominantly positive emotion (Stress/Relaxation). The distribution of Addiction/Health and Procrastination/Boredom representations were different across substance use and problem behaviors, indicating meaningful differences in the underlying cognitive evaluation processes. The Addiction/Health representation was more frequent for substances, while for other addictive behaviors, the Procrastination/Boredom representation was more frequent, and its frequency increased with the self-reported intensity of the behavior. Guilt/Shame/Relief was equally common for both substances and behaviors, but importantly, for substances its' likelihood increased with the intensity of use., Conclusion: The common part of representations for substance use and other potentially addictive behaviors supports the scientific viewpoint, that real addictions can exist even in the absence of psychoactive drugs. Based on the results, a novel proposition is posited, that a more appropriate indicator of tolerance for problem behaviors might be the perceived amount of time wasted on the activity rather than the actual time spent., Competing Interests: ELTE Eötvös Loránd University receives funding from the Szerencsejáték Ltd. to maintain a telephone helpline service for problematic gambling. ZD has also been involved in research on responsible gambling funded by Szerencsejáték Ltd. and the Gambling Supervision Board and provided educational materials for the Szerencsejáték Ltd’s responsible gambling program. The University of Gibraltar receives funding from the Gibraltar Gambling Care Foundation. MDG’s university has received research funding from Norsk Tipping (the gambling operator owned by the Norwegian Government). MDG has also received funding for a number of research projects in the area of gambling education for young people, social responsibility in gambling and gambling treatment from Gamble Aware (formerly the Responsible Gambling Trust), a charitable body which funds its research program based on donations from the gambling industry. MDG regularly undertakes consultancy for various gaming companies in the area of social responsibility in gambling. However, these funding sources are not related to the present study and the funding institution had no role in the study design or the collection, analysis, and interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 File et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Based on the two-factor model of creativity, two distinct types of creative problem solving can be differentiated: innovative ("do things differently") and adaptive ("do things better"). Flexible cognitive control is a crucial concept in connection with both general and specific styles of creativity: innovative problem-solving benefits from broader attention and flexible mental set shifting; while adaptive creativity relies on focused attention and persistent goal-oriented processes. We applied an informatively cued task-switching paradigm which is suitable for measuring different cognitive control processes and mechanisms like proactive and reactive control. We hypothesized that adaptive creativity is connected to effective proactive control processes, while innovative creativity is based on reactive task-execution. As we have found no previous evidence how age-related changes in cognitive control affects creative cognition; we also examined the effect of healthy aging on different problem-solving styles in an explorative way., Methods: Our participants, 37 younger (18-30 years) and 37 older (60-75 years) adults, were divided into innovative and adaptive creative groups according to the Torrance Test of Creative Thinking's Figural Subtest (Hungarian version)., Results: Our results showed that among younger adults the adaptively creative group had larger cue-locked CNV component (effective preparatory activity connected to proactive control), while the innovatively creative group had a larger target-locked P3b component (effective target evaluation and categorization in line with reactive control) which supports a functional difference in the two creative styles. By contrast, in older adults innovative problem-solving showed larger mixing costs (less effective maintenance and selection of task sets), and the lack of trial type effect on target-locked N2b (target-induced goal reactivation and less effective conflict resolution); while adaptive problem-solving caused them to make fewer errors (accuracy-oriented behavior)., Discussion: All in all, innovative and adaptive creativity is based on distinct cognitive control mechanisms in both age-groups, but their processing level is affected by age-related changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nagy, Czigler, Csizmadia, File, Fáy and Gaál.)

Change blindness experiments had demonstrated that detection of significant changes in natural images is extremely difficult when brief blank fields are placed between alternating displays of an original and a modified scene. On the other hand, research on the visual mismatch negativity (vMMN) component of the event-related potentials (ERPs) identified sensitivity to events (deviants) different from the regularity of stimulus sequences (standards), even if the deviant and standard events are non-attended. The present study sought to investigate the apparent controversy between the experience under the change blindness paradigm and the ERP results. To this end, the stimulus of Rensink, O'Reagen, and Clark (1997) was adapted to a passive oddball ERP paradigm to investigate the underlying processing differences between the standard (original) and deviant (altered) stimuli measured in 22 subjects. Posterior negativity within the 280-330 ms latency range emerged as the difference between ERPs elicited by standard and deviant stimuli, identified as visual mismatch negativity (vMMN). These results raise the possibility that change blindness is not based on the lack of detailed visual representations or the deficiency of comparing two representations. However, effective discrimination of the two scene versions requires considerable frequency differences between them., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 File, Petro, Gaál, Csikós and Czigler.)

A few studies have examined the changes in substance- and behavior-related "wanting" and "liking" of human subjects, the key properties of Incentive Sensitization Theory (IST). The aim of this study was to examine the dissociation between "wanting" and "liking" as a function of usage frequency, intensity, and subjective severity in individuals across four substances (alcohol, nicotine, cannabis, and other drugs) and ten behaviors (gambling, overeating, gaming, pornography use, sex, social media use, Internet use, TV-series watching, shopping, and work). Also, the potential roles of impulsivity and reward deficiency were investigated in "wanting," "liking," and wellbeing. The sex differences between "wanting" and "liking" were also examined. Based on our findings using structural equation modeling with 749 participants (503 women, M age = 35.7 years, SD = 11.84), who completed self-report questionnaires, "wanting" increased with the severity, frequency, and intensity of potentially problematic use, while "liking" did not change. Impulsivity positively predicted "wanting," and "wanting" positively predicted problem uses/behaviors. Reward deficiency positively predicted problem uses/behaviors, and both impulsivity and problem uses/behaviors negatively predicted wellbeing. Finally, women showed higher levels of "wanting," compared to men. These findings demonstrate the potential roles of incentive sensitization in both potentially problematic substance uses and behaviors., Competing Interests: ELTE Eötvös Loránd University receives funding from the Szerencsejáték Ltd. to maintain a telephone helpline service for problematic gambling. ZD has also been involved in research on responsible gambling funded by Szerencsejáték Ltd. and the Gambling Supervision Board and provided educational materials for the Szerencsejáték Ltd's responsible gambling program., (Copyright © 2022 File, Bőthe, File and Demetrovics.)

Visual mismatch negativity (vMMN) is the electrophysiological correlate of automatic detection of unattended changes in the visual environment. However, vMMNs' relatedness to spatial attention has not been explicitly tested. Thus, the aim of the study was to investigate the effects of spatial attention on the vMMN event-related potential component. To this end, participants were instructed to fixate and attend to task-related stimuli. In an oddball sequence, offset stimuli were applied, i.e., from time-to time, the two sides of permanently presented objects disappeared. Distance between the task-related and unrelated events resulted in the typical finding of spatial attention; the amplitude of the N1 component was larger at the shorter distance between the two kinds of events. VMMN was elicited by the deviant vanishing parts, with no reliable effect of distance between the task-field and vMMN-related stimuli. In terms of the difference potentials, vMMN was followed by a positive posterior component in the 270-330 ms range. This positivity was much larger when the task-field was close to vMMN-related stimuli. The reappearance of the vanishing parts was also investigated. The reappearance of the whole objects after a deviant offset elicited vMMN but only when the task-field was close to the oddball sequence. We concluded that infrequently vanishing parts of objects are detected automatically. However, these deviant events initiate orientation only if the objects are close to the field of task-relevant events. Similarly, automatic registration of the rare but expected events are registered only in the visual field close to the focus of attention., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: The efficacy of alcohol reduction applications is variable, and the underlying factors are largely unknown. The aim of this study is threefold: evaluate the relationship between user engagement and intervention efficacy, investigate the efficacy of the different functions applied, and investigate the efficacy of the intervention application compared to control groups., Methods: A randomized controlled trial will be conducted to determine the efficacy of a newly developed smartphone application compared to the controls in reducing alcohol consumption at a 30, 60, 90, 120, 150, and 180 days follow-up. Hazardous drinkers, aged 18 years or older, will be recruited through web articles and will be randomized (blinded to their allocation), to receive one of the two versions of the application (educational or control application) for 30 days, or will be allocated to a wait-list control group. Function usage times will be recorded on a single-user level to determine the association between application usage and efficacy., Results: Data collection will be completed by July 2020, and follow-up will be completed by January 2021., Conclusions: The evaluation of intervention efficacy as a function of user behavior will hopefully contribute to the science of developing more efficient alcohol intervention applications in the future., (© 2020 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons, Ltd.)

We studied whether, due to deteriorating inhibitory functions, older people are more likely to process irrelevant stimuli; and if so, could they later use this information better than young adults. In the study phase of our experiment, a Posner-type gaze-cued version of a Simon task was performed in which we presented task-irrelevant cues, where faces or patches with either left- or right-looking dots for the pupil of the eye preceded the task to press a button congruent or incongruent with the presentation side of the target stimulus. In the follow-up test phase, participants completed an unexpected facial recognition test. In the study phase not only a decreased P1, but also an increased N170 amplitude of the event-related potentials (ERPs) were found in older, compared to younger adults, and also for faces compared to patches. Even though in the test phase both age-groups could recognize the faces better than statistically by chance, neither the older nor the younger participants could discriminate them effectively. The late positive component (LPC)-the ERP correlates of the old/new effect, being the higher amplitude for the earlier presented stimuli when compared with the unseen stimuli during the recognition test-was not evolved in the older group, while a reversed old/new effect was seen in younger participants: higher amplitude was found in New-Right and Old-Wrong conditions (for faces they did not recognize independent of seeing them before) compared to Old-Right and New-Wrong conditions (for faces they thought they recognized from the study phase). In conclusion, although older adults showed enhanced processing of task-irrelevant stimuli compared to younger adults, as indicated by the N170 amplitude, however, they were not able to utilize this information in a later task, as was suggested by the recognition rate and LPC amplitude results., (Copyright © 2020 Gaál, Nagy, File and Czigler.)

We studied a Posner-type gaze-cued version of a Simon task to characterize age-related changes in visuospatial attention and inhibitory control. Earlier results had indicated that the direction of gaze is a strong social cue that speeds response times; so we wondered whether, as a task-irrelevant stimulus, it could compensate for age-related impairment of inhibitory processes in the elderly. Our results assessed the Simon effect by: reaction time, error rate, the P3 component and the lateralized readiness potential (LRP). We found that the Simon effect was larger in the older group confirming an increased sensitivity to interference and also suggesting a decreased inhibitory control in older adults. LRP results showed that aging and stimulus-response incongruency delayed the selection of the responses-indexed by longer s-LRP latency data-, and also decreased the efficiency of motor inhibition in the Simon task-the s-LRP amplitude of both wrong- and correct-side activation was larger in older adults, and the latency difference of these two components was longer in this age-group. Also a larger N2pc amplitude in the congruent, compared to incongruent gaze condition, showed an increased visuospatial attention when the gaze-cueing drew attention to the target stimulus. This gaze-cueing could not be ignored and hence it modified task processing in the older age group, which was evident in the incongruent Simon condition where the congruent gaze increased older adults' reaction time and their error rate; but there was no difference observed in the congruent Simon condition. Since the anticipated facilitation of reaction times did not occur, we suggest that general slowing and decreased inhibitory functions in the elderly caused the social cue not to be a supporting stimulus but rather to be a further burden on their cognitive processing., Competing Interests: The authors have declared that no competing interests exist.

Untreated, HER2+ disease is the most aggressive breast cancer phenotype; however, the development of multiple highly effective HER2-targeting drugs has transformed treatment and survival. These drugs include the anti-HER2 monoclonal antibodies trastuzumab and pertuzumab; small molecule inhibitors lapatinib, neratinib, and tucatinib; and antibody-drug conjugates trastuzumab emtansine (T-DM1) and now trastuzumab deroxtecan. More complex regimens using these drugs continue to improve outcomes, but the incremental benefits of these advances are often modest. Improved outcomes came from the addition of HER2-targeted therapies to conventional chemotherapy, beginning with trastuzumab, then pertuzumab added to trastuzumab, or with neratinib given for the year after trastuzumab. Neoadjuvant, or preoperative, administration of chemotherapy plus HER2-targeting allows surgical deescalation and tailoring treatment by pathologic complete response (pCR) to therapy. Patients with pCR after conventional therapy have excellent outcomes; what we now know is that the poorer outcomes associated with residual disease can be ameliorated with adjuvant T-DM1. However, as we have developed more complex, effective, and expensive therapy to maximize outcomes, it is also true that we are overtreating many patients. In stage I HER2+ breast cancer, there are excellent outcomes with paclitaxel plus trastuzumab or T-DM1 alone. Higher clinical stage HER2+ disease is still treated aggressively, although intrinsic subtype or activated immune tumor microenvironment may identify those with augmented treatment response or better outcome. It is likely that future strategies to escalate and de-escalate treatment with less chemotherapy, fewer anti-HER2 drugs, or shorter duration will depend upon integrated clinical and genomic modeling.

We investigated the effect of spatial attention on an event-related potential signature of automatic detection of violations of statistical regularities, namely, the visual mismatch negativity (vMMN). To vary the task-field and the location of vMMN-related stimulation, in the attentional field the stimuli of a tracking task with a steady and a moving (target) bar were presented. The target stimuli of the task appeared either relatively close or far from a passive (task-irrelevant) oddball or equiprobable sequence at the lower part of the screen. Stimuli of the oddball sequence were shapes tilted either 45° (standard, p = 0.8) or 135° (deviant, p = 0.2), while the equiprobable sequence consisted of additional three shapes with identical number of lines to the oddball stimuli. Deviant stimuli in close proximity to a continuously attended field elicited larger vMMN than similar stimuli farther away from the stimulus field. In the condition with a smaller distance between the field of the tracking task and the vMMN-related field, the deviant stimuli and the vMMN was followed by a posterior positivity. According to these results, spatial attention modulates vMMN and is capable of initiating further processing of the deviant stimuli., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The present study investigated the function of the brain activity underlying the visual mismatch negativity (vMMN) event-related potential (ERP) component. Snowflake patterns (complex stimuli) were presented as deviants and oblique bar patterns (simple stimuli) as standards, and vice versa in a passive oddball paradigm. Control (equiprobable) sequences of either complex shape patterns or oblique bar patterns with various orientations were also presented. VMMN appeared as the difference between the ERP to the oddball deviant and the ERP to the control (deviant minus control ERP difference). Apart from the shorter latency of the vMMN to the oblique bar pattern as deviant, vMMN to both deviants was similar, i.e., there was no amplitude difference. We attributed the function of the brain processes underlying vMMN to the detection of the infrequent stimulus type (also represented in memory) instead of a call for further processing (a possibility for acquiring more precise representation) of the deviant. An unexpected larger adaptation (control minus standard ERP difference) to the snowflake pattern was also obtained. We suggest that this was due to the acquisition of a more elaborate memory representation of the more complex stimulus.

Visual mismatch negativity (vMMN), an event-related signature of automatic detection of events violating sequential regularities is traditionally investigated at the onset of frequent (standard) and rare (deviant) events. In a previous study we obtained vMMN to vanishing parts of continuously presented objects (diamonds with diagonals), and we concluded that the offset-related vMMN is a model of sensitivity to irregular partial occlusion of objects. In the present study we replicated the previous results, but in order to test the object-related interpretation we applied a new condition with a set of separate visual stimuli: a texture of bars with two orientations. In the texture condition (offset of bars with irregular vs. regular orientation) we obtained vMMN, showing that the continuous presence of objects is unnecessary for offset-related vMMN. However, unlike in the object-related condition, reappearance of the previously vanishing lines also elicited vMMN. In principle reappearance of the stimuli is an event with probability 1.0, and according to our results, the object condition reappearance was an expected event. However, the offset and onset of texture elements seems to be treated separately by the system underlying vMMN. As an advantage of the present method, the whole stimulus set during the inter-stimulus interval saturates the visual structures sensitive to stimulus input. Accordingly, the offset-related vMMN is less sensitive to low-level adaptation that differs between the deviant and standard stimuli., Competing Interests: The authors have declared that no competing interests exist.

In this study we compared the event-related potentials (ERPs) obtained in two different paradigms: a passive visual oddball paradigm and an adaptation paradigm. The aim of the study was to investigate the relation between the effects of activity decrease following an adaptor (stimulus-specific adaptation) and the effects of an infrequent stimulus within sequences of frequent ones. In Experiment 1, participants were presented with different line textures. The frequent (standard) and rare (deviant) texture elements differed in their orientation. In Experiment 2, windmill pattern stimuli were presented in which the number of vanes differentiated the deviant and standard stimuli. In Experiment 1 the ERP differences elicited between the oddball deviant and the standard were similar to the differences between the ERPs to the nonadapted and adapted stimuli in the adaptation paradigm. In both paradigms the differences appeared as a posterior negativity with the latency of 120-140 ms. This finding demonstrates that the representation of a sequential rule (successive presentation of the standard) and the violation of this rule are not necessary for deviancy effects to emerge. In Experiment 2 (windmill pattern), in the oddball paradigm the difference potentials appeared as a long-lasting negativity. In the adaptation condition, the later part of this negativity (after 200 ms) was absent. We identified the later part of the oddball difference potential as the genuine visual mismatch negativity-that is, an ERP correlate of sequence violations. The latencies of the difference potentials (deviant minus standard) and the endogenous components (P1 and N1) diverged; therefore, the adaptation of these particular ERP components cannot explain the deviancy effect. Accordingly, the sources contributing to the standard-versus-deviant modulations differed from those related to visual adaptation; that is, they generated distinct ERP components.

The aim of our studies was to separate the effects of violating a sequential rule (genuine visual mismatch negativity; gvMMN) from the decreased activity in response to repeated stimuli (stimulus-specific adaptation; SSA) for simple and more complex stimuli. To accomplish this goal, different control procedures were applied with the aim of finding the correct control for vMMN studies. Event-related brain electric activity (ERPs) was measured in response to nonattended visual stimuli that were presented either in an oddball manner or in various control sequences. To identify the cortical sources of the different processes, the sLORETA inverse solution was applied to the average ERP time series. In Experiment 1, the stimuli were line textures, and the deviancy was different line orientations. SSA fully explained the deviant-related ERP effects (increased posterior negativity in the 105-190 ms range). In Experiments 2 and 3, windmill patterns were used. Infrequent windmill patterns with 12 vanes elicited gvMMN (posterior negativities in the 100-200 and 200-340 ms ranges), whereas in the case of the less complex (six vanes) stimuli, SSA explained the negative deflection in both latency ranges (178-216 and 270-346 ms). In Experiment 3, infrequent stimuli with six vanes elicited deviant-related posterior negativity within the sequence of less complex (four vanes) frequent patterns. We reconcile the discrepant results by proposing that the underlying processes of vMMN are not uniform but depend strongly on the eliciting stimulus and that the complexity difference between the infrequent and frequent stimuli has considerable influence on the deviant-related response.

Background: The airway epithelium can express factors that drive subepithelial airway remodeling. TGF-β2, vascular epithelial growth factor (VEGF), a disintegrin and metalloprotease 33 (ADAM33), and periostin are hypothesized to be involved in subepithelial remodeling and are overexpressed in adult asthmatic airways. Epidemiologic data suggest that lung function deficits in asthmatic patients are acquired in childhood., Objectives: We sought to determine whether airway epithelial cells (AECs) from asthmatic children differentially express TGF-β2, VEGF, ADAM33, or periostin compared with cells from atopic nonasthmatic and healthy children intrinsically or in response to IL-4/IL-13 stimulation., Methods: Bronchial and nasal epithelial cells were obtained from brushings from well-characterized asthmatic (n = 16), atopic nonasthmatic (n = 9), and healthy (n = 15) children after achievement of anesthesia for elective procedures. After differentiation at an air-liquid interface (ALI) for 3 weeks, conditioned media were sampled and RNA was extracted from unstimulated and IL-4/IL-13-stimulated cultures. TGF-β2 and VEGF levels were measured with ELISA. ADAM33 and periostin expression was assessed by using real-time PCR., Results: TGF-β2 and VEGF production was significantly greater in bronchial and nasal ALI cultures from asthmatic children than in cultures from atopic nonasthmatic and healthy children. TGF-β2 levels increased significantly in asthmatic cultures after IL-4/IL-13 stimulation. Within-subject correlation between nasal and bronchial ALI production of TGF-β2 (r = 0.64, P = .001) and VEGF (r = 0.73, P < .001) was good. Periostin expression was 3.7-fold higher in bronchial cells (P < .001) and 3.9-fold higher in nasal cells (P < .004) from asthmatic children than in cells from atopic nonasthmatic or healthy children. ADAM33 was not differentially expressed by AECs from asthmatic patients compared with that from cells from atopic nonasthmatic or healthy children., Conclusion: AECs from asthmatic children differentially express TGF-β2, VEGF, and periostin compared with cells from atopic nonasthmatic and healthy children. Nasal epithelial cells might be a suitable surrogate for bronchial cells that could facilitate investigation of the airway epithelium in future longitudinal pediatric studies., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

