Comparative study of the stability of bimatoprost 0.03% and latanoprost 0.005%: A patient-use study

<p>Abstract</p> <p>Background</p> <p>The stability of ophthalmic preparations in multidose containers is influenced by the preservative as well as the stability of the active ingredient. Unstable drugs may require refrigeration to preserve their active ingredient level and they are more likely to degrade over time, therefore becoming more susceptible to degradation based on patient mishandling. The purpose of this study was to determine the degree of molecular degradation that occurs in bimatoprost and latanoprost in a patient-use setting.</p> <p>Methods</p> <p>This was an open-label, laboratory evaluation of the relative stability of bimatoprost and latanoprost. Patients presently using bimatoprost (n = 31) or latanoprost (n = 34) were identified at 2 clinical sites in Brazil. Patients were instructed to use and store their drops as usual and return all used medication bottles between day 28 and day 34 after opening.</p> <p>Results</p> <p>Bimatoprost demonstrated no degradation, but latanoprost degraded at various levels. The mean age of bimatoprost was 43.0 ± 3.4 days and the mean age of latanoprost was 43.9 ± 2.8 days (P = .072). The mean percentage of labeled concentration was 103.7% in the bimatoprost bottles and 88.1% in the latanoprost bottles (P < 001).</p> <p>Conclusion</p> <p>This study showed that bimatoprost maintained ≥100% concentration throughout the study period while latanoprost did not.</p

Seek Help from Teachers or Fight Back? Student Perceptions of Teachers’ Actions during Conflicts and Responses to Peer Victimization

Previous research has shown that teachers’ actions when addressing conflict on school grounds can shape adolescent perceptions regarding how well the school manages victimization. Our objective in this study was to determine how these perceptions influenced the likelihood that adolescent students would react to victimization scenarios by either seeking help from school authority or physically fighting back. Vignettes describing two events of victimization were administered to 148 ethnic minority adolescents (Latino, African American, and Asian backgrounds; 49% female) attending an urban high school with high rates of conflict. Positive perceptions of teachers’ actions during conflicts—assessed via a questionnaire tapping how teachers manage student conflicts both generally and in a specific instance of strife—predicted a greater willingness to seek help from school authority, which in turn negatively predicted self-reported aggressive responses to the victimization scenarios. Path analysis established the viability of this indirect effect model, even when we controlled for sex, beliefs about the acceptability of aggression, and previous levels of reactive aggression. Adolescents’ perceptions of teachers’ actions during conflicts are discussed in relation to social information processing models, improving student–teacher relations, and decreasing aggression at schools

Morphology of powerful suction organs from blepharicerid larvae living in raging torrents

BackgroundSuction organs provide powerful yet dynamic attachments for many aquatic animals, including octopus, squid, remora, and clingfish. While the functional morphology of suction organs from some cephalopods and fishes has been investigated in detail, there are only few studies on such attachment devices in insects. Here we characterise the morphology and ultrastructure of the suction attachment organs of net-winged midge larvae (genus Liponeura; Diptera: Blephariceridae) – aquatic insects that live on rocks in rapid alpine waterways where flow speeds can reach 3 m s− 1 – using scanning electron microscopy, confocal laser scanning microscopy, and X-ray computed micro-tomography (micro-CT). Furthermore, we study the function of these organs in vivo using interference reflection microscopy.ResultsWe identified structural adaptations important for the function of the suction attachment organs in L. cinerascens and L. cordata. First, a dense array of spine-like microtrichia covering each suction disc comes into contact with the substrate upon attachment, analogous to hairy structures on suction organs from octopus, clingfish, and remora fish. These spine-like microtrichia may contribute to the seal and provide increased shear force resistance in high-drag environments. Second, specialised rim microtrichia at the suction disc periphery were found to form a continuous ring in close contact and may serve as a seal on a variety of surfaces. Third, a V-shaped cut on the suction disc (“V-notch“) is actively opened via two cuticular apodemes inserting on its flanks. The apodemes are attached to dedicated V-notch opening muscles, thereby providing a unique detachment mechanism. The complex cuticular design of the suction organs, along with specialised muscles that attach to them, allows blepharicerid larvae to generate powerful attachments which can withstand strong hydrodynamic forces and quickly detach for locomotion.ConclusionThe suction organs from Liponeura are underwater attachment devices specialised for resisting extremely fast flows. Structural adaptations from these suction organs could translate into future bioinspired attachment systems that perform well on a wide range of surfaces

Anaplastic Lymphoma Kinase Is Required for Neurogenesis in the Developing Central Nervous System of Zebrafish

10.1371/journal.pone.0063757PLoS ONE85

Brokering Trust to Enhance Leadership: A Self-Monitoring Approach to Leadership Emergence

What kind of person is likely to emerge as an informal leader in the workplace? Experimental research shows that high self-monitors—who tend to adjust their attitudes and behaviors to the demands of different situations—emerge as informal leaders in temporary groups. By contrast, low self-monitors—who tend to be true to themselves in terms of consistency in attitudes and behaviors across different situations—are less likely to emerge as leaders. But this prior research does not address the criticism that the emergence of high self-monitors as leaders represents ephemeral impression management in the context of laboratory experiments. To address this issue, we collected and analyzed data from a 116-member high-technology firm. Our results show that self-monitoring is related not only to leadership emergence, but also to the provision of advice to co-workers. Further, people who occupied brokerage positions (being trusted by those who did not trust each other) tended to be seen as leaders if they were high rather than low self-monitors. From these results, we build a picture of the high self-monitoring emergent leader as someone who notices problems and ameliorates them through the provision of advice and the brokerage of relationships across social divides. The occupation of a structurally advantageous position may well be more advantageous for some (i.e., high self-monitors) relative to others (i.e., low self-monitors)

Nudel and FAK as Antagonizing Strength Modulators of Nascent Adhesions through Paxillin

Competition for binding to the cellular protein paxillin by the proteins Nudel and focal adhesion kinase is important for the proper regulation of cell adhesion and migration

Oxidative discolouration in whole-head and cut lettuce: biochemical and environmental influences on a complex phenotype and potential breeding strategies to improve shelf-life

Lettuce discolouration is a key post-harvest trait. The major enzyme controlling oxidative discolouration has long been considered to be polyphenol oxidase (PPO) however, levels of PPO and subsequent development of discolouration symptoms have not always correlated. The predominance of a latent state of the enzyme in plant tissues combined with substrate activation and contemporaneous suicide inactivation mechanisms are considered as potential explanations for this phenomenon. Leaf tissue physical properties have been associated with subsequent discolouration and these may be influenced by variation in nutrient availability, especially excess nitrogen and head maturity at harvest. Mild calcium and irrigation stress has also been associated with a reduction in subsequent discolouration, although excess irrigation has been linked to increased discolouration potentially through leaf physical properties. These environmental factors, including high temperature and UV light intensities, often have impacts on levels of phenolic compounds linking the environmental responses to the biochemistry of the PPO pathway. Breeding strategies targeting the PALand PPOpathway biochemistry and environmental response genes are discussed as a more cost-effective method of mitigating oxidative discolouration then either modified atmosphere packaging or post-harvest treatments, although current understanding of the biochemistry means that such programs are likely to be limited in nature and it is likely that they will need to be deployed alongside other methods for the foreseeable future

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was &gt;20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was &gt;20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to &gt; 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus