Design synthesis and biological evaluation of non-peptide neuropeptide FF ligands

Neuropeptide FF is an endogenous RF-amide with two receptor subtypes originally described as having anti-opioid characteristics. While peptide work helped to elucidate key features for targeting the subtypes of the neuropeptide FF receptor, non-peptide small molecules offer a more refined tool to discover features that affect selectivity and affinity. Improvements in small molecule ligands for neuropeptide FF support lead development and offer a clearer understanding of the binding pocket of each receptor subtype. Previous work on the lead 4–anilindopiperidine structure clarified a key feature between agonist and antagonist behavior. Early modifications of substituents of the piperidine nitrogen were tolerated and created selective ligands. Therefore, syntheses of aliphatic and aromatic substitutions of the piperidine nitrogen of a 4–anilinopiperdine lead molecule were conducted. In vitro evaluation of the novel compounds was conducted through a collaborator. Binding affinities of the novel compounds were determined through displacement of a radioligand ([3H]-NPVF for NPFF1 receptors and [3H]-EYF for NPFF2 receptors) and were conducted for each subtype. Though some of the compounds, such as cycloheptylmethyl substituted analog, did not bind within the limits of the assay to either subtype, other compounds, such as the cyclopropylmethyl and methylindole derivatives, did bind. The cyclopentylmethyl and methylindole derivatives offered a weak preference for the second subtype. The formalin assay offers an opportunity to evaluate neuropeptide FF in a tonic pain model. In summation, selective non-peptide ligands for each neuropeptide FF receptor offer a key tool to elucidating the evolving role of neuropeptide FF and creating potentially useful therapeutics in the future

Evaluating the Use of a Mobile App in High School Seniors to Monitor Cellphone Use While Driving: A Quality Improvement Project

Background: Motor vehicle accidents are the leading cause of death in teenagers in the United States. Driver distraction is responsible for more than 58% of teen crashes. Evidence from 9 critically appraised articles including two systematic reviews support the need to reduce distracted driving among teenagers; mobile applications along with education can impact behavioral change to encourage teens to refrain from this unsafe practice. Purpose: The use of the mobile application “Safe2Save” that financially rewards users for not unlocking their cellphone while driving may motivate teenagers to reduce this high-risk behavior. The global aim for this project is to incorporate education on distracted driving and the use of mobile apps into High School curriculum. The specific aim of this project is to decrease the amount students unlock their cellphone while driving over a 4-week period measured by the app “Safe2Save” and improve their perception related to distracted driving after education measured by the Distracted Driving Survey (DDS). Methods: Seniors at a high school volunteered to participate in this QI project. Baseline DDS results were collected, then students downloaded the app, received education, and submitted post-surveys. Data was collected from 11/2021 to 1/2022. Evaluation and adjustments were discussed allowing for recommendations for sustainability using IHI’s model of the Plan-Do-Study-Act. Results: Comparing students driving statistics showed an inconsistent correlation between using the app and decreasing cellphone use while driving. Comparison between pre-and post-DDS scores were not done. There was significant drop in post-DDS responses (n=6) compared to pre-DDS responses (n=15). Additionally, the responses to the survey were anonymous. However, both survey responses demonstrated viewing maps as the most prevalent reason to use a cellphone while driving. This calls for more concrete findings whether a mobile app and education reduces the amount teenagers use their cellphone while driving. Discussion: The outcome information suggests that it is uncertain if the use of a mobile app that financially rewards users will influence the amount individuals use their cellphone while driving. This project calls for additional studies to support the incorporation of education including mobile apps into High School curriculum

Manifestations of symbolism in architecture of postmodernism

The article analyses expression of symbolism in Lithuanian postmodern architecture. It discusses the concept of symbolism and transformations of its meaning in comparison to the period of modernism as well as examines its most significant aspects in semantic understanding of postmodernist architecture. The article seeks to disclose the forms of symbolism represented in Lithuanian architecture by the end of the 20th – the beginning of the 21st century. It searches for the most expressive examples of Lithuanian architecture of the given period by clarifying the character of postmodernist use of symbols. Attempts have been made to trace the expression trajectories of symbolism in contemporary architecture that have been influenced by postmodernism

Manifestations of postmodern ideas in Lithuanian architecture at the end of 20th – the beginning of the 21st century

Disertacijoje nagrinėjama Lietuvos postmodernizmo architektūra. Tyrimo tikslas yra atskleisti, kaip šis reiškinys, XX a. pab. jį perkėlus į sovietinį kontekstą, buvo lokaliai suvokiamas ir vertinamas; kaip ir kokiais būdais šio laikotarpio objektai Lietuvoje atliepia esmines postmodernizmo idėjas, kiek šios idėjos yra ypatingos ir specifinės; kokios buvo jų raiškos ypatybės; kaip jos nulėmė architektūros objektų koncepcijas, formas, estetinę raišką. Darbe sprendžiami šie uždaviniai: apžvelgiant postmodernizmo sampratą Vakarų filosofijoje bei kultūros teorijoje, atskleisti jos perkėlimo į architektūrą ypatybes; išnagrinėti, kaip postmodernizmas Lietuvoje buvo suvokiamas kultūros lauke, kaip jis buvo vertinamas architektų, architektūros kritikų ir visuomenės; nustatyti postmodernizmo architektūros diskurso Lietuvos architektūroje formavimosi aplinkybes, santykį su XX a. pabaigos sociokultūriniais procesais, jo dėsningumus ir ypatybes; įvardinti reikšmingiausius postmodernizmo architektūros objektus Lietuvoje, ištirti svarbiausius jų raiškos bruožus; atskleisti, kaip postmodernizmo idėjos įtakojo Lietuvos architektūros raidą, kokie postmodernizmo bruožai integravosi į architektų kūrybą, išnagrinėti jų vertę vadovaujantis chronologiniais, estetiniais, sociokultūriniais kriterijais. Mokslinio darbo naujumas – kompleksiškai ištirta postmodernizmo architektūros Lietuvoje raiška, nustatyti jos raidos pokyčiai, įvertintos meninės raiškos savybės. Kitas naujumo aspektas yra ne tik estetinė, bet ir socialinė šio reiškinio analizė, gilinantis į tai, kokiomis visuomenės gyvenimo aplinkybėmis buvo aktuali postmodernizmo architektūra. Nagrinėjamo laikotarpio pastatų bruožų ir savybių analizė naudinga XX a. pab. – XXI a. pr. Lietuvos architektūros menotyrinio ištirtumo plėtrai ir turi edukacinę reikšmę. Ištirti postmodernizmo architektūros pavyzdžiai ir jų vertingųjų savybių nustatymas padeda šio laikotarpio architektūros dokumentavimo, saugojimo ir vertinimo procesams, tyrimo metu gauti rezultatai gali būti pritaikyti naujausiojo paveldo vertingųjų savybių metodikai pagerinti

Gained in Translation. Postmodern Architecture in Late Soviet Lithuania

After being widely explored in the historiography of Western architecture, postmodernism has only recently started receiving adequate attention in Eastern and Central Europe. The phenomenon of postmodernism developed beyond the borders of the Soviet world, so the so-called “cultural logic of late capitalism” crossing the boundaries of the Iron Curtain has to be considered a consequence of globalization. On the other hand, this global trend was synchronized with the local expression of architecture: the pursuit of identity, attention to context and continuation of architectural traditions. Soviet publications presented postmodernism as a foreign phenomenon, but simultaneously noted that it could be useful to local architects as well. This did not imply an invitation to imitate Western colleagues, but rather signalled that certain architectural values had become globally significant to both, the capitalist and socialist industrial world. The text aims to uncover the local translations of (post)modernity in Lithuania in the context of the tendency’s peak period: the final decades of Soviet rule

ASSESSMENT OF THE REASONS FOR MIGRATION OF YOUNG PEOPLE OF WORKING AGE

Based on the analysis of scientific literature, the article explains the concept of emigration, the causes, and its negative and positive consequences. Mathematical and statistical analyses of emigration indicators in the context of the Baltic States and calculate statistical emigration forecasts. Research of Baltic statistics has shown that many highly qualified specialists emigrate from the countries that bring income. The article‘s main aim is to find out and investigate the reasons for the emigration of people of working age in Lithuania. To achieve the aim of the article, an empirical study is used, based on which it was found that the following reasons influence emigration from Lithuania: poor economic situation, desire to go to study, expanding the circle of acquaintances, and a feeling of social exclusion and personal problems that they seek to solve abroad. Keywords: Lithuania, emigration, reasons for emigration

Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol

AbstractDevelopment of physiologically relevant test methods to analyse potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimisation of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway™ tissue is a highly differentiated in vitro human airway culture derived from primary human tracheal/bronchial epithelial cells grown at the air–liquid interface, which can be exposed to aerosols generated by the VITROCELL® smoking robot. Method development was supported by understanding the compatibility of these tissues within the VITROCELL® system, in terms of airflow (L/min), vacuum rate (mL/min) and exposure time. Dosimetry tools (QCM) were used to measure deposited mass, to confirm the provision of e-cigarette aerosol to the tissues. EpiAirway™ tissues were exposed to cigarette smoke and aerosol generated from two commercial e-cigarettes for up to 6h. Cigarette smoke reduced cell viability in a time dependent manner to 12% at 6h. E-cigarette aerosol showed no such decrease in cell viability and displayed similar results to that of the untreated air controls. Applicability of the EpiAirway™ model and exposure system was demonstrated, showing little cytotoxicity from e-cigarette aerosol and different aerosol formulations when compared directly with reference cigarette smoke, over the same exposure time

A micro-CT-based method for quantitative brain lesion characterization and electrode localization

Lesion verification and quantification is traditionally done via histological examination of sectioned brains, a time-consuming process that relies heavily on manual estimation. Such methods are particularly problematic in posterior cortical regions (e.g. visual cortex), where sectioning leads to significant damage and distortion of tissue. Even more challenging is the post hoc localization of micro-electrodes, which relies on the same techniques, suffers from similar drawbacks and requires even higher precision. Here, we propose a new, simple method for quantitative lesion characterization and electrode localization that is less labor-intensive and yields more detailed results than conventional methods. We leverage staining techniques standard in electron microscopy with the use of commodity micro-CT imaging. We stain whole rat and zebra finch brains in osmium tetroxide, embed these in resin and scan entire brains in a micro-CT machine. The scans result in 3D reconstructions of the brains with section thickness dependent on sample size (12–15 and 5–6 microns for rat and zebra finch respectively) that can be segmented manually or automatically. Because the method captures the entire intact brain volume, comparisons within and across studies are more tractable, and the extent of lesions and electrodes may be studied with higher accuracy than with current methods