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To compare the intraocular pressure (IOP)-lowering efficacy and safety of netarsudil once daily (QD) and timolol twice daily (BID).Double-masked, randomized, phase 3, noninferiority study.Patients with open-angle glaucoma or ocular hypertension (unmedicated baseline IOP20 to30 mm Hg at 8:00 AM) were randomized to netarsudil ophthalmic solution 0.02% QD (PM) or timolol ophthalmic solution 0.5% BID. The primary endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3 in patients with baseline IOP25 mm Hg (per-protocol population). Safety was recorded over the 6-month treatment period.A total of 186 patients from each treatment arm were included in the primary efficacy analysis. Netarsudil QD met the criteria for noninferiority to timolol BID. Mean treated IOP ranged from 16.3 to 17.9 mm Hg for netarsudil and 16.7 to 17.6 for timolol, with mean reductions from baseline of 3.9 to 4.7 mm Hg and 3.8 to 5.2 mm Hg, respectively. In prespecified secondary analyses, netarsudil demonstrated noninferiority to timolol in patients with baseline IOP27 mm Hg and30 mm Hg. The IOP-lowering effects of netarsudil were sustained over 6 months of treatment. No treatment-related serious adverse event (AE) was reported for either study drug. However, statistically significant reductions in mean heart rate were recorded at all study visits for the timolol group. The most frequent ocular AE among netarsudil-treated patients was conjunctival hyperemia (47.9%), which was predominately mild.Netarsudil QD (PM), a first-in-class IOP-lowering medication, was noninferior to timolol BID and was associated with tolerable ocular AEs.

Entrepreneurship in higher education increasingly values entrepreneurial creativity as a key driver to enhance the innovation ability of university students. This study examines the relationship between entrepreneurship education and entrepreneurial creativity under a newly proposed framework that recognizes the role of inspiration in the creativity processes, and administered questionnaires among 1873 students across 36 universities in China, who have participated in entrepreneurship classes or maker space. Results reveal that effectiveness of entrepreneurship education has a strong positive correlation with entrepreneurial creativity, which is partially mediated by entrepreneurial inspiration through a bootstrap method test and a robustness test of the SEM model. This finding contributes to understanding the process of enhancing entrepreneurial creativity and promoting university creativity through entrepreneurship education.

Atypical asymmetries have been reported in individuals diagnosed with schizophrenia, linking higher symptom severity to weaker lateralization. Furthermore, both lateralization and schizophrenia are influenced by the dopaminergic system. However, whether a direct link between the etiology of schizophrenia and atypical asymmetries exists is yet to be investigated. In this study, we examined whether maternal immune activation (MIA), a developmental animal model for schizophrenia and known to alter the dopaminergic system, induces atypical lateralization in adolescent and adult offspring. As the dopaminergic system is a key player in both, we analyzed neuronal dopamine D2 receptor (DRD2) mRNA expression. MIA was induced by injecting pregnant rats with 10 mg/kg polyinosinic:polycytidylic (PolyI:C) at gestational day 15. Controls were injected with 0.9 % NaCl. Offspring were tested at adolescence or early adulthood for asymmetry of turning behavior in the open field test. The total number of left and right turns per animal was assessed using DeepLabCut. Strength and preferred side of asymmetry were analyzed by calculating lateralization quotients. Additionally, DRD2 mRNA expression in the prefrontal cortex of offspring at both ages was analyzed using real-time PCR. MIA was associated with a rightward turning behavior in adolescents. In adults, MIA was associated with an absence of turning bias, indicating reduced asymmetry after MIA. The analysis of DRD2 mRNA expression revealed significantly lower mRNA levels after MIA compared to controls in adolescent, but not adult animals. Our results reinforce the association between atypical asymmetries, reduced DRD2 mRNA expression, and schizophrenia. However, more preclinical research is needed.

Epigenetische Modifikation der DNA sind ein wichtiger Faktor in der Gehirnentwicklung, da sie die Genexpression unabhängig vom Genotyp verändern können. Umwelteinflüsse können epigenetische Muster verändern und so zu Psychopathologien führen. In dieser Arbeit wurden Untersuchungen in Menschen, Ratten und Mäusen kombiniert, um Veränderungen von Methylierungsmuster der DNA und Genexpression während der Gehirnentwicklung und bei Psychopathologien zu untersuchen. In Ratten wurde frühkindlicher Stress mittles \(\textit {maternal separation}\) induziert, was zu gesteigerter Angst und atypischer links Lateralisierung führte. Desweiteren wurden zwei Gene, \(\textit {MORC1}\) und \(\textit {GDAP1}\), auf ihre Sensitivität gegenüber Umwelteinflüssen und Psychopathologie charakterisiert, um mögliche Biomarker zu identifizieren. Die Studien deuten auf verschiedene vulnerable Zeitpunkte und besonders betroffene Gehirnregionen hin. Die Untersuchung von Methylierungsmustern in psychiatrischen Erkankungen birgt somit großes Potential.

Current therapies for treating pancreatic ductal adenocarcinoma (PDAC) are largely ineffective, with the desmoplastic environment established within these tumors being considered a central issue. We established a 3D spheroid co-culture in vitro model using a PDAC cell line (either PANC-1 or Capan-2), combined with stellate cells freshly isolated from pancreatic tumors (PSC) or hepatic lesions (HSC), and human type I collagen to analyze the efficiency of the chemotherapeutic gemcitabine (GEM) as well as two novel drug candidates derived from natural products: pseudopterosin (PsA-D) and O-methyltylophorinidine (TYLO). Traditional 2D in vitro testing of these agents for cytotoxicity on PANC-1 demonstrated IC50 values of 4.6 (&plusmn, 0.47) nM, 34.02 (&plusmn, 1.35) &micro, M, and 1.99 (&plusmn, 0.13) &micro, M for Tylo, PsA-D, and GEM, respectively, these values were comparable for Capan-2: 5.58 (&plusmn, 1.74) nM, 33.94 (&plusmn, 1.02) &micro, M, and 0.41 (&plusmn, 0.06) &micro, M for Tylo, PsA-D, and GEM, respectively. Importantly, by assessing the extent of viable cells within 3D co-culture spheroids of PANC-1 with PSC or HSC, we could demonstrate a significant lack of efficacy for GEM, while TYLO remained active and PsA-D showed slightly reduced efficacy: GEM in PANC-1/PSC (IC50 = &gt, 100 &micro, M) or PANC-1/HSC (IC50 = &gt, M) spheroids, TYLO in PANC-1/PSC (IC50 = 3.57 &plusmn, 1.30 nM) or PANC-1/HSC (IC50 = 6.39 &plusmn, 2.28 nM) spheroids, and to PsA-D in PANC-1/PSC (IC50 = 54.42 &plusmn, 12.79 &micro, M) or PANC-1/HSC (IC50 = 51.75 &plusmn, 0.60 &micro, M). Microscopic 3D rendering supported these cytotoxicity outcomes, showing little or no morphological spheroid structure change during this period of rapid cell death. Our results support the use of this 3D spheroid co-culture in vitro model having a desmoplastic microenvironment for the identification of possible novel chemotherapeutic drug candidates for PDAC, such as TYLO and PsA-D.

Atypical leftward behavioral asymmetries have been associated with early life stress and psychopathologies in humans and animals. Maternal separation (MS) is a frequently used model to investigate early life stress and psychopathologies but has not yet been studied in terms of asymmetries. This study aims to investigate whether prolonged MS induces atypical leftward asymmetries in the turning behavior of rats. MS was performed from postnatal days 2-20 followed by a second stressor from postnatal days 21-40. Asymmetry of turning behavior was then examined in the elevated plus-maze test upon weaning (juveniles and dams) or adolescence. The number of left and right turns was calculated per animal using the deep learning software package DeepLabCut enabling markerless pose estimation. Then, a lateralization quotient (LQ) was determined for each animal allowing to investigate the strength as well as the preferred side of asymmetry. LQ analysis revealed a significant leftward asymmetry in the prolonged stress group. Moreover, analyzing the number of turns revealed significantly more left than right turns in total in this group. Control animals showed no asymmetries in turning behavior. These results indicate that prolonged stress during the early postnatal days led to atypical leftward turning behavior. The stress-induced atypical asymmetry might be a mediator of early life stress and the development of psychiatric disorders.

Introduction. While school-based kitchen garden programs are shown to improve fruit and vegetable consumption and knowledge among children, there has been little research on participant perceptions of these programs, specifically among minority populations that are disproportionately affected by and at high risk for overweight and obesity. This qualitative study examined the perceptions of and values associated with participation in school-based kitchen garden programs implemented through Edible Schoolyard New Orleans in low-income, predominantly African American schools in New Orleans, Louisiana. Method. Qualitative data were collected through semistructured focus group discussions with key stakeholder groups at schools offering Edible Schoolyard New Orleans. Results. A total of 10 focus groups were conducted across 4 middle schools with students ( n = 27), parents ( n = 17), and teachers ( n = 17). Four primary themes emerged during data analysis: development of life skills, food and health, family and community, and experiential and participatory learning. Conclusions. To strengthen the sustainability and potential impact of school-based kitchen garden programs, future intervention strategies should place specific emphasis on the themes that emerged from this study. School-based kitchen garden programs may be a promising strategy to positively influence the individual, social, and physical environmental factors that contribute to overweight and obesity in low-income, African American communities.

Objectives To clarify the effectiveness of perinatal social support interventions in reducing postpartum depression among minority, low-income women. Methods The Transdisciplinary Research Consortium for Gulf Resilience on Women's Health supported a community-based participatory research project to improve perinatal health among low-income, first-time pregnant women living in a vulnerable Gulf Coast region. Community health workers (CHWs) were partnered with recruited women, and used a mix of mobile technology and home visits to develop a supportive relationship during the perinatal period. Results Women enrolled in the CHW-led intervention had lower (F: 2.38, p = 0.04) average postpartum depression scores (EPDS) 6 months postpartum than a comparison population. The difference, however, was not seen among women in the intervention group who reported relatively poor relationships with their CHWs. Conclusions for Practice Results reinforce the evidence that perinatal social support can affect postpartum depression outcomes. CHWs are increasingly utilized by public programs to reach at-risk populations. We discuss the potential efficacy of CHW programs, but also, the need to pair outreach with effective monitoring and evaluation of the relationship development between CHW and clients.

Computational studies of low spin d6 cis– and trans–[M(DABF)2A2]+ complexes (M = Co, Rh, Ir; A = anionic ligand) employing multiple model chemistries find that cis geometries are preferred for complexes where the binding atom in A is high and/or to the left in the Periodic Table, while trans geometries are preferred for complexes where the binding atom is heavy or to the right of the Periodic Table. This holds despite the fact that consideration of the trans influence for the π-acceptor spectator DABF ligand suggest that all such complexes should prefer cis geometries. Energy decomposition analysis ties the phenomenon mostly to the degree of DFT exchange; that this benefits trans geometries more than cis geometries is thought to arise from the greater electronic symmetry of the former. This is supported by predictions for haloborane complexes [M(DABF)2(BX2)2]+. In contrast, [M(CO)4A2]+ complexes, containing better π-accepting CO spectator ligands (presumably higher in the trans influence series), are predicted to prefer cis geometries except for the halogen complexes [M(CO)4X2]+ (X = F, Cl, I), where no distinct preferences exist.

To describe the changes in endothelial cell density (ECD), the coefficient of variation (CV), and the percent of hexagonal cells (%HEX) after 3 months of therapy with netarsudil (Rhopressa; Aerie Pharmaceuticals Inc, Durham, NC) 0.02% dosed once daily (QD) or twice daily (BID) and to compare these changes with those seen with timolol 0.5% BID in eyes with ocular hypertension (OHTN) or open-angle glaucoma (OAG).Post hoc analysis of data from a phase 3 evaluation of the intraocular pressure (IOP)-lowering efficacy and safety of netarsudil 0.02% versus timolol 0.5%.A subset of study subjects underwent corneal endothelial cell imaging by specular microscopy at baseline and after 3 months of therapy.Images were evaluated in a masked fashion at an independent reading center. The ECD, CV, and %HEX were determined using a standardized protocol for image analysis.Changes in ECD, CV, and %HEX from baseline to 3 months were compared between treatment groups using 2-sample t tests.Data from 386 subjects from whom analyzable specular microscopy images were obtained at both baseline and month 3 were included in this analysis. Mean ECD, CV, and %HEX values were comparable between groups at baseline. There were no statistically significant between-group differences in changes from baseline to month 3 in ECD, CV, or %HEX between either of the netarsudil groups and the timolol group. Within groups, CV declined in a statistically significant fashion from baseline to month 3 in all 3 groups by 1.4% to 2.1% (P0.001), and %HEX increased by a statistically significant amount (0.7%, P = 0.030) in the timolol group. These small changes were unlikely to be of clinical significance. No statistically significant changes in ECD were seen in any group.Netarsudil 0.02% showed no clinically significant effects on ECD, CV, or %HEX when dosed QD or BID for 3 months in eyes with OHTN or OAG.

Following environmental health disasters such as Hurricane Katrina and the Gulf Oil Spill, U.S. Gulf residents expressed concern regarding air quality. Women with children make many decisions that mitigate household air quality risks; however, research examining culture's influence in their risk perception and the influence which this has on their behaviour is limited. In this article we examine the cultural connection between low-income women with children along the U.S. Gulf concerning the local threat of air quality. We used cultural consensus analysis to examine the perceptions of low-income, first-time pregnant women. We undertook an interview survey of 112 women living in Southeast Louisiana, USA between May 2014 and March 2015. In this article we examine if there was a shared (cultural) understanding among these women on how to manage air quality threats, to evaluate what determined cultural sharing in the group, and to explore what role cultural beliefs played in their intended household strategies. We found that although air quality was rarely discussed by the women in our study, we were able to identify two multi-centric cultural models of how these women sought to make sense of air quality issues. In one model they relied on their immediate social network of family and friends while in the other model they were willing to make use of official sources of information. These two models helped explain what measures these women planned to take to address air quality issues in an around their household. Our findings show that cultural norms permeate the assessment of risk in a community and that programmes designed to improve public health need to take into account the cultural context of the population.

Even though lithium is widely used as treatment for mood disorders, the exact mechanisms of lithium in the brain remain unknown. A potential mechanism affects the downstream target of the Wnt/β-catenin signaling pathway, specifically glutamine synthetase (GS). Here, we investigate the effect of lithium on GS-promoter activity in the brain. Over seven days, B6C3H-Glultm(T2A-LacZ) mice that carry LacZ as a reporter gene fused to the GS-promotor received either daily intraperitoneal injections of lithium carbonate (25 mg/kg) or NaCl, or no treatment. Following histochemical staining of β-galactosidase relative GS-promotor activity was measured by analyzing the intensity of the staining. Furthermore cell counts were conducted. GS-promotor activity was significantly decreased in female compared to male mice. Treatment group differences were only found in male hippocampi, with increased activity after NaCl treatment compared to both the lithium treatment and no treatment. Lithium treatment increased the overall number of cells in the CA1 region in males. Daily injections of NaCl might have been sufficient to induce stress-related GS-promotor activity changes in male mice; however, lithium was able to reverse the effect. Taken together, the current study indicates that lithium acts to prevent stress, rather affecting general GS-promoter activity.

Background: Both the fitness and gamification industry are booming with no signs of slowing down in the near future. Gamified applications are entering the markets, attempting to induce gameful elements into tedious environments to enhance intrinsic motivation. The same goes for the gym sector, as market leaders, such as the Swedish gym chain Nordic Wellness, are increasingly implementing gamification elements into their business models. Problem: The true effectiveness of gamification on intrinsic motivation remains underdeveloped. Literature highlights the necessity of adapting gamification design towards the end-user, by considering the different effects from the individual game elements and the context. However, the gym context has been completely neglected, even though gamification has become increasingly utilized in this sector. Purpose: The purpose of this study is to increase the body of knowledge on how extrinsic mechanisms such as gamification can influence intrinsic motivation. This study utilizes the context of a gamified gym application for Nordic Wellness to determine the motivational potential of game elements. Thereby, the research team attempts to add to the body of literature by expanding on the effectiveness of gamification on intrinsic motivation, while also contributing through entering a currently undiscovered domain of gamification in the gym context. Method: A qualitative approach with fifteen semi-structured interviews has been conducted on young Swedish adults attending the Swedish gym chain Nordic Wellness. Results: The findings suggest Self-Determination Theory as a valid framework to examine the effects of gamification on intrinsic motivations. Through connecting the identified themes and theory, a framework is proposed for the evaluation on the effectiveness of game elements on intrinsic motivation. From evaluating the discussed game elements through this framework, recommendations are made for a gamified gym application that is argued to positively satisfy the psychological needs and therefore enhance the intrinsic motivations in a gym context.

DNA methylation and demethylation can be influenced by several environmental factors including diet, smoking, drug consumption, parental behavior and stress. Given that methylation changes can lead to altered gene transcription their impact can be enormous. Therefore, it is very important to understand the processes and underlying factors influencing methylation. Changes in DNA methylation that occur early during development induce altered gene expression that can affect the development of the brain and other organs right from the beginning. Stress during early development is linked to an increased risk for psychiatric and physiological disorders and altered DNA methylation could be the mediating factor. Whether the addition or the removal of methyl groups is linked to psychiatric outcome depends on several factors like the specific gene and the exposure. There are different approaches to investigate this relationship and to identify risk genes. Some groups focus on the mediating effect of gene methylation on early life stress exposure and psychiatric outcome. Another approach is the study of gene methylation in adults with already diagnosed psychiatric disorders. Others investigated the reversible effect of psychotherapy on gene methylation in patients. Only a few studies correlate gene methylation in healthy adults with subclinical symptoms.

Flugreisen werden immer popul��rer, allein 2014 wurden in ��sterreich 4,3 Millionen Fl��ge durchgef��hrt. An gro��en Flugh��fen ist es f��r Reisende jedoch problematisch sich zu orientieren. Aktuelle Fluginformationen werden h��ufig nur mittels ��bersichtstafeln angeboten. Zudem sind Wegweiser und Beschilderungen der vorhandenen Gesch��fte und Services oft sp��rlich. Viele Flughafenbetreiber scheinen die rasante technische Entwicklung der letzten Jahre nicht nutzen zu k��nnen, um diese Situation zu verbessern. Die vorliegende Diplomarbeit greift diese Problematik auf und untersucht das Optimierungspotenzial durch die Verwendung einer mobilen Anwendung. Smartphones und Tablets, die heutzutage von den meisten Reisenden mitgef��hrt werden, bieten eine hervorragende Plattform f��r ein mobiles Informationsund Orientierungssystem. Die Ziele dieser Diplomarbeit sind die Ermittlung wichtiger Funktionen f��r Flughafen-Apps, das Aufzeigen von Schw��chen in bestehenden L��sungen und die Pr��sentation einer konkreten Umsetzung anhand eines Prototypen. Zu diesem Zweck wurde ein Kriterienkatalog definiert, der wichtige Funktionen von Flughafen-Apps umfasst. Basierend auf diesem Kriterienkatalog wurden sieben ausgew��hlte Flughafen-Apps analysiert und 10 Hauptfunktionen identifiziert. Nahezu jede der getesteten Apps bot diese 10 Funktionen an. Dar��ber hinaus wurden Anwendungsszenarien entwickelt, anhand derer die ausgew��hlten Flughafen-Apps ein weiteres Mal analysiert wurden. Ziel der zweiten Analyse war die Bewertung der Anwenderfreundlichkeit auf Basis von Heuristiken. Die gewonnenen Erkenntnisse konnten anschlie��end verwendet werden, um einen Prototypen zu entwickeln, der die aufgedeckten Schw��chen vermeidet. Die Entwicklung des Prototypen folgte einem benutzerorientierten Prozessmodell, beginnend bei der Identifizierung potentieller Anwender und deren Bed��rfnisse. F��r die erarbeiteten Benutzergruppen wurde in weiterer Folge ein entsprechend abgestimmtes Design entworfen. Anwendertests zur Bewertung der Benutzeroberfl��che waren ein wesentlicher Bestandteil des Entwicklungsprozesses. Die Evaluierung bestehender Flughafen-Apps zeigte, dass diese zum Teil gravierende Designschw��chen aufweisen. Bereits der erste Entwurf des entwickelten Prototypen konnte bessere Ergebnisse erzielen als die meisten getesteten Apps. Im Zuge dieser Diplomarbeit wurde ein Prozessmodell vorgestellt, das konkrete Techniken zur Entwicklung neuer Flughafen-Apps pr��sentiert. Der Kriterienkatalog und das Prozessmodell wurden speziell f��r Flughafen-Apps entwickelt. Die Verwendung des Modells in anderen Anwendungsbereichen wird im Rahmen der Arbeit diskutiert. Weiterhin konnten auf Basis der Marktanalyse und der Anwendertests des Prototypen Design-Richtlinien extrahiert werden, die bei der Entwicklung neuer Flughafen-Apps unterst��tzen., Air travel has become increasingly popular. In Austria, there were 4.3 million flights in 2014. At airports, typical problems for travelers include orientation and information retrieval regarding flights, available shops or offered services. Most often, this information is provided only by signposts and flight overview panels. This thesis presents ideas and approaches for a mobile application to optimize the time for travelers at airports. Smartphones and tablets, which are carried by most travelers today, would be ideal platforms to implement an information and orientation system for the everyday traveler. The objectives of this thesis are to determine important functions for airport applications, reveal weaknesses of existing solutions and develop a prototype that solves the presented problems. To this end, a criteria catalog was developed that covers important features of airport applications. Using this catalog, seven selected airport applications were evaluated. As a result, 10 main features implemented by nearly every tested application were determined. Additionally, use case scenarios were developed based on the main features. These scenarios were used to analyze the airport applications a second time. The objective of this second analysis was to assess the usability through defined heuristics. Results were used to develop a prototype that avoids the detected weaknesses. The prototype development followed a user-centered design process. First, potential users and their needs were identified. The resulting user groups contributed significantly to the design process of an appropriate user interface. User tests of the developed design were a central element of this process model. The evaluation of existing airport applications revealed serious design weaknesses. Even the first draft of the developed prototype achieved better results than most tested applications. As part of this thesis, a process model is introduced, which presents concrete techniques to create new airport applications. The criteria catalog and the process model have been designed for the field of airport applications. The applicability of the presented process model in different areas of mobile application development is discussed. Finally, relevant airport application design guidelines were presented as a guidance for future airport application development teams.

Repressor protein period (PER) complexes play a central role in the molecular oscillator mechanism of the mammalian circadian clock. While the main role of nuclear PER complexes is transcriptional repression, much less is known about the functions of cytoplasmic PER complexes. We found with a biochemical screen for PER2-interacting proteins that the small GTPase regulator GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), which has been identified previously as a component of cytoplasmic PER complexes in mice, is also a bona fide component of human PER complexes. We show that in situ GAPVD1 is closely associated with casein kinase 1 delta (CSNK1D), a kinase that regulates PER2 levels through a phosphoswitch mechanism, and that CSNK1D regulates the phosphorylation of GAPVD1. Moreover, phosphorylation determines the kinetics of GAPVD1 degradation and is controlled by PER2 and a C-terminal autoinhibitory domain in CSNK1D, indicating that the regulation of GAPVD1 phosphorylation is a novel function of cytoplasmic PER complexes and might be part of the oscillator mechanism or an output function of the circadian clock.