Dry powder pulmonary delivery of cationic PGA-co-PDL nanoparticles with surface adsorbed model protein.

Pulmonary delivery of macromolecules has been the focus of attention as an alternate route of delivery with benefits such as; large surface area, thin alveolar epithelium, rapid absorption and extensive vasculature. In this study, a model protein, bovine serum albumin (BSA) was adsorbed onto cationic PGA-co-PDL polymeric nanoparticles (NPs) prepared by a single emulsion solvent evaporation method using a cationic surfactant didodecyldimethylammonium bromide (DMAB) at 2% w/w (particle size: 128.64±06.01nm and zeta-potential: +42.32±02.70mV). The optimum cationic NPs were then surface adsorbed with BSA, NP:BSA (100:4) ratio yielded 10.01±1.19μg of BSA per mg of NPs. The BSA adsorbed NPs (5mg/ml) were then spray-dried in an aqueous suspension of L-leucine (7.5mg/ml, corresponding to a ratio of 1:1.5/NP:l-leu) using a Büchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae<4.46μm) of 70.67±4.07% and mass median aerodynamic diameter (MMAD) of 2.80±0.21μm suggesting a deposition in the respiratory bronchiolar region of the lungs.The cell viability was 75.76±03.55% (A549 cell line) at 156.25μg/ml concentration after 24h exposure. SDS-PAGE and circular dichroism (CD) confirmed that the primary and secondary structure of the released BSA was maintained. Moreover, the released BSA showed 78.76±1.54% relative esterolytic activity compared to standard BSA

Financial estimates against investors’ preferences:anchoring, denial and spillover effects

This experimental study investigates how the characteristics of an estimate in a sensitivity disclosure and the level of threat it presents to investors' preferences interact to influence investors’ risk judgments. Firstly, I predict and find that variation in an estimate affects not only investors’ judgment on a related issue but also their future judgments on an unrelated issue. Secondly, I predict and find that investors are more sensitive to variations in an estimate when information contained in the estimate presents less threat to their preferred conclusions than when it presents greater threat. Finally, I predict and find that investors perceive more uncertainty regarding the association between the disclosed risk factor and the estimated financial reporting item in the estimate when the information presents greater threat

Vague heuristics

Even when they are defined with precision, one can often read and hear judgments about the vagueness of heuristics in debates about heuristic reasoning. This opinion is not just frequent but also quite reasonable. In fact, during the 1990s, there was a certain controversy concerning this topic that confronted two of the leading groups in the field of heuristic reasoning research, each of whom held very different perspectives. In the present text, we will focus on two of the papers published in Psychological Review, wherein the arguments of each of these groups were presented:

Stimmensplitting und Koalitionswahl

Hat sich die Unabhängigkeitsstrategie der FDP bei der letzten Bundestagswahl ausgezahlt? Wäre die FDP erfolgreicher gewesen, wenn sie im Vorfeld klar signalisiert hätte, dass man eine Koalition mit der Union anstrebt? Wie war das bei den Grünen, die ja im Gegensatz zur FDP keine Zweifel aufkommen ließen? Natürlich können wir nicht wie in einer Simulation oder einem Experiment einfach den Wahlkampf wiederholen und noch einmal wählen lassen. Um eine befriedigende Antwort auf diese Frage zu finden, vergleichen wir den Kontext der Bundestagswahl 2002 mit den zurückliegenden Bundestagswahlen. Aus dem Längsschnittvergleich versuchen wir Rückschlüsse auf den substanziellen Einfluss von strategischem Stimmensplitting im Sinne einer Koalitionswahl auf das Wahlergebnis gerade der kleinen Parteien zu ziehen. Um unsere Forschungsfrage zu beantworten und substanzielle Schlüsse ziehen zu können, muss zuerst klar sein, in welcher Form und warum Stimmensplitting relevant sein kann, welche Rolle dabei Koalitionsabsprachen vor einer jeden Wahl spielen und, schließlich, welche alternativen Erklärungsmöglichkeiten die Literatur zum Thema Stimmensplitting und strategischem Wählen anzubieten hat. Nur wenn wir auch die Wirkung alternativer und zum Teil konkurrierender Hypothesen zulassen, können wir unserer Schlußfolgerungen sicher sein

Abi1 gene silencing by short hairpin RNA impairs Bcr-Abl-induced cell adhesion and migration in vitro and leukemogenesis in vivo

Abl interactor (Abi) 1 was first identified as the downstream target of Abl tyrosine kinases and was found to be dysregulated in leukemic cells expressing oncogenic Bcr-Abl and v-Abl. Although the accumulating evidence supports a role of Abi1 in actin cytoskeleton remodeling and growth factor/receptor signaling, it is not clear how it contributes to Bcr-Abl-induced leukemogenesis. We show here that Abi1 gene silencing by short hairpin RNA attenuated the Bcr-Abl-induced abnormal actin remodeling, membrane-type 1 metalloproteinase clustering and inhibited cell adhesion and migration on fibronectin-coated surfaces. Although the knock down of Abi1 expression did not affect growth factor-independent growth of Bcr-Abl-transformed Ba/F3 cells in vitro, it impeded competitive expansion of these cells in non obese diabetic (NOD)/ severe combined immuno-deficiency (SCID) mice. Remarkably, the knock down of Abi1 expression in Bcr-Abl-transformed Ba/F3 cells impaired the leukemogenic potential of these cells in NOD/SCID mice. Abi1 contributes to Bcr-Abl-induced leukemogenesis in part through Src family kinases, as the knock down of Abi1 expression attenuates Bcr-Abl-stimulated activation of Lyn. Together, these data provide for the first time the direct evidence that supports a critical role of Abi1 pathway in the pathogenesis of Bcr-Abl-induced leukemia

Rethinking the Target Corollary: The Effects of Social Distance, Perceived Exposure, and Perceived Predispositions on First-Person and Third-Person Perceptions

This study examines the effects of social distance, perceived exposure, and perceived predispositions on perceived media effects for desirable and undesirable health messages. It finds support for the effect social distance as traditionally measured; that is, groups that are more socially distant from the self, like the public, are perceived to be more affected by cigarette ads than close groups, such as friends. However, individual measures of respondents' social distance from any given comparison group generally are unrelated to perceived effects on the group. The influence of a group's perceived exposure on perceived message effects is confirmed for cigarette ads but not for desirable messages. Perceived attitudes of comparison groups toward message-relevant behaviors emerge as a factor that deserves inclusion in models of perceived effects.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Responses to gestational weight management guidance: a thematic analysis of comments made by women in online parenting forums

Background: The National Institute for Health and Clinical Excellence (NICE) published guidance on weight management in pregnancy in July 2010[1], and this received considerable press coverage across a range of media. This offered an opportunity to examine how gestational weight management guidance was received by UK women. Methods: A thematic analysis was conducted of 400 posts made in UK-based parenting internet forums in the week following the publication of the NICE guidance. This allowed us to examine the naturally occurring comments from 202 women who posted about the guidance on public forums. Results: Three main themes were identified and explored: i) Perceived control/responsibility ii) Risk perception iii) Confused messages. Conclusions: Women differed in their perceptions of the level of control that they had over being overweight with some feeling responsible and motivated to maintain a healthy lifestyle. Others felt there were multiple factors influencing their weight issues beyond their control. There were reports of feeling guilty about the impact of weight on the growing baby and experiencing significant obesity stigma from the public and health professionals. Information about the risks of overweight and obesity in pregnancy were difficult messages for women to hear, and for health professionals to deliver. Women reported being confused by the messages that they received. Health messages need to be delivered sensitively to women, and health professionals need support and training to do this. Risk information should always be accompanied with clear advice and support to help women to manage their weight in pregnancy. Keywords: internet-mediated research, gestational weight gain, parenting forums, NICE, women, views, risk perception</p

Genomic features of resistant <i>Klebsiella pneumonia</i>, isolated from the bloodstream and cerebrospinal fluid of pediatric hospital patients

Introduction. Carbapenemase-producing Klebsiella pneumoniae (CP-Kp), which are international high-risk clones, have become a problem of utmost importance. CP-Kps, adapting to the hospital environment, evolve into convergent pathotypes. Such variants combine traits of two genetic lineages: multidrug resistant (MDR) and hypervirulent. The pathotypes, along with MDR K. pneumoniae, pose an exceptional threat to young patients during systemic infection. The objective of this study is the detailed molecular genetic analysis of MDR isolates of K. pneumoniae detected during the monitoring of resistant Gram-negative bacteria at the National Medical Research Center for Children’s Health in 2014–2021. Materials and methods. Whole-genome sequencing with a subsequent bioinformatics analysis of eight MDR isolates from the bloodstream and cerebrospinal fluid. Results. MDR isolates belonged to 4 sublineages (SL): SL307, SL395, SL29 and SL1198. In the genomes of 6 pangrug-resistant (PDR) isolates, genes associated with resistance to all categories of antibiotics recommended for Enterobacteriaceae therapy were identified. Plasmids were present in all genomes. In 6 isolates, plasmids contained heavy metal ion resistance operons in addition to antibiotic resistance genes. Prophages within the plasmids were also involved in the transfer of resistance genes. The ST395 isolate from the cerebrospinal fluid belonged to the convergent pathotype in terms of resistance and virulence. Comparison of genomes within SLs revealed recombination events in the K- and O-locus regions and the Yersiniabactin operon. Conclusion. Thus, in a sample of resistant K. pneumoniae isolated from bloodstream and cerebrospinal fluid, 6 PDR isolates were detected, one of which belongs to the convergent pathotype ST395

Embracing the otherness of others: an approach for teacher educators to assuage social and political tribalism

We live in a corrosively polarized climate where sharply divided beliefs about globalization and populism magnify existing biases. This problem is exacerbated by the fact that those who want to educate the next generation – teacher candidates – have been schooled in systems that focus on obedience, conformity, and docility. This breadcrumbs approach to education bears the danger of reproducing the status quo rather than changing it. This chapter explores the promises, perils, and provocations of curriculum regarding how we think about diversity and delineates a learning experience for pre-service teachers that allows them to identify, approach, and become the Other. The lived experience illuminates the cultural and experiential origins of their beliefs while reconciling the uncomfortable notion that bias is part of the human condition. In times where sharpened divisions intensify social and political tribalism it is essential to understand that it is the way one acts upon one’s biases that determines what kind of world one creates