This study examined the potential contribution that access to a database of biomedical information may offer in support of problem-solving exercises when personal knowledge is inadequate. Thirty-six medical students were assessed over four occasions and three domains in the basic sciences: bacteriology, pharmacology, and toxicology. Each assessment consisted of a two-pass protocol in which students were first assessed for their personal knowledge of a domain with a short-answer problem set. Then, for a sample of problems they had missed, they were asked to use a database, INQUIRER, to respond to questions which they had been unable to address with their personal knowledge. Results indicate that for a domain in which the database is well-integrated in course activities, useful retrieval of information which augmented personal knowledge increased over three assessment occasions, even continuing to increase several months after course exposure and experience with the database. For all domains, even at assessments prior to course exposure, students were able to moderately extend their ability to solve problems through access to the INQUIRER database.

Secondary ion mass spectrometry (SIMS) is a surface analytical technique with high sensitivity for elemental detection and microlocalization capabilities within the micrometre range. Quantitative analysis of epoxy resins and gelatin have been reported (Burns-Bellhorn & File, 1979). We report here the first application of this technique to quantitative microlocalization in the context of a physiological problem--analyses of sodium, potassium and calcium in normal and galactose-induced cataract in rat lens. It is known that during the development of galactose-induced cataract the whole lens content of potassium is decreased, sodium is increased and, in late stages, calcium concentration increases. Whether these alterations in diffusible ions occur homogeneously or heterogeneously is not known. Standard curves were generated from epoxy resins containing known concentrations of sodium, potassium or calcium organometallic compounds using the Cameca IMS 300 Secondary Ion Mass Spectrometer. Normal and cataractous lenses were prepared by freezing in isopentane in a liquid nitrogen bath followed by freeze-drying at -30 degrees C. After dry embedding in epoxy resin, 10 microns thick sections of lens were pressure mounted on silicon wafers, overcoated with gold, and ion emission measured under the same instrumental conditions used to obtain the standard curves. Quantitative analysis of an area 27 microns in diameter, or a total analysed volume of 1.1 microns3, was performed by using a mechanical aperture in the ion optical system. Ion images provided qualitative microanalysis with a lateral resolution of 1 micron. Control rat lenses gave values for sodium and potassium content with a precision of +/- 17% or less. These values were compared to flame photometry and atomic absorption measurements of normal lenses and were accurate within 25%. Analysis of serum and blood also gave accurate and precise measurements of these elements. Normal rat lenses had a gradient of sodium, and, to a lesser degree, of potassium from the cortex to the nucleus. Development of galactose-induced cataract was heterogeneous by morphological criteria, beginning at the lens equator and spreading from the cortex into the nucleus. However, the loss of potassium and increase in sodium concentration occurred at early stages in both the cortex and nucleus cells, possibly because these cells are interconnected by gap junctions. There is a local alteration in elemental content prior to morphologically demonstrable cataract formation.(ABSTRACT TRUNCATED AT 400 WORDS)

We introduced a computerized database as part of a problem-oriented component of bacteriology instruction for first year medical students. This paper explores utilization of the computer resource and its effects on students' knowledge in the field.

We have made several observations during the course of our studies that show the presence of matrix effects in soft biological tissue and standards. The sputtering rate of gelatin is approximately twice that of epoxy resin, but the ion yield of lithium in gelatin is an order of magnitude less than in epoxy. Osmium impregnation of freeze-dried material significantly alters the localization of calcium, but not potassium and barium. The absolute count rate for calcium in osmicated tissue is increased several-fold above that in freeze-dried tissue. Scanning electron microscopy of sputtered material shows the formation of cones during sputtering, which is particularly, but not exclusively, associated with melanin granules and red blood cells. These structures are known to be highly emissive for Na, K, and Ca. Boron implanted tissue also exhibits selective boron emission from melanin granules. Relative proportions of monoatomic and polyatomic emission vary in epoxy, gelatin and tissue. Ion images of carbon, chlorine and vanadium in tissue embedded with a vanadium-doped epoxy resin show variations in local regions that correspond to tissue structure. The energy distributions of common secondary ions differed somewhat in resin and two different tissue regions. These examples show the existence of potential matrix effects in soft biological tissue that involve both differential sputtering and ion yield effects.