Red Blood Cells from Individuals with Abdominal Obesity or Metabolic Abnormalities Exhibit Less Deformability upon Entering a Constriction.

Abdominal obesity and metabolic syndrome (MS) are multifactorial conditions associated with increased risk of cardiovascular disease and type II diabetes mellitus. Previous work has demonstrated that the hemorheological profile is altered in patients with abdominal obesity and MS, as evidenced for example by increased whole blood viscosity. To date, however, no studies have examined red blood cell (RBC) deformability of blood from individuals with obesity or metabolic abnormalities under typical physiological flow conditions. In this study, we pumped RBCs through a constriction in a microfluidic device and used high speed video to visualize and track the mechanical behavior of ~8,000 RBCs obtained from either healthy individuals (n = 5) or obese participants with metabolic abnormalities (OMA) (n = 4). We demonstrate that the OMA+ cells stretched on average about 25% less than the healthy controls. Furthermore, we examined the effects of ingesting a high-fat meal on RBC mechanical dynamics, and found that the postprandial period has only a weak effect on the stretching dynamics exhibited by OMA+ cells. The results suggest that chronic rigidification of RBCs plays a key role in the increased blood pressure and increased whole blood viscosity observed in OMA individuals and was independent of an acute response triggered by consumption of a high-fat meal

Positive Attitudes as a Mediator Between Moral Disengagement and Cyberbullying Behaviors

Objective. The current study examined whether (1) higher moral disengagement scores would be positively correlated with higher frequencies of engaging in cyberbullying, (2) positive attitude scores would be positively correlated with higher frequencies of engaging in cyberbullying, and (3) positive attitudes towards cyberbullying would mediate links between moral disengagement and frequency of engaging in cyberbullying. Method. Three surveys, the Mechanisms of Moral Disengagement Scale (MMD), Cyberbullying Perpetration Measure (CPM), and Positive Attitudes towards Cyberbullying Questionnaire (PATC) were administered to 114 undergraduate students. Results. Correlational analysis indicated significant positive correlations between PATC and CPM scores (r = .442, p \u3c .01), CPM and MMD scores (r = .199, p \u3c .05) and MMD and PATC scores (r = .591, p \u3c .01). Therefore all preconditions for mediation analysis were met. Several regression analyses were conducted to determine the mediation effects of positive attitudes toward cyberbullying on the relationship between cyberbullying behaviors, moral disengagement, and sex. Moral disengagement regressed onto cyberbullying behaviors with statistical significance, indicating there was a relationship that could be mediated (R = .246, p \u3c .05) Moral disengagement also regressed significantly onto positive attitudes toward cyberbullying, establishing a link between the two predictors (R = .596, p \u3c .001). A large, positive correlation was found between self-reported cyberbullying behavior in college students and the optimal linear combination of predictors (R = .462, p \u3c .001), such that as self-reported cyberbullying behaviors increased, so did positive attitudes towards cyberbullying and moral disengagement. In the final regression model, moral disengagement was not statistically significant (B = -.041, p = .250), resulting in complete mediation by positive attitudes toward cyberbullying. Implications. While previous research has shown moral disengagement to be a potential factor in reasons for cyberbullying perpetration behaviors, the current study found that moral disengagement required positive attitudes toward cyberbullying in order to evoke higher rates of cyberbullying. As there is relatively little research examining the relationship between cyberbullying behaviors, moral disengagement, and positive attitudes towards cyberbullying, future research would do well to further investigate these links. Concerning educational bullying prevention and awareness programs, program developers are advised to target attitude change and to include information regarding moral disengagement and its potentially harmful effects

Macrophages and Intravascular OCT Bright Spots A Quantitative Study

ObjectivesThis study hypothesized that bright spots in intravascular optical coherence tomography (IVOCT) images may originate by colocalization of plaque materials of differing indexes of refraction. To quantitatively identify bright spots, we developed an algorithm that accounts for factors including tissue depth, distance from light source, and signal-to-noise ratio. We used this algorithm to perform a bright spot analysis of IVOCT images and compared these results with histological examination of matching tissue sections.BackgroundBright spots are thought to represent macrophages in IVOCT images, and studies of alternative etiologies have not been reported.MethodsFresh human coronary arteries (n = 14 from 10 hearts) were imaged with IVOCT in a mock catheterization laboratory and then processed for histological analysis. The quantitative bright spot algorithm was applied to all images.ResultsResults are reported for 1,599 IVOCT images co-registered with histology. Macrophages alone were responsible for only 23% of the bright spot-positive regions, although they were present in 57% of bright spot-positive regions (as determined by histology). Additional etiologies for bright spots included cellular fibrous tissue (8%), interfaces between calcium and fibrous tissue (10%), calcium and lipids (5%), and fibrous cap and lipid pool (3%). Additionally, we showed that large pools of macrophages in CD68(+) histology sections corresponded to dark regions in comparative IVOCT images; this is due to the fact that a pool of lipid-rich macrophages will have the same index of refraction as a pool of lipid and thus will not cause bright spots.ConclusionsBright spots in IVOCT images were correlated with a variety of plaque components that cause sharp changes in the index of refraction. Algorithms that incorporate these correlations may be developed to improve the identification of some types of vulnerable plaque and allow standardization of IVOCT image interpretation

Functions of Candida albicans cell wall glycosidases Dfg5p and Dcw1p in biofilm formation and HOG MAPK pathway

Background Candida albicans is a commensal fungus that inhabits the oral mucosal surface and causes oral and systemic candidiasis. Oral candidiasis most commonly occurs in patients with AIDS, denture wearers and newborn children. Systemic candidiasis occurs mainly in immunocompromised patients and patients admitted to hospitals for prolonged periods. C. albicans homologous genes, DFG5 and DCW1, encode for two closely related cell wall proteins with putative glycosyltransferase enzyme activity and C-terminal GPI-anchors. Past studies have shown that individual DFG5 and DCW1 mutations are viable but simultaneous deletion of DFG5 and DCW1 in C. albicans results in lethality. However, the exact functions of these cell wall based enzymes, which represent potential drug targets, are not understood. Methods C. albicans DFG5/DCW1 heterologous and conditional double mutant strains were assessed for growth and biofilm formation in comparison to wild type and parental strains. Cell wall and heat stress susceptibility of the mutant and control strains were assessed using agar spotting assays. Growth was assessed under normal and osmotic stress conditions along with light microscopy imaging. Biofilm dry weight and microscopic imaging analysis of biofilms was performed. Hypha formation in response to serum was analyzed using light microscopy imaging. Western blot analysis of mutant strains and control strains was performed to assess Hog1 basal levels and phosphorylation status. Results Analysis of the heterologous mutants indicated that Dfg5p is more important for growth while Dcw1p appeared to play a role in cell wall integrity response. The conditional double mutant was observed to be less resistant to cell wall stress. However, growth of the mutants was similar under control and osmotic stress conditions. The mutants were also able to grow similar to wild type under heat stress. Biofilm formation was reduced in the mutants where DFG5 was deleted or suppressed. Hyphal morphogenesis was reduced although germ tube formation was observed in the biofilms of the mutant strains. Basal Hog1 protein levels were reduced or absent in the DFG5 and DCW1 mutants. However, osmotic stress was able to induce Hog1 protein levels comparable to wild type. Hog1 phosphorylation appeared to be slightly reduced although not significantly. In addition to biofilm assays, serum dose response imaging analysis indicated that hyphae formation in DFG5 and DCW1 mutants was defective. Conclusions These data indicate that DFG5 and DCW1 are required for hyphal morphogenesis and biofilm formation in C. albicans. These functions may be regulated via basal Hog1 MAPK which is required for transcriptional regulation of chitin synthesis

Advancing Health Equity in the US Military

Eliminating health disparities and achieving health equity are central to US national health objectives and the Military Health System’s “quadruple aim,” which has readiness as its core aim. Because military service members enjoy universal eligibility for health care, it is sometimes assumed that health disparities do not exist in the Department of Defense (DoD). However, while some studies have shown that disparities have been attenuated or eliminated in the DoD, others suggest that significant disparities remain. Reasons these disparities may remain include that universal eligibility for care does not necessarily result in equal to access to care, and that equal access to care does not necessarily result in health equity. Priority groups for DoD health equity research and advocacy efforts should include: racial and ethnic minorities, sexual and gender minorities, women, and enlisted ranks. The DoD can advance health equity by improving data quality, increasing relevant population health research, targeting interventions towards the social determinants of health, improving the health care experience, and integrating DoD health equity efforts with those in the US society at large

Helicity-Selective Enhancement and Polarization Control of Attosecond High Harmonic Waveforms Driven by Bichromatic Circularly Polarized Laser Fields

source of bright, circularly polarized, extreme ultraviolet, and soft x-ray beams, where the individual harmonics themselves are completely circularly polarized. Here, we demonstrate the ability to preferentially select either the right or left circularly polarized harmonics simply by adjusting the relative intensity ratio of the bichromatic circularly polarized driving laser field. In the frequency domain, this significantly enhances the harmonic orders that rotate in the same direction as the higher-intensity driving laser. In the time domain, this helicity-dependent enhancement corresponds to control over the polarization of the resulting attosecond waveforms. This helicity control enables the generation of circularly polarized high harmonics with a user-defined polarization of the underlying attosecond bursts. In the future, this technique should allow for the production of bright highly elliptical harmonic supercontinua as well as the generation of isolated elliptically polarized attosecond pulses.H. K. and M. M. graciously acknowledge support from the Department of Energy BES Award No. DE-FG02- 99ER14982 for the experimental implementation, as well as a MURI grant from the Air Force Office of Scientific Research under Award No. FA9550-16-1-0121 for the theory. J. E. and C. M. acknowledge support from National Science Foundation Graduate Research Fellowships (Grant No. DGE-1144083). C. H.-G. acknowl- edges support from the Marie Curie International Outgoing Fellowship within the EU Seventh Framework Programme for Research and Technological Development (2007-2013), under REA Grant No. 328334, from Junta de Castilla y León (Project No. SA046U16) and Spanish Ministerio de Economía y Competitividad, MINECO (Projects No. FIS2013-44174-P and No. FIS2016-75652-P). Part of this work utilized the Janus supercomputer, which is sup- ported by the U.S. National Science Foundation (Grant No. CNS-0821794) and the University of Colorado Boulder

Phase matching of noncollinear sum and difference frequency high harmonic generation above and below the critical ionization level

We investigate the macroscopic physics of noncollinear high harmonic generation (HHG) at high pressures. We make the first experimental demonstration of phase matching of noncollinear high-order-difference-frequency generation at ionization fractions above the critical ionization level, which normally sets an upper limit on the achievable cutoff photon energies. Additionally, we show that noncollinear high-order-sum-frequency generation requires much higher pressures for phase matching than single-beam HHG does, which mitigates the short interaction region in this geometry. We also dramatically increase the experimentally realized cutoff energy of noncollinear circularly polarized HHG, reaching photon energies of 90 eV. Finally, we achieve complete angular separation of high harmonic orders without the use of a spectrometer.Department of Energy BES Award DE-FG02-99ER14982. MURI grant from the Air Force Office of Scientific Research under Award Number FA9550-16-1-0121. National Science Foundation Graduate Research Fellowship (DGE-1144083). Junta de Castilla y León (Project SA046U16) and Spanish MINECO (FIS2013-44174-P, FIS2016-75652-P)

Acute effects of nicotine on visual search tasks in young adult smokers

Rationale Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